SYRE Spyre Therapeutics Inc

This Amendment No. 2 on Form 10-K/A (this “Amendment”) amends the Annual Report on Form 10-K of Spyre Therapeutics, Inc. (the “Company”) for the fiscal year ended December 31, 2023, as filed with the Securities and Exchange Commission on February 29, 2024, as amended by Form 10-K/A of the Company filed with the Securities and Exchange Commission on March 1, 2024 (as amended, the "Original Filing").

Subsequent to the filing of its Form 10-Q for the three and nine months ended September 30, 2024, the Company became aware of a misapplication of Generally Accepted Accounting Principles in the United States ("U.S. GAAP") as it relates to the Company's exclusion of its Series A non-voting convertible preferred stock and Series B non-voting convertible preferred stock in the calculation of basic and diluted net loss per share and a finding of a material weakness in internal control over financial reporting solely related to such matter. This Amendment is being filed for the sole purpose of amending certain disclosures from the Original Filing related to the aforementioned misapplication of U.S. GAAP and related finding of material weakness in internal control over financial reporting.

Specifically, this Amendment amends: (i) Part II, Item 8. "Financial Statements and Supplementary Data" to update the Company's Consolidated Statement of Operations and related footnote disclosures for the twelve months ended December 31, 2023, (ii) Part II, Item 9A. "Controls and Procedures" to address management's re-evaluation of disclosure controls and procedures as of December 31, 2023 and to reflect the identification of a material weakness in our internal control over financial reporting and (iii) Part IV, Item 15. "Exhibits and Financial Statement Schedules" to include, in accordance with Rule 12b-15 under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), updated certifications from our Chief Executive Officer and Chief Financial Officer as required by Sections 302 and 906 of the Sarbanes-Oxley Act of 2002 as Exhibits 31.1, 31.2 and 32.1 and an updated Consent of Independent Registered Public Accounting Firm as Exhibit 23.1. In accordance with Rule 12b-15 under the Exchange Act, this Amendment amends and restates in their entirety each item identified in the paragraph above.

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Spyre Therapeutics, Inc., formerly Aeglea BioTherapeutics, Inc., (“Spyre” or the “Company”) is a preclinical stage biotechnology company focused on developing next generation therapeutics for patients living with inflammatory bowel disease. The Company was formed as a Limited Liability Company ("LLC") in Delaware on December 16, 2013 under the name Aeglea BioTherapeutics Holdings, LLC and was converted from a Delaware LLC to a Delaware corporation on March 10, 2015. On November 27, 2023, the Company completed its corporate rebranding, changing the name of the Company to Spyre Therapeutics, Inc. The Company operates in one segment and has its principal offices in Waltham, Massachusetts.

On September 8, 2023, the Company effected a reverse stock split of its Common Stock at a ratio of 1-for-25 (the “Reverse Split”). Except as indicated otherwise, all share numbers related to the Company's Common Stock disclosed in these financial statements have been adjusted on a post-Reverse Split basis.

On April 12, 2023, based on the review of the inconclusive interim results from the Company's Phase 1/2 clinical trial of pegtarviliase for the treatment of Classical Homocystinuria and other business considerations, the Company announced that it had initiated a process to explore strategic alternatives to maximize stockholder value and engaged an independent exclusive financial advisor to support this process. As a result, in April 2023, the Company implemented a restructuring plan resulting in an approximate 83% reduction of the Company’s existing headcount.

On June 22, 2023, the Company acquired, in accordance with the terms of the Agreement and Plan of Merger (the "Acquisition Agreement"), the assets of Spyre Therapeutics, Inc. (“Pre-Merger Spyre”) as disclosed in Note 7 and 8, a privately held biotechnology company advancing a pipeline of antibody therapeutics with the potential to transform the treatment of inflammatory bowel disease through a research and development option agreement ("Paragon Agreement") with Paragon Therapeutics ("Paragon"). The asset acquisition was accomplished through a two-step reverse triangular merger whereby a wholly owned subsidiary of the Company merged with and into Pre-Merger Spyre, which existed at the time the Acquisition Agreement was entered into, became a wholly owned subsidiary of the Company in accordance with the terms of the Acquisition Agreement. Immediately following this merger, Pre-Merger Spyre merged with an into a second wholly subsidiary of the Company (“Merger Sub”) in accordance with the terms of the Acquisition Agreement and Pre-Merger Spyre ceased to exist. Subsequently, Aeglea BioTherapeutics, Inc. was renamed Spyre Therapeutics, Inc. and is a different entity than Pre-Merger Spyre, which ceased to exist upon merging with Merger Sub. The transaction was structured as a stock-for-stock transaction pursuant to which all of Pre-Merger Spyre's outstanding equity interests were exchanged based on a fixed exchange ratio of 0.5494488 to 1 for consideration from the Company of 517,809 shares of common stock and 364,887 shares of Series A non-voting convertible preferred stock, par value of $0.0001 per share ("Series A Preferred Stock") (convertible on a 40 to 1 basis), in addition to the assumption of outstanding and unexercised stock options to purchase 2,734 shares of common stock from the Amended and Restated Spyre 2023 Equity Incentive Plan (the "Asset Acquisition"). The common stock and Series A Preferred Stock related to the Asset Acquisition were issued to the Pre-Merger Spyre stockholders on July 7, 2023. For additional information, see Note 8.

In connection with the Asset Acquisition, on June 26, 2023, the Company completed a private placement of shares of Series A Preferred Stock (the “Series A PIPE”) to a group of investors (the “Series A Investors”). The Company sold an aggregate of 721,452 shares of Series A Preferred Stock (the “Series A PIPE Securities”) for an aggregate purchase price of approximately $210.0 million before deducting approximately $12.7 million of placement agent and other offering expenses. For additional information, see Note 11.

In connection with the Asset Acquisition, a non-transferable contingent value right ("CVR") was distributed to stockholders of record of the Company as of the close of business on July 3, 2023 (the "Legacy Stockholders"), but was not distributed to the holders of shares of common stock or Series A Preferred Stock issued to the former stockholders of Pre-Merger Spyre or Investors in the Transactions. Holders of the CVRs will be entitled to receive cash payments from proceeds received by the Company for a 3-year period related to the disposition or monetization of its legacy assets for a period of one-year following the closing of the Asset Acquisition. For additional information, see Note 3.

On November 21, 2023, the Company's stockholders approved the conversion of the Company's Series A non-voting convertible preferred stock to Common Stock. For additional information, see Note 11.

On December 11, 2023, the Company completed a private placement of shares of common stock and Series B non-voting convertible preferred stock, par value of $0.0001 per share ("Series B Preferred Stock") (convertible on a 40 to 1 basis) (collectively, the “December 2023 PIPE”) to a group of investors (the “December 2023 PIPE Investors”). The Company sold an aggregate of 6,000,000 shares of Common Stock and 150,000 shares of Series B Preferred Stock (the “December 2023 PIPE Securities”) for an aggregate purchase price of approximately $180.0 million before deducting approximately $10.9 million of placement agent and other offering expenses. For additional information, see Note 11.

Liquidity

The Company is a preclinical stage biotechnology company with a limited operating history, and due to its significant research and development expenditures, the Company has generated operating losses since its inception and has not generated any revenue from the commercial sale of any products. There can be no assurance that profitable operations will ever be achieved, and, if achieved, whether profitability can be sustained on a continuing basis.

Since its inception and through December 31, 2023, the Company has funded our operations by raising an aggregate of approximately $896.2 million of gross proceeds from the sale and issuance of convertible preferred stock and common stock, pre-funded warrants, the collection of grant proceeds, and the licensing of its product rights for commercialization of pegzilarginase in Europe and certain countries in the Middle East. As of December 31, 2023, Spyre had an accumulated deficit of $764.4 million, and cash, cash equivalents, and marketable securities of $339.3 million.

Based on current operating plans, the Company has sufficient resources to fund operations for at least one year from the issuance date of these financial statements with existing cash, cash equivalents, and marketable securities. Spyre will need to secure additional financing in the future to fund additional research and development, and before a commercial drug can be produced, marketed and sold. If the Company is unable to obtain additional financing or generate license or product revenue, the lack of liquidity could have a material adverse effect on the Company.

Basis of Presentation

The consolidated financial statements have been prepared in conformity with generally accepted accounting principles in the United States (“U.S. GAAP”) as defined by the Financial Accounting Standards Board (“FASB”) and include the accounts of the Company and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation.

Use of Estimates

The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets, liabilities, and equity and the amount of revenues and expenses. Actual results could differ significantly from those estimates. The most significant estimates and assumptions that management considers in the preparation of the Company's financial statements relate to the valuation of consideration transferred in acquiring in-process research & development ("IPR&D"); the discount rate, probabilities of success, and timing of estimated cash flows in the valuation of the CVR liability; inputs used in the Black-Scholes model for stock-based compensation expense; estimated future cash flows used in calculating the impairment of right-of-use lease assets; and estimated cost to complete performance obligations related to revenue recognition. The consideration transferred in acquiring IPR&D in connection with the acquisition of Pre-Merger Spyre was comprised of shares of the Company’s Common Stock and shares of Series A Preferred Stock. To determine the fair value of the equity transferred, the Company considered the per share value of the Series A PIPE securities, which was a financing event involving a group of accredited investors.

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Cash and Cash Equivalents

The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist of money market funds and debt securities and are stated at fair value.

Marketable Securities

All investments have been classified as available-for-sale and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments in debt securities at the time of purchase. The Company may hold securities with stated maturities greater than one year until maturity. All available-for-sale securities are considered available to support current operations and are classified as current assets. The Company presents credit losses as an allowance rather than as a reduction in the amortized cost of the available-for-sale securities.

For available-for-sale debt securities in an unrealized loss position, the Company first assesses whether it intends to sell, or it is more likely than not that it will be required to sell the security before recovery of its amortized cost basis. If either of the criteria regarding intent or requirement to sell is met, the security’s amortized cost basis is written down to fair value and recognized in other income (expense) in the results of operations. For available-for-sale debt securities that do not meet the aforementioned criteria, the Company evaluates whether the decline in fair value has resulted from credit losses or other factors. In making this assessment, management considers the extent to which fair value is less than amortized cost, any changes to the rating of the security by a rating agency, and adverse conditions specifically related to the security, among other factors. If this assessment indicates that a credit loss exists, an allowance is recorded for the difference between the present value of cash flows expected to be collected and the amortized cost basis of the security. Impairment losses attributable to credit loss factors are charged against the allowance when management believes an available-for-sale security is uncollectible or when either of the criteria regarding intent or requirement to sell is met.

Any unrealized losses from declines in fair value below the amortized cost basis as a result of non-credit loss factors is recognized as a component of accumulated other comprehensive (loss) income, along with unrealized gains. Realized gains and losses and declines in fair value, if any, on available-for-sale securities are included in other income (expense) in the results of operations. The cost of securities sold is based on the specific-identification method.

Restricted Cash

Restricted cash consisted of money market accounts held by financial institutions as collateral for the Company’s obligations under a credit agreement and a facility lease for the Company’s corporate headquarters in Austin, Texas. The lease was terminated in August 2023 and the cash was subsequently unrestricted. Remaining restricted cash balances relate to the Company's operations in the United Kingdom.

Concentration of Credit Risk

Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, marketable securities, and restricted cash. The Company’s investment policy limits investments to high credit quality securities issued by the U.S. government, U.S. government-sponsored agencies, highly rated banks, and corporate issuers, subject to certain concentration limits and restrictions on maturities. The Company’s cash, cash equivalents, marketable securities, and restricted cash are held by financial institutions that management believes are of high credit quality. The financial instruments that potentially subject the Company to a concentration of credit risk consist principally of cash deposits. Accounts at each of the Company's two U.S. banking institutions are insured by the Federal Deposit Insurance Corporation (“FDIC”) up to $250,000 per depositor. As of December 31, 2023 and 2022, balances at the Company's U.S. banking institutions exceeded the FDIC limits. The Company has not experienced any losses on its deposits of cash, cash equivalents, and restricted cash and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash, cash equivalents, and restricted cash, and bond issuers.

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Property and Equipment

Property and equipment are stated at cost, net of accumulated depreciation and amortization. Depreciation and amortization are computed using the straight-line method over the estimated useful lives of the assets. Repairs and maintenance that do not extend the life or improve an asset are expensed as incurred. Upon retirement or sale, the cost of disposed assets and their related accumulated depreciation and amortization are removed from the balance sheet. Any gain or loss is credited or charged to operations.

The useful lives of the property and equipment are as follows:

Laboratory equipment			5 years
Furniture and office equipment			5 years
Computer equipment			3 years
Software			3 years
Leasehold improvements			Shorter of remaining lease term or estimated useful life

Impairment of Long-Lived Assets

Long-lived assets are reviewed for indications of possible impairment whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable. Recoverability is measured by comparison of the carrying amounts to the future undiscounted cash flows attributable to these assets. An impairment loss is recognized to the extent an asset group is not recoverable, and the carrying amount exceeds the fair value. The Company recognized a $2.6 million impairment loss for the year ended December 31, 2023 related to its leased office space in Austin, Texas (see Note 17 for additional information). There were no impairments of long-lived assets for the years ended December 31, 2022 and 2021.

Accrued Research and Development Costs

The Company records the costs associated with research nonclinical studies, clinical trials, and manufacturing development as incurred. These costs are a significant component of the Company’s research and development expenses, with a substantial portion of the Company’s on-going research and development activities conducted by third-party service providers, including contract research organizations ("CROs") and contract manufacturing organizations ("CMOs"), and the Company's related-party Paragon.

The Company accrues for expenses resulting from obligations under the Paragon Agreement and agreements with CROs, CMOs, and other outside service providers for which payment flows do not match the periods over which materials or services are provided to the Company. Accruals are recorded based on estimates of services received and efforts expended pursuant to agreements established with Paragon, CROs, CMOs, and other outside service providers. These estimates are typically based on contracted amounts applied to the proportion of work performed and determined through analysis with internal personnel and external service providers as to the progress or stage of completion of the services. The Company makes significant judgments and estimates in determining the accrual balance in each reporting period. In the event advance payments are made to Paragon, a CRO, CMO, or outside service provider, the payments will be recorded as a prepaid asset which will be amortized as the contracted services are performed. As actual costs become known, the Company adjusts its accruals. Inputs, such as the services performed, the number of patients enrolled, or the study duration, may vary from the Company’s estimates, resulting in adjustments to research and development expense in future periods. Changes in these estimates that result in material changes to the Company’s accruals could materially affect the Company’s results of operations. Historically, the Company has not experienced any material deviations between accrued and actual research and development expenses.

Leases

The Company determines if an arrangement is a lease at inception. Right-of-use ("ROU") assets represent the Company's right to use an underlying asset for the lease term and lease liabilities represent the Company's obligation to make lease payments arising from the lease. The classification of the Company's leases as operating or finance leases along with the initial measurement and recognition of the associated ROU assets and lease liabilities is performed at the lease commencement date. The measurement of lease liabilities

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is based on the present value of future lease payments over the lease term. As the Company's leases do not provide an implicit rate, the Company uses its incremental borrowing rate based on the information available at the lease commencement date in determining the present value of future lease payments. To determine the incremental borrowing rate, the Company uses the lease-term appropriate current treasury bond rates adjusted for collateral and inflation risks combined with quoted bank financing rates. The ROU asset is based on the measurement of the lease liability and also includes any lease payments made prior to or on lease commencement and excludes lease incentives and initial direct costs incurred, as applicable. The lease terms may include options to extend or terminate the lease when it is reasonably certain the Company will exercise any such options. Rent expense for the Company's operating leases is recognized on a straight-line basis over the lease term. Amortization expense for the ROU asset associated with its finance leases is recognized on a straight-line basis over the term of the lease and interest expense associated with its finance leases is recognized on the balance of the lease liability using the effective interest method based on the estimated incremental borrowing rate.

Prior to the Company's restructuring, as described in Note 17, the Company had lease agreements with lease and non-lease components. As allowed under Topic 842, the Company elected to not separate lease and non-lease components for any leases involving real estate and office equipment classes of assets and, as a result, accounted for the lease and non-lease components as a single lease component. The Company also elected to not apply the recognition requirement of Topic 842 to leases with a term of 12 months or less for all classes of assets.

Fair Value of Financial Instruments

The Company uses fair value measurements to record fair value adjustments to certain financial and non-financial assets and liabilities and to determine fair value disclosures. The accounting standards define fair value, establish a framework for measuring fair value, and require disclosures about fair value measurements. Fair value is defined as the price that would be received from selling an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. When determining the fair value measurements for assets and liabilities required to be recorded at fair value, the principal or most advantageous market in which the Company would transact are considered along with assumptions that market participants would use when pricing the asset or liability, such as inherent risk, transfer restrictions, and risk of nonperformance.

The accounting standard for fair value establishes a fair value hierarchy based on three levels of inputs, the first two of which are considered observable and the last unobservable, that requires an entity to maximize the use of observable inputs and minimize the use of unobservable inputs when measuring fair value. A financial instrument’s categorization within the fair value hierarchy is based upon the lowest level of input that is significant to the fair value measurement.

The three levels of inputs that may be used to measure fair value are as follows:

Level 1:			Observable inputs, such as quoted prices in active markets for identical assets or liabilities.
Level 2:			Observable inputs other than Level 1 prices, such as quoted prices for similar assets or liabilities, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities.
Level 3:			Valuations based on unobservable inputs to the valuation methodology and including data about assumptions that market participants would use in pricing the asset or liability based on the best information available under the circumstances.

Financial instruments carried at fair value include cash equivalents and marketable securities. The carrying amounts of accounts payable and accrued liabilities approximate fair value due to their relatively short maturities.

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Revenue Recognition

Under ASC Topic 606, “Revenue from Contracts with Customers” (“Topic 606”), an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration that the entity expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that an entity determines are within the scope of Topic 606, the entity performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price, including variable consideration, if any; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the entity satisfies a performance obligation.

The Company assesses its license arrangements within the scope of Topic 606 in accordance with this framework as follows:

License revenue

The Company assesses whether the goods or services promised within each contract are distinct to identify those that are performance obligations. This assessment involves subjective determinations and requires management to make judgments about the individual promised goods or services and whether such are separable from the other aspects of the contractual relationship. In assessing whether a promised good or service is distinct, and therefore a performance obligation, the Company considers factors such as the research, stage of development of the licensed product, manufacturing and commercialization capabilities of the customer and the availability of the associated expertise in the general marketplace. The Company also considers the intended benefit of the contract in assessing whether a promised good or service is separately identifiable from other promises in the contract. If a promised good or service is not distinct, the Company is required to combine that good or service with other promised goods or services until it identifies a bundle of goods or services that is distinct. Arrangements that include rights to additional goods or services that are exercisable at a customer’s discretion are generally considered options. The Company assesses if these options provide a material right to the customer and if so, they are considered performance obligations.

The transaction price is determined and allocated to the identified performance obligations in proportion to their stand-alone selling prices (“SSP”) on a relative SSP basis. SSP is based on observable prices of the performance obligations or, when such prices are not observable, are estimated. The estimation of SSP may include factors such as forecasted revenues or costs, development timelines, discount rates, probabilities of technical and regulatory success, and considerations such as market conditions and entity-specific factors. In certain circumstances, the Company may apply the residual method to determine the SSP of a good or service if the SSP is considered highly variable or uncertain. The Company validates the SSP for performance obligations by evaluating whether changes in the key assumptions used to determine the SSP will have a significant effect on the allocation of arrangement consideration between multiple performance obligations.

If the consideration promised in a contract includes a variable amount, the Company estimates the amount of consideration to which it will be entitled in exchange for transferring the promised goods or services to a customer. The Company determines the amount of variable consideration by using the expected value method or the most likely amount method. The Company includes the amount of estimated variable consideration in the transaction price to the extent that it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis in the period of adjustment.

If an arrangement includes development, regulatory or commercial milestone payments, the Company evaluates whether the milestones are considered likely of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant cumulative revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control or the licensee’s control, such as regulatory approvals, are generally not considered likely of being achieved until those approvals are received.

In determining the transaction price, the Company adjusts consideration for the effects of the time value of money if the timing of payments provides the Company with a significant benefit of financing. The Company

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does not assess whether a contract has a significant financing component if the expectation at contract inception is such that the period between payment by the licensee and the transfer of the promised goods or services to the licensees will be one year or less. For arrangements with licenses of intellectual property that include sales-based royalties, including milestone payments based on the level of sales, and if the license is deemed to be the predominant item to which the royalties relate, the Company recognizes royalty revenue and sales-based milestones at the later of (i) when the related sales occur, or (ii) when the performance obligation to which the royalty has been allocated has been satisfied.

The Company recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied at a point in time or over time, and if over time, recognition is based on the use of an output or input method.

The Company’s contracts may be modified for changes in the customer’s requirements. If contract modifications are for additional goods and services that are distinct from the existing contract, the modification will be accounted for as either a separate contract or a termination of the existing contract, depending on whether the additional goods or services reflects the SSP.

If the additional goods or services in a contract modification are not distinct from the existing contract, they are accounted for as if they were part of the original contract. The effect of the contract modification on the transaction price and the measure of progress for the performance obligation to which it relates is recognized as an adjustment to revenue on a cumulative catch-up basis. The cumulative catch-up adjustment is calculated using an updated measure of progress applied to the sum of (1) the remaining consideration allocated to the partially satisfied performance obligation and (2) the revenue already recognized on that performance obligation. The revenue recognized for fully satisfied goods or services and distinct from the remaining performance obligations is not altered by the modification.

Collaborative arrangements

The Company analyzes its license arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, Collaborative Arrangements (“Topic 808”). This assessment is performed throughout the life of the arrangement based on changes in the responsibilities of all parties in the arrangement. For arrangements within the scope of Topic 808 that contain multiple elements, the Company first determines which elements of the collaboration are deemed to be within the scope of Topic 808 and which elements of the collaboration are more reflective of a vendor-customer relationship and therefore within the scope of Topic 606. For elements of collaboration arrangements that are accounted for pursuant to Topic 808, an appropriate recognition method is determined and applied consistently, either by analogy to authoritative accounting literature or by applying a reasonable and rational policy election. For those elements of the arrangement that are accounted for pursuant to Topic 606, the Company applies the five-step model described above.

Research and Development Costs

Research and development costs are expensed as incurred. Research and development costs include, but are not limited to, salaries, benefits, travel, stock-based compensation, consulting costs, contract research service costs, laboratory supplies and facilities, contract manufacturing costs, and costs paid to other third parties that conduct research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense.

Advance payments for goods or services to be rendered in the future for use in research and development activities are recorded as a prepaid asset and expensed as the related goods are delivered or the services are performed.

Stock-Based Compensation

The Company recognizes the cost of stock-based awards granted to employees and non-employees based on the estimated grant-date fair values of the awards. The fair values of stock options are estimated on the date of grant using the Black-Scholes option pricing model. The fair values of restricted stock units (“RSUs”) are based on the fair value of the Company’s common stock on the date of the grant. The value of the award is

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recognized as compensation expense on a straight-line basis over the requisite service period. Forfeitures are recognized when they occur, which may result in the reversal of compensation costs in subsequent periods as the forfeitures arise. Compensation expense for employee and non-employee share-based payment awards with performance conditions is recognized when the performance condition is deemed probable.

Convertible Preferred Stock Issued through PIPE

The Company records shares of convertible preferred stock at their respective fair values on the dates of issuance, net of issuance costs. The Company classified the Series B Preferred Stock outside of stockholders’ equity because, if conversion to Common Stock is not approved by the stockholders, the Series B Preferred Stock will be redeemable at the option of the holders for cash equal to the closing price of the Common Stock on the last trading day prior to the holder’s redemption request. The Company has determined that the conversion and redemption are outside of the Company’s control. Additionally, the Company determined the Series B Preferred Stock did not contain any embedded derivatives and therefore the conversion and redemption features did not require bifurcation.

Contingent Milestone Proceeds

The Company recognizes contingent milestone proceeds associated from the sale of in-process research and development assets in earnings once the achievement of the milestone becomes probable and payment to the Company is contractually required.

Acquisitions

The Company evaluates acquisitions of assets and other similar transactions to assess whether or not the transaction should be accounted for as a business combination or asset acquisition by first applying a screen test to determine whether substantially all of the fair value of the gross assets acquired is concentrated in a single identifiable asset or group of similar identifiable assets. If so, the transaction is accounted for as an asset acquisition. If not, further determination is required as to whether or not the Company has acquired inputs and processes that have the ability to create outputs, which would meet the definition of a business. Significant judgment is required in the application of the test to determine whether an acquisition is a business combination or an acquisition of assets.

Acquisitions meeting the definition of business combinations are accounted for using the acquisition method of accounting, which requires that the purchase price be allocated to the net assets acquired at their respective fair values. In a business combination, any excess of the purchase price over the estimated fair values of the net assets acquired is recorded as goodwill.

The Company measures and recognizes asset acquisitions that are not deemed to be business combinations based on the cost to acquire the assets, which includes pre-acquisition direct costs recorded in accrued professional and consulting fees. Goodwill is not recognized in asset acquisitions. When a transaction accounted for as an asset acquisition includes an IPR&D asset, the IPR&D asset is only capitalized if it has an alternative future use other than in a particular research and development project. Otherwise, the cost allocated to acquire an IPR&D asset with no alternative future use is charged to expense at the acquisition date.

Contingent Value Rights

The Company evaluates its contracts to determine if those contracts qualify as derivatives under ASC 815, Derivatives and Hedging (“ASC 815”). For derivative financial instruments that are accounted for as liabilities, the derivative instrument is initially recorded at its fair value and is then re-valued at each reporting date. Any changes in fair value are recorded as other income or expense for each reporting period. Derivative instrument liabilities are classified in the balance sheet as current or non-current based on whether or not net-cash settlement of the derivative instrument is probable within the next 12 months from the balance sheet date. The Company determined that certain contingent payments under the CVR Agreement qualified as derivatives under ASC 815, and as such, were recorded as a liability on the balance sheet. This value is then remeasured for future expected payout as well as the increase in fair value due to the time value of money. These gains or

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losses, if any, are recognized in the consolidated statements of operations and comprehensive loss within Other (expense) income, net.

The Company applies a scenario-based method and weighs them based on the possible achievement of certain milestones. The milestone payments are contingent on formal reimbursement decisions by national authorities in key European markets and pegzilarginase approval by the U.S. Food and Drug Administration ("FDA"), among other events. This fair value measurement is based on significant inputs not observable in the market and thus represents a Level 3 measurement as defined in ASC 820, Fair Value Measurement. The key assumptions used include the discount rate, probability of regulatory success, and reimbursement rates from certain government agencies. The estimated value of the CVR consideration is based upon available information and certain assumptions which the Company's management believes are reasonable under the circumstances. The ultimate payout under the CVRs may differ materially from the assumptions used in determining the fair value of the CVR consideration.

Income Taxes

The Company uses the asset and liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are recognized for the expected future tax consequences of temporary differences between the financial statements and the tax bases of assets and liabilities. Additionally, any changes in income tax laws are immediately recognized in the year of enactment.

A valuation allowance is established against the deferred tax assets to reduce their carrying value to an amount that is more likely than not to be realized. The deferred tax assets and liabilities are classified as noncurrent along with the related valuation allowance. Due to a lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance.

The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on the technical merits, as the largest amount of benefits that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the unrecognized tax benefits as a component of income tax expense, if applicable. As of December 31, 2023 and 2022, the Company had no unrecognized tax benefits and there were no interest or penalties incurred by the Company in the years ended December 31, 2023, 2022, or 2021.

Comprehensive Loss

Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive income (loss) is currently comprised of changes in unrealized losses and gains on available-for-sale securities and foreign currency translation adjustments reflecting the cumulative effect of changes in exchange rates between the foreign entity’s functional currency and the reporting currency.

Recently Adopted Accounting Pronouncement

The Company early adopted the Financial Accounting Standards Board’s Accounting Standards Update 2020-06, Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity (“ASU 2020-06”), effective as of January 1, 2023 using the modified retrospective method. Among other amendments, ASU 2020-06 eliminates the cash conversion and beneficial conversion feature models in ASC 470-20 that required an issuer of certain convertible debt and preferred stock to separately account for embedded conversion features as a component of equity, as well as changes the accounting for diluted earnings‑per‑share for convertible instruments and contracts that may be settled in cash or stock. Additionally, ASU 2020-06 requires the if‑converted method, which is more dilutive than the treasury stock method, be used for all convertible instruments. The Company applied ASU 2020-06 to all Series A Preferred Stock and Series B Preferred Stock during fiscal year 2023, and, accordingly, the Company did not apply the cash conversion or beneficial conversion feature models in its analysis of the Series A Preferred Stock and Series B Preferred Stock. The adoption of ASU 2020-06 did not have a material impact on the Company's consolidated financial statements.

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Recently Issued Accounting Pronouncements

In November 2023, the FASB issued ASU 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures to update reportable segment disclosure requirements, primarily through enhanced disclosures about significant segment expenses and information used to assess segment performance and requires companies to disclose all annual disclosures about segments in interim periods. The ASU also requires companies with a single reportable segment to provide all disclosures required by Topic 280 – Segment Reporting. This update is effective beginning with the Company’s 2024 fiscal year annual reporting period and interim periods beginning thereafter. The Company is currently evaluating the impact that the adoption of this standard will have on its consolidated financial statements.

In December 2023, the FASB issued ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures. This ASU expands disclosures in an entity’s income tax rate reconciliation table and disclosures regarding taxes paid both in the U.S. and foreign jurisdictions. This update is effective beginning with the Company’s 2025 fiscal year annual reporting period. This ASU will have no impact on the Company’s consolidated financial condition or results of operations. The Company is currently evaluating the impact to its income tax disclosures.

The Company measures and reports certain financial instruments as assets and liabilities at fair value on a recurring basis. The following tables sets forth the fair value of the Company’s financial assets and liabilities at fair value on a recurring basis based on the three-tier fair value hierarchy (in thousands):

			December 31, 2023
			Level 1						Level 2						Level 3						Total
Financial Assets
Money market funds			$	150,648					$	—					$	—					$	150,648
U.S. government treasury securities			32,843						—						—						32,843
U.S. government agency securities			—						16,257						—						16,257
Commercial paper			—						104,141						—						104,141
Corporate bonds			—						33,064						—						33,064
Total financial assets			$	183,491					$	153,462					$	—					$	336,953
Liabilities:
CVR liability			$	—					$	—					$	42,700					$	42,700
Total liabilities			$	—					$	—					$	42,700					$	42,700

			December 31, 2022
			Level 1						Level 2						Level 3						Total
Financial Assets
Money market funds			$	15,250					$	—					$	—					$	15,250
Commercial paper			—						23,641						—						23,641
U.S. government agency securities			—						4,230												4,230
Corporate bonds			—						3,732						—						3,732
Total financial assets			$	15,250					$	31,603					$	—					$	46,853

The Company measures the fair value of money market funds on quoted prices in active markets for identical asset or liabilities. The Level 2 assets include U.S. government agency securities, commercial paper and corporate bonds, and are valued based on quoted prices for similar assets in active markets and inputs other than quoted prices that are derived from observable market data.

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The Company evaluates transfers between levels at the end of each reporting period. There were no transfers between Level 1 and Level 2 during the periods presented.

As of December 31, 2022, the Company had no financial liabilities outstanding measured at fair value.

Forward Contract Liability

In connection with the Asset Acquisition, the Company entered into a contract for the issuance of 364,887 shares of Series A Preferred Stock as part of the consideration transferred. This forward contract was classified as a liability because the underlying preferred shares were contingently redeemable. Further, the forward contract liability was considered a Level 2 liability based on observable market data for substantially the full term of the liability and was initially measured at its estimated fair value on the transaction date based on the underlying price per share on an as-converted basis of the Series A PIPE Securities issued in the Series A PIPE. Subsequent remeasurement of the fair value of the forward contract liability through its settlement date was based on the market price of the Company's Common Stock, which represents the redemption value of the Series A Preferred Stock.

The fair value of the forward contract at the transaction date, June 22, 2023, was $106.2 million. The liability was settled with the issuance of the Series A Preferred Stock on July 7, 2023 for $189.7 million. For the year ended December 31, 2023, $83.5 million was recorded as Other (expense) income in the consolidated statements of operations in connection with the change in fair value of the forward contract liability. There was no similar expense for the year ended December 31, 2022 and 2021.

The following table presents changes in the forward contract liability for the periods presented (in millions):

			Forward Contract Liability
Beginning balance as of June 22, 2023			$	106.2
Change in fair value			83.5
Issuance of Series A Preferred Stock on July 7, 2023			(189.7)
Ending balance as of December 31, 2023			$	—

CVR Liability

In connection with the Asset Acquisition, a non-transferable contingent value right was distributed to the Legacy Stockholders, but was not distributed to holders of shares of Common Stock or Series A Preferred Stock issued to the Investors or former stockholders of Pre-Merger Spyre in connection with the Transactions. Holders of the CVR will be entitled to receive certain cash payments from proceeds received by the Company for a three-year period, if any, related to the disposition or monetization of the Company’s legacy assets for a period of one year following the closing of the Asset Acquisition.

The fair value of the CVR liability was determined using the probability weighted discounted cash flow method to estimate future cash flows associated with the sale of the legacy assets. Analogous to a dividend being declared/approved in one period and paid out in another, the liability was recorded at the date of approval, June 22, 2023, as a Common Stock dividend, returning capital to the Legacy Stockholders. Changes in fair value of the liability will be recognized as a component of Other income (expense) in the consolidated statement of operations and comprehensive loss in each reporting period. The liability value is based on significant inputs not observable in the market such as estimated cash flows, estimated probabilities of regulatory success, and

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discount rates, which represent a Level 3 measurement within the fair value hierarchy. The significant inputs used to estimate the fair value of the CVR liability were as follows:

			December 31, 2023
Estimated cash flow dates			2/28/24 - 06/22/26
Estimated probability of success			39% - 100%
Estimated reimbursement rate compared to reimbursement target			81% - 100%
Risk-adjusted discount rates			5.91% - 6.32%

The change in fair value between the issuance of the CVR and December 31, 2023 was a $19.0 million increase, and was primarily driven by changes in the expected timing of achievement of certain milestones, changes in the likelihood of certain milestones related to the approval received from the European Medicines Agency by Immedica Pharma AB ("Immedica"), partially offset by a change in the likelihood of a successful disposition of pegtarviliase and updates to expenses and deductions.

The following table presents changes in the CVR liability for the periods presented (in thousands):

			CVR Liability
Beginning balance as of December 31, 2022			$	—
Fair value at CVR issuance			29,500
Changes in the fair value of the CVR liability since issuance			18,986
Payments			(5,786)
Ending Balance as of December 31, 2023			$	42,700

The following tables summarize the estimated fair value of the Company’s cash equivalents and marketable securities and the gross unrealized gains and losses (in thousands):

			December 31, 2023
			Amortized Cost						Gross Unrealized Gains						Gross Unrealized Losses						Estimated Fair Value
Cash equivalents:
Money market funds			$	150,648					$	—					$	—					$	150,648
Commercial paper			24,950						5						—						24,955
U.S. government treasury securities			10,965						1						—						10,966
Total cash equivalents			186,563						6						—						186,569
Marketable securities:
Commercial paper			79,124						62						—						79,186
Corporate bonds			32,984						81						(1)						33,064
U.S. government treasury securities			21,846						31						—						21,877
U.S. government agency securities			16,147						110						—						16,257
Total marketable securities			$	150,101					$	284					$	(1)					$	150,384

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			December 31, 2022
			Amortized Cost						Gross Unrealized Gains						Gross Unrealized Losses						Estimated Fair Value
Cash equivalents:
Money market funds			$	15,250					$	—					$	—					$	15,250
Commercial paper			7,021						1						(2)						7,020
U.S. government agency securities			3,736						—						(1)						3,735
Total cash equivalents			$	26,007					$	1					$	(3)					$	26,005
Marketable securities:
Commercial paper			$	16,644					$	2					$	(25)					$	16,621
Corporate bonds			3,738						—						(6)						3,732
U.S. government agency securities			495						—						—						495
Total marketable securities			$	20,877					$	2					$	(31)					$	20,848

The following table summarizes the available-for-sale securities in an unrealized loss position for which an allowance for credit losses has not been recorded as of December 31, 2023 and 2022, aggregated by major security type and length of time in a continuous unrealized loss position:

			December 31, 2023
			Less Than 12 Months												12 Months or Longer												Total
			Fair Value						Unrealized Losses						Fair Value						Unrealized Losses						Fair Value						Unrealized Losses
Commercial paper			$	—					$	—					$	—					$	—					$	—					$	—
Corporate bonds			9,907						(1)						—						—						9,907						(1)
U.S. government treasury securities			4,831						—						—						—						4,831						—
Total marketable securities			$	14,738					$	(1)					$	—					$	—					$	14,738					$	(1)

			December 31, 2022
			Less Than 12 Months												12 Months or Longer												Total
			Fair Value						Unrealized Losses						Fair Value						Unrealized Losses						Fair Value						Unrealized Losses
Commercial paper			$	17,699					$	(27)					$	—					$	—					$	17,699					$	(27)
Corporate bonds			3,732						(6)						—						—						3,732						(6)
U.S. government agency securities			3,735						(1)						—						—						3,735						(1)
Total marketable securities			$	25,166					$	(34)					$	—					$	—					$	25,166					$	(34)

The Company evaluated its securities for credit losses and considered the decline in market value to be primarily attributable to current economic and market conditions and not to a credit loss or other factors. Additionally, the Company does not intend to sell the securities in an unrealized loss position and does not expect they will be required to sell the securities before recovery of the unamortized cost basis. As of December 31, 2023 and 2022, an allowance for credit losses had not been recognized. Given the Company's intent and ability to hold such securities until recovery, and the lack of significant change in credit risk of these investments, the Company does not consider these marketable securities to be impaired as of December 31, 2023 and 2022.

There were $0.3 million unrealized gains on marketable securities for the year ended December 31, 2023. There were no realized gains on marketable securities for the year ended December 31, 2023, 2022 and

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2021. Interest on marketable securities is included in interest income. Accrued interest receivable on available-for-sale debt securities totaled $0.9 million and $0.1 million as of December 31, 2023 and 2022, respectively, and is excluded from the estimate of credit losses.

The following table summarizes the contractual maturities of the Company's marketable securities at estimated fair value (in thousands):

			December 31,
			2023						2022
Due in one year or less			$	115,784					$	20,848
Due in 1 - 2 years			34,600						—
Total marketable securities			$	150,384					$	20,848

The Company may sell investments at any time for use in current operations even if they have not yet reached maturity. As a result, the Company classifies marketable securities, including securities with maturities beyond twelve months as current assets.

Property and equipment, net consist of the following (in thousands):

			December 31,
			2023						2022
Laboratory equipment			$	—					$	2,257
Furniture and office equipment			—						520
Computer equipment			—						73
Software			—						121
Leasehold improvements			—						4,393
Property and equipment, gross			—						7,364
Less: Accumulated depreciation and amortization			—						(4,144)
Property and equipment, net			$	—					$	3,220

Depreciation and amortization expense for the years ended December 31, 2023, 2022, and 2021 was $0.7 million, $1.4 million, and $1.4 million, respectively. All of the Company’s long-lived assets were located in the United States.

Sale of Assets

On April 12, 2023, based on the review of the inconclusive interim results from the Company's Phase 1/2 clinical trial of pegtarviliase for the treatment of classical homocystinuria and other business considerations, the Company announced that it had initiated a process to explore strategic alternatives to maximize stockholder value and engaged an independent exclusive financial advisor to support this process. As a result, the Company implemented a restructuring plan resulting in an approximate 83% reduction of the Company’s existing headcount by June 30, 2023.

During the second quarter of 2023, the Company sold various lab equipment, consumables, and furniture and fixtures for total consideration of $0.5 million. After recording the disposal of all the Company's property and equipment net of proceeds, the Company recorded a $0.7 million and $0.2 million loss on disposal of long lived assets which is included in Research and development and General and administrative expenses, respectively.

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Accrued and other current liabilities consist of the following (in thousands):

			December 31,
			2023						2022
Accrued compensation			$	4,054					$	4,589
Accrued contracted research and development costs			7,092						6,972
Accrued professional and consulting fees			1,474						946
Other			488						330
Total accrued and other current liabilities			$	13,108					$	12,837

Paragon and Parapyre Holding LLC ("Parapyre") each beneficially own less than 5% of the Company's capital stock through their respective holdings of the Company's common stock. Fairmount Funds Management LLC ("Fairmount") beneficially owns more than 5% of the Company's capital stock on an as-converted basis, has two seats on the Board and beneficially owns more than 5% of Paragon, which is a joint venture between Fairmount and Fair Journey Biologics. Fairmount appointed Paragon's board of directors and has the contractual right to approve the appointment of any executive officers. Parapyre is an entity formed by Paragon as a vehicle to hold equity in Spyre in order to share profits with certain employees of Paragon.

In connection with the Asset Acquisition, the Company assumed the rights and obligations of Pre-Merger Spyre under the Paragon Agreement. Under the Paragon Agreement, Spyre is obligated to compensate Paragon for its services performed under each research program based on the actual costs incurred with mark-up costs pursuant to the terms of the Paragon Agreement. As of the date of the Asset Acquisition, Pre-Merger Spyre had incurred total expenses of $19.0 million under the Paragon Agreement since inception, which included the $3.0 million research initiation fee and $16.0 million of reimbursable expenses under the Paragon Agreement for historical costs owed to Paragon. As of the acquisition date, $19.0 million was unpaid and was assumed by the Company through the Asset Acquisition.

For the year ended December 31, 2023, the Company recognized expenses related to services provided by Paragon subsequent to the Asset Acquisition totaling $48.5 million, which included $11.4 million of stock-based compensation expense, and were recorded as Research and development expenses in the consolidated statements of operations. As of December 31, 2023, $16.6 million was unpaid and was included in Related party accounts payable and other current liabilities on the Company's consolidated balance sheets.

For the year ended December 31, 2023, the Company made payments totaling $39.5 million to Paragon.

On July 12, 2023 and December 14, 2023, the Company exercised the Option available under the Paragon Agreement with respect to the SPY001 and SPY002 research programs, respectively, and expects to enter into the SPY001 License Agreement and the SPY002 License Agreement.

Following the execution of each of the SPY001 License Agreement and SPY002 License Agreement, the Company will be obligated to pay Paragon up to $22.0 million upon the achievement of specific development, regulatory and clinical milestones for the first product under each agreement, respectively, that achieves such specified milestones. Upon execution of each of the SPY001 License Agreement and the SPY002 License Agreement, we expect to pay Paragon a $1.5 million fee for nomination of a development candidate, as applicable, and the Company expects to be obligated to make a further milestone payment of $2.5 million upon the first dosing of a human patient in a Phase 1 trial.

The following is the summary of expenses related to the Paragon Agreement recognized within research and development expenses, which were ultimately settled in cash (in millions):

			December 31,
			2023						2022						2021
Reimbursable costs under the Paragon Agreement			$	37.1					$	—					$	—

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Parapyre Option Obligation

As part of the Paragon Agreement, the Company is obligated to issue Parapyre a stock option grant on the last business day of 2023 and 2024 (the "Parapyre Option Obligation"). See Note 15 for additional information.

The following is the summary of Related party accounts payable and other current liabilities (in millions):

			December 31, 2023						December 31, 2022
Reimbursable costs under the Paragon Agreement			$	16.6					$	—
Related party accounts payable and other current liabilities			$	16.6					$	—

December 2023 PIPE

The December 2023 Investors included Fairmount, a related party. Fairmount's participation in the December 2023 PIPE was approved by the Company's board of directors. Fairmount's investment accounted for $10.0 million of the $180.0 million gross proceeds raised in the December 2023 PIPE.

Mark McKenna Option Grant

On February 1, 2024, the Board appointed Mark McKenna as a Class I director. Mr. McKenna and the Company are parties to a consulting agreement, pursuant to which Mr. McKenna agreed to continue to provide consulting services as an independent contractor to the Company, with an effective date of August 1, 2023 (the “Vesting Commencement Date”). As compensation for Mr. McKenna’s consulting services, on November 22, 2023, he was granted non-qualified stock options to purchase 477,000 shares of the Company’s common stock under the Company's equity incentive plan with an exercise price of $10.39 per share, which vest as to 25% on the one year anniversary of the Vesting Commencement Date and thereafter vest and become exercisable in 48th equal monthly installments, subject to Mr. McKenna’s continued service to the Company through each applicable vesting date. For the twelve months ended December 31, 2023, the Company recognized $0.1 million in stock-based compensation expense related to Mr. McKenna's consulting agreement. There was no such expense for the twelve months ended December 31, 2022 and 2021.

On June 22, 2023, the Company acquired Pre-Merger Spyre pursuant to the Acquisition Agreement, by and among the Company, Aspen Merger Sub I, Inc., a Delaware corporation and a wholly owned subsidiary of the Company (“First Merger Sub”), Sequoia Merger Sub II, LLC, a Delaware limited liability company and a wholly owned subsidiary of the Company (“Second Merger Sub”), and Pre-Merger Spyre. Pursuant to the Acquisition Agreement, First Merger Sub merged with and into Pre-Merger Spyre, pursuant to which Pre-Merger Spyre was the surviving corporation and became the Company's wholly owned subsidiary (the “First Merger”). Immediately following the First Merger, Pre-Merger Spyre merged with and into Second Merger Sub, pursuant to which Second Merger Sub became the surviving entity. Pre-Merger Spyre was a pre-clinical stage biotechnology company that was incorporated on April 28, 2023 under the direction of Peter Harwin, a Managing Member of Fairmount, for the purpose of holding rights to certain intellectual property being developed by Paragon. Fairmount is a founder of Paragon.

With respect to the Asset Acquisition, the Company determined that Aeglea was the acquirer for accounting purposes under ASC 805. The primary factors considered were a) the relative voting rights in the combined entity not resulting in a change of control, b) legacy members of the Company's Board of Directors maintained control of the Board of Directors, and c) the only change in the composition of senior management was the appointment of a new Chief Operating Officer. Next, the Company considered whether the Asset Acquisition should be defined as a business under ASC 805. ASC 805-10-55-5A through 55-5C describe a screen test to determine whether an acquired set of assets and activities is not a business. We determined that substantially all (greater than 90%) of the fair value of the assets acquired were concentrated in a single asset, Spyre’s Option to license intellectual property rights related to SPY001, SPY002, SPY003 and SPY004

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pursuant to the Paragon Agreement. Accordingly, the Company treated the Asset Acquisition as an asset acquisition for accounting purposes. Even if the transaction would have failed the screen test, Pre-Merger Spyre lacked the financial resources to have inputs, processes, and outputs to constitute a business under ASC 805.

The Company completed the Asset Acquisition of Pre-Merger Spyre, in accordance with the terms of the Acquisition Agreement. Under the terms of the Acquisition Agreement, the Company issued 517,809 shares of Common Stock and 364,887 shares of Series A Preferred Stock to former Pre-Merger Spyre security holders. In addition, outstanding and unexercised stock options to purchase 2,734 shares of common stock were assumed from the Amended and Restated Spyre 2023 Equity Incentive Plan.

At the acquisition date, the Company recorded forward contracts to represent the obligation to issue shares of the Company's Common Stock and shares of Series A Preferred Stock. The forward contract related to the Common Stock was recorded as Additional paid-in capital as the instrument is indexed to the Company's Common Stock. The forward contract related to the Series A Preferred Stock was recorded as a liability, as the underlying stock has a cash redemption feature. On July 7, 2023, both the shares of Common Stock and Series A Preferred Stock were issued and the forward contract liability associated with the Series A Preferred Stock was settled accordingly.

The Company concluded that the arrangement meets the definition of an asset acquisition rather than a business combination, as substantially all of the fair value of the gross assets acquired is concentrated in a single identifiable asset, the Option to exclusively license IPR&D. The Company determined that the Option to license IPR&D was a single asset as the Company's strategy relies on developing the entire portfolio of individual treatments to create combination treatments that simultaneously address different mechanisms of irritable bowel disease with a single treatment. The Company also determined that the pipeline candidates within the portfolio are similar in nature and risk profile. In addition, the Company did not obtain any substantive processes, assembled workforce, or employees capable of producing outputs in connection with the Asset Acquisition.

The Company determined that the cost to acquire the asset was $113.2 million which was recorded as acquired IPR&D. The fair value of the consideration issued consisted of the 364,887 shares of Series A Preferred Stock (14,595,480 shares of Common Stock on an as-converted basis) and 517,809 shares of Common Stock, valued at $291.08 per share and $7.277 per share, respectively.

The Asset Acquisition Costs are shown on the following table (in millions):

			June 22, 2023
Consideration transferred in Series A Preferred Stock and Common Stock			$	110.0
Transaction costs incurred by the Company			3.2
Total cost to acquire asset			$	113.2

The allocation of the purchase price to net assets acquired is as a follows:

			June 22, 2023
Acquired in-process research and development			$	130.2
Cash acquired			3.0
Assumed liabilities			(20.0)
Total cost to acquire asset			$	113.2

In May 2023, Pre-Merger Spyre entered into the Paragon Agreement with Paragon and Parapyre. Pursuant to the Paragon Agreement, the Option provided for the right to acquire the intellectual property rights related to four research programs from Paragon in accordance with a license agreement to be entered into following each exercise of the Option. Under the Paragon Agreement, the terms of such license agreement

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would be consistent with the economics and other terms set out in the Paragon Agreement and, in the event of failure to reach an agreement on the definitive terms, the matter would be resolved via arbitration. In consideration for the Option granted under the Paragon Agreement, Pre-Merger Spyre was obligated to pay Paragon an upfront cash amount of $3.0 million in research initiation fees. In addition, Pre-Merger Spyre was obligated to compensate Paragon on a quarterly basis for its services performed under each research program based on the actual costs incurred with mark-up costs pursuant to the terms of the Paragon Agreement. As of the date of the Asset Acquisition, Pre-Merger Spyre had incurred total expenses of $19.0 million under the Paragon Agreement since inception, which included the $3.0 million research initiation fee and $16.0 million of historical reimbursable expenses owed to Paragon. As of June 22, 2023, $19.0 million was unpaid and was assumed by the Company through the Asset Acquisition. Furthermore, the Paragon Agreement provided for an annual equity grant of options to purchase 1% of the then outstanding shares of Spyre’s common stock, on a fully diluted basis, on the last business day of each calendar year, during the term of the Paragon Agreement, at the fair market value determined by the board of directors of Spyre.

As a result of the Asset Acquisition, the Company assumed the rights and obligations of Pre-Merger Spyre under the Paragon Agreement, including the Parapyre Option Obligation. Pursuant to the Paragon Agreement, on a research program-by-research program basis following the finalization of the research plan for each respective research program, the Company is required to pay Paragon a nonrefundable fee in cash of $0.8 million. For the year ended December 31, 2023, the Company incurred $48.5 million, in costs reimbursable to Paragon, which were recorded as Research and development expenses in the consolidated statements of operations.

For the year ended December 31, 2023, the Company made payments totaling $39.5 million to Paragon.

On July 12, 2023 and December 14, 2023, the Company exercised the Option available under the Paragon Agreement with respect to the SPY001 and SPY002 research programs, respectively, and expects to enter into the SPY001 License Agreement and the SPY002 License Agreement. Our Option available under the Paragon Agreement with respect to the SPY003 and SPY004 programs remains unexercised.

Following the execution of each of the SPY001 License Agreement and SPY002 License Agreement, the Company will be obligated to pay Paragon up to $22.0 million upon the achievement of specific development, regulatory and clinical milestones for the first product under each agreement, respectively, that achieves such specified milestones. Upon execution of each of the SPY001 License Agreement and the SPY002 License Agreement, the Company expects to pay Paragon a $1.5 million fee for nomination of a development candidate, as applicable, and the Company expects to be obligated to make a further milestone payment of $2.5 million upon the first dosing of a human patient in a Phase 1 trial. Subject to the execution of the Option with respect to the SPY003 or SPY004 research programs, the Company expects to be obligated to make similar payments upon and following the execution of license agreements with respect to these research programs, respectively.

Prior to the Company's restructuring, as described in Note 17, the Company leased certain office space, laboratory facilities, and equipment. These leases required monthly lease payments that were subject to annual increases throughout the lease term. Certain of these leases also included renewal options at the election of the Company to renew or extend the lease for an additional three to five years. These optional periods were not considered in the determination of the right-of-use assets or lease liabilities associated with these leases as the Company did not consider it reasonably certain it would exercise the options. The Company performed evaluations of its contracts and determined it has both operating and finance leases. Variable lease expense for these leases primarily consisted of common area maintenance and other operating costs.

In April 2019, the Company entered into a lease agreement (the “Las Cimas Lease”) for its corporate headquarters and laboratory space located in Austin, Texas. The Las Cimas Lease included approximately 30,000 square feet and commenced on April 30, 2019, with an expiration on April 30, 2028. The Company posted a customary letter of credit in the amount of $1.5 million as security, which is subject to automatic reductions per the terms of the Las Cimas Lease. A tenant allowance of up to $1.0 million was provided by the lessor and fully reimbursed to the Company.

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In August 2023, the Company terminated its building lease in Austin, Texas. The negotiated termination agreement obligated the Company to pay the lessor a $2.0 million termination fee in exchange for releasing the Company of all further obligations under the lease including terminating the associated letter of credit.

The following table summarizes the Company’s recognition of its operating and finance leases (in thousands):

						December 31,
			Classification			2023						2022
Assets
Operating			Operating lease right-of-use assets			$	—					$	3,430
Finance			Other non-current assets			—						597
Total leased assets						—						4,027
Leases
Current
Operating			Operating lease liabilities			—						625
Finance			Accrued and other current liabilities			—						16
Non-current
Operating			Non-current operating lease liabilities			—						4,004
Total lease liabilities						$	—					$	4,645

The following table summarizes the weighted-average remaining lease term and discount rates for the Company’s operating and finance leases:

			December 31,
			2023						2022
Lease term (years)
Operating leases			0.0						5.3
Finance leases			0.0						0.6
Discount rate
Operating leases			—		%				10.6		%
Finance leases			—		%				10.2		%

The following table summarizes the lease costs pertaining to the Company’s operating leases (in thousands):

			Year Ended December 31,
			2023						2022						2021
Operating lease cost			$	455					$	910					$	991
Variable lease cost			471						472						519
Total lease cost			$	926					$	1,382					$	1,510

Cash paid for amounts included in the measurement of operating lease liabilities during the years ended December 31, 2023 and 2022 was $0.5 million and $0.9 million, respectively, and was included within net cash used in operating activities in the cash flows.

As of December 31, 2023, the Company had no operating or finance lease obligations.

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The Company is authorized to issue 410,000,000 shares of capital stock of which 400,000,000 shares are designated as Common Stock and 10,000,000 shares are designated as preferred stock, all with a par value of $0.0001 per share. Each holder of Common Stock is entitled to one vote for each share of Common Stock held. The Common Stock is not entitled to preemptive rights, and is not subject to conversion, redemption or sinking fund provisions. Subject to preferences that may apply to any shares of preferred stock outstanding at the time, the holders of Common Stock are entitled to receive dividends out of funds legally available if the board of directors, in its discretion, determines to issue dividends and then only at the times and in the amounts that the board of directors may determine.

As of December 31, 2023 and 2022, no Common Stock dividends had been declared by the board of directors. As of December 31, 2023 there were 437,037 shares of Series A preferred stock and 150,000 shares of Series B preferred stock outstanding. There were no shares of Series A preferred stock or shares of Series B preferred stock outstanding as of December 31, 2022.

Registered Direct Offering

In May 2022, the Company issued and sold 430,107 shares of Common Stock at an offering price of $40.00 per share and pre-funded warrants to purchase up to 694,892 shares of Common Stock at an offering price of $39.9975 per warrant (representing the price per share of Common Stock sold in the offering minus the $0.0025 exercise price per warrant) in a registered direct offering pursuant to a shelf registration statement on Form S-3. The net proceeds to the Company from this offering were approximately $42.9 million, after deducting placement agent fees and offering costs of $2.1 million.

June 2023 PIPE

In June 2023, in connection with the Asset Acquisition, the Company issued and sold 721,452 shares of Series A Preferred Stock at approximately $291.08 per share through a private placement to a group of accredited investors. The net proceeds from this offering were approximately $197.3 million, after deducting placement agent fees and offering costs of $12.7 million.

December 2023 PIPE

In December 2023, the Company issued and sold 6,000,000 shares of Common Stock at an offering price of $15.00 per share and 150,000 shares of Series B Preferred Stock at $600 per share through a private placement to a group of accredited investors. The net proceeds from this offering were approximately $169.1 million, after deducting placement agent fees and offering costs of $10.9 million.

Parapyre Warrants

The Company settled its 2023 obligations under the Parapyre Option Obligation by issuing Parapyre 684,407 warrants to purchase the Company's common stock, less the $21.52 per share exercise price of each warrant. As of December 31, 2023, none of the warrants issued under the Parapyre Option Obligation have been exercised. See Note 15 for additional information on the Parapyre Option Obligation.

Pre-Funded Warrants

In May 2022, the Company issued pre-funded warrants to purchase shares of Common Stock in underwritten public offerings at the offering price of the Common Stock, less the $0.0025 per share exercise price of each warrant. The warrants were recorded as a component of stockholders’ equity within additional paid-in capital and have no expiration date. Per the terms of the warrant agreements, the outstanding warrants to purchase shares of Common Stock may not be exercised if the holder’s ownership of the Common Stock would exceed 4.99% (“Maximum Ownership Percentage”) or 9.99% for certain holders. By written notice to the Company, each holder may increase or decrease the Maximum Ownership Percentage to any other percentage (not in excess of 19.99% for the majority of such warrants). The revised Maximum Ownership Percentage would be effective 61 days after the notice is received by the Company.

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As of December 31, 2023, the following pre-funded warrants to purchase Common Stock were issued and outstanding:

Issue Date

Expiration Date

Exercise Price

Number of Warrants Outstanding

May 2022

None

$

0.0025

250,000

Total pre-funded warrants

250,000

Series A Non-Voting Convertible Preferred Stock

On June 22, 2023, the Company filed a Certificate of Designation of Preferences, Rights and Limitations of the Series A Preferred Stock with the Secretary of State of the State of Delaware (the “Certificate of Designation”) in connection with the Asset Acquisition and the PIPE.

Pursuant to the Certificate of Designation, holders of Series A Preferred Stock are entitled to receive dividends on shares of Series A Preferred Stock equal to, on an as-if-converted-to-Common Stock basis, and in the same form as, dividends actually paid on shares of Common Stock. Except as provided in the Certificate of Designation or as otherwise required by law, the Series A Preferred Stock does not have voting rights. However, as long as any shares of Series A Preferred Stock are outstanding, the Company will not, without the affirmative vote of the holders of a majority of the then outstanding shares of the Series A Preferred Stock: (a) alter or change adversely the powers, preferences or rights given to the Series A Preferred Stock, or alter or amend the Certificate of Designation, amend or repeal any provision of, or add any provision to, the Company’s Certificate of Incorporation or its Bylaws, or file any articles of amendment, certificate of designations, preferences, limitations and relative rights of any series of Preferred Stock, if such action would adversely alter or change the preferences, rights, privileges or powers of, or restrictions provided for the benefit of the Series A Preferred Stock, regardless of whether any of the foregoing actions will be by means of amendment to the Certificate of Incorporation or by merger, consolidation, recapitalization, reclassification, conversion or otherwise, (b) issue further shares of Series A Preferred Stock or increase or decrease (other than by conversion) the number of authorized shares of Series A Preferred Stock, (c) prior to the stockholder approval of the conversion of the Series A Preferred Stock into shares of Common Stock in accordance with Nasdaq Stock Market Rules (the “Conversion Proposal”) or at any time while at least 30% of the originally issued Series A Preferred Stock remains issued and outstanding, consummate (x) any Fundamental Transaction (as defined in the Certificate of Designation) or (y) any merger or consolidation of the Company with or into another entity or any stock sale to, or other business combination in which our stockholders immediately before such transaction do not hold at least a majority of our capital stock immediately after such transaction or (d) enter into any agreement with respect to any of the foregoing. The Series A Preferred Stock does not have a preference upon any liquidation, dissolution or winding-up of the Company.

The Company held a stockholders’ meeting to submit the following matters to its stockholders for their consideration: (i) the approval of the Conversion Proposal, and (ii) if deemed necessary or appropriate by the Company or as otherwise required by law or contract, the approval of an amendment to the Certificate of Incorporation to authorize sufficient shares of Common Stock for the conversion of the Series A Preferred Stock issued pursuant to the Acquisition Agreement. In connection with these matters, the Company filed with the SEC a definitive proxy statement and other relevant materials.

Following stockholder approval of the Conversion Proposal, each share of Series A Preferred Stock automatically converted into 40 shares of Common Stock, subject to certain limitations, including that a holder of Series A Preferred Stock is prohibited from converting shares of Series A Preferred Stock into shares of Common Stock if, as a result of such conversion, such holder, together with its affiliates, would beneficially own more than a specified percentage (established by the holder between 0.0% and 20.0%) of the total number of shares of Common Stock issued and outstanding immediately after giving effect to such conversion.

On June 26, 2023, the Company completed a private placement of 721,452 shares of Series A PIPE Securities in exchange for gross proceeds of $210.0 million, or net proceeds of $197.3 million, after deducting placement agent and other offering costs.

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On July 7, 2023, the Company issued 364,887 shares of Series A Preferred Stock as part of its consideration transferred in connection with the Asset Acquisition that closed on June 22, 2023 which settled the related forward contract liability. For additional information, see Note 3.

On November 21, 2023, the Company's stockholders approved the Conversion Proposal, among other matters, at a special meeting of stockholders. As a result of the approval of the Conversion Proposal, all conditions that could have required cash redemption of the Series A Preferred Stock were satisfied. Since the Series A Preferred Stock is no longer redeemable, the associated balances of the Series A Preferred Stock were reclassified from mezzanine equity to permanent equity during the fourth quarter of 2023. In addition, 649,302 shares of Series A Preferred Stock automatically converted to 25,972,080 shares of Common Stock; 437,037 shares of Series A Preferred Stock did not automatically convert and remain outstanding as of December 31, 2023 due to beneficial ownership limitations. This conversion was recorded as a reclassification between Series A Preferred Stock and Common Stock based on the historical per-share contributed capital amount, inclusive of any forward-contract valuation adjustments, of the Series A Preferred Stock.

Series B Non-Voting Convertible Preferred Stock

On December 8, 2023, the Company filed a Certificate of Designation of Preferences, Rights and Limitations of Series B Non-Voting Convertible Preferred Stock with the Secretary of State of the State of Delaware (the “Series B Certificate of Designation”) in connection with the December 2023 PIPE.

Pursuant to the Series B Certificate of Designation, holders of Series B Preferred Stock are entitled to receive dividends on shares of Series B Preferred Stock equal to, on an as-if-converted-to-Common Stock basis, and in the same form as, dividends actually paid on shares of Common Stock. Except as provided in the Series B Certificate of Designation or as otherwise required by law, the Series B Preferred Stock does not have voting rights. However, as long as any shares of Series B Preferred Stock are outstanding, the Company will not, without the affirmative vote of the holders of a majority of the then outstanding shares of the Series B Preferred Stock, alter or change adversely the powers, preferences or rights given to the Series B Preferred Stock, or alter or amend the Series B Certificate of Designation, amend or repeal any provision of, or add any provision to, the Company’s Certificate of Incorporation or its Bylaws, or file any articles of amendment, certificate of designations, preferences, limitations and relative rights of any series of Preferred Stock, if such action would adversely alter or change the preferences, rights, privileges or powers of, or restrictions provided for the benefit of the Series B Preferred Stock, regardless of whether any of the foregoing actions will be by means of amendment to the Certificate of Incorporation or by merger, consolidation, recapitalization, reclassification, conversion or otherwise. The Series B Preferred Stock does not have a preference upon any liquidation, dissolution or winding-up of the Company.

The Company has agreed to use its best efforts to obtain stockholder approval of the conversion of all issued and outstanding Series B Preferred Stock into shares of Common Stock in accordance with the Nasdaq Stock Market Rules (the "Series B Conversion Proposal") at its 2024 annual meeting of stockholders, which the Company agreed to hold no later than May 15, 2024. The Series B Preferred Stock is recorded outside of stockholders’ equity because, if conversion to Common Stock is not approved by the stockholders, the Series B Preferred Stock will be redeemable at the option of the holders for cash equal to the closing price of the Common Stock per share of Common Stock underlying the Series B Preferred Stock, on the last trading day prior to the holder’s redemption request. As of December 31, 2023, the redemption value of the Company's outstanding Series B Preferred Stock was $129.1 million based on the closing stock price of the Company's Common Stock on December 31, 2023 of $21.52 per share. The Company has determined that the Series B Preferred Stock did not contain any embedded derivatives and therefore the conversion and redemption features did not require bifurcation.

Following stockholder approval of the Series B Conversion Proposal, each share of Series B Preferred Stock will automatically convert into 40 shares of the Common Stock, subject to certain limitations, including that a holder of Series B Preferred Stock is prohibited from converting shares of Series B Preferred Stock into shares of Common Stock if, as a result of such conversion, such holder, together with its affiliates, would beneficially own more than a specified percentage (established by the holder between 0% and 19.99%) of the total number of shares of Common Stock issued and outstanding immediately after giving effect to such conversion.

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Immedica Pharma AB License and Development Agreement

On March 21, 2021, the Company entered into an exclusive license and supply agreement with Immedica Pharma AB (“Immedica”). By entering into this agreement, the Company agreed to provide Immedica the following goods and services:

i.Deliver an exclusive, sublicensable, license and know-how (the “License”) to develop and commercialize pegzilarginase (the “Product”) in the territory comprising the members states of the European Economic Area, United Kingdom, Switzerland, Andorra, Monaco, San Marino, Vatican City, Turkey, Saudi Arabia, United Arab Emirates, Qatar, Kuwait, Bahrain, and Oman (the “Territory”);

ii.Complete the global pivotal PEACE (Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints) Phase 3 trial (“PEACE Trial”) and related Biologics License Application (“BLA”) package to file with the United States Food and Drug Administration (“FDA”), which will be leveraged by Immedica in obtaining the necessary regulatory approvals in the Territory; and

iii.Perform a Pediatric Investigation Plan trial (“PIP Trial”) in order for Immedica to be able to receive certain regulatory approvals within the Territory.

In addition, the Company and Immedica formed a Joint Steering Committee (“JSC”) to provide oversight to the activities performed under the agreement; however, the substance of the Company’s participation in the JSC does not represent an additional promised service, but rather, a right of the Company to protect its own interests in the arrangement.

Further, the Company agreed to supply to Immedica, and Immedica agreed to purchase from the Company, substantially all commercial requirements of the Product. The terms of the agreement do not provide for either (i) an option to Immedica to purchase the Product from the Company at a discount from the standalone selling price or (ii) minimum purchase quantities. Finally, Immedica will bear (i) all costs and expenses for any development or commercialization of the Product in the Territory subject to the License exclusive of the Company’s promised goods and services summarized above and (ii) all costs and fees associated with applying for regulatory approval of the Product in the Territory. In July 2021, the Company modified the agreement with Immedica to provide certain additional services in relation to the PEACE Phase 3 Trial and BLA package performance obligation in exchange for the reimbursement of up to $3.0 million of the actual costs incurred in relation to such incremental services.

The Company received a non-refundable payment of $21.5 million and Immedica agreed to provide payment of 50% of the Company’s costs incurred in performing the PIP Trial up to a maximum of $1.8 million. In addition, the Company has the ability to receive additional payments under the agreement of up to approximately $120.8 million in regulatory and commercial milestone payments, assuming an exchange rate of $1.07 to €1.00. The Company is also entitled to receive royalties in the mid-20 percent range on net sales of the Product in the Territory.

The Company concluded that Immedica meets the definition to be accounted for as a customer because the Company is delivering intellectual property and other services within the Company’s normal course of business, in which the parties are not jointly sharing the risks and rewards. Therefore, the Company concluded that the promises summarized above represent transactions with a customer within the scope of ASC 606. The Company determined that the following promises represent distinct promised services, and therefore, performance obligations: (i) the License, (ii) the PEACE Trial and BLA package, and (iii) the PIP Trial.

Specifically, in making these determinations, the Company considered the following factors:

-As of inception of the agreement, the Company had completed the Phase 1/2 clinical trial related to the Product and were conducting the ongoing PEACE Trial. Accordingly, the

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Company is not promising, nor expecting, to perform additional research and development activities pursuant to the agreement that would either significantly modify, customize or be considered highly interdependent or interrelated with pegzilarginase.

-The License represents functional intellectual property given the functionality of the License is not expected to change substantially as a result of the company’s ongoing activities.

-The services necessary to complete the PEACE Trial, BLA package and PIP Trial could be performed by other parties.

Given that Immedica was not obligated to purchase any minimum amount or quantities of the Product, the supply of the Product for commercial use to Immedica was determined to be an option for Immedica, rather than a performance obligation of the Company at contract inception and will be accounted for if and when exercised. The Company also determined that Immedica’s option to purchase the Product does not create a material right as the expected pricing is not at a discount.

The Company determined that the upfront fixed payment amount of $21.5 million must be included in the transaction price. Additionally, the Company determined at inception of the arrangement that 50% of the estimated costs to be incurred in relation to the PIP Trial exceeded $1.8 million and included the full reimbursement amount of $1.8 million in the transaction price. Upon subsequent re-evaluation due to changing facts and circumstances, the Company determined the estimated costs are now less than the maximum allowable reimbursement and a portion of the variable consideration was constrained, which did not materially impact the revenue recognized to date. Additionally, upon the modification of the agreement in July 2021, the Company determined that the estimated costs to perform the additional services related to the PEACE Trial and BLA package exceeds the maximum allowable reimbursement of $3.0 million. Therefore, the Company included an estimated total of $3.6 million that will be due in relation to the PIP Trial, PEACE Trial, and BLA package in the transaction price and it is probable that a significant reversal will not occur in the future. In total, the modified transaction price was determined to be $25.1 million.

The Company has allocated $9.6 million and $3.5 million of the modified transaction price to the PEACE Trial and BLA package and PIP Trial performance obligations, respectively, based on the stand-alone selling prices ("SSP"), which was based on the estimated costs that a third-party would charge in performing such services on a stand-alone basis. The SSP for the License was established at inception of the arrangement using a residual value approach due to the uniqueness of and lack of observable data related to the License, and without a specific analog from which to make reliable estimates, resulting in an allocation of $12.0 million.

The potential regulatory milestone payments that the Company is eligible to receive were excluded from the transaction price, as the milestone amounts were fully constrained based on the probability of achievement, since the milestones relate to successful achievement of certain regulatory approvals, which might not be achieved. The Company determined that the royalties and commercial milestone payments relate predominantly to the license of intellectual property and are therefore excluded from the transaction price under the sales- or usage-based royalty exception of ASC 606. The Company will reevaluate the transaction price, including all constrained amounts, at the end of each reporting period and as uncertain events are resolved or other changes in circumstances occur, the Company will adjust its estimate of the transaction price as necessary. The Company will recognize the royalties and commercial milestone payments as revenue when the associated sales occur, and relevant sales-based thresholds are met. The Company assessed the arrangement with Immedica and concluded that a significant financing component does not exist.

The Company recognized revenue allocated to the License performance obligation at a point in time and upon transfer of the License. The Company completed the transfer of the know-how necessary for Immedica to benefit from the License in June 2021 and recognized $12.0 million of revenue at that time. The development fee allocated to the PEACE Trial, BLA package and PIP Trial performance obligations will be recognized over time using an input method of costs incurred related to the performance obligations.

For the years ended December 31, 2023 and 2022, the Company recognized revenue of $0.9 million and $2.3 million, respectively, related to the PEACE Trial and BLA package performance obligation using a cost to cost model. The Company recognized revenue of $6.7 million related to the PEACE Trial and BLA package performance obligation using a cost to cost model and $12.0 million related to the transfer of the License for the year ended December 31, 2021. As of December 31, 2022, the Company recorded deferred revenue of $2.7

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million associated with the license and supply agreement with Immedica, of which $0.5 million was classified as current.

On July 27, 2023, the Company announced that it had entered into an agreement to sell the global rights to pegzilarginase to Immedica for $15.0 million in upfront cash proceeds and up to $100.0 million in contingent milestone payments. The sale of pegzilarginase to Immedica superseded and terminated the previous license agreement between the Company and Immedica. On July 27, 2023, the carrying value of the asset was zero as it was internally developed. Accordingly, the Company recognized a $16.4 million gain within Gain on Sale of in-process research and development, which is comprised of $15.0 million in upfront cash proceeds and the reimbursement of $1.8 million in pre-paid manufacturing costs that was contingent upon a favorable opinion being received by the CHMP, net of transaction costs and the derecognition of pegzilarginase related nonfinancial assets and liabilities totaling $0.4 million.

The milestone payments are contingent on formal reimbursement decisions by national authorities in key European markets and pegzilarginase approval by the FDA, among other events. The upfront payment and contingent milestone payments if paid, net of expenses and adjustments, will reduce the CVR liability and will be distributed to CVR holders pursuant to the CVR Agreement resulting from the Asset Acquisition.

Contract Balances from Customer Contract

The timing of revenue recognition, billings and cash collections results in contract assets and contract liabilities on the balance sheets. The Company recognizes license and development receivables based on billed services, which are derecognized upon reimbursement. When consideration is received, or such consideration is unconditionally due, from a customer prior to transferring goods or services to the customer under the terms of a contract, a contract liability is recorded. Contract liabilities are recognized as revenue after control of the goods or services is transferred to the customer and all revenue recognition criteria have been met.

The following table presents changes in the Company’s contract liabilities for the periods presented (in thousands):

Year Ended December 31, 2022						December 31, 2022						Additions						Deductions						December 31, 2023
Contract liabilities:
Deferred revenue						$	2,696					$	575					$	(3,271)					$	—

The Company had no contract assets during the years ended December 31, 2023 and 2022.

On July 27, 2023, the Company announced that it had entered into an agreement to sell the global rights to pegzilarginase to Immedica for $15.0 million in upfront cash proceeds and up to $100.0 million in contingent milestone payments. The sale of pegzilarginase to Immedica superseded and terminated the previous license agreement between the Company and Immedica. On July 27, 2023, the carrying value of the asset was zero as it was internally developed. Accordingly the Company recognized a $16.4 million gain within Gain on sale of in-process research and development, which is comprised of $15.0 million in upfront cash proceeds and the reimbursement of $1.8 million in pre-paid manufacturing costs that was contingent upon a favorable opinion being received by the Committee for Medicinal Products for Human Use, net of transaction costs and the derecognition of pegzilarginase related nonfinancial assets and liabilities totaling $0.4 million.

The milestone payments are contingent on formal reimbursement decisions by national authorities in key European markets and pegzilarginase approval by the FDA, among other events. Accordingly, the Company will recognize any future milestone payments once the contingency is resolved and payment is contractually required. The upfront payment and contingent milestone payments if paid, net of expenses and

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adjustments, will be distributed to CVR holders pursuant to the CVR Agreement resulting from the Asset Acquisition.

Pursuant to a Novation Agreement dated September 19, 2023 (the “Novation Agreement”), by and between the Company, Paragon and WuXi Biologics (Hong Kong) Limited (“WuXi Biologics”), the Company novated (i) a Biologics Master Services Agreement (the “WuXi Biologics MSA”) and (ii) a Cell Line License Agreement (the “Cell Line License Agreement”).

Biologics Master Services Agreement

In April 2023, Paragon and WuXi Biologics entered into the WuXi Biologics MSA, which was subsequently novated to the Company by Paragon on September 19, 2023 pursuant to the Novation Agreement. The WuXi Biologics MSA governs certain development activities and GMP manufacturing and testing for the SPY001 program, as well as potential future programs, on a work order basis. Under the WuXi Biologics MSA, the Company is obligated to pay WuXi Biologics a service fee and all non-cancellable obligations in the amount specified in each work order associated with the agreement for the provision of services.

The WuXi Biologics MSA terminates on the later of (i) June 20, 2027 or (ii) the completion of services under all work orders executed by the parties prior to June 20, 2027, unless terminated earlier. The term of each work order terminates upon completion of the services under such work order, unless terminated earlier. The Company can terminate the WuXi Biologics MSA or any work order at any time upon 30 days' prior written notice and immediately upon written notice if WuXi Biologics fails to obtain or maintain required material governmental licenses or approvals. Either party may terminate a work order (i) at any time upon six months prior notice with reasonable cause, provided however that if WuXi Biologics terminates a work order in such manner, no termination or cancellation fees shall be paid by the Company and (ii) immediately for cause upon (a) the other party’s material breach that remains uncured for 30 days after notice of such breach, (b) the other party’s bankruptcy or (c) a force majeure event that prevents performance for a period of at least 90 days.

Cell Line License Agreement

In April 2023, Paragon and WuXi Biologics entered into the Cell Line License Agreement, which was subsequently novated to the Company by Paragon pursuant to the Novation Agreement. Under the Cell Line License Agreement, the Company received a non-exclusive, worldwide, sublicensable license to certain of WuXi Biologics’s know-how, cell line, biological materials (the “WuXi Biologics Licensed Technology”) and media and feeds to make, have made, use, sell and import certain therapeutic products produced through the use of the cell line licensed by WuXi Biologics under the Cell Line License Agreement (the “WuXi Biologics Licensed Products”). Specifically, the WuXi Biologics Licensed Technology is used in certain manufacturing activities in support of the SPY001 program.

In consideration for the license, the Company agreed to pay WuXi Biologics a non-refundable license fee of $0.2 million. Additionally, if the Company manufactures all of its commercial supplies of bulk drug product with a manufacturer other than WuXi Biologics or its affiliates, the Company is required to make royalty payments to WuXi Biologics of less than one percent of global net sales of WuXi Biologics Licensed Products manufactured by a third-party manufacturer (the “Royalty”). If the Company manufactures part of its commercial supplies of the WuXi Biologics Licensed Products with WuXi Biologics or its affiliates, then the Royalty will be reduced accordingly on a pro rata basis.

The Cell Line License Agreement will continue indefinitely unless terminated (i) by the Company upon six months prior written notice and our payment of all undisputed amounts due to WuXi Biologics through the effective date of termination, (ii) by WuXi Biologics for a material breach by the Company that remains uncured for 60 days after written notice, (iii) by WuXi Biologics if the Company fails to make a payment and such failure continues for 30 days after receiving notice of such failure, or (iv) by either party upon the other party’s bankruptcy.

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2015 Equity Incentive Plan

In March 2015, the Company adopted the 2015 Equity Incentive Plan (“2015 Plan”), administered by the board of directors, and provides for the Company to sell or issue share of Common Stock or restricted Common Stock, or to grant incentive stock options or nonqualified stock options for the purchase of Common Stock, to employees, members of the board of directors and consultants of the Company. Under the terms of the 2015 Plan, the exercise prices, vesting and other restrictions may be determined at the discretion of the board of directors, or their committee if so delegated, except that the exercise price per share of stock options may not be less than 100% of the fair market value of the share of common stock on the date of grant, the term of stock options may not be greater than ten years for all grants, and for grantees holding more than 10% of the total combined voting power of all classes of stock, the term may not be greater than five years.

The Company granted options under the 2015 Plan until April 2016 when it was terminated as to future awards, although it continues to govern the terms of options that remain outstanding under the 2015 Plan.

As of December 31, 2023, a total of 3,029 shares of Common Stock are subject to options outstanding under the 2015 Plan and will become available under the 2016 Equity Incentive Plan (“2016 Plan”) to the extent the options are forfeited or lapse unexercised.

2016 Equity Incentive Plan

The 2016 Plan became effective in April 2016 and serves as the successor to the 2015 Plan. Under the 2016 Plan, the Company may grant stock options, stock appreciation rights, restricted stock awards, restricted stock units, performance awards, and stock bonuses. The 2016 Plan provides for an initial reserve of 44,000 shares of Common Stock, plus 20,395 shares of Common Stock remaining under the 2015 Plan, and any share awards that subsequently are forfeited or lapse unexercised under the 2015 Plan. The shares reserved exclude shares of Common Stock reserved for issuance under the 2015 Plan.

In October 2018, the 2016 Plan was amended to increase the number of shares of Common Stock reserved for issuance thereunder by 70,384 shares, extend the term of the 2016 Plan through August 7, 2028, and provide for an automatic increase in the number of shares reserved for issuance thereunder on January 1 of each year for the remaining term of the plan equal to (a) 4.0% of the number of issued and outstanding shares of Common Stock on December 31 of the immediately preceding year, or (b) a lesser amount as approved by the board each year (the "Evergreen Provision"). As a result of the operation of each of these provisions, on January 1, 2023, 2022, and 2021, an additional 104,561, 78,968, and 76,735 shares, respectively, became available for issuance under the 2016 Plan.

In November 2023, the 2016 Plan was amended to (i) increase the number of shares of Common Stock reserved for issuance thereunder by 4,481,152 shares, (ii) revise the annual limit on non-employee director compensation from 4,000 shares to (a) $750,000 in total value or (b) $1,000,000 in the year of the director’s initial service as a non-employee director or in any year a director serves as chairman of the Board of Directors, in either case, applicable to fees paid in both cash and equity, (iii) remove the fixed termination date of the 2016 Plan and, (iv) revise the Evergreen Provision from 4% to 5% of issued and outstanding shares of Common Stock on December 31 of the preceding calendar year and to include shares issuable upon the exercise of pre-funded warrants and the conversion of outstanding shares of non-voting convertible preferred stock in the calculation.

As of December 31, 2023, the total number of shares reserved for issuance under the 2016 Plan was 5,019,177, of which 3,294,962 shares were subject to outstanding option awards and restricted unit awards.

2018 Equity Inducement Plan

In February 2018, the board of directors approved and adopted the 2018 Equity Inducement Plan (“2018 Plan”), which became effective on the same date. The board of directors approved an initial reserve of 44,000 shares of Common Stock to be used exclusively for individuals who were not previously employees or directors, or following a bona fide period of non-employment, as an inducement material to the individual entering into employment with the Company. Nonqualified stock options or restricted stock units may be granted

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under the 2018 Plan at the discretion of the Compensation Committee or the board of directors. The Company did not seek stockholder approval of the 2018 Plan pursuant to Nasdaq Rule 5635(c)(4).

During 2023, the 2018 Plan was amended to increase the number of shares of Common Stock reserved for issuance by 6,000,000.

Under the 2016 Plan and 2018 Plan, the Company may grant stock-based awards with service conditions (“service-based” awards), performance conditions (“performance-based” awards), and market conditions (“market-based” awards). Service-based awards granted under the 2018 Plan, 2016 Plan, and 2015 Plan generally vest over four years and expire after ten years, although awards have been granted with vesting terms less than four years.

The Company granted 153,865 service-based restricted stock units (“RSUs”) during the year ended December 31, 2023 to certain employees under the 2018 Plan.

As of December 31, 2023, the total number of shares reserved for issuance under the 2018 Plan was 6,044,000, of which 5,350,595 shares were subject to outstanding awards.

Spyre 2023 Equity Incentive Plan

On June 22, 2023, in connection with the Asset Acquisition, the Company assumed the Amended and Restated Spyre 2023 Equity Incentive Plan (the "Spyre Equity Plan") and its outstanding and unexercised stock options, which were converted to options to purchase 2,734 shares of Common Stock. The acquisition-date fair value of these grants will be recognized as an expense on a pro-rata basis over the vesting period.

Parapyre Option Obligation

On June 22, 2023, in connection with the Asset Acquisition, the Company assumed the Parapyre Option Obligation which provided for an annual equity grant of warrants for Parapyre to purchase 1% of the then outstanding shares of Pre-Merger Spyre's common stock, on a fully diluted basis, on the last business day of each calendar year during the term of the Paragon Agreement, at the fair market value determined by the board of directors of Pre-Merger Spyre.

On September 29, 2023, the Company amended the Paragon Agreement to amend and restate certain terms of the option grant pertaining to the Parapyre Option Obligation, including but not limited to (i) defining that the annual equity grant of warrants is based on the outstanding shares of the Company’s Common Stock, (ii) establishing the grant date as the last business day of 2023 and 2024, and (iii) defining the term of the warrants granted as ten years. The Company determined that the 2023 and 2024 grants are two separate grants, as there would be no obligation for the 2024 grant had the Company exercised or terminated all of the options under the Paragon Agreement prior to December 31, 2023. The service inception period for the grant precedes the grant date, with the full award being vested as of the grant date with no post-grant date service requirement. Accordingly, a liability related to the Parapyre Option Obligation was recorded pursuant to the amended Paragon Agreement during 2023 interim periods. The Company determined that the grant date of the award was December 31, 2023, as all terms of the award, including number of shares and exercise price, were known by all parties. Accordingly, the Company measured the grant-date fair value of the warrants granted at approximately $11.5 million as an equity-classified award, of which $0.1 million was recognized as part of the liabilities assumed with the Asset Acquisition on June 22, 2023. For the year ended December 31, 2023, $11.4 million was recognized as stock compensation expense related to the Parapyre Option Obligation. There was no similar expense for the years ended December 31, 2022 and 2021.

As of December 31, 2023, the unamortized expense related to the Parapyre Option Obligation was nil.

---

The following table summarizes employee and non-employee stock option activity for the year ended December 31, 2023:

			Shares Issuable Under Options						Weighted Average Exercise Price						Weighted Average Remaining Contractual Term						Aggregate Intrinsic Value
															(in years)						(in thousands)
Outstanding as of December 31, 2022			405,082						$	113.75					6.72						$	2
Granted			8,776,245						9.67
Exercised			(46,246)						8.22
Forfeited			(637,686)						43.00
Outstanding as of December 31, 2023			8,497,395						$	12.13					8.40						$	98,928
Options vested and expected to vest as of December 31, 2023			8,497,395						$	12.13					8.40						$	98,928
Options exercisable as of December 31, 2023			1,065,700						$	24.72					5.62						$	13,328

The aggregate intrinsic value of options outstanding, exercisable, vested and expected to vest were calculated as the difference between the exercise price of the options and the fair value of the Company’s Common Stock as of the reporting date.

For the years ended December 31, 2023, 2022, and 2021, the weighted-average grant date fair value of options granted was $9.67, $1.80, and $4.96, per share, respectively. The total intrinsic value of options exercised during the years ended December 31, 2023, and 2021 was $0.4 million and $0.7 million, respectively. No options were exercised in the year ended December 31, 2022.

There were 477,000 stock options issued to non-employees during the years ended December 31, 2023. There were no stock options issued to non-employees during the years ended December 31, 2022 and 2021. For the years ended December 31, 2023, 2022 and 2021, no non-employee stock options vested in the period.

2016 Employee Stock Purchase Plan

The 2016 Employee Stock Purchase Plan (“2016 ESPP”) became effective in April 2016. A total of 6,600 shares of Common Stock were reserved for issuance under the 2016 ESPP. Eligible employees may purchase shares of Common Stock under the 2016 ESPP at 85% of the lower of the fair market value of the Common Stock as of the first or the last day of each offering period. Employees are limited to contributing 15% of the employee’s eligible compensation and may not purchase more than $25,000 of stock during any calendar year. The 2016 ESPP will terminate ten years from the first purchase date under the plan, unless terminated earlier by the board of directors.

In June 2018, the 2016 ESPP was amended to provide for an automatic annual increase in the number of shares reserved for issuance thereunder on January 1 of each year for the remaining term of the year equal to (a) 1.0% of the number of issued and outstanding shares of Common Stock on December 31 of the immediately preceding year, or (b) a lesser amount as approved by the board of directors each year. As a result of the operation of this provision, on January 1, 2023, 2022 and 2021, an additional 26,140, 19,742, and 19,184 shares, respectively, became available for issuance under the 2016 ESPP. As of December 31, 2023, the reserve remaining and available for future issuance under the 2016 ESPP was 72,404 shares.

In February 2023, the 2016 ESPP was amended to increase the maximum shares purchased during any one period from 80 shares to 400 shares or a lesser amount determined by the board of directors.

For the year ended December 31, 2023, stock-based compensation expense related to the 2016 ESPP plan was di minimis. For the years ended 2022 and 2021, stock-based compensation expense related to the 2016 ESPP plan was $0.1 million and $0.2 million, respectively.

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Restricted Common Stock Units

In July 2020, the Company granted 9,128 restricted stock units to certain employees, with vesting terms subject to regulatory, commercial, and clinical milestones, in addition to a service condition. As of December 31, 2023 none of these restricted stock units had vested and all restricted stock units were forfeited since the performance milestones were not met within the required time frame. No stock-based compensation expense was recognized on these awards.

The Company granted 153,865 service-based restricted stock units during the year ended December 31, 2023. There were no restricted stock units granted during the years ended December 31, 2022 and 2021.

The following table summarizes employee restricted stock activity for the year ended December 31, 2023:

			Shares						Weighted Average Grant Date Fair Value
Unvested restricted stock units as of December 31, 2022			5,660						$	203.25
Granted			153,865						18.17
Vested			—						—
Forfeited			(5,660)						203.25
Unvested restricted stock units as of December 31, 2023			153,865						$	18.17

There were no restricted stock units granted to non-employees during the years ended December 31, 2023, 2022, and 2021.

Stock-Based Compensation Expense

Total stock-based compensation expense recognized from the Company’s equity incentive plans, 2018 Plan, and the 2016 ESPP for the years ended December 31, 2023, 2022, and 2021 was as follows (in thousands):

			Year Ended December 31,
			2023												2022												2021
			Employees						Non- Employees						Employees						Non- Employees						Employees						Non- Employees
Research and development			$	2,910					$	11,328					$	2,591					$	—					$	2,723					$	—
General and administrative			11,327						109						4,520						—						5,315						—
Total stock-based compensation expense			$	14,237					$	11,437					$	7,111					$	—					$	8,038					$	—

    

No related tax benefits were recognized for the years ended December 31, 2023, 2022, and 2021 (see Note 18).

The employee and non-employee awards contain both performance and service-based vesting conditions. No expense was recognized for the unvested employee and non-employee awards with only a performance condition for the years ended December 31, 2023, 2022, and 2021. The performance-based vesting conditions represent specific performance targets. Compensation expense for employee and non-employee share-based payment awards with performance conditions is recognized when the performance condition is deemed probable of achievement.

---

As of December 31, 2023, the Company had an aggregate of $64.4 million of unrecognized stock-based compensation expense for options outstanding, which is expected to be recognized over a weighted average period of 3.5 years.

In determining the fair value of the stock-based awards, the Company uses the Black-Scholes option-pricing model and assumptions discussed below. Each of these inputs is subjective and generally requires significant judgment to determine.

Expected Term

The Company’s expected term represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method (based on the midpoint between the vesting date and the end of the contractual term). The Company utilizes this method due to lack of historical exercise data and the plain-vanilla nature of the Company’s stock-based awards.

Expected Volatility

Since the Company was privately held through April 2016 and transitioned from a clinical stage company to a pre-clinical stage company in 2023, it alone does not have the relevant company-specific historical data to support its expected volatility. As such, the Company has used an average of expected volatilities based on the volatilities of a representative group of publicly traded biopharmaceutical companies over a period equal to the expected term of the stock option grants. Subsequent to the Company’s initial public offering, it began to consider the Company’s own historic volatility. However, due to the transition from a clinical stage company to a pre-clinical stage company, the Company still uses peer company data to assist in this analysis. For purposes of identifying comparable companies, the Company selected companies with comparable characteristics to it, including enterprise value, risk profiles, position within the industry, and with historical share price information sufficient to meet the expected life of the stock-based awards. The historical volatility data was computed using the daily closing prices for the selected companies’ shares during the equivalent period of the calculated expected term of the stock-based awards. The Company intends to consistently apply this process using the same or similar comparable entities until a sufficient amount of historical information regarding the volatility of the Company’s own share price post transition becomes available.

Risk-Free Interest Rate

The risk-free interest rate is based on the U.S. Treasury zero coupon issues in effect at the time of grant for periods corresponding with the expected term of option.

Expected Dividend

The Company has never paid dividends on its Common Stock and has no plans to pay dividends on its Common Stock. Therefore, the Company used an expected dividend yield of zero.

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Valuation of Stock Options and 2016 ESPP

The fair value of the stock options granted under the the Company's equity incentive plans, as well as the shares available for purchase under the 2016 ESPP were determined using the Black-Scholes option-pricing model. The following table summarizes the weighted-average assumptions used in calculating the fair value of the awards:

			Year Ended December 31,
			2023						2022						2021
Stock Options Granted
Expected term (in years)			5.88						6.00						5.99
Expected volatility			107		%				84		%				83		%
Risk-free interest			4.37		%				2.93		%				0.88		%
Dividend yield			0		%				0		%				0		%
2016 ESPP
Expected term (in years)			0.49						0.49						0.50
Expected volatility			181		%				84		%				86		%
Risk-free interest			4.99		%				1.95		%				0.08		%
Dividend yield			0		%				0		%				0		%

The Company sponsors a 401(k) retirement plan in which substantially all of its full-time employees are eligible to participate. Participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. During the years ended December 31, 2023, 2022, 2021, the Company provided $0.2 million, $0.6 million, and $0.6 million, respectively, in contributions to the plan.

Severance and Stock Compensation

On April 12, 2023, based on the review of the inconclusive interim results from the Company's Phase 1/2 clinical trial of pegtarviliase for the treatment of classical homocystinuria and other business considerations, the Company announced that it had initiated a process to explore strategic alternatives to maximize stockholder value and engaged an independent exclusive financial advisor to support this process.

As a result, the Company implemented a restructuring plan resulting in an approximate 83% reduction of the Company’s existing headcount by June 30, 2023. The Company recognized restructuring expenses consisting of cash severance payments and other employee-related costs of $6.4 million during the year ended December 31, 2023. Cash payments for employee related restructuring charges of $5.3 million were paid as of December 31, 2023. In addition, the Company recognized $1.0 million in non-cash stock-based compensation expense related to the accelerated vesting of stock-based awards for certain employees. The Company recorded these restructuring charges based on each employee’s role to the respective research and development and general and administrative operating expense categories on its consolidated statements of operations and comprehensive loss.

The following table summarizes the changes in the Company's accrued restructuring balance (in thousands):

			Beginning Balance December 31, 2022						Charges						Payments						Ending Balance December 31, 2023
Severance liability			$	—					$	6,448					$	(5,325)					$	1,123

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Sale of Assets

During the second quarter of 2023, the Company sold various lab equipment, consumables, and furniture and fixtures for total consideration of $0.5 million. After recording the disposal of all the Company's property and equipment net of proceeds, the Company recorded a $0.7 million and $0.2 million loss on disposal of long lived assets which is included in Research and development and General and administrative expenses, respectively.

Lease Right-of-use Asset and Leasehold Improvement Impairment

Effective June 30, 2023, the Company abandoned its leased office space in Austin, Texas. As a result, the Company recognized an impairment loss of $0.9 million related to the operating lease right-of-use asset and $1.7 million related to leasehold improvements. On August 7, 2023, the Company terminated its building lease in Austin, Texas. The negotiated termination agreement obligated the Company to pay the lessor a $2.0 million termination fee in exchange for releasing the Company of all further obligations under the lease.

All charges related to the restructuring activities were recognized during the second quarter of 2023. No further restructuring charges will be incurred under the restructuring plan. A summary of the charges related to the restructuring activities is as follows (in thousands):

			Severance Related Expenses						Stock Compensation Expenses						Loss on Disposal of Long Lived Assets						Lease Asset Impairment						Total Restructuring Costs
Research and development			$	3,182					$	123					$	749					$	1,405					$	5,459
General and administrative			3,266						870						182						1,175						5,493
Total			$	6,448					$	993					$	931					$	2,580					$	10,952

The following table summarizes the (loss) income before income tax expense by jurisdiction for the periods indicated:

			Year Ended December 31,
			2023						2022						2021
Domestic			$	(338,942)					$	(84,113)					$	(65,940)
Foreign			126						162						280
Loss before income tax expense			$	(338,816)					$	(83,951)					$	(65,660)

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For the year ended December 31, 2023, the Company recognized no provision or benefit from income taxes. For both the years ended December 31, 2022 and 2021, the Company recognized an income tax expense of $0.1 million, related to foreign subsidiaries income tax expense and the Texas margins tax. The difference between the Company’s provision for income taxes and the amounts computed by applying the statutory federal income tax rate to income before income taxes is as follows (in thousands):

			Year Ended December 31,
			2023						2022						2021
Tax provision derived by applying the federal statutory rate to income before income taxes			$	(71,151)					$	(17,630)					$	(13,789)
Loss on forward contract valuation			17,541						—						—
Acquired IPR&D			27,340						—						—
Loss on CVR revaluation			3,987						—						—
Other permanent differences			4,472						1,042						1,002
Federal tax credits			(1)						(3,559)						(3,815)
State tax credits			—						(640)						(152)
Effect of tax rate on foreign jurisdiction			(53)						42						(5)
Change in the valuation allowance			17,839						20,609						16,900
Income tax (benefit) expense			$	(26)					$	(136)					$	141

The components of the deferred tax assets and liabilities consist of the following (in thousands):

			December 31,
			2023						2022
Deferred tax assets
Net operating loss carryforward			$	74,454					$	68,917
Capitalized 174 R&D costs			22,532						11,097
Intangible assets			47						52
Deferred revenue			—						566
Accrued expense			579						668
Stock-based compensation			4,246						3,293
Federal tax credits			21,914						21,914
State tax credits			1,631						1,631
Other			88						190
Total deferred tax assets			125,491						108,328
Deferred tax liabilities
Depreciable assets			—						(676)
Total deferred tax liabilities			—						(676)
Less: Valuation allowance			(125,491)						(107,652)
Deferred tax assets, net			$	—					$	—

The Company has established a full federal and state valuation allowance equal to the net deferred tax assets due to uncertainties regarding the realization of the deferred tax asset based on the Company’s lack of earnings history. The valuation allowance increased by $17.8 million, $20.6 million, and $16.9 million during the years ended December 31, 2023, 2022, and 2021, respectively, primarily due to continuing loss from operations.

As of December 31, 2023 and 2022, the Company had U.S. net operating loss carryforwards (“NOL”) of $354.5 million and $328.2 million, respectively. For both the years ended December 31, 2023 and 2022, the Company had U.S. tax credit carryforwards and state tax credit carryforwards of $21.9 million and $1.6 million, respectively. Of the net operating loss and tax credit carryforwards $58.4 million and $21.9 million, respectively,

---

will expire in 2033, if not utilized. Any remaining net operating loss will carry forward indefinitely and can be utilized to offset up to 80% of the taxable income in any tax year. The net operating loss and credit carryforwards are subject to Internal Revenue Service adjustments until the statute closes on the year the net operating loss or tax credits are utilized.

The Company has not completed a study to assess whether an ownership change has occurred or whether there have been multiple ownership changes since the Company’s formation due to the complexity and cost associated with such a study, and the fact that there may be additional such ownership changes in the future. If the Company has experienced an ownership change at any time since its formation, utilization of the NOL or research and development credit carryforwards would be subject to an annual limitation under Section 382 or 383 of the Internal Revenue Code, which is determined by first multiplying the value of the Company’s stock at the time of the ownership change by the applicable long-term, tax-exempt rate, and then could be subject to additional adjustments, as required. Additionally, the separate return limitation year (“SRLY”) rules may apply to losses of the Company’s eight wholly owned U.S. subsidiary corporations. The SRLY rules limit the consolidated group’s use of a subsidiary corporation’s net operating losses to the amount of income generated by the subsidiary corporation after it becomes a member of the group. Any limitation may result in expiration of a portion of the NOL or research and development credit carryforwards before utilization. Further, until a study is completed and any limitation known, no amounts are being considered as an uncertain tax position or disclosed as an unrecognized tax benefit. Additionally, the Company does not expect any unrecognized tax benefits to change significantly over the next twelve months. Due to the existence of the valuation allowance, future changes in the Company’s unrecognized tax benefits will not impact its effective tax rate. Any carryforwards that will expire prior to utilization as a result of such limitations will be removed from deferred tax assets with a corresponding reduction of the valuation allowance.

The Company is subject to examination by taxing authorities in its significant jurisdictions for the 2019 and subsequent years. However, due to NOL and tax attribute carryovers, the taxing authorities have the ability to adjust the NOLs and other tax attributes related to closed years. As of December 31, 2023 and 2022, there were no amounts recorded for uncertain tax positions. As of December 31, 2023, undistributed earnings of the Company’s incorporated foreign subsidiaries are immaterial. Under the Global Intangible Low-Taxed Income (“GILTI”) provisions of the 2017 Tax Cuts and Jobs Act, U.S. income taxes have been incurred on the undistributed earnings of the foreign subsidiaries and therefore, the tax impact upon distribution is limited to state income and withholding taxes and is not material.

Restatement

Subsequent to the filing of its Quarterly Report on Form 10-Q for the period ended September 30, 2024, management identified an error related to the calculation and presentation of loss per share. The Company had previously concluded that the Series A Preferred Stock and Series B Preferred Stock had preferences over the Company's Common Stock and were therefore excluded from the calculation of basic and dilutive net loss per share pursuant to the two-class method. The Company has now determined that the Series A Preferred Stock and Series B Preferred Stock do not have preferential rights over the Company’s Common Stock and, accordingly, are considered to be a second and third class of common stock for purposes of calculating net loss per share. Consequently, the Company has now separately calculated and presented net loss per share for its Common Stock, Series A Preferred Stock and Series B Preferred Stock. Loss per share attributable to common stockholders for the year ended December 31, 2023 as previously presented was $49.12 and as restated is $13.76. Net loss per share attributable to holders of Series A Preferred Stock and Series B Preferred Stock was not previously presented.

All related amounts have been updated to reflect the effects of the restatement throughout the financial statements and related footnotes, as applicable.

The Company computes net loss per share of Common Stock, Series A Preferred Stock, and Series B Preferred Stock using the two-class method required for multiple classes of common stock and other participating securities.

The two-class method is an earnings (loss) allocation method under which earnings (loss) per share is calculated for each class of common stock. The Company has determined that the Series A Preferred Stock and

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Series B Preferred Stock do not have preferential rights when compared to the Company's Common Stock and therefore it must allocate losses to these other classes of common stock, as illustrated in the table below.

Basic and diluted net loss per share is computed by dividing the net loss by the weighted-average number of shares and pre-funded warrants outstanding during the period, without consideration of potential dilutive securities. The pre-funded warrants are included in the computation of basic net loss per share as the exercise price is negligible and they are fully vested and exercisable. For periods in which the Company generated a net loss, the Company does not include potential shares of common stock in diluted net loss per share when the impact of these items is anti-dilutive. The Company has generated a net loss for all periods presented, therefore diluted net loss per share is the same as basic net loss per share since the inclusion of potential shares of common stock would be anti-dilutive.

---

The following table sets forth the computation of basic and diluted net loss per share of Common Stock, Series A Preferred Stock, and Series B Preferred Stock (in thousands, except share and per share amounts):

			Year Ended December 31, 2023
			Series A Preferred Stock						Series B Preferred Stock						Common Stock
Net loss per share, basic and diluted:
Numerator
Allocation of losses			$	(239,158)					$	(4,749)					$	(94,883)
Denominator
Weighted-average shares outstanding			434,612						8,630						6,201,954
Weighted-average pre-funded warrants outstanding			—						—						695,111
Number of shares used in per share computation			434,612						8,630						6,897,065
Net loss per share, basic and diluted			$	(550.28)					$	(550.29)					$	(13.76)
			Year Ended December 31, 2022
			Series A Preferred Stock						Series B Preferred Stock						Common Stock
Net loss per share, basic and diluted:
Numerator
Allocation of losses			$	—					$	—					$	(83,815)
Denominator
Weighted-average shares outstanding			—						—						2,307,668
Weighted-average pre-funded warrants outstanding			—						—						1,063,563
Number of shares used in per share computation			—						—						3,371,231
Net loss per share, basic and diluted			$	—					$	—					$	(24.86)
			Year Ended December 31, 2021
			Series A Preferred Stock						Series B Preferred Stock						Common Stock
Net loss per share, basic and diluted:
Numerator
Allocation of losses			$	—					$	—					$	(65,801)
Denominator
Weighted-average shares outstanding			—						—						1,956,933
Weighted-average pre-funded warrants outstanding			—						—						672,851
Number of shares used in per share computation			—						—						2,629,784
Net loss per share, basic and diluted			$	—					$	—					$	(25.02)

The following weighted-average equity instruments were excluded from the calculation of diluted net loss per share because their effect would have been anti-dilutive for the periods presented:

			Year Ended December 31,
			2023						2022						2021
Options to purchase Common Stock			2,583,226						346,331						264,858
Unvested restricted stock units			4,240						6,983						7,975
Outstanding Parapyre Warrants			5,625						—						—

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v3.24.3

Cover - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Feb. 21, 2024	Jun. 30, 2023
Cover [Abstract]
Document Type	10-K/A
Document Annual Report	true
Document Period End Date	Dec. 31, 2023
Current Fiscal Year End Date	--12-31
Document Transition Report	false
Entity File Number	001-37722
Entity Registrant Name	SPYRE THERAPEUTICS, INC.
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	46-4312787
Entity Address, Address Line One	221 Crescent Street
Entity Address, Address Line Two	Building 23, Suite 105
Entity Address, City or Town	Waltham
Entity Address, State or Province	MA
Entity Address, Postal Zip Code	02453
City Area Code	617
Local Phone Number	651-5940
Title of 12(b) Security	Common Stock, $0.0001 Par Value Per Share
Trading Symbol	SYRE
Security Exchange Name	NASDAQ
Entity Well-known Seasoned Issuer	No
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Non-accelerated Filer
Entity Small Business	true
Entity Emerging Growth Company	false
ICFR Auditor Attestation Flag	false
Document Financial Statement Error Correction	true
Document Financial Statement Restatement Recovery Analysis [Flag]	true
Entity Shell Company	false
Entity Public Float			$ 26.2
Entity Common Stock Shares Outstanding		36,150,941
Entity Central Index Key	0001636282
Document Fiscal Year Focus	2023
Document Fiscal Period Focus	FY
Amendment Flag	true
Amendment Description	This Amendment No. 2 on Form 10-K/A (this “Amendment”) amends the Annual Report on Form 10-K of Spyre Therapeutics, Inc. (the “Company”) for the fiscal year ended December 31, 2023, as filed with the Securities and Exchange Commission on February 29, 2024, as amended by Form 10-K/A of the Company filed with the Securities and Exchange Commission on March 1, 2024 (as amended, the "Original Filing").Subsequent to the filing of its Form 10-Q for the three and nine months ended September 30, 2024, the Company became aware of a misapplication of Generally Accepted Accounting Principles in the United States ("U.S. GAAP") as it relates to the Company's exclusion of its Series A non-voting convertible preferred stock and Series B non-voting convertible preferred stock in the calculation of basic and diluted net loss per share and a finding of a material weakness in internal control over financial reporting solely related to such matter. This Amendment is being filed for the sole purpose of amending certain disclosures from the Original Filing related to the aforementioned misapplication of U.S. GAAP and related finding of material weakness in internal control over financial reporting.Specifically, this Amendment amends: (i) Part II, Item 8. "Financial Statements and Supplementary Data" to update the Company's Consolidated Statement of Operations and related footnote disclosures for the twelve months ended December 31, 2023, (ii) Part II, Item 9A. "Controls and Procedures" to address management's re-evaluation of disclosure controls and procedures as of December 31, 2023 and to reflect the identification of a material weakness in our internal control over financial reporting and (iii) Part IV, Item 15. "Exhibits and Financial Statement Schedules" to include, in accordance with Rule 12b-15 under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), updated certifications from our Chief Executive Officer and Chief Financial Officer as required by Sections 302 and 906 of the Sarbanes-Oxley Act of 2002 as Exhibits 31.1, 31.2 and 32.1 and an updated Consent of Independent Registered Public Accounting Firm as Exhibit 23.1. In accordance with Rule 12b-15 under the Exchange Act, this Amendment amends and restates in their entirety each item identified in the paragraph above.Other than as described above, this Amendment does not amend, update or change any other items or disclosures contained in the Original Filing, and accordingly, all other information contained in this Amendment is as of the date of the original filing and does not reflect subsequent information or events beyond the original filing date, February 29, 2024. Accordingly, this Amendment should be read in conjunction with other filings made with the SEC subsequent to the filing of the Original Filing, including any amendments to those filings. Capitalized terms used but not defined herein shall have the meanings ascribed to such terms in the Original Filing.

v3.24.3

Audit Information	12 Months Ended
	Dec. 31, 2023
Audit Information [Abstract]
Auditor Firm ID	238
Auditor Name	PricewaterhouseCoopers LLP
Auditor Location	Austin, Texas

v3.24.3

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
CURRENT ASSETS
Cash and cash equivalents	$ 188,893	$ 34,863
Marketable securities	150,384	20,848
Development receivables	0	375
Prepaid expenses and other current assets	2,251	6,172
Total current assets	341,528	62,258
Restricted cash	322	1,553
Property and equipment, net	0	3,220
Operating lease right-of-use assets	0	3,430
Other non-current assets	9	683
TOTAL ASSETS	341,859	71,144
CURRENT LIABILITIES
Accounts payable	896	677
CVR liability	1,390	0
Operating lease liabilities	0	625
Deferred revenue	0	517
Accrued and other current liabilities	13,108	12,837
Related party accounts payable and other current liabilities	16,584	0
Total current liabilities	31,978	14,656
Non-current CVR liability	41,310	0
Non-current operating lease liabilities	0	4,004
Deferred revenue, net of current portion	0	2,179
TOTAL LIABILITIES	73,288	20,839
Commitments and Contingencies (Note 9)
Series B non-voting convertible preferred stock, $0.0001 par value; 150,000 and no shares authorized as of December 31, 2023 and December 31, 2022, respectively; 150,000 and no shares issued and outstanding as of December 31, 2023 and December 31, 2022, respectively.	84,555	0
STOCKHOLDERS’ EQUITY
Common stock, $0.0001 par value; 400,000,000 and 20,000,000 shares authorized as of December 31, 2023 and December 31, 2022, respectively; 36,057,109 shares and 2,614,014 shares issued and outstanding as of December 31, 2023 and December 31, 2022, respectively.	10	6
Additional paid-in capital	763,191	475,971
Accumulated other comprehensive income (loss)	302	(48)
Accumulated deficit	(764,414)	(425,624)
TOTAL STOCKHOLDERS’ EQUITY	184,016	50,305
TOTAL LIABILITIES, CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS’ EQUITY	341,859	71,144
Series A Non-Voting Convertible Preferred Stock
STOCKHOLDERS’ EQUITY
Preferred stock	184,927	0
Preferred Stock
STOCKHOLDERS’ EQUITY
Preferred stock	$ 0	$ 0

v3.24.3

Consolidated Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2023	Dec. 31, 2022
Series B non-voting convertible preferred stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Series B non-voting convertible preferred stock, authorized (in shares)	150,000	0
Series B non-voting convertible preferred stock, issued (in shares)	150,000	0
Series B non-voting convertible preferred stock, outstanding (in shares)	150,000	0
Preferred stock, par value (in dollars per share)	$ 0.0001
Preferred stock, authorized (in shares)	10,000,000
Common stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Common stock, authorized (in shares)	400,000,000	20,000,000
Common stock, issued (in shares)	36,057,109	2,614,014
Common stock, outstanding (in shares)	36,057,109	2,614,014
Series A Non-Voting Convertible Preferred Stock
Preferred stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Preferred stock, authorized (in shares)	1,086,341	0
Preferred stock, issued (in shares)	437,037	0
Preferred stock, outstanding (in shares)	437,037	0
Preferred Stock
Preferred stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Preferred stock, authorized (in shares)	8,763,659	10,000,000
Preferred stock, issued (in shares)	0	0
Preferred stock, outstanding (in shares)	0	0

v3.24.3

Consolidated Statements of Operations - USD ($) $ in Thousands		12 Months Ended
		Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Revenue:
Total revenue		$ 886	$ 2,329	$ 18,739
Operating expenses:
Research and development	[1]	89,504	58,579	57,069
General and administrative		39,946	28,531	27,319
Acquired in-process research and development		130,188	0	0
Gain on sale of in-process research and development asset		(16,449)	0	0
Total operating expenses		243,189	87,110	84,388
Loss from operations		(242,303)	(84,781)	(65,649)
Other (expense) income:
Interest income		6,147	837	111
Other expense, net		(19,130)	(7)	(122)
Total other (expense) income		(96,513)	830	(11)
Loss before income tax expense		(338,816)	(83,951)	(65,660)
Income tax benefit (expense)		26	136	(141)
Net loss		$ (338,790)	$ (83,815)	$ (65,801)
Net loss per share, basic (in dollars per share)		$ 13.76
Net loss per share, diluted (in dollars per share)		$ 13.76
Weighted-average common shares outstanding, basic (in shares)		6,897,065	3,371,231	2,629,784
Weighted-average common shares outstanding, diluted (in shares)		6,897,065	3,371,231	2,629,784
Series A Preferred Stock
Other (expense) income:
Net loss		$ (239,158)	$ 0	$ 0
Net loss per share, basic (in dollars per share)		$ (550.28)	$ 0	$ 0
Net loss per share, diluted (in dollars per share)		$ (550.28)	$ 0	$ 0
Weighted-average common shares outstanding, basic (in shares)		434,612	0	0
Weighted-average common shares outstanding, diluted (in shares)		434,612	0	0
Series B Preferred Stock
Other (expense) income:
Net loss		$ (4,749)	$ 0	$ 0
Net loss per share, basic (in dollars per share)		$ (550.29)	$ 0	$ 0
Net loss per share, diluted (in dollars per share)		$ (550.29)	$ 0	$ 0
Weighted-average common shares outstanding, basic (in shares)		8,630	0	0
Weighted-average common shares outstanding, diluted (in shares)		8,630	0	0
Common Stock
Other (expense) income:
Net loss		$ (94,883)	$ (83,815)	$ (65,801)
Net loss per share, basic (in dollars per share)		$ (13.76)	$ (24.86)	$ (25.02)
Net loss per share, diluted (in dollars per share)		$ (13.76)	$ (24.86)	$ (25.02)
Weighted-average common shares outstanding, basic (in shares)		6,201,954	2,307,668	1,956,933
Weighted-average common shares outstanding, diluted (in shares)		6,897,065	3,371,231	2,629,784
Forward Contract Liability
Other (expense) income:
Change in fair value of forward contract liability		$ (83,530)	$ 0	$ 0
License
Revenue:
Total revenue		0	0	12,000
Development fee and royalty
Revenue:
Total revenue		$ 886	$ 2,329	$ 6,739
[1] Includes $48.5 million in related party expenses for the year ended December 31, 2023 and no related party expenses for the year ended months ended December 31, 2022 and 2021.

v3.24.3

Consolidated Statements of Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Statement of Comprehensive Income [Abstract]
Net loss	$ (338,790)	$ (83,815)	$ (65,801)
Other comprehensive income (loss):
Foreign currency translation adjustment	37	(35)	(1)
Unrealized gain (loss) on marketable securities	313	7	(30)
Total comprehensive loss	$ (338,440)	$ (83,843)	$ (65,832)

v3.24.3

Consolidated Statements of Changes in Convertible Preferred Stock and Stockholders’ Equity - USD ($) $ in Thousands	Total	Private Placement	Conversion Of Series A Non-Voting Convertible Preferred Stock	Series A Non-Voting Convertible Preferred Stock	Series A Non-Voting Convertible Preferred Stock Series A Non-Voting Convertible Preferred Stock	Series A Non-Voting Convertible Preferred Stock Series A Non-Voting Convertible Preferred Stock Conversion Of Series A Non-Voting Convertible Preferred Stock	Common Stock	Common Stock Private Placement	Common Stock Conversion Of Series A Non-Voting Convertible Preferred Stock	Common Stock Conversion Of Pre-Funded Warrants	Additional Paid-in Capital	Additional Paid-in Capital Private Placement	Additional Paid-in Capital Conversion Of Series A Non-Voting Convertible Preferred Stock	Accumulated Other Comprehensive (Loss) Income	Accumulated Deficit
Beginning balance (in shares) at Dec. 31, 2020	0
Beginning balance at Dec. 31, 2020	$ 0
Ending balance (in shares) at Dec. 31, 2021	0
Ending balance at Dec. 31, 2021	$ 0
Beginning balance (in shares) at Dec. 31, 2020					0
Beginning balance (in shares) at Dec. 31, 2020							1,918,000
Beginning balance at Dec. 31, 2020	139,832				$ 0		$ 5				$ 415,824			$ 11	$ (276,008)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock upon conversion (in shares)							40,000
Issuance of common stock in connection with exercise of stock options and employee stock purchase plan (in shares)							16,000
Issuance of common stock in connection with exercise of stock options and employee stock purchase plan	1,903										1,903
Stock-based compensation expense	8,038										8,038
Foreign currency translation adjustment	(1)													(1)
Unrealized gain (loss) on marketable securities	(30)													(30)
Net loss	(65,801)														(65,801)
Ending balance (in shares) at Dec. 31, 2021					0
Ending balance (in shares) at Dec. 31, 2021							1,974,000
Ending balance at Dec. 31, 2021	$ 83,941				$ 0		$ 5				425,765			(20)	(341,809)
Ending balance (in shares) at Dec. 31, 2022	0
Ending balance at Dec. 31, 2022	$ 0
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock and pre-funded warrants in connection with registered direct offering, net of offering costs (in shares)							430,000
Issuance of common stock and pre-funded warrants in connection with registered direct offering, net of offering costs	42,874						$ 1				42,873
Issuance of common stock upon conversion (in shares)							204,000
Issuance of common stock in connection with employee stock purchase plan (in shares)							6,000
Issuance of common stock in connection with employee stock purchase plan	222										222
Stock-based compensation expense	7,111										7,111
Foreign currency translation adjustment	(35)													(35)
Unrealized gain (loss) on marketable securities	7													7
Net loss	$ (83,815)														(83,815)
Ending balance (in shares) at Dec. 31, 2022				0	0
Ending balance (in shares) at Dec. 31, 2022	2,614,014						2,614,000
Ending balance at Dec. 31, 2022	$ 50,305				$ 0		$ 6				475,971			(48)	(425,624)
Series B Non-Voting Convertible Preferred Stock
Issuance of Series B non-voting convertible preferred stock in connection with private placement, net of financing costs (in shares)	150,000
Issuance of Series B non-voting convertible preferred stock in connection with private placement, net of financing costs	$ 84,555
Ending balance (in shares) at Dec. 31, 2023	150,000
Ending balance at Dec. 31, 2023	$ 84,555
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock upon conversion (in shares)						(649,000)			25,972,000	905,000
Issuance of common stock upon conversion			$ 0			$ (202,178)			$ 3				$ 202,175
Issuance of stock (in shares)					721,000			6,000,000
Issuance of stock	197,364	$ 84,555			$ 197,364							$ 84,555
Issuance of Series A non-voting convertible preferred stock in connection with the asset acquisition of Spyre and settlement of related forward contract (in shares)					365,000
Issuance of Series A non-voting convertible preferred stock in connection with the asset acquisition of Spyre and settlement of related forward contract	189,741				$ 189,741
Issuance of common stock in connection with the asset acquisition of Spyre (in shares)							518,000
Issuance of common stock in connection with the asset acquisition of Spyre	3,768						$ 1				3,767
Issuance of common stock in connection with exercise of stock options and employee stock purchase plan (in shares)							48,000
Issuance of common stock in connection with exercise of stock options and employee stock purchase plan	405										405
CVR distribution to common stockholders	(29,500)										(29,500)
Stock-based compensation expense	14,347										14,347
Issuance of Parapyre Option Obligation warrants	11,471										11,471
Foreign currency translation adjustment	37													37
Unrealized gain (loss) on marketable securities	313													313
Net loss	$ (338,790)														(338,790)
Ending balance (in shares) at Dec. 31, 2023				437,037	437,000
Ending balance (in shares) at Dec. 31, 2023	36,057,109						36,057,000
Ending balance at Dec. 31, 2023	$ 184,016				$ 184,927		$ 10				$ 763,191			$ 302	$ (764,414)

v3.24.3

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
CASH FLOWS FROM OPERATING ACTIVITIES
Net loss	$ (338,790)	$ (83,815)	$ (65,801)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	744	1,567	1,576
Stock-based compensation	25,675	7,111	8,038
Acquired in-process research and development	130,188	0	0
Gain on sale of in-process research and development asset	(16,449)	0	0
Lease ROU asset and leasehold improvement impairment loss	2,580	0	0
Loss on disposal of long-lived assets	915	0	0
Net (accretion of discount) amortization of premium on marketable securities	(2,318)	(327)	548
Amortization of operating lease assets	220	397	425
Other	15	426	(335)
Changes in operating assets and liabilities:
Development receivables	375	440	(815)
Accounts payable	218	(2,641)	1,065
Prepaid expenses and other assets	3,245	(1,144)	(1,216)
Deferred revenue	575	(880)	3,576
Operating lease liabilities	(2,326)	(435)	(404)
Accrued and other liabilities	(4,891)	(843)	(373)
Related party payable	(2,402)	0	0
Net cash used in operating activities	(99,910)	(80,144)	(53,716)
CASH FLOWS FROM INVESTING ACTIVITIES
Cash assumed from asset acquisition of Spyre	3,035	0	0
Proceeds from sale of in-process research & development asset	15,000	0	0
Purchases of property and equipment	0	(38)	(573)
Proceeds from the sale of property plant and equipment	475	0	0
Purchases of marketable securities	(166,803)	(39,500)	(133,079)
Proceeds from maturities and sales of marketable securities	39,900	96,546	111,033
Net cash provided by (used in) investing activities	(108,393)	57,008	(22,619)
CASH FLOWS FROM FINANCING ACTIVITIES
Proceeds from issuance of Series A non-voting convertible preferred stock in connection with private placement, net of placement and other offering costs	197,364	0	0
Proceeds from issuance of Series B non-voting convertible preferred stock in connection with private placement, net of placement and other offering costs	84,555	0	0
Proceeds from issuance of common stock in connection with private placement, net of placement and other offering costs	84,555	0	0
Payment of contingent value rights liability	(5,786)	0	0
Proceeds from issuance of common stock and pre-funded warrants in registered direct offering, net of offering costs	0	42,874	0
Proceeds from employee stock plan purchases and stock option exercises	405	222	1,903
Principal payments on finance lease obligation	(16)	(418)	(510)
Net cash provided by financing activities	361,077	42,678	1,393
Effect of exchange rate on cash, cash equivalents, and restricted cash	25	(106)	(15)
NET INCREASE (DECREASE) IN CASH, CASH EQUIVALENTS, AND RESTRICTED CASH	152,799	19,436	(74,957)
CASH, CASH EQUIVALENTS, AND RESTRICTED CASH
Beginning of period	36,416	16,980	91,937
End of period	189,215	36,416	16,980
Supplemental Disclosure of Non-Cash Investing and Financing Information:
Settlement of forward contract liability and issuance of Series A non-voting convertible preferred stock in connection with the asset acquisition of Spyre	189,741	0	0
Conversion of Series A non-voting convertible preferred stock into common stock	202,178	0	0
Leased assets obtained in exchange for lease obligations	0	21	872
CVR liability
Adjustments to reconcile net loss to net cash used in operating activities:
Change in fair value of derivative liability	18,986	0	0
Forward Contract Liability
Adjustments to reconcile net loss to net cash used in operating activities:
Change in fair value of derivative liability	$ 83,530	$ 0	$ 0

v3.24.3

Consolidated Statements of Operations (Parenthetical) $ in Thousands	12 Months Ended
	Dec. 31, 2023 USD ($)
Research and development	$ 89,504	[1]
Related Party
Research and development	$ 48,500
[1] Includes $48.5 million in related party expenses for the year ended December 31, 2023 and no related party expenses for the year ended months ended December 31, 2022 and 2021.

v3.24.3

The Company and Basis of Presentation	12 Months Ended
	Dec. 31, 2023
Organization, Consolidation and Presentation of Financial Statements [Abstract]
The Company and Basis of Presentation	The Company and Basis of Presentation Spyre Therapeutics, Inc., formerly Aeglea BioTherapeutics, Inc., (“Spyre” or the “Company”) is a preclinical stage biotechnology company focused on developing next generation therapeutics for patients living with inflammatory bowel disease. The Company was formed as a Limited Liability Company ("LLC") in Delaware on December 16, 2013 under the name Aeglea BioTherapeutics Holdings, LLC and was converted from a Delaware LLC to a Delaware corporation on March 10, 2015. On November 27, 2023, the Company completed its corporate rebranding, changing the name of the Company to Spyre Therapeutics, Inc. The Company operates in one segment and has its principal offices in Waltham, Massachusetts. On September 8, 2023, the Company effected a reverse stock split of its Common Stock at a ratio of 1-for-25 (the “Reverse Split”). Except as indicated otherwise, all share numbers related to the Company's Common Stock disclosed in these financial statements have been adjusted on a post-Reverse Split basis. On April 12, 2023, based on the review of the inconclusive interim results from the Company's Phase 1/2 clinical trial of pegtarviliase for the treatment of Classical Homocystinuria and other business considerations, the Company announced that it had initiated a process to explore strategic alternatives to maximize stockholder value and engaged an independent exclusive financial advisor to support this process. As a result, in April 2023, the Company implemented a restructuring plan resulting in an approximate 83% reduction of the Company’s existing headcount. On June 22, 2023, the Company acquired, in accordance with the terms of the Agreement and Plan of Merger (the "Acquisition Agreement"), the assets of Spyre Therapeutics, Inc. (“Pre-Merger Spyre”) as disclosed in Note 7 and 8, a privately held biotechnology company advancing a pipeline of antibody therapeutics with the potential to transform the treatment of inflammatory bowel disease through a research and development option agreement ("Paragon Agreement") with Paragon Therapeutics ("Paragon"). The asset acquisition was accomplished through a two-step reverse triangular merger whereby a wholly owned subsidiary of the Company merged with and into Pre-Merger Spyre, which existed at the time the Acquisition Agreement was entered into, became a wholly owned subsidiary of the Company in accordance with the terms of the Acquisition Agreement. Immediately following this merger, Pre-Merger Spyre merged with an into a second wholly subsidiary of the Company (“Merger Sub”) in accordance with the terms of the Acquisition Agreement and Pre-Merger Spyre ceased to exist. Subsequently, Aeglea BioTherapeutics, Inc. was renamed Spyre Therapeutics, Inc. and is a different entity than Pre-Merger Spyre, which ceased to exist upon merging with Merger Sub. The transaction was structured as a stock-for-stock transaction pursuant to which all of Pre-Merger Spyre's outstanding equity interests were exchanged based on a fixed exchange ratio of 0.5494488 to 1 for consideration from the Company of 517,809 shares of common stock and 364,887 shares of Series A non-voting convertible preferred stock, par value of $0.0001 per share ("Series A Preferred Stock") (convertible on a 40 to 1 basis), in addition to the assumption of outstanding and unexercised stock options to purchase 2,734 shares of common stock from the Amended and Restated Spyre 2023 Equity Incentive Plan (the "Asset Acquisition"). The common stock and Series A Preferred Stock related to the Asset Acquisition were issued to the Pre-Merger Spyre stockholders on July 7, 2023. For additional information, see Note 8. In connection with the Asset Acquisition, on June 26, 2023, the Company completed a private placement of shares of Series A Preferred Stock (the “Series A PIPE”) to a group of investors (the “Series A Investors”). The Company sold an aggregate of 721,452 shares of Series A Preferred Stock (the “Series A PIPE Securities”) for an aggregate purchase price of approximately $210.0 million before deducting approximately $12.7 million of placement agent and other offering expenses. For additional information, see Note 11. In connection with the Asset Acquisition, a non-transferable contingent value right ("CVR") was distributed to stockholders of record of the Company as of the close of business on July 3, 2023 (the "Legacy Stockholders"), but was not distributed to the holders of shares of common stock or Series A Preferred Stock issued to the former stockholders of Pre-Merger Spyre or Investors in the Transactions. Holders of the CVRs will be entitled to receive cash payments from proceeds received by the Company for a 3-year period related to the disposition or monetization of its legacy assets for a period of one-year following the closing of the Asset Acquisition. For additional information, see Note 3. On November 21, 2023, the Company's stockholders approved the conversion of the Company's Series A non-voting convertible preferred stock to Common Stock. For additional information, see Note 11. On December 11, 2023, the Company completed a private placement of shares of common stock and Series B non-voting convertible preferred stock, par value of $0.0001 per share ("Series B Preferred Stock") (convertible on a 40 to 1 basis) (collectively, the “December 2023 PIPE”) to a group of investors (the “December 2023 PIPE Investors”). The Company sold an aggregate of 6,000,000 shares of Common Stock and 150,000 shares of Series B Preferred Stock (the “December 2023 PIPE Securities”) for an aggregate purchase price of approximately $180.0 million before deducting approximately $10.9 million of placement agent and other offering expenses. For additional information, see Note 11. Liquidity The Company is a preclinical stage biotechnology company with a limited operating history, and due to its significant research and development expenditures, the Company has generated operating losses since its inception and has not generated any revenue from the commercial sale of any products. There can be no assurance that profitable operations will ever be achieved, and, if achieved, whether profitability can be sustained on a continuing basis. Since its inception and through December 31, 2023, the Company has funded our operations by raising an aggregate of approximately $896.2 million of gross proceeds from the sale and issuance of convertible preferred stock and common stock, pre-funded warrants, the collection of grant proceeds, and the licensing of its product rights for commercialization of pegzilarginase in Europe and certain countries in the Middle East. As of December 31, 2023, Spyre had an accumulated deficit of $764.4 million, and cash, cash equivalents, and marketable securities of $339.3 million. Based on current operating plans, the Company has sufficient resources to fund operations for at least one year from the issuance date of these financial statements with existing cash, cash equivalents, and marketable securities. Spyre will need to secure additional financing in the future to fund additional research and development, and before a commercial drug can be produced, marketed and sold. If the Company is unable to obtain additional financing or generate license or product revenue, the lack of liquidity could have a material adverse effect on the Company. Basis of Presentation The consolidated financial statements have been prepared in conformity with generally accepted accounting principles in the United States (“U.S. GAAP”) as defined by the Financial Accounting Standards Board (“FASB”) and include the accounts of the Company and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation.

v3.24.3

Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2023
Accounting Policies [Abstract]
Summary of Significant Accounting Policies	Summary of Significant Accounting Policies Use of Estimates The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets, liabilities, and equity and the amount of revenues and expenses. Actual results could differ significantly from those estimates. The most significant estimates and assumptions that management considers in the preparation of the Company's financial statements relate to the valuation of consideration transferred in acquiring in-process research & development ("IPR&D"); the discount rate, probabilities of success, and timing of estimated cash flows in the valuation of the CVR liability; inputs used in the Black-Scholes model for stock-based compensation expense; estimated future cash flows used in calculating the impairment of right-of-use lease assets; and estimated cost to complete performance obligations related to revenue recognition. The consideration transferred in acquiring IPR&D in connection with the acquisition of Pre-Merger Spyre was comprised of shares of the Company’s Common Stock and shares of Series A Preferred Stock. To determine the fair value of the equity transferred, the Company considered the per share value of the Series A PIPE securities, which was a financing event involving a group of accredited investors. Cash and Cash Equivalents The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist of money market funds and debt securities and are stated at fair value. Marketable Securities All investments have been classified as available-for-sale and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments in debt securities at the time of purchase. The Company may hold securities with stated maturities greater than one year until maturity. All available-for-sale securities are considered available to support current operations and are classified as current assets. The Company presents credit losses as an allowance rather than as a reduction in the amortized cost of the available-for-sale securities. For available-for-sale debt securities in an unrealized loss position, the Company first assesses whether it intends to sell, or it is more likely than not that it will be required to sell the security before recovery of its amortized cost basis. If either of the criteria regarding intent or requirement to sell is met, the security’s amortized cost basis is written down to fair value and recognized in other income (expense) in the results of operations. For available-for-sale debt securities that do not meet the aforementioned criteria, the Company evaluates whether the decline in fair value has resulted from credit losses or other factors. In making this assessment, management considers the extent to which fair value is less than amortized cost, any changes to the rating of the security by a rating agency, and adverse conditions specifically related to the security, among other factors. If this assessment indicates that a credit loss exists, an allowance is recorded for the difference between the present value of cash flows expected to be collected and the amortized cost basis of the security. Impairment losses attributable to credit loss factors are charged against the allowance when management believes an available-for-sale security is uncollectible or when either of the criteria regarding intent or requirement to sell is met. Any unrealized losses from declines in fair value below the amortized cost basis as a result of non-credit loss factors is recognized as a component of accumulated other comprehensive (loss) income, along with unrealized gains. Realized gains and losses and declines in fair value, if any, on available-for-sale securities are included in other income (expense) in the results of operations. The cost of securities sold is based on the specific-identification method. Restricted Cash Restricted cash consisted of money market accounts held by financial institutions as collateral for the Company’s obligations under a credit agreement and a facility lease for the Company’s corporate headquarters in Austin, Texas. The lease was terminated in August 2023 and the cash was subsequently unrestricted. Remaining restricted cash balances relate to the Company's operations in the United Kingdom. Concentration of Credit Risk Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, marketable securities, and restricted cash. The Company’s investment policy limits investments to high credit quality securities issued by the U.S. government, U.S. government-sponsored agencies, highly rated banks, and corporate issuers, subject to certain concentration limits and restrictions on maturities. The Company’s cash, cash equivalents, marketable securities, and restricted cash are held by financial institutions that management believes are of high credit quality. The financial instruments that potentially subject the Company to a concentration of credit risk consist principally of cash deposits. Accounts at each of the Company's two U.S. banking institutions are insured by the Federal Deposit Insurance Corporation (“FDIC”) up to $250,000 per depositor. As of December 31, 2023 and 2022, balances at the Company's U.S. banking institutions exceeded the FDIC limits. The Company has not experienced any losses on its deposits of cash, cash equivalents, and restricted cash and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash, cash equivalents, and restricted cash, and bond issuers. Property and Equipment Property and equipment are stated at cost, net of accumulated depreciation and amortization. Depreciation and amortization are computed using the straight-line method over the estimated useful lives of the assets. Repairs and maintenance that do not extend the life or improve an asset are expensed as incurred. Upon retirement or sale, the cost of disposed assets and their related accumulated depreciation and amortization are removed from the balance sheet. Any gain or loss is credited or charged to operations. The useful lives of the property and equipment are as follows: Laboratory equipment 5 years Furniture and office equipment 5 years Computer equipment 3 years Software 3 years Leasehold improvements Shorter of remaining lease term or estimated useful life Impairment of Long-Lived Assets Long-lived assets are reviewed for indications of possible impairment whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable. Recoverability is measured by comparison of the carrying amounts to the future undiscounted cash flows attributable to these assets. An impairment loss is recognized to the extent an asset group is not recoverable, and the carrying amount exceeds the fair value. The Company recognized a $2.6 million impairment loss for the year ended December 31, 2023 related to its leased office space in Austin, Texas (see Note 17 for additional information). There were no impairments of long-lived assets for the years ended December 31, 2022 and 2021. Accrued Research and Development Costs The Company records the costs associated with research nonclinical studies, clinical trials, and manufacturing development as incurred. These costs are a significant component of the Company’s research and development expenses, with a substantial portion of the Company’s on-going research and development activities conducted by third-party service providers, including contract research organizations ("CROs") and contract manufacturing organizations ("CMOs"), and the Company's related-party Paragon. The Company accrues for expenses resulting from obligations under the Paragon Agreement and agreements with CROs, CMOs, and other outside service providers for which payment flows do not match the periods over which materials or services are provided to the Company. Accruals are recorded based on estimates of services received and efforts expended pursuant to agreements established with Paragon, CROs, CMOs, and other outside service providers. These estimates are typically based on contracted amounts applied to the proportion of work performed and determined through analysis with internal personnel and external service providers as to the progress or stage of completion of the services. The Company makes significant judgments and estimates in determining the accrual balance in each reporting period. In the event advance payments are made to Paragon, a CRO, CMO, or outside service provider, the payments will be recorded as a prepaid asset which will be amortized as the contracted services are performed. As actual costs become known, the Company adjusts its accruals. Inputs, such as the services performed, the number of patients enrolled, or the study duration, may vary from the Company’s estimates, resulting in adjustments to research and development expense in future periods. Changes in these estimates that result in material changes to the Company’s accruals could materially affect the Company’s results of operations. Historically, the Company has not experienced any material deviations between accrued and actual research and development expenses. Leases The Company determines if an arrangement is a lease at inception. Right-of-use ("ROU") assets represent the Company's right to use an underlying asset for the lease term and lease liabilities represent the Company's obligation to make lease payments arising from the lease. The classification of the Company's leases as operating or finance leases along with the initial measurement and recognition of the associated ROU assets and lease liabilities is performed at the lease commencement date. The measurement of lease liabilities is based on the present value of future lease payments over the lease term. As the Company's leases do not provide an implicit rate, the Company uses its incremental borrowing rate based on the information available at the lease commencement date in determining the present value of future lease payments. To determine the incremental borrowing rate, the Company uses the lease-term appropriate current treasury bond rates adjusted for collateral and inflation risks combined with quoted bank financing rates. The ROU asset is based on the measurement of the lease liability and also includes any lease payments made prior to or on lease commencement and excludes lease incentives and initial direct costs incurred, as applicable. The lease terms may include options to extend or terminate the lease when it is reasonably certain the Company will exercise any such options. Rent expense for the Company's operating leases is recognized on a straight-line basis over the lease term. Amortization expense for the ROU asset associated with its finance leases is recognized on a straight-line basis over the term of the lease and interest expense associated with its finance leases is recognized on the balance of the lease liability using the effective interest method based on the estimated incremental borrowing rate. Prior to the Company's restructuring, as described in Note 17, the Company had lease agreements with lease and non-lease components. As allowed under Topic 842, the Company elected to not separate lease and non-lease components for any leases involving real estate and office equipment classes of assets and, as a result, accounted for the lease and non-lease components as a single lease component. The Company also elected to not apply the recognition requirement of Topic 842 to leases with a term of 12 months or less for all classes of assets. Fair Value of Financial Instruments The Company uses fair value measurements to record fair value adjustments to certain financial and non-financial assets and liabilities and to determine fair value disclosures. The accounting standards define fair value, establish a framework for measuring fair value, and require disclosures about fair value measurements. Fair value is defined as the price that would be received from selling an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. When determining the fair value measurements for assets and liabilities required to be recorded at fair value, the principal or most advantageous market in which the Company would transact are considered along with assumptions that market participants would use when pricing the asset or liability, such as inherent risk, transfer restrictions, and risk of nonperformance. The accounting standard for fair value establishes a fair value hierarchy based on three levels of inputs, the first two of which are considered observable and the last unobservable, that requires an entity to maximize the use of observable inputs and minimize the use of unobservable inputs when measuring fair value. A financial instrument’s categorization within the fair value hierarchy is based upon the lowest level of input that is significant to the fair value measurement. The three levels of inputs that may be used to measure fair value are as follows: Level 1: Observable inputs, such as quoted prices in active markets for identical assets or liabilities. Level 2: Observable inputs other than Level 1 prices, such as quoted prices for similar assets or liabilities, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities. Level 3: Valuations based on unobservable inputs to the valuation methodology and including data about assumptions that market participants would use in pricing the asset or liability based on the best information available under the circumstances. Financial instruments carried at fair value include cash equivalents and marketable securities. The carrying amounts of accounts payable and accrued liabilities approximate fair value due to their relatively short maturities. Revenue Recognition Under ASC Topic 606, “Revenue from Contracts with Customers” (“Topic 606”), an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration that the entity expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that an entity determines are within the scope of Topic 606, the entity performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price, including variable consideration, if any; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the entity satisfies a performance obligation. The Company assesses its license arrangements within the scope of Topic 606 in accordance with this framework as follows: License revenue The Company assesses whether the goods or services promised within each contract are distinct to identify those that are performance obligations. This assessment involves subjective determinations and requires management to make judgments about the individual promised goods or services and whether such are separable from the other aspects of the contractual relationship. In assessing whether a promised good or service is distinct, and therefore a performance obligation, the Company considers factors such as the research, stage of development of the licensed product, manufacturing and commercialization capabilities of the customer and the availability of the associated expertise in the general marketplace. The Company also considers the intended benefit of the contract in assessing whether a promised good or service is separately identifiable from other promises in the contract. If a promised good or service is not distinct, the Company is required to combine that good or service with other promised goods or services until it identifies a bundle of goods or services that is distinct. Arrangements that include rights to additional goods or services that are exercisable at a customer’s discretion are generally considered options. The Company assesses if these options provide a material right to the customer and if so, they are considered performance obligations. The transaction price is determined and allocated to the identified performance obligations in proportion to their stand-alone selling prices (“SSP”) on a relative SSP basis. SSP is based on observable prices of the performance obligations or, when such prices are not observable, are estimated. The estimation of SSP may include factors such as forecasted revenues or costs, development timelines, discount rates, probabilities of technical and regulatory success, and considerations such as market conditions and entity-specific factors. In certain circumstances, the Company may apply the residual method to determine the SSP of a good or service if the SSP is considered highly variable or uncertain. The Company validates the SSP for performance obligations by evaluating whether changes in the key assumptions used to determine the SSP will have a significant effect on the allocation of arrangement consideration between multiple performance obligations. If the consideration promised in a contract includes a variable amount, the Company estimates the amount of consideration to which it will be entitled in exchange for transferring the promised goods or services to a customer. The Company determines the amount of variable consideration by using the expected value method or the most likely amount method. The Company includes the amount of estimated variable consideration in the transaction price to the extent that it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis in the period of adjustment. If an arrangement includes development, regulatory or commercial milestone payments, the Company evaluates whether the milestones are considered likely of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant cumulative revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control or the licensee’s control, such as regulatory approvals, are generally not considered likely of being achieved until those approvals are received. In determining the transaction price, the Company adjusts consideration for the effects of the time value of money if the timing of payments provides the Company with a significant benefit of financing. The Company does not assess whether a contract has a significant financing component if the expectation at contract inception is such that the period between payment by the licensee and the transfer of the promised goods or services to the licensees will be one year or less. For arrangements with licenses of intellectual property that include sales-based royalties, including milestone payments based on the level of sales, and if the license is deemed to be the predominant item to which the royalties relate, the Company recognizes royalty revenue and sales-based milestones at the later of (i) when the related sales occur, or (ii) when the performance obligation to which the royalty has been allocated has been satisfied. The Company recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied at a point in time or over time, and if over time, recognition is based on the use of an output or input method. The Company’s contracts may be modified for changes in the customer’s requirements. If contract modifications are for additional goods and services that are distinct from the existing contract, the modification will be accounted for as either a separate contract or a termination of the existing contract, depending on whether the additional goods or services reflects the SSP. If the additional goods or services in a contract modification are not distinct from the existing contract, they are accounted for as if they were part of the original contract. The effect of the contract modification on the transaction price and the measure of progress for the performance obligation to which it relates is recognized as an adjustment to revenue on a cumulative catch-up basis. The cumulative catch-up adjustment is calculated using an updated measure of progress applied to the sum of (1) the remaining consideration allocated to the partially satisfied performance obligation and (2) the revenue already recognized on that performance obligation. The revenue recognized for fully satisfied goods or services and distinct from the remaining performance obligations is not altered by the modification. Collaborative arrangements The Company analyzes its license arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, Collaborative Arrangements (“Topic 808”). This assessment is performed throughout the life of the arrangement based on changes in the responsibilities of all parties in the arrangement. For arrangements within the scope of Topic 808 that contain multiple elements, the Company first determines which elements of the collaboration are deemed to be within the scope of Topic 808 and which elements of the collaboration are more reflective of a vendor-customer relationship and therefore within the scope of Topic 606. For elements of collaboration arrangements that are accounted for pursuant to Topic 808, an appropriate recognition method is determined and applied consistently, either by analogy to authoritative accounting literature or by applying a reasonable and rational policy election. For those elements of the arrangement that are accounted for pursuant to Topic 606, the Company applies the five-step model described above. Research and Development Costs Research and development costs are expensed as incurred. Research and development costs include, but are not limited to, salaries, benefits, travel, stock-based compensation, consulting costs, contract research service costs, laboratory supplies and facilities, contract manufacturing costs, and costs paid to other third parties that conduct research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense. Advance payments for goods or services to be rendered in the future for use in research and development activities are recorded as a prepaid asset and expensed as the related goods are delivered or the services are performed. Stock-Based Compensation The Company recognizes the cost of stock-based awards granted to employees and non-employees based on the estimated grant-date fair values of the awards. The fair values of stock options are estimated on the date of grant using the Black-Scholes option pricing model. The fair values of restricted stock units (“RSUs”) are based on the fair value of the Company’s common stock on the date of the grant. The value of the award is recognized as compensation expense on a straight-line basis over the requisite service period. Forfeitures are recognized when they occur, which may result in the reversal of compensation costs in subsequent periods as the forfeitures arise. Compensation expense for employee and non-employee share-based payment awards with performance conditions is recognized when the performance condition is deemed probable. Convertible Preferred Stock Issued through PIPE The Company records shares of convertible preferred stock at their respective fair values on the dates of issuance, net of issuance costs. The Company classified the Series B Preferred Stock outside of stockholders’ equity because, if conversion to Common Stock is not approved by the stockholders, the Series B Preferred Stock will be redeemable at the option of the holders for cash equal to the closing price of the Common Stock on the last trading day prior to the holder’s redemption request. The Company has determined that the conversion and redemption are outside of the Company’s control. Additionally, the Company determined the Series B Preferred Stock did not contain any embedded derivatives and therefore the conversion and redemption features did not require bifurcation. Contingent Milestone Proceeds The Company recognizes contingent milestone proceeds associated from the sale of in-process research and development assets in earnings once the achievement of the milestone becomes probable and payment to the Company is contractually required. Acquisitions The Company evaluates acquisitions of assets and other similar transactions to assess whether or not the transaction should be accounted for as a business combination or asset acquisition by first applying a screen test to determine whether substantially all of the fair value of the gross assets acquired is concentrated in a single identifiable asset or group of similar identifiable assets. If so, the transaction is accounted for as an asset acquisition. If not, further determination is required as to whether or not the Company has acquired inputs and processes that have the ability to create outputs, which would meet the definition of a business. Significant judgment is required in the application of the test to determine whether an acquisition is a business combination or an acquisition of assets. Acquisitions meeting the definition of business combinations are accounted for using the acquisition method of accounting, which requires that the purchase price be allocated to the net assets acquired at their respective fair values. In a business combination, any excess of the purchase price over the estimated fair values of the net assets acquired is recorded as goodwill. The Company measures and recognizes asset acquisitions that are not deemed to be business combinations based on the cost to acquire the assets, which includes pre-acquisition direct costs recorded in accrued professional and consulting fees. Goodwill is not recognized in asset acquisitions. When a transaction accounted for as an asset acquisition includes an IPR&D asset, the IPR&D asset is only capitalized if it has an alternative future use other than in a particular research and development project. Otherwise, the cost allocated to acquire an IPR&D asset with no alternative future use is charged to expense at the acquisition date. Contingent Value Rights The Company evaluates its contracts to determine if those contracts qualify as derivatives under ASC 815, Derivatives and Hedging (“ASC 815”). For derivative financial instruments that are accounted for as liabilities, the derivative instrument is initially recorded at its fair value and is then re-valued at each reporting date. Any changes in fair value are recorded as other income or expense for each reporting period. Derivative instrument liabilities are classified in the balance sheet as current or non-current based on whether or not net-cash settlement of the derivative instrument is probable within the next 12 months from the balance sheet date. The Company determined that certain contingent payments under the CVR Agreement qualified as derivatives under ASC 815, and as such, were recorded as a liability on the balance sheet. This value is then remeasured for future expected payout as well as the increase in fair value due to the time value of money. These gains or losses, if any, are recognized in the consolidated statements of operations and comprehensive loss within Other (expense) income, net. The Company applies a scenario-based method and weighs them based on the possible achievement of certain milestones. The milestone payments are contingent on formal reimbursement decisions by national authorities in key European markets and pegzilarginase approval by the U.S. Food and Drug Administration ("FDA"), among other events. This fair value measurement is based on significant inputs not observable in the market and thus represents a Level 3 measurement as defined in ASC 820, Fair Value Measurement. The key assumptions used include the discount rate, probability of regulatory success, and reimbursement rates from certain government agencies. The estimated value of the CVR consideration is based upon available information and certain assumptions which the Company's management believes are reasonable under the circumstances. The ultimate payout under the CVRs may differ materially from the assumptions used in determining the fair value of the CVR consideration. Income Taxes The Company uses the asset and liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are recognized for the expected future tax consequences of temporary differences between the financial statements and the tax bases of assets and liabilities. Additionally, any changes in income tax laws are immediately recognized in the year of enactment. A valuation allowance is established against the deferred tax assets to reduce their carrying value to an amount that is more likely than not to be realized. The deferred tax assets and liabilities are classified as noncurrent along with the related valuation allowance. Due to a lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance. The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on the technical merits, as the largest amount of benefits that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the unrecognized tax benefits as a component of income tax expense, if applicable. As of December 31, 2023 and 2022, the Company had no unrecognized tax benefits and there were no interest or penalties incurred by the Company in the years ended December 31, 2023, 2022, or 2021. Comprehensive Loss Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive income (loss) is currently comprised of changes in unrealized losses and gains on available-for-sale securities and foreign currency translation adjustments reflecting the cumulative effect of changes in exchange rates between the foreign entity’s functional currency and the reporting currency. Recently Adopted Accounting Pronouncement The Company early adopted the Financial Accounting Standards Board’s Accounting Standards Update 2020-06, Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity (“ASU 2020-06”), effective as of January 1, 2023 using the modified retrospective method. Among other amendments, ASU 2020-06 eliminates the cash conversion and beneficial conversion feature models in ASC 470-20 that required an issuer of certain convertible debt and preferred stock to separately account for embedded conversion features as a component of equity, as well as changes the accounting for diluted earnings‑per‑share for convertible instruments and contracts that may be settled in cash or stock. Additionally, ASU 2020-06 requires the if‑converted method, which is more dilutive than the treasury stock method, be used for all convertible instruments. The Company applied ASU 2020-06 to all Series A Preferred Stock and Series B Preferred Stock during fiscal year 2023, and, accordingly, the Company did not apply the cash conversion or beneficial conversion feature models in its analysis of the Series A Preferred Stock and Series B Preferred Stock. The adoption of ASU 2020-06 did not have a material impact on the Company's consolidated financial statements. Recently Issued Accounting Pronouncements In November 2023, the FASB issued ASU 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures to update reportable segment disclosure requirements, primarily through enhanced disclosures about significant segment expenses and information used to assess segment performance and requires companies to disclose all annual disclosures about segments in interim periods. The ASU also requires companies with a single reportable segment to provide all disclosures required by Topic 280 – Segment Reporting. This update is effective beginning with the Company’s 2024 fiscal year annual reporting period and interim periods beginning thereafter. The Company is currently evaluating the impact that the adoption of this standard will have on its consolidated financial statements. In December 2023, the FASB issued ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures. This ASU expands disclosures in an entity’s income tax rate reconciliation table and disclosures regarding taxes paid both in the U.S. and foreign jurisdictions. This update is effective beginning with the Company’s 2025 fiscal year annual reporting period. This ASU will have no impact on the Company’s consolidated financial condition or results of operations. The Company is currently evaluating the impact to its income tax disclosures.

v3.24.3

Fair Value Measurements	12 Months Ended
	Dec. 31, 2023
Fair Value Disclosures [Abstract]
Fair Value Measurements	Fair Value Measurements The Company measures and reports certain financial instruments as assets and liabilities at fair value on a recurring basis. The following tables sets forth the fair value of the Company’s financial assets and liabilities at fair value on a recurring basis based on the three-tier fair value hierarchy (in thousands):   December 31, 2023   Level 1 Level 2 Level 3 Total Financial Assets Money market funds $ 150,648  $ —  $ —  $ 150,648  U.S. government treasury securities 32,843  —  —  32,843  U.S. government agency securities —  16,257  —  16,257  Commercial paper —  104,141  —  104,141  Corporate bonds —  33,064  —  33,064  Total financial assets $ 183,491  $ 153,462  $ —  $ 336,953  Liabilities: CVR liability $ —  $ —  $ 42,700  $ 42,700  Total liabilities $ —  $ —  $ 42,700  $ 42,700  December 31, 2022 Level 1 Level 2 Level 3 Total Financial Assets Money market funds $ 15,250  $ —  $ —  $ 15,250  Commercial paper —  23,641  —  23,641  U.S. government agency securities —  4,230  4,230  Corporate bonds —  3,732  —  3,732  Total financial assets $ 15,250  $ 31,603  $ —  $ 46,853  The Company measures the fair value of money market funds on quoted prices in active markets for identical asset or liabilities. The Level 2 assets include U.S. government agency securities, commercial paper and corporate bonds, and are valued based on quoted prices for similar assets in active markets and inputs other than quoted prices that are derived from observable market data. The Company evaluates transfers between levels at the end of each reporting period. There were no transfers between Level 1 and Level 2 during the periods presented. As of December 31, 2022, the Company had no financial liabilities outstanding measured at fair value. Forward Contract Liability In connection with the Asset Acquisition, the Company entered into a contract for the issuance of 364,887 shares of Series A Preferred Stock as part of the consideration transferred. This forward contract was classified as a liability because the underlying preferred shares were contingently redeemable. Further, the forward contract liability was considered a Level 2 liability based on observable market data for substantially the full term of the liability and was initially measured at its estimated fair value on the transaction date based on the underlying price per share on an as-converted basis of the Series A PIPE Securities issued in the Series A PIPE. Subsequent remeasurement of the fair value of the forward contract liability through its settlement date was based on the market price of the Company's Common Stock, which represents the redemption value of the Series A Preferred Stock. The fair value of the forward contract at the transaction date, June 22, 2023, was $106.2 million. The liability was settled with the issuance of the Series A Preferred Stock on July 7, 2023 for $189.7 million. For the year ended December 31, 2023, $83.5 million was recorded as Other (expense) income in the consolidated statements of operations in connection with the change in fair value of the forward contract liability. There was no similar expense for the year ended December 31, 2022 and 2021. The following table presents changes in the forward contract liability for the periods presented (in millions): Forward Contract Liability Beginning balance as of June 22, 2023 $ 106.2  Change in fair value 83.5  Issuance of Series A Preferred Stock on July 7, 2023 (189.7) Ending balance as of December 31, 2023 $ —  CVR Liability In connection with the Asset Acquisition, a non-transferable contingent value right was distributed to the Legacy Stockholders, but was not distributed to holders of shares of Common Stock or Series A Preferred Stock issued to the Investors or former stockholders of Pre-Merger Spyre in connection with the Transactions. Holders of the CVR will be entitled to receive certain cash payments from proceeds received by the Company for a three-year period, if any, related to the disposition or monetization of the Company’s legacy assets for a period of one year following the closing of the Asset Acquisition. The fair value of the CVR liability was determined using the probability weighted discounted cash flow method to estimate future cash flows associated with the sale of the legacy assets. Analogous to a dividend being declared/approved in one period and paid out in another, the liability was recorded at the date of approval, June 22, 2023, as a Common Stock dividend, returning capital to the Legacy Stockholders. Changes in fair value of the liability will be recognized as a component of Other income (expense) in the consolidated statement of operations and comprehensive loss in each reporting period. The liability value is based on significant inputs not observable in the market such as estimated cash flows, estimated probabilities of regulatory success, and discount rates, which represent a Level 3 measurement within the fair value hierarchy. The significant inputs used to estimate the fair value of the CVR liability were as follows: December 31, 2023 Estimated cash flow dates 2/28/24 - 06/22/26 Estimated probability of success 39% - 100% Estimated reimbursement rate compared to reimbursement target 81% - 100% Risk-adjusted discount rates 5.91% - 6.32% The change in fair value between the issuance of the CVR and December 31, 2023 was a $19.0 million increase, and was primarily driven by changes in the expected timing of achievement of certain milestones, changes in the likelihood of certain milestones related to the approval received from the European Medicines Agency by Immedica Pharma AB ("Immedica"), partially offset by a change in the likelihood of a successful disposition of pegtarviliase and updates to expenses and deductions. The following table presents changes in the CVR liability for the periods presented (in thousands):   CVR Liability Beginning balance as of December 31, 2022 $ —  Fair value at CVR issuance 29,500  Changes in the fair value of the CVR liability since issuance 18,986  Payments (5,786) Ending Balance as of December 31, 2023 $ 42,700

v3.24.3

Cash Equivalents and Marketable Securities	12 Months Ended
	Dec. 31, 2023
Cash and Cash Equivalents [Abstract]
Cash Equivalents and Marketable Securities	Cash Equivalents and Marketable Securities The following tables summarize the estimated fair value of the Company’s cash equivalents and marketable securities and the gross unrealized gains and losses (in thousands): December 31, 2023 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Estimated Fair Value Cash equivalents: Money market funds $ 150,648  $ —  $ —  $ 150,648  Commercial paper 24,950  5  —  24,955  U.S. government treasury securities 10,965  1  —  10,966  Total cash equivalents 186,563  6  —  186,569  Marketable securities: Commercial paper 79,124  62  —  79,186  Corporate bonds 32,984  81  (1) 33,064  U.S. government treasury securities 21,846  31  —  21,877  U.S. government agency securities 16,147  110  —  16,257  Total marketable securities $ 150,101  $ 284  $ (1) $ 150,384  December 31, 2022 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Estimated Fair Value Cash equivalents: Money market funds $ 15,250  $ —  $ —  $ 15,250  Commercial paper 7,021  1  (2) 7,020  U.S. government agency securities 3,736  —  (1) 3,735  Total cash equivalents $ 26,007  $ 1  $ (3) $ 26,005  Marketable securities: Commercial paper $ 16,644  $ 2  $ (25) $ 16,621  Corporate bonds 3,738  —  (6) 3,732  U.S. government agency securities 495  —  —  495  Total marketable securities $ 20,877  $ 2  $ (31) $ 20,848  The following table summarizes the available-for-sale securities in an unrealized loss position for which an allowance for credit losses has not been recorded as of December 31, 2023 and 2022, aggregated by major security type and length of time in a continuous unrealized loss position: December 31, 2023 Less Than 12 Months 12 Months or Longer Total Fair Value Unrealized Losses Fair Value Unrealized Losses Fair Value Unrealized Losses Commercial paper $ —  $ —  $ —  $ —  $ —  $ —  Corporate bonds 9,907  (1) —  —  9,907  (1) U.S. government treasury securities 4,831  —  —  —  4,831  —  Total marketable securities $ 14,738  $ (1) $ —  $ —  $ 14,738  $ (1) December 31, 2022 Less Than 12 Months 12 Months or Longer Total Fair Value Unrealized Losses Fair Value Unrealized Losses Fair Value Unrealized Losses Commercial paper $ 17,699  $ (27) $ —  $ —  $ 17,699  $ (27) Corporate bonds 3,732  (6) —  —  3,732  (6) U.S. government agency securities 3,735  (1) —  —  3,735  (1) Total marketable securities $ 25,166  $ (34) $ —  $ —  $ 25,166  $ (34) The Company evaluated its securities for credit losses and considered the decline in market value to be primarily attributable to current economic and market conditions and not to a credit loss or other factors. Additionally, the Company does not intend to sell the securities in an unrealized loss position and does not expect they will be required to sell the securities before recovery of the unamortized cost basis. As of December 31, 2023 and 2022, an allowance for credit losses had not been recognized. Given the Company's intent and ability to hold such securities until recovery, and the lack of significant change in credit risk of these investments, the Company does not consider these marketable securities to be impaired as of December 31, 2023 and 2022. There were $0.3 million unrealized gains on marketable securities for the year ended December 31, 2023. There were no realized gains on marketable securities for the year ended December 31, 2023, 2022 and 2021. Interest on marketable securities is included in interest income. Accrued interest receivable on available-for-sale debt securities totaled $0.9 million and $0.1 million as of December 31, 2023 and 2022, respectively, and is excluded from the estimate of credit losses. The following table summarizes the contractual maturities of the Company's marketable securities at estimated fair value (in thousands): December 31, 2023 2022 Due in one year or less $ 115,784  $ 20,848  Due in 1 - 2 years 34,600  —  Total marketable securities $ 150,384  $ 20,848  The Company may sell investments at any time for use in current operations even if they have not yet reached maturity. As a result, the Company classifies marketable securities, including securities with maturities beyond twelve months as current assets.

v3.24.3

Property and Equipment, Net	12 Months Ended
	Dec. 31, 2023
Property, Plant and Equipment [Abstract]
Property and Equipment, Net	Property and Equipment, Net Property and equipment, net consist of the following (in thousands): December 31, 2023 2022 Laboratory equipment $ —  $ 2,257  Furniture and office equipment —  520  Computer equipment —  73  Software —  121  Leasehold improvements —  4,393  Property and equipment, gross —  7,364  Less: Accumulated depreciation and amortization —  (4,144) Property and equipment, net $ —  $ 3,220  Depreciation and amortization expense for the years ended December 31, 2023, 2022, and 2021 was $0.7 million, $1.4 million, and $1.4 million, respectively. All of the Company’s long-lived assets were located in the United States. Sale of Assets On April 12, 2023, based on the review of the inconclusive interim results from the Company's Phase 1/2 clinical trial of pegtarviliase for the treatment of classical homocystinuria and other business considerations, the Company announced that it had initiated a process to explore strategic alternatives to maximize stockholder value and engaged an independent exclusive financial advisor to support this process. As a result, the Company implemented a restructuring plan resulting in an approximate 83% reduction of the Company’s existing headcount by June 30, 2023. During the second quarter of 2023, the Company sold various lab equipment, consumables, and furniture and fixtures for total consideration of $0.5 million. After recording the disposal of all the Company's property and equipment net of proceeds, the Company recorded a $0.7 million and $0.2 million loss on disposal of long lived assets which is included in Research and development and General and administrative expenses, respectively.

v3.24.3

Accrued and Other Current Liabilities	12 Months Ended
	Dec. 31, 2023
Accrued Liabilities and Other Liabilities [Abstract]
Accrued and Other Current Liabilities	Accrued and Other Current Liabilities Accrued and other current liabilities consist of the following (in thousands): December 31, 2023 2022 Accrued compensation $ 4,054  $ 4,589  Accrued contracted research and development costs 7,092  6,972  Accrued professional and consulting fees 1,474  946  Other 488  330  Total accrued and other current liabilities $ 13,108  $ 12,837

v3.24.3

Related Party Transactions	12 Months Ended
	Dec. 31, 2023
Related Party Transactions [Abstract]
Related Party Transactions	Related Party Transactions Paragon and Parapyre Holding LLC ("Parapyre") each beneficially own less than 5% of the Company's capital stock through their respective holdings of the Company's common stock. Fairmount Funds Management LLC ("Fairmount") beneficially owns more than 5% of the Company's capital stock on an as-converted basis, has two seats on the Board and beneficially owns more than 5% of Paragon, which is a joint venture between Fairmount and Fair Journey Biologics. Fairmount appointed Paragon's board of directors and has the contractual right to approve the appointment of any executive officers. Parapyre is an entity formed by Paragon as a vehicle to hold equity in Spyre in order to share profits with certain employees of Paragon. In connection with the Asset Acquisition, the Company assumed the rights and obligations of Pre-Merger Spyre under the Paragon Agreement. Under the Paragon Agreement, Spyre is obligated to compensate Paragon for its services performed under each research program based on the actual costs incurred with mark-up costs pursuant to the terms of the Paragon Agreement. As of the date of the Asset Acquisition, Pre-Merger Spyre had incurred total expenses of $19.0 million under the Paragon Agreement since inception, which included the $3.0 million research initiation fee and $16.0 million of reimbursable expenses under the Paragon Agreement for historical costs owed to Paragon. As of the acquisition date, $19.0 million was unpaid and was assumed by the Company through the Asset Acquisition. For the year ended December 31, 2023, the Company recognized expenses related to services provided by Paragon subsequent to the Asset Acquisition totaling $48.5 million, which included $11.4 million of stock-based compensation expense, and were recorded as Research and development expenses in the consolidated statements of operations. As of December 31, 2023, $16.6 million was unpaid and was included in Related party accounts payable and other current liabilities on the Company's consolidated balance sheets. For the year ended December 31, 2023, the Company made payments totaling $39.5 million to Paragon. On July 12, 2023 and December 14, 2023, the Company exercised the Option available under the Paragon Agreement with respect to the SPY001 and SPY002 research programs, respectively, and expects to enter into the SPY001 License Agreement and the SPY002 License Agreement. Following the execution of each of the SPY001 License Agreement and SPY002 License Agreement, the Company will be obligated to pay Paragon up to $22.0 million upon the achievement of specific development, regulatory and clinical milestones for the first product under each agreement, respectively, that achieves such specified milestones. Upon execution of each of the SPY001 License Agreement and the SPY002 License Agreement, we expect to pay Paragon a $1.5 million fee for nomination of a development candidate, as applicable, and the Company expects to be obligated to make a further milestone payment of $2.5 million upon the first dosing of a human patient in a Phase 1 trial. The following is the summary of expenses related to the Paragon Agreement recognized within research and development expenses, which were ultimately settled in cash (in millions): December 31, 2023 2022 2021 Reimbursable costs under the Paragon Agreement $ 37.1  $ —  $ —  Parapyre Option Obligation As part of the Paragon Agreement, the Company is obligated to issue Parapyre a stock option grant on the last business day of 2023 and 2024 (the "Parapyre Option Obligation"). See Note 15 for additional information. The following is the summary of Related party accounts payable and other current liabilities (in millions): December 31, 2023 December 31, 2022 Reimbursable costs under the Paragon Agreement $ 16.6  $ —  Related party accounts payable and other current liabilities $ 16.6  $ —  December 2023 PIPE The December 2023 Investors included Fairmount, a related party. Fairmount's participation in the December 2023 PIPE was approved by the Company's board of directors. Fairmount's investment accounted for $10.0 million of the $180.0 million gross proceeds raised in the December 2023 PIPE. Mark McKenna Option Grant On February 1, 2024, the Board appointed Mark McKenna as a Class I director. Mr. McKenna and the Company are parties to a consulting agreement, pursuant to which Mr. McKenna agreed to continue to provide consulting services as an independent contractor to the Company, with an effective date of August 1, 2023 (the “Vesting Commencement Date”). As compensation for Mr. McKenna’s consulting services, on November 22, 2023, he was granted non-qualified stock options to purchase 477,000 shares of the Company’s common stock under the Company's equity incentive plan with an exercise price of $10.39 per share, which vest as to 25% on the one year anniversary of the Vesting Commencement Date and thereafter vest and become exercisable in 48th equal monthly installments, subject to Mr. McKenna’s continued service to the Company through each applicable vesting date. For the twelve months ended December 31, 2023, the Company recognized $0.1 million in stock-based compensation expense related to Mr. McKenna's consulting agreement. There was no such expense for the twelve months ended December 31, 2022 and 2021.

v3.24.3

Asset Acquisition	12 Months Ended
	Dec. 31, 2023
Business Combination and Asset Acquisition [Abstract]
Asset Acquisition	Asset Acquisition On June 22, 2023, the Company acquired Pre-Merger Spyre pursuant to the Acquisition Agreement, by and among the Company, Aspen Merger Sub I, Inc., a Delaware corporation and a wholly owned subsidiary of the Company (“First Merger Sub”), Sequoia Merger Sub II, LLC, a Delaware limited liability company and a wholly owned subsidiary of the Company (“Second Merger Sub”), and Pre-Merger Spyre. Pursuant to the Acquisition Agreement, First Merger Sub merged with and into Pre-Merger Spyre, pursuant to which Pre-Merger Spyre was the surviving corporation and became the Company's wholly owned subsidiary (the “First Merger”). Immediately following the First Merger, Pre-Merger Spyre merged with and into Second Merger Sub, pursuant to which Second Merger Sub became the surviving entity. Pre-Merger Spyre was a pre-clinical stage biotechnology company that was incorporated on April 28, 2023 under the direction of Peter Harwin, a Managing Member of Fairmount, for the purpose of holding rights to certain intellectual property being developed by Paragon. Fairmount is a founder of Paragon. With respect to the Asset Acquisition, the Company determined that Aeglea was the acquirer for accounting purposes under ASC 805. The primary factors considered were a) the relative voting rights in the combined entity not resulting in a change of control, b) legacy members of the Company's Board of Directors maintained control of the Board of Directors, and c) the only change in the composition of senior management was the appointment of a new Chief Operating Officer. Next, the Company considered whether the Asset Acquisition should be defined as a business under ASC 805. ASC 805-10-55-5A through 55-5C describe a screen test to determine whether an acquired set of assets and activities is not a business. We determined that substantially all (greater than 90%) of the fair value of the assets acquired were concentrated in a single asset, Spyre’s Option to license intellectual property rights related to SPY001, SPY002, SPY003 and SPY004 pursuant to the Paragon Agreement. Accordingly, the Company treated the Asset Acquisition as an asset acquisition for accounting purposes. Even if the transaction would have failed the screen test, Pre-Merger Spyre lacked the financial resources to have inputs, processes, and outputs to constitute a business under ASC 805. The Company completed the Asset Acquisition of Pre-Merger Spyre, in accordance with the terms of the Acquisition Agreement. Under the terms of the Acquisition Agreement, the Company issued 517,809 shares of Common Stock and 364,887 shares of Series A Preferred Stock to former Pre-Merger Spyre security holders. In addition, outstanding and unexercised stock options to purchase 2,734 shares of common stock were assumed from the Amended and Restated Spyre 2023 Equity Incentive Plan. At the acquisition date, the Company recorded forward contracts to represent the obligation to issue shares of the Company's Common Stock and shares of Series A Preferred Stock. The forward contract related to the Common Stock was recorded as Additional paid-in capital as the instrument is indexed to the Company's Common Stock. The forward contract related to the Series A Preferred Stock was recorded as a liability, as the underlying stock has a cash redemption feature. On July 7, 2023, both the shares of Common Stock and Series A Preferred Stock were issued and the forward contract liability associated with the Series A Preferred Stock was settled accordingly. The Company concluded that the arrangement meets the definition of an asset acquisition rather than a business combination, as substantially all of the fair value of the gross assets acquired is concentrated in a single identifiable asset, the Option to exclusively license IPR&D. The Company determined that the Option to license IPR&D was a single asset as the Company's strategy relies on developing the entire portfolio of individual treatments to create combination treatments that simultaneously address different mechanisms of irritable bowel disease with a single treatment. The Company also determined that the pipeline candidates within the portfolio are similar in nature and risk profile. In addition, the Company did not obtain any substantive processes, assembled workforce, or employees capable of producing outputs in connection with the Asset Acquisition. The Company determined that the cost to acquire the asset was $113.2 million which was recorded as acquired IPR&D. The fair value of the consideration issued consisted of the 364,887 shares of Series A Preferred Stock (14,595,480 shares of Common Stock on an as-converted basis) and 517,809 shares of Common Stock, valued at $291.08 per share and $7.277 per share, respectively. The Asset Acquisition Costs are shown on the following table (in millions): June 22, 2023 Consideration transferred in Series A Preferred Stock and Common Stock $ 110.0  Transaction costs incurred by the Company 3.2  Total cost to acquire asset $ 113.2  The allocation of the purchase price to net assets acquired is as a follows: June 22, 2023 Acquired in-process research and development $ 130.2  Cash acquired 3.0  Assumed liabilities (20.0) Total cost to acquire asset $ 113.2

v3.24.3

Paragon Agreement	12 Months Ended
	Dec. 31, 2023
Related Party Transactions [Abstract]
Paragon Agreement	Paragon Agreement In May 2023, Pre-Merger Spyre entered into the Paragon Agreement with Paragon and Parapyre. Pursuant to the Paragon Agreement, the Option provided for the right to acquire the intellectual property rights related to four research programs from Paragon in accordance with a license agreement to be entered into following each exercise of the Option. Under the Paragon Agreement, the terms of such license agreement would be consistent with the economics and other terms set out in the Paragon Agreement and, in the event of failure to reach an agreement on the definitive terms, the matter would be resolved via arbitration. In consideration for the Option granted under the Paragon Agreement, Pre-Merger Spyre was obligated to pay Paragon an upfront cash amount of $3.0 million in research initiation fees. In addition, Pre-Merger Spyre was obligated to compensate Paragon on a quarterly basis for its services performed under each research program based on the actual costs incurred with mark-up costs pursuant to the terms of the Paragon Agreement. As of the date of the Asset Acquisition, Pre-Merger Spyre had incurred total expenses of $19.0 million under the Paragon Agreement since inception, which included the $3.0 million research initiation fee and $16.0 million of historical reimbursable expenses owed to Paragon. As of June 22, 2023, $19.0 million was unpaid and was assumed by the Company through the Asset Acquisition. Furthermore, the Paragon Agreement provided for an annual equity grant of options to purchase 1% of the then outstanding shares of Spyre’s common stock, on a fully diluted basis, on the last business day of each calendar year, during the term of the Paragon Agreement, at the fair market value determined by the board of directors of Spyre. As a result of the Asset Acquisition, the Company assumed the rights and obligations of Pre-Merger Spyre under the Paragon Agreement, including the Parapyre Option Obligation. Pursuant to the Paragon Agreement, on a research program-by-research program basis following the finalization of the research plan for each respective research program, the Company is required to pay Paragon a nonrefundable fee in cash of $0.8 million. For the year ended December 31, 2023, the Company incurred $48.5 million, in costs reimbursable to Paragon, which were recorded as Research and development expenses in the consolidated statements of operations. For the year ended December 31, 2023, the Company made payments totaling $39.5 million to Paragon. On July 12, 2023 and December 14, 2023, the Company exercised the Option available under the Paragon Agreement with respect to the SPY001 and SPY002 research programs, respectively, and expects to enter into the SPY001 License Agreement and the SPY002 License Agreement. Our Option available under the Paragon Agreement with respect to the SPY003 and SPY004 programs remains unexercised. Following the execution of each of the SPY001 License Agreement and SPY002 License Agreement, the Company will be obligated to pay Paragon up to $22.0 million upon the achievement of specific development, regulatory and clinical milestones for the first product under each agreement, respectively, that achieves such specified milestones. Upon execution of each of the SPY001 License Agreement and the SPY002 License Agreement, the Company expects to pay Paragon a $1.5 million fee for nomination of a development candidate, as applicable, and the Company expects to be obligated to make a further milestone payment of $2.5 million upon the first dosing of a human patient in a Phase 1 trial. Subject to the execution of the Option with respect to the SPY003 or SPY004 research programs, the Company expects to be obligated to make similar payments upon and following the execution of license agreements with respect to these research programs, respectively.

v3.24.3

Leases	12 Months Ended
	Dec. 31, 2023
Leases [Abstract]
Leases	Leases Prior to the Company's restructuring, as described in Note 17, the Company leased certain office space, laboratory facilities, and equipment. These leases required monthly lease payments that were subject to annual increases throughout the lease term. Certain of these leases also included renewal options at the election of the Company to renew or extend the lease for an additional three to five years. These optional periods were not considered in the determination of the right-of-use assets or lease liabilities associated with these leases as the Company did not consider it reasonably certain it would exercise the options. The Company performed evaluations of its contracts and determined it has both operating and finance leases. Variable lease expense for these leases primarily consisted of common area maintenance and other operating costs. In April 2019, the Company entered into a lease agreement (the “Las Cimas Lease”) for its corporate headquarters and laboratory space located in Austin, Texas. The Las Cimas Lease included approximately 30,000 square feet and commenced on April 30, 2019, with an expiration on April 30, 2028. The Company posted a customary letter of credit in the amount of $1.5 million as security, which is subject to automatic reductions per the terms of the Las Cimas Lease. A tenant allowance of up to $1.0 million was provided by the lessor and fully reimbursed to the Company. In August 2023, the Company terminated its building lease in Austin, Texas. The negotiated termination agreement obligated the Company to pay the lessor a $2.0 million termination fee in exchange for releasing the Company of all further obligations under the lease including terminating the associated letter of credit. The following table summarizes the Company’s recognition of its operating and finance leases (in thousands): December 31, Classification 2023 2022 Assets Operating Operating lease right-of-use assets $ —  $ 3,430  Finance Other non-current assets —  597  Total leased assets —  4,027  Leases Current Operating Operating lease liabilities —  625  Finance Accrued and other current liabilities —  16  Non-current Operating Non-current operating lease liabilities —  4,004  Total lease liabilities $ —  $ 4,645  The following table summarizes the weighted-average remaining lease term and discount rates for the Company’s operating and finance leases: December 31, 2023 2022 Lease term (years) Operating leases 0.0 5.3 Finance leases 0.0 0.6 Discount rate Operating leases —  % 10.6  % Finance leases —  % 10.2  % The following table summarizes the lease costs pertaining to the Company’s operating leases (in thousands): Year Ended December 31, 2023 2022 2021 Operating lease cost $ 455  $ 910  $ 991  Variable lease cost 471  472  519  Total lease cost $ 926  $ 1,382  $ 1,510  Cash paid for amounts included in the measurement of operating lease liabilities during the years ended December 31, 2023 and 2022 was $0.5 million and $0.9 million, respectively, and was included within net cash used in operating activities in the cash flows. As of December 31, 2023, the Company had no operating or finance lease obligations.
Leases	Leases Prior to the Company's restructuring, as described in Note 17, the Company leased certain office space, laboratory facilities, and equipment. These leases required monthly lease payments that were subject to annual increases throughout the lease term. Certain of these leases also included renewal options at the election of the Company to renew or extend the lease for an additional three to five years. These optional periods were not considered in the determination of the right-of-use assets or lease liabilities associated with these leases as the Company did not consider it reasonably certain it would exercise the options. The Company performed evaluations of its contracts and determined it has both operating and finance leases. Variable lease expense for these leases primarily consisted of common area maintenance and other operating costs. In April 2019, the Company entered into a lease agreement (the “Las Cimas Lease”) for its corporate headquarters and laboratory space located in Austin, Texas. The Las Cimas Lease included approximately 30,000 square feet and commenced on April 30, 2019, with an expiration on April 30, 2028. The Company posted a customary letter of credit in the amount of $1.5 million as security, which is subject to automatic reductions per the terms of the Las Cimas Lease. A tenant allowance of up to $1.0 million was provided by the lessor and fully reimbursed to the Company. In August 2023, the Company terminated its building lease in Austin, Texas. The negotiated termination agreement obligated the Company to pay the lessor a $2.0 million termination fee in exchange for releasing the Company of all further obligations under the lease including terminating the associated letter of credit. The following table summarizes the Company’s recognition of its operating and finance leases (in thousands): December 31, Classification 2023 2022 Assets Operating Operating lease right-of-use assets $ —  $ 3,430  Finance Other non-current assets —  597  Total leased assets —  4,027  Leases Current Operating Operating lease liabilities —  625  Finance Accrued and other current liabilities —  16  Non-current Operating Non-current operating lease liabilities —  4,004  Total lease liabilities $ —  $ 4,645  The following table summarizes the weighted-average remaining lease term and discount rates for the Company’s operating and finance leases: December 31, 2023 2022 Lease term (years) Operating leases 0.0 5.3 Finance leases 0.0 0.6 Discount rate Operating leases —  % 10.6  % Finance leases —  % 10.2  % The following table summarizes the lease costs pertaining to the Company’s operating leases (in thousands): Year Ended December 31, 2023 2022 2021 Operating lease cost $ 455  $ 910  $ 991  Variable lease cost 471  472  519  Total lease cost $ 926  $ 1,382  $ 1,510  Cash paid for amounts included in the measurement of operating lease liabilities during the years ended December 31, 2023 and 2022 was $0.5 million and $0.9 million, respectively, and was included within net cash used in operating activities in the cash flows. As of December 31, 2023, the Company had no operating or finance lease obligations.

v3.24.3

Convertible Preferred Stock and Stockholders’ Equity	12 Months Ended
	Dec. 31, 2023
Equity [Abstract]
Convertible Preferred Stock and Stockholders’ Equity	Convertible Preferred Stock and Stockholders’ Equity The Company is authorized to issue 410,000,000 shares of capital stock of which 400,000,000 shares are designated as Common Stock and 10,000,000 shares are designated as preferred stock, all with a par value of $0.0001 per share. Each holder of Common Stock is entitled to one vote for each share of Common Stock held. The Common Stock is not entitled to preemptive rights, and is not subject to conversion, redemption or sinking fund provisions. Subject to preferences that may apply to any shares of preferred stock outstanding at the time, the holders of Common Stock are entitled to receive dividends out of funds legally available if the board of directors, in its discretion, determines to issue dividends and then only at the times and in the amounts that the board of directors may determine. As of December 31, 2023 and 2022, no Common Stock dividends had been declared by the board of directors. As of December 31, 2023 there were 437,037 shares of Series A preferred stock and 150,000 shares of Series B preferred stock outstanding. There were no shares of Series A preferred stock or shares of Series B preferred stock outstanding as of December 31, 2022. Registered Direct Offering In May 2022, the Company issued and sold 430,107 shares of Common Stock at an offering price of $40.00 per share and pre-funded warrants to purchase up to 694,892 shares of Common Stock at an offering price of $39.9975 per warrant (representing the price per share of Common Stock sold in the offering minus the $0.0025 exercise price per warrant) in a registered direct offering pursuant to a shelf registration statement on Form S-3. The net proceeds to the Company from this offering were approximately $42.9 million, after deducting placement agent fees and offering costs of $2.1 million. June 2023 PIPE In June 2023, in connection with the Asset Acquisition, the Company issued and sold 721,452 shares of Series A Preferred Stock at approximately $291.08 per share through a private placement to a group of accredited investors. The net proceeds from this offering were approximately $197.3 million, after deducting placement agent fees and offering costs of $12.7 million. December 2023 PIPE In December 2023, the Company issued and sold 6,000,000 shares of Common Stock at an offering price of $15.00 per share and 150,000 shares of Series B Preferred Stock at $600 per share through a private placement to a group of accredited investors. The net proceeds from this offering were approximately $169.1 million, after deducting placement agent fees and offering costs of $10.9 million. Parapyre Warrants The Company settled its 2023 obligations under the Parapyre Option Obligation by issuing Parapyre 684,407 warrants to purchase the Company's common stock, less the $21.52 per share exercise price of each warrant. As of December 31, 2023, none of the warrants issued under the Parapyre Option Obligation have been exercised. See Note 15 for additional information on the Parapyre Option Obligation. Pre-Funded Warrants In May 2022, the Company issued pre-funded warrants to purchase shares of Common Stock in underwritten public offerings at the offering price of the Common Stock, less the $0.0025 per share exercise price of each warrant. The warrants were recorded as a component of stockholders’ equity within additional paid-in capital and have no expiration date. Per the terms of the warrant agreements, the outstanding warrants to purchase shares of Common Stock may not be exercised if the holder’s ownership of the Common Stock would exceed 4.99% (“Maximum Ownership Percentage”) or 9.99% for certain holders. By written notice to the Company, each holder may increase or decrease the Maximum Ownership Percentage to any other percentage (not in excess of 19.99% for the majority of such warrants). The revised Maximum Ownership Percentage would be effective 61 days after the notice is received by the Company. As of December 31, 2023, the following pre-funded warrants to purchase Common Stock were issued and outstanding: Issue Date Expiration Date Exercise Price Number of Warrants Outstanding May 2022 None $ 0.0025  250,000 Total pre-funded warrants 250,000 Series A Non-Voting Convertible Preferred Stock On June 22, 2023, the Company filed a Certificate of Designation of Preferences, Rights and Limitations of the Series A Preferred Stock with the Secretary of State of the State of Delaware (the “Certificate of Designation”) in connection with the Asset Acquisition and the PIPE. Pursuant to the Certificate of Designation, holders of Series A Preferred Stock are entitled to receive dividends on shares of Series A Preferred Stock equal to, on an as-if-converted-to-Common Stock basis, and in the same form as, dividends actually paid on shares of Common Stock. Except as provided in the Certificate of Designation or as otherwise required by law, the Series A Preferred Stock does not have voting rights. However, as long as any shares of Series A Preferred Stock are outstanding, the Company will not, without the affirmative vote of the holders of a majority of the then outstanding shares of the Series A Preferred Stock: (a) alter or change adversely the powers, preferences or rights given to the Series A Preferred Stock, or alter or amend the Certificate of Designation, amend or repeal any provision of, or add any provision to, the Company’s Certificate of Incorporation or its Bylaws, or file any articles of amendment, certificate of designations, preferences, limitations and relative rights of any series of Preferred Stock, if such action would adversely alter or change the preferences, rights, privileges or powers of, or restrictions provided for the benefit of the Series A Preferred Stock, regardless of whether any of the foregoing actions will be by means of amendment to the Certificate of Incorporation or by merger, consolidation, recapitalization, reclassification, conversion or otherwise, (b) issue further shares of Series A Preferred Stock or increase or decrease (other than by conversion) the number of authorized shares of Series A Preferred Stock, (c) prior to the stockholder approval of the conversion of the Series A Preferred Stock into shares of Common Stock in accordance with Nasdaq Stock Market Rules (the “Conversion Proposal”) or at any time while at least 30% of the originally issued Series A Preferred Stock remains issued and outstanding, consummate (x) any Fundamental Transaction (as defined in the Certificate of Designation) or (y) any merger or consolidation of the Company with or into another entity or any stock sale to, or other business combination in which our stockholders immediately before such transaction do not hold at least a majority of our capital stock immediately after such transaction or (d) enter into any agreement with respect to any of the foregoing. The Series A Preferred Stock does not have a preference upon any liquidation, dissolution or winding-up of the Company. The Company held a stockholders’ meeting to submit the following matters to its stockholders for their consideration: (i) the approval of the Conversion Proposal, and (ii) if deemed necessary or appropriate by the Company or as otherwise required by law or contract, the approval of an amendment to the Certificate of Incorporation to authorize sufficient shares of Common Stock for the conversion of the Series A Preferred Stock issued pursuant to the Acquisition Agreement. In connection with these matters, the Company filed with the SEC a definitive proxy statement and other relevant materials. Following stockholder approval of the Conversion Proposal, each share of Series A Preferred Stock automatically converted into 40 shares of Common Stock, subject to certain limitations, including that a holder of Series A Preferred Stock is prohibited from converting shares of Series A Preferred Stock into shares of Common Stock if, as a result of such conversion, such holder, together with its affiliates, would beneficially own more than a specified percentage (established by the holder between 0.0% and 20.0%) of the total number of shares of Common Stock issued and outstanding immediately after giving effect to such conversion. On June 26, 2023, the Company completed a private placement of 721,452 shares of Series A PIPE Securities in exchange for gross proceeds of $210.0 million, or net proceeds of $197.3 million, after deducting placement agent and other offering costs. On July 7, 2023, the Company issued 364,887 shares of Series A Preferred Stock as part of its consideration transferred in connection with the Asset Acquisition that closed on June 22, 2023 which settled the related forward contract liability. For additional information, see Note 3. On November 21, 2023, the Company's stockholders approved the Conversion Proposal, among other matters, at a special meeting of stockholders. As a result of the approval of the Conversion Proposal, all conditions that could have required cash redemption of the Series A Preferred Stock were satisfied. Since the Series A Preferred Stock is no longer redeemable, the associated balances of the Series A Preferred Stock were reclassified from mezzanine equity to permanent equity during the fourth quarter of 2023. In addition, 649,302 shares of Series A Preferred Stock automatically converted to 25,972,080 shares of Common Stock; 437,037 shares of Series A Preferred Stock did not automatically convert and remain outstanding as of December 31, 2023 due to beneficial ownership limitations. This conversion was recorded as a reclassification between Series A Preferred Stock and Common Stock based on the historical per-share contributed capital amount, inclusive of any forward-contract valuation adjustments, of the Series A Preferred Stock. Series B Non-Voting Convertible Preferred Stock On December 8, 2023, the Company filed a Certificate of Designation of Preferences, Rights and Limitations of Series B Non-Voting Convertible Preferred Stock with the Secretary of State of the State of Delaware (the “Series B Certificate of Designation”) in connection with the December 2023 PIPE. Pursuant to the Series B Certificate of Designation, holders of Series B Preferred Stock are entitled to receive dividends on shares of Series B Preferred Stock equal to, on an as-if-converted-to-Common Stock basis, and in the same form as, dividends actually paid on shares of Common Stock. Except as provided in the Series B Certificate of Designation or as otherwise required by law, the Series B Preferred Stock does not have voting rights. However, as long as any shares of Series B Preferred Stock are outstanding, the Company will not, without the affirmative vote of the holders of a majority of the then outstanding shares of the Series B Preferred Stock, alter or change adversely the powers, preferences or rights given to the Series B Preferred Stock, or alter or amend the Series B Certificate of Designation, amend or repeal any provision of, or add any provision to, the Company’s Certificate of Incorporation or its Bylaws, or file any articles of amendment, certificate of designations, preferences, limitations and relative rights of any series of Preferred Stock, if such action would adversely alter or change the preferences, rights, privileges or powers of, or restrictions provided for the benefit of the Series B Preferred Stock, regardless of whether any of the foregoing actions will be by means of amendment to the Certificate of Incorporation or by merger, consolidation, recapitalization, reclassification, conversion or otherwise. The Series B Preferred Stock does not have a preference upon any liquidation, dissolution or winding-up of the Company. The Company has agreed to use its best efforts to obtain stockholder approval of the conversion of all issued and outstanding Series B Preferred Stock into shares of Common Stock in accordance with the Nasdaq Stock Market Rules (the "Series B Conversion Proposal") at its 2024 annual meeting of stockholders, which the Company agreed to hold no later than May 15, 2024. The Series B Preferred Stock is recorded outside of stockholders’ equity because, if conversion to Common Stock is not approved by the stockholders, the Series B Preferred Stock will be redeemable at the option of the holders for cash equal to the closing price of the Common Stock per share of Common Stock underlying the Series B Preferred Stock, on the last trading day prior to the holder’s redemption request. As of December 31, 2023, the redemption value of the Company's outstanding Series B Preferred Stock was $129.1 million based on the closing stock price of the Company's Common Stock on December 31, 2023 of $21.52 per share. The Company has determined that the Series B Preferred Stock did not contain any embedded derivatives and therefore the conversion and redemption features did not require bifurcation. Following stockholder approval of the Series B Conversion Proposal, each share of Series B Preferred Stock will automatically convert into 40 shares of the Common Stock, subject to certain limitations, including that a holder of Series B Preferred Stock is prohibited from converting shares of Series B Preferred Stock into shares of Common Stock if, as a result of such conversion, such holder, together with its affiliates, would beneficially own more than a specified percentage (established by the holder between 0% and 19.99%) of the total number of shares of Common Stock issued and outstanding immediately after giving effect to such conversion. On December 11, 2023, as part of the December 2023 PIPE, the Company completed a private placement of 150,000 shares of Series B Preferred Stock in exchange for gross proceeds of $90.0 million.

v3.24.3

Strategic License Agreements	12 Months Ended
	Dec. 31, 2023
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Strategic License Agreements	Strategic License Agreements Immedica Pharma AB License and Development Agreement On March 21, 2021, the Company entered into an exclusive license and supply agreement with Immedica Pharma AB (“Immedica”). By entering into this agreement, the Company agreed to provide Immedica the following goods and services: i.Deliver an exclusive, sublicensable, license and know-how (the “License”) to develop and commercialize pegzilarginase (the “Product”) in the territory comprising the members states of the European Economic Area, United Kingdom, Switzerland, Andorra, Monaco, San Marino, Vatican City, Turkey, Saudi Arabia, United Arab Emirates, Qatar, Kuwait, Bahrain, and Oman (the “Territory”); ii.Complete the global pivotal PEACE (Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints) Phase 3 trial (“PEACE Trial”) and related Biologics License Application (“BLA”) package to file with the United States Food and Drug Administration (“FDA”), which will be leveraged by Immedica in obtaining the necessary regulatory approvals in the Territory; and iii.Perform a Pediatric Investigation Plan trial (“PIP Trial”) in order for Immedica to be able to receive certain regulatory approvals within the Territory. In addition, the Company and Immedica formed a Joint Steering Committee (“JSC”) to provide oversight to the activities performed under the agreement; however, the substance of the Company’s participation in the JSC does not represent an additional promised service, but rather, a right of the Company to protect its own interests in the arrangement. Further, the Company agreed to supply to Immedica, and Immedica agreed to purchase from the Company, substantially all commercial requirements of the Product. The terms of the agreement do not provide for either (i) an option to Immedica to purchase the Product from the Company at a discount from the standalone selling price or (ii) minimum purchase quantities. Finally, Immedica will bear (i) all costs and expenses for any development or commercialization of the Product in the Territory subject to the License exclusive of the Company’s promised goods and services summarized above and (ii) all costs and fees associated with applying for regulatory approval of the Product in the Territory. In July 2021, the Company modified the agreement with Immedica to provide certain additional services in relation to the PEACE Phase 3 Trial and BLA package performance obligation in exchange for the reimbursement of up to $3.0 million of the actual costs incurred in relation to such incremental services. The Company received a non-refundable payment of $21.5 million and Immedica agreed to provide payment of 50% of the Company’s costs incurred in performing the PIP Trial up to a maximum of $1.8 million. In addition, the Company has the ability to receive additional payments under the agreement of up to approximately $120.8 million in regulatory and commercial milestone payments, assuming an exchange rate of $1.07 to €1.00. The Company is also entitled to receive royalties in the mid-20 percent range on net sales of the Product in the Territory. The Company concluded that Immedica meets the definition to be accounted for as a customer because the Company is delivering intellectual property and other services within the Company’s normal course of business, in which the parties are not jointly sharing the risks and rewards. Therefore, the Company concluded that the promises summarized above represent transactions with a customer within the scope of ASC 606. The Company determined that the following promises represent distinct promised services, and therefore, performance obligations: (i) the License, (ii) the PEACE Trial and BLA package, and (iii) the PIP Trial. Specifically, in making these determinations, the Company considered the following factors: -As of inception of the agreement, the Company had completed the Phase 1/2 clinical trial related to the Product and were conducting the ongoing PEACE Trial. Accordingly, the Company is not promising, nor expecting, to perform additional research and development activities pursuant to the agreement that would either significantly modify, customize or be considered highly interdependent or interrelated with pegzilarginase. -The License represents functional intellectual property given the functionality of the License is not expected to change substantially as a result of the company’s ongoing activities. -The services necessary to complete the PEACE Trial, BLA package and PIP Trial could be performed by other parties. Given that Immedica was not obligated to purchase any minimum amount or quantities of the Product, the supply of the Product for commercial use to Immedica was determined to be an option for Immedica, rather than a performance obligation of the Company at contract inception and will be accounted for if and when exercised. The Company also determined that Immedica’s option to purchase the Product does not create a material right as the expected pricing is not at a discount. The Company determined that the upfront fixed payment amount of $21.5 million must be included in the transaction price. Additionally, the Company determined at inception of the arrangement that 50% of the estimated costs to be incurred in relation to the PIP Trial exceeded $1.8 million and included the full reimbursement amount of $1.8 million in the transaction price. Upon subsequent re-evaluation due to changing facts and circumstances, the Company determined the estimated costs are now less than the maximum allowable reimbursement and a portion of the variable consideration was constrained, which did not materially impact the revenue recognized to date. Additionally, upon the modification of the agreement in July 2021, the Company determined that the estimated costs to perform the additional services related to the PEACE Trial and BLA package exceeds the maximum allowable reimbursement of $3.0 million. Therefore, the Company included an estimated total of $3.6 million that will be due in relation to the PIP Trial, PEACE Trial, and BLA package in the transaction price and it is probable that a significant reversal will not occur in the future. In total, the modified transaction price was determined to be $25.1 million. The Company has allocated $9.6 million and $3.5 million of the modified transaction price to the PEACE Trial and BLA package and PIP Trial performance obligations, respectively, based on the stand-alone selling prices ("SSP"), which was based on the estimated costs that a third-party would charge in performing such services on a stand-alone basis. The SSP for the License was established at inception of the arrangement using a residual value approach due to the uniqueness of and lack of observable data related to the License, and without a specific analog from which to make reliable estimates, resulting in an allocation of $12.0 million. The potential regulatory milestone payments that the Company is eligible to receive were excluded from the transaction price, as the milestone amounts were fully constrained based on the probability of achievement, since the milestones relate to successful achievement of certain regulatory approvals, which might not be achieved. The Company determined that the royalties and commercial milestone payments relate predominantly to the license of intellectual property and are therefore excluded from the transaction price under the sales- or usage-based royalty exception of ASC 606. The Company will reevaluate the transaction price, including all constrained amounts, at the end of each reporting period and as uncertain events are resolved or other changes in circumstances occur, the Company will adjust its estimate of the transaction price as necessary. The Company will recognize the royalties and commercial milestone payments as revenue when the associated sales occur, and relevant sales-based thresholds are met. The Company assessed the arrangement with Immedica and concluded that a significant financing component does not exist. The Company recognized revenue allocated to the License performance obligation at a point in time and upon transfer of the License. The Company completed the transfer of the know-how necessary for Immedica to benefit from the License in June 2021 and recognized $12.0 million of revenue at that time. The development fee allocated to the PEACE Trial, BLA package and PIP Trial performance obligations will be recognized over time using an input method of costs incurred related to the performance obligations. For the years ended December 31, 2023 and 2022, the Company recognized revenue of $0.9 million and $2.3 million, respectively, related to the PEACE Trial and BLA package performance obligation using a cost to cost model. The Company recognized revenue of $6.7 million related to the PEACE Trial and BLA package performance obligation using a cost to cost model and $12.0 million related to the transfer of the License for the year ended December 31, 2021. As of December 31, 2022, the Company recorded deferred revenue of $2.7 million associated with the license and supply agreement with Immedica, of which $0.5 million was classified as current. On July 27, 2023, the Company announced that it had entered into an agreement to sell the global rights to pegzilarginase to Immedica for $15.0 million in upfront cash proceeds and up to $100.0 million in contingent milestone payments. The sale of pegzilarginase to Immedica superseded and terminated the previous license agreement between the Company and Immedica. On July 27, 2023, the carrying value of the asset was zero as it was internally developed. Accordingly, the Company recognized a $16.4 million gain within Gain on Sale of in-process research and development, which is comprised of $15.0 million in upfront cash proceeds and the reimbursement of $1.8 million in pre-paid manufacturing costs that was contingent upon a favorable opinion being received by the CHMP, net of transaction costs and the derecognition of pegzilarginase related nonfinancial assets and liabilities totaling $0.4 million. The milestone payments are contingent on formal reimbursement decisions by national authorities in key European markets and pegzilarginase approval by the FDA, among other events. The upfront payment and contingent milestone payments if paid, net of expenses and adjustments, will reduce the CVR liability and will be distributed to CVR holders pursuant to the CVR Agreement resulting from the Asset Acquisition. Contract Balances from Customer Contract The timing of revenue recognition, billings and cash collections results in contract assets and contract liabilities on the balance sheets. The Company recognizes license and development receivables based on billed services, which are derecognized upon reimbursement. When consideration is received, or such consideration is unconditionally due, from a customer prior to transferring goods or services to the customer under the terms of a contract, a contract liability is recorded. Contract liabilities are recognized as revenue after control of the goods or services is transferred to the customer and all revenue recognition criteria have been met. The following table presents changes in the Company’s contract liabilities for the periods presented (in thousands): Year Ended December 31, 2022 December 31, 2022 Additions Deductions December 31, 2023 Contract liabilities: Deferred revenue $ 2,696  $ 575  $ (3,271) $ —  The Company had no contract assets during the years ended December 31, 2023 and 2022.

v3.24.3

Sale of Pegzilarginase to Immedica	12 Months Ended
	Dec. 31, 2023
Discontinued Operations and Disposal Groups [Abstract]
Sale of Pegzilarginase to Immedica	Sale of Pegzilarginase to Immedica On July 27, 2023, the Company announced that it had entered into an agreement to sell the global rights to pegzilarginase to Immedica for $15.0 million in upfront cash proceeds and up to $100.0 million in contingent milestone payments. The sale of pegzilarginase to Immedica superseded and terminated the previous license agreement between the Company and Immedica. On July 27, 2023, the carrying value of the asset was zero as it was internally developed. Accordingly the Company recognized a $16.4 million gain within Gain on sale of in-process research and development, which is comprised of $15.0 million in upfront cash proceeds and the reimbursement of $1.8 million in pre-paid manufacturing costs that was contingent upon a favorable opinion being received by the Committee for Medicinal Products for Human Use, net of transaction costs and the derecognition of pegzilarginase related nonfinancial assets and liabilities totaling $0.4 million. The milestone payments are contingent on formal reimbursement decisions by national authorities in key European markets and pegzilarginase approval by the FDA, among other events. Accordingly, the Company will recognize any future milestone payments once the contingency is resolved and payment is contractually required. The upfront payment and contingent milestone payments if paid, net of expenses and adjustments, will be distributed to CVR holders pursuant to the CVR Agreement resulting from the Asset Acquisition.

v3.24.3

Novation of Manufacturing Agreements	12 Months Ended
	Dec. 31, 2023
Commitments and Contingencies Disclosure [Abstract]
Novation of Manufacturing Agreements	Novation of Manufacturing Agreements Pursuant to a Novation Agreement dated September 19, 2023 (the “Novation Agreement”), by and between the Company, Paragon and WuXi Biologics (Hong Kong) Limited (“WuXi Biologics”), the Company novated (i) a Biologics Master Services Agreement (the “WuXi Biologics MSA”) and (ii) a Cell Line License Agreement (the “Cell Line License Agreement”). Biologics Master Services Agreement In April 2023, Paragon and WuXi Biologics entered into the WuXi Biologics MSA, which was subsequently novated to the Company by Paragon on September 19, 2023 pursuant to the Novation Agreement. The WuXi Biologics MSA governs certain development activities and GMP manufacturing and testing for the SPY001 program, as well as potential future programs, on a work order basis. Under the WuXi Biologics MSA, the Company is obligated to pay WuXi Biologics a service fee and all non-cancellable obligations in the amount specified in each work order associated with the agreement for the provision of services. The WuXi Biologics MSA terminates on the later of (i) June 20, 2027 or (ii) the completion of services under all work orders executed by the parties prior to June 20, 2027, unless terminated earlier. The term of each work order terminates upon completion of the services under such work order, unless terminated earlier. The Company can terminate the WuXi Biologics MSA or any work order at any time upon 30 days' prior written notice and immediately upon written notice if WuXi Biologics fails to obtain or maintain required material governmental licenses or approvals. Either party may terminate a work order (i) at any time upon six months prior notice with reasonable cause, provided however that if WuXi Biologics terminates a work order in such manner, no termination or cancellation fees shall be paid by the Company and (ii) immediately for cause upon (a) the other party’s material breach that remains uncured for 30 days after notice of such breach, (b) the other party’s bankruptcy or (c) a force majeure event that prevents performance for a period of at least 90 days. Cell Line License Agreement In April 2023, Paragon and WuXi Biologics entered into the Cell Line License Agreement, which was subsequently novated to the Company by Paragon pursuant to the Novation Agreement. Under the Cell Line License Agreement, the Company received a non-exclusive, worldwide, sublicensable license to certain of WuXi Biologics’s know-how, cell line, biological materials (the “WuXi Biologics Licensed Technology”) and media and feeds to make, have made, use, sell and import certain therapeutic products produced through the use of the cell line licensed by WuXi Biologics under the Cell Line License Agreement (the “WuXi Biologics Licensed Products”). Specifically, the WuXi Biologics Licensed Technology is used in certain manufacturing activities in support of the SPY001 program. In consideration for the license, the Company agreed to pay WuXi Biologics a non-refundable license fee of $0.2 million. Additionally, if the Company manufactures all of its commercial supplies of bulk drug product with a manufacturer other than WuXi Biologics or its affiliates, the Company is required to make royalty payments to WuXi Biologics of less than one percent of global net sales of WuXi Biologics Licensed Products manufactured by a third-party manufacturer (the “Royalty”). If the Company manufactures part of its commercial supplies of the WuXi Biologics Licensed Products with WuXi Biologics or its affiliates, then the Royalty will be reduced accordingly on a pro rata basis. The Cell Line License Agreement will continue indefinitely unless terminated (i) by the Company upon six months prior written notice and our payment of all undisputed amounts due to WuXi Biologics through the effective date of termination, (ii) by WuXi Biologics for a material breach by the Company that remains uncured for 60 days after written notice, (iii) by WuXi Biologics if the Company fails to make a payment and such failure continues for 30 days after receiving notice of such failure, or (iv) by either party upon the other party’s bankruptcy.

v3.24.3

Stock-Based Compensation	12 Months Ended
	Dec. 31, 2023
Share-Based Payment Arrangement [Abstract]
Stock-Based Compensation	Stock-Based Compensation 2015 Equity Incentive Plan In March 2015, the Company adopted the 2015 Equity Incentive Plan (“2015 Plan”), administered by the board of directors, and provides for the Company to sell or issue share of Common Stock or restricted Common Stock, or to grant incentive stock options or nonqualified stock options for the purchase of Common Stock, to employees, members of the board of directors and consultants of the Company. Under the terms of the 2015 Plan, the exercise prices, vesting and other restrictions may be determined at the discretion of the board of directors, or their committee if so delegated, except that the exercise price per share of stock options may not be less than 100% of the fair market value of the share of common stock on the date of grant, the term of stock options may not be greater than ten years for all grants, and for grantees holding more than 10% of the total combined voting power of all classes of stock, the term may not be greater than five years. The Company granted options under the 2015 Plan until April 2016 when it was terminated as to future awards, although it continues to govern the terms of options that remain outstanding under the 2015 Plan. As of December 31, 2023, a total of 3,029 shares of Common Stock are subject to options outstanding under the 2015 Plan and will become available under the 2016 Equity Incentive Plan (“2016 Plan”) to the extent the options are forfeited or lapse unexercised. 2016 Equity Incentive Plan The 2016 Plan became effective in April 2016 and serves as the successor to the 2015 Plan. Under the 2016 Plan, the Company may grant stock options, stock appreciation rights, restricted stock awards, restricted stock units, performance awards, and stock bonuses. The 2016 Plan provides for an initial reserve of 44,000 shares of Common Stock, plus 20,395 shares of Common Stock remaining under the 2015 Plan, and any share awards that subsequently are forfeited or lapse unexercised under the 2015 Plan. The shares reserved exclude shares of Common Stock reserved for issuance under the 2015 Plan. In October 2018, the 2016 Plan was amended to increase the number of shares of Common Stock reserved for issuance thereunder by 70,384 shares, extend the term of the 2016 Plan through August 7, 2028, and provide for an automatic increase in the number of shares reserved for issuance thereunder on January 1 of each year for the remaining term of the plan equal to (a) 4.0% of the number of issued and outstanding shares of Common Stock on December 31 of the immediately preceding year, or (b) a lesser amount as approved by the board each year (the "Evergreen Provision"). As a result of the operation of each of these provisions, on January 1, 2023, 2022, and 2021, an additional 104,561, 78,968, and 76,735 shares, respectively, became available for issuance under the 2016 Plan. In November 2023, the 2016 Plan was amended to (i) increase the number of shares of Common Stock reserved for issuance thereunder by 4,481,152 shares, (ii) revise the annual limit on non-employee director compensation from 4,000 shares to (a) $750,000 in total value or (b) $1,000,000 in the year of the director’s initial service as a non-employee director or in any year a director serves as chairman of the Board of Directors, in either case, applicable to fees paid in both cash and equity, (iii) remove the fixed termination date of the 2016 Plan and, (iv) revise the Evergreen Provision from 4% to 5% of issued and outstanding shares of Common Stock on December 31 of the preceding calendar year and to include shares issuable upon the exercise of pre-funded warrants and the conversion of outstanding shares of non-voting convertible preferred stock in the calculation. As of December 31, 2023, the total number of shares reserved for issuance under the 2016 Plan was 5,019,177, of which 3,294,962 shares were subject to outstanding option awards and restricted unit awards. 2018 Equity Inducement Plan In February 2018, the board of directors approved and adopted the 2018 Equity Inducement Plan (“2018 Plan”), which became effective on the same date. The board of directors approved an initial reserve of 44,000 shares of Common Stock to be used exclusively for individuals who were not previously employees or directors, or following a bona fide period of non-employment, as an inducement material to the individual entering into employment with the Company. Nonqualified stock options or restricted stock units may be granted under the 2018 Plan at the discretion of the Compensation Committee or the board of directors. The Company did not seek stockholder approval of the 2018 Plan pursuant to Nasdaq Rule 5635(c)(4). During 2023, the 2018 Plan was amended to increase the number of shares of Common Stock reserved for issuance by 6,000,000. Under the 2016 Plan and 2018 Plan, the Company may grant stock-based awards with service conditions (“service-based” awards), performance conditions (“performance-based” awards), and market conditions (“market-based” awards). Service-based awards granted under the 2018 Plan, 2016 Plan, and 2015 Plan generally vest over four years and expire after ten years, although awards have been granted with vesting terms less than four years. The Company granted 153,865 service-based restricted stock units (“RSUs”) during the year ended December 31, 2023 to certain employees under the 2018 Plan. As of December 31, 2023, the total number of shares reserved for issuance under the 2018 Plan was 6,044,000, of which 5,350,595 shares were subject to outstanding awards. Spyre 2023 Equity Incentive Plan On June 22, 2023, in connection with the Asset Acquisition, the Company assumed the Amended and Restated Spyre 2023 Equity Incentive Plan (the "Spyre Equity Plan") and its outstanding and unexercised stock options, which were converted to options to purchase 2,734 shares of Common Stock. The acquisition-date fair value of these grants will be recognized as an expense on a pro-rata basis over the vesting period. Parapyre Option Obligation On June 22, 2023, in connection with the Asset Acquisition, the Company assumed the Parapyre Option Obligation which provided for an annual equity grant of warrants for Parapyre to purchase 1% of the then outstanding shares of Pre-Merger Spyre's common stock, on a fully diluted basis, on the last business day of each calendar year during the term of the Paragon Agreement, at the fair market value determined by the board of directors of Pre-Merger Spyre. On September 29, 2023, the Company amended the Paragon Agreement to amend and restate certain terms of the option grant pertaining to the Parapyre Option Obligation, including but not limited to (i) defining that the annual equity grant of warrants is based on the outstanding shares of the Company’s Common Stock, (ii) establishing the grant date as the last business day of 2023 and 2024, and (iii) defining the term of the warrants granted as ten years. The Company determined that the 2023 and 2024 grants are two separate grants, as there would be no obligation for the 2024 grant had the Company exercised or terminated all of the options under the Paragon Agreement prior to December 31, 2023. The service inception period for the grant precedes the grant date, with the full award being vested as of the grant date with no post-grant date service requirement. Accordingly, a liability related to the Parapyre Option Obligation was recorded pursuant to the amended Paragon Agreement during 2023 interim periods. The Company determined that the grant date of the award was December 31, 2023, as all terms of the award, including number of shares and exercise price, were known by all parties. Accordingly, the Company measured the grant-date fair value of the warrants granted at approximately $11.5 million as an equity-classified award, of which $0.1 million was recognized as part of the liabilities assumed with the Asset Acquisition on June 22, 2023. For the year ended December 31, 2023, $11.4 million was recognized as stock compensation expense related to the Parapyre Option Obligation. There was no similar expense for the years ended December 31, 2022 and 2021. As of December 31, 2023, the unamortized expense related to the Parapyre Option Obligation was nil. The following table summarizes employee and non-employee stock option activity for the year ended December 31, 2023: Shares Issuable Under Options Weighted Average Exercise Price Weighted Average Remaining Contractual Term Aggregate Intrinsic Value (in years) (in thousands) Outstanding as of December 31, 2022 405,082 $ 113.75  6.72 $ 2  Granted 8,776,245 9.67  Exercised (46,246) 8.22  Forfeited (637,686) 43.00  Outstanding as of December 31, 2023 8,497,395 $ 12.13  8.40 $ 98,928  Options vested and expected to vest as of December 31, 2023 8,497,395 $ 12.13  8.40 $ 98,928  Options exercisable as of December 31, 2023 1,065,700 $ 24.72  5.62 $ 13,328  The aggregate intrinsic value of options outstanding, exercisable, vested and expected to vest were calculated as the difference between the exercise price of the options and the fair value of the Company’s Common Stock as of the reporting date. For the years ended December 31, 2023, 2022, and 2021, the weighted-average grant date fair value of options granted was $9.67, $1.80, and $4.96, per share, respectively. The total intrinsic value of options exercised during the years ended December 31, 2023, and 2021 was $0.4 million and $0.7 million, respectively. No options were exercised in the year ended December 31, 2022. There were 477,000 stock options issued to non-employees during the years ended December 31, 2023. There were no stock options issued to non-employees during the years ended December 31, 2022 and 2021. For the years ended December 31, 2023, 2022 and 2021, no non-employee stock options vested in the period. 2016 Employee Stock Purchase Plan The 2016 Employee Stock Purchase Plan (“2016 ESPP”) became effective in April 2016. A total of 6,600 shares of Common Stock were reserved for issuance under the 2016 ESPP. Eligible employees may purchase shares of Common Stock under the 2016 ESPP at 85% of the lower of the fair market value of the Common Stock as of the first or the last day of each offering period. Employees are limited to contributing 15% of the employee’s eligible compensation and may not purchase more than $25,000 of stock during any calendar year. The 2016 ESPP will terminate ten years from the first purchase date under the plan, unless terminated earlier by the board of directors. In June 2018, the 2016 ESPP was amended to provide for an automatic annual increase in the number of shares reserved for issuance thereunder on January 1 of each year for the remaining term of the year equal to (a) 1.0% of the number of issued and outstanding shares of Common Stock on December 31 of the immediately preceding year, or (b) a lesser amount as approved by the board of directors each year. As a result of the operation of this provision, on January 1, 2023, 2022 and 2021, an additional 26,140, 19,742, and 19,184 shares, respectively, became available for issuance under the 2016 ESPP. As of December 31, 2023, the reserve remaining and available for future issuance under the 2016 ESPP was 72,404 shares. In February 2023, the 2016 ESPP was amended to increase the maximum shares purchased during any one period from 80 shares to 400 shares or a lesser amount determined by the board of directors. For the year ended December 31, 2023, stock-based compensation expense related to the 2016 ESPP plan was di minimis. For the years ended 2022 and 2021, stock-based compensation expense related to the 2016 ESPP plan was $0.1 million and $0.2 million, respectively. Restricted Common Stock Units In July 2020, the Company granted 9,128 restricted stock units to certain employees, with vesting terms subject to regulatory, commercial, and clinical milestones, in addition to a service condition. As of December 31, 2023 none of these restricted stock units had vested and all restricted stock units were forfeited since the performance milestones were not met within the required time frame. No stock-based compensation expense was recognized on these awards. The Company granted 153,865 service-based restricted stock units during the year ended December 31, 2023. There were no restricted stock units granted during the years ended December 31, 2022 and 2021. The following table summarizes employee restricted stock activity for the year ended December 31, 2023: Shares Weighted Average Grant Date Fair Value Unvested restricted stock units as of December 31, 2022 5,660 $ 203.25  Granted 153,865 18.17  Vested — —  Forfeited (5,660) 203.25  Unvested restricted stock units as of December 31, 2023 153,865 $ 18.17  There were no restricted stock units granted to non-employees during the years ended December 31, 2023, 2022, and 2021. Stock-Based Compensation Expense Total stock-based compensation expense recognized from the Company’s equity incentive plans, 2018 Plan, and the 2016 ESPP for the years ended December 31, 2023, 2022, and 2021 was as follows (in thousands): Year Ended December 31, 2023 2022 2021 Employees Non- Employees Employees Non- Employees Employees Non- Employees Research and development $ 2,910  $ 11,328  $ 2,591  $ —  $ 2,723  $ —  General and administrative 11,327  109  4,520  —  5,315  —  Total stock-based compensation expense $ 14,237  $ 11,437  $ 7,111  $ —  $ 8,038  $ —       No related tax benefits were recognized for the years ended December 31, 2023, 2022, and 2021 (see Note 18). The employee and non-employee awards contain both performance and service-based vesting conditions. No expense was recognized for the unvested employee and non-employee awards with only a performance condition for the years ended December 31, 2023, 2022, and 2021. The performance-based vesting conditions represent specific performance targets. Compensation expense for employee and non-employee share-based payment awards with performance conditions is recognized when the performance condition is deemed probable of achievement. As of December 31, 2023, the Company had an aggregate of $64.4 million of unrecognized stock-based compensation expense for options outstanding, which is expected to be recognized over a weighted average period of 3.5 years. In determining the fair value of the stock-based awards, the Company uses the Black-Scholes option-pricing model and assumptions discussed below. Each of these inputs is subjective and generally requires significant judgment to determine. Expected Term The Company’s expected term represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method (based on the midpoint between the vesting date and the end of the contractual term). The Company utilizes this method due to lack of historical exercise data and the plain-vanilla nature of the Company’s stock-based awards. Expected Volatility Since the Company was privately held through April 2016 and transitioned from a clinical stage company to a pre-clinical stage company in 2023, it alone does not have the relevant company-specific historical data to support its expected volatility. As such, the Company has used an average of expected volatilities based on the volatilities of a representative group of publicly traded biopharmaceutical companies over a period equal to the expected term of the stock option grants. Subsequent to the Company’s initial public offering, it began to consider the Company’s own historic volatility. However, due to the transition from a clinical stage company to a pre-clinical stage company, the Company still uses peer company data to assist in this analysis. For purposes of identifying comparable companies, the Company selected companies with comparable characteristics to it, including enterprise value, risk profiles, position within the industry, and with historical share price information sufficient to meet the expected life of the stock-based awards. The historical volatility data was computed using the daily closing prices for the selected companies’ shares during the equivalent period of the calculated expected term of the stock-based awards. The Company intends to consistently apply this process using the same or similar comparable entities until a sufficient amount of historical information regarding the volatility of the Company’s own share price post transition becomes available. Risk-Free Interest Rate The risk-free interest rate is based on the U.S. Treasury zero coupon issues in effect at the time of grant for periods corresponding with the expected term of option. Expected Dividend The Company has never paid dividends on its Common Stock and has no plans to pay dividends on its Common Stock. Therefore, the Company used an expected dividend yield of zero. Valuation of Stock Options and 2016 ESPP The fair value of the stock options granted under the the Company's equity incentive plans, as well as the shares available for purchase under the 2016 ESPP were determined using the Black-Scholes option-pricing model. The following table summarizes the weighted-average assumptions used in calculating the fair value of the awards: Year Ended December 31, 2023 2022 2021 Stock Options Granted Expected term (in years) 5.88 6.00 5.99 Expected volatility 107  % 84  % 83  % Risk-free interest 4.37  % 2.93  % 0.88  % Dividend yield 0  % 0  % 0  % 2016 ESPP Expected term (in years) 0.49 0.49 0.50 Expected volatility 181  % 84  % 86  % Risk-free interest 4.99  % 1.95  % 0.08  % Dividend yield 0  % 0  % 0  %

v3.24.3

Defined Contribution Plan	12 Months Ended
	Dec. 31, 2023
Retirement Benefits [Abstract]
Defined Contribution Plan	Defined Contribution Plan The Company sponsors a 401(k) retirement plan in which substantially all of its full-time employees are eligible to participate. Participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. During the years ended December 31, 2023, 2022, 2021, the Company provided $0.2 million, $0.6 million, and $0.6 million, respectively, in contributions to the plan.

v3.24.3

Restructuring Charges	12 Months Ended
	Dec. 31, 2023
Restructuring and Related Activities [Abstract]
Restructuring Charges	Restructuring Charges Severance and Stock Compensation On April 12, 2023, based on the review of the inconclusive interim results from the Company's Phase 1/2 clinical trial of pegtarviliase for the treatment of classical homocystinuria and other business considerations, the Company announced that it had initiated a process to explore strategic alternatives to maximize stockholder value and engaged an independent exclusive financial advisor to support this process. As a result, the Company implemented a restructuring plan resulting in an approximate 83% reduction of the Company’s existing headcount by June 30, 2023. The Company recognized restructuring expenses consisting of cash severance payments and other employee-related costs of $6.4 million during the year ended December 31, 2023. Cash payments for employee related restructuring charges of $5.3 million were paid as of December 31, 2023. In addition, the Company recognized $1.0 million in non-cash stock-based compensation expense related to the accelerated vesting of stock-based awards for certain employees. The Company recorded these restructuring charges based on each employee’s role to the respective research and development and general and administrative operating expense categories on its consolidated statements of operations and comprehensive loss. The following table summarizes the changes in the Company's accrued restructuring balance (in thousands): Beginning Balance December 31, 2022 Charges Payments Ending Balance December 31, 2023 Severance liability $ —  $ 6,448  $ (5,325) $ 1,123  Sale of Assets During the second quarter of 2023, the Company sold various lab equipment, consumables, and furniture and fixtures for total consideration of $0.5 million. After recording the disposal of all the Company's property and equipment net of proceeds, the Company recorded a $0.7 million and $0.2 million loss on disposal of long lived assets which is included in Research and development and General and administrative expenses, respectively. Lease Right-of-use Asset and Leasehold Improvement Impairment Effective June 30, 2023, the Company abandoned its leased office space in Austin, Texas. As a result, the Company recognized an impairment loss of $0.9 million related to the operating lease right-of-use asset and $1.7 million related to leasehold improvements. On August 7, 2023, the Company terminated its building lease in Austin, Texas. The negotiated termination agreement obligated the Company to pay the lessor a $2.0 million termination fee in exchange for releasing the Company of all further obligations under the lease. All charges related to the restructuring activities were recognized during the second quarter of 2023. No further restructuring charges will be incurred under the restructuring plan. A summary of the charges related to the restructuring activities is as follows (in thousands): Severance Related Expenses Stock Compensation Expenses Loss on Disposal of Long Lived Assets Lease Asset Impairment Total Restructuring Costs Research and development $ 3,182  $ 123  $ 749  $ 1,405  $ 5,459  General and administrative 3,266  870  182  1,175  5,493  Total $ 6,448  $ 993  $ 931  $ 2,580  $ 10,952

v3.24.3

Income Taxes	12 Months Ended
	Dec. 31, 2023
Income Tax Disclosure [Abstract]
Income Taxes	Income Taxes The following table summarizes the (loss) income before income tax expense by jurisdiction for the periods indicated: Year Ended December 31, 2023 2022 2021 Domestic $ (338,942) $ (84,113) $ (65,940) Foreign 126  162  280  Loss before income tax expense $ (338,816) $ (83,951) $ (65,660) For the year ended December 31, 2023, the Company recognized no provision or benefit from income taxes. For both the years ended December 31, 2022 and 2021, the Company recognized an income tax expense of $0.1 million, related to foreign subsidiaries income tax expense and the Texas margins tax. The difference between the Company’s provision for income taxes and the amounts computed by applying the statutory federal income tax rate to income before income taxes is as follows (in thousands): Year Ended December 31, 2023 2022 2021 Tax provision derived by applying the federal statutory rate to income before income taxes $ (71,151) $ (17,630) $ (13,789) Loss on forward contract valuation 17,541  —  —  Acquired IPR&D 27,340  —  —  Loss on CVR revaluation 3,987  —  —  Other permanent differences 4,472  1,042  1,002  Federal tax credits (1) (3,559) (3,815) State tax credits —  (640) (152) Effect of tax rate on foreign jurisdiction (53) 42  (5) Change in the valuation allowance 17,839  20,609  16,900  Income tax (benefit) expense $ (26) $ (136) $ 141  The components of the deferred tax assets and liabilities consist of the following (in thousands): December 31, 2023 2022 Deferred tax assets Net operating loss carryforward $ 74,454  $ 68,917  Capitalized 174 R&D costs 22,532  11,097  Intangible assets 47  52  Deferred revenue —  566  Accrued expense 579  668  Stock-based compensation 4,246  3,293  Federal tax credits 21,914  21,914  State tax credits 1,631  1,631  Other 88  190  Total deferred tax assets 125,491  108,328  Deferred tax liabilities Depreciable assets —  (676) Total deferred tax liabilities —  (676) Less: Valuation allowance (125,491) (107,652) Deferred tax assets, net $ —  $ —  The Company has established a full federal and state valuation allowance equal to the net deferred tax assets due to uncertainties regarding the realization of the deferred tax asset based on the Company’s lack of earnings history. The valuation allowance increased by $17.8 million, $20.6 million, and $16.9 million during the years ended December 31, 2023, 2022, and 2021, respectively, primarily due to continuing loss from operations. As of December 31, 2023 and 2022, the Company had U.S. net operating loss carryforwards (“NOL”) of $354.5 million and $328.2 million, respectively. For both the years ended December 31, 2023 and 2022, the Company had U.S. tax credit carryforwards and state tax credit carryforwards of $21.9 million and $1.6 million, respectively. Of the net operating loss and tax credit carryforwards $58.4 million and $21.9 million, respectively, will expire in 2033, if not utilized. Any remaining net operating loss will carry forward indefinitely and can be utilized to offset up to 80% of the taxable income in any tax year. The net operating loss and credit carryforwards are subject to Internal Revenue Service adjustments until the statute closes on the year the net operating loss or tax credits are utilized. The Company has not completed a study to assess whether an ownership change has occurred or whether there have been multiple ownership changes since the Company’s formation due to the complexity and cost associated with such a study, and the fact that there may be additional such ownership changes in the future. If the Company has experienced an ownership change at any time since its formation, utilization of the NOL or research and development credit carryforwards would be subject to an annual limitation under Section 382 or 383 of the Internal Revenue Code, which is determined by first multiplying the value of the Company’s stock at the time of the ownership change by the applicable long-term, tax-exempt rate, and then could be subject to additional adjustments, as required. Additionally, the separate return limitation year (“SRLY”) rules may apply to losses of the Company’s eight wholly owned U.S. subsidiary corporations. The SRLY rules limit the consolidated group’s use of a subsidiary corporation’s net operating losses to the amount of income generated by the subsidiary corporation after it becomes a member of the group. Any limitation may result in expiration of a portion of the NOL or research and development credit carryforwards before utilization. Further, until a study is completed and any limitation known, no amounts are being considered as an uncertain tax position or disclosed as an unrecognized tax benefit. Additionally, the Company does not expect any unrecognized tax benefits to change significantly over the next twelve months. Due to the existence of the valuation allowance, future changes in the Company’s unrecognized tax benefits will not impact its effective tax rate. Any carryforwards that will expire prior to utilization as a result of such limitations will be removed from deferred tax assets with a corresponding reduction of the valuation allowance. The Company is subject to examination by taxing authorities in its significant jurisdictions for the 2019 and subsequent years. However, due to NOL and tax attribute carryovers, the taxing authorities have the ability to adjust the NOLs and other tax attributes related to closed years. As of December 31, 2023 and 2022, there were no amounts recorded for uncertain tax positions. As of December 31, 2023, undistributed earnings of the Company’s incorporated foreign subsidiaries are immaterial. Under the Global Intangible Low-Taxed Income (“GILTI”) provisions of the 2017 Tax Cuts and Jobs Act, U.S. income taxes have been incurred on the undistributed earnings of the foreign subsidiaries and therefore, the tax impact upon distribution is limited to state income and withholding taxes and is not material.

v3.24.3

Net Loss Per Share (as restated)	12 Months Ended
	Dec. 31, 2023
Earnings Per Share [Abstract]
Net Loss Per Share (as restated)	Net Loss Per Share (as restated) Restatement Subsequent to the filing of its Quarterly Report on Form 10-Q for the period ended September 30, 2024, management identified an error related to the calculation and presentation of loss per share. The Company had previously concluded that the Series A Preferred Stock and Series B Preferred Stock had preferences over the Company's Common Stock and were therefore excluded from the calculation of basic and dilutive net loss per share pursuant to the two-class method. The Company has now determined that the Series A Preferred Stock and Series B Preferred Stock do not have preferential rights over the Company’s Common Stock and, accordingly, are considered to be a second and third class of common stock for purposes of calculating net loss per share. Consequently, the Company has now separately calculated and presented net loss per share for its Common Stock, Series A Preferred Stock and Series B Preferred Stock. Loss per share attributable to common stockholders for the year ended December 31, 2023 as previously presented was $49.12 and as restated is $13.76. Net loss per share attributable to holders of Series A Preferred Stock and Series B Preferred Stock was not previously presented. All related amounts have been updated to reflect the effects of the restatement throughout the financial statements and related footnotes, as applicable. The Company computes net loss per share of Common Stock, Series A Preferred Stock, and Series B Preferred Stock using the two-class method required for multiple classes of common stock and other participating securities. The two-class method is an earnings (loss) allocation method under which earnings (loss) per share is calculated for each class of common stock. The Company has determined that the Series A Preferred Stock and Series B Preferred Stock do not have preferential rights when compared to the Company's Common Stock and therefore it must allocate losses to these other classes of common stock, as illustrated in the table below. Basic and diluted net loss per share is computed by dividing the net loss by the weighted-average number of shares and pre-funded warrants outstanding during the period, without consideration of potential dilutive securities. The pre-funded warrants are included in the computation of basic net loss per share as the exercise price is negligible and they are fully vested and exercisable. For periods in which the Company generated a net loss, the Company does not include potential shares of common stock in diluted net loss per share when the impact of these items is anti-dilutive. The Company has generated a net loss for all periods presented, therefore diluted net loss per share is the same as basic net loss per share since the inclusion of potential shares of common stock would be anti-dilutive. The following table sets forth the computation of basic and diluted net loss per share of Common Stock, Series A Preferred Stock, and Series B Preferred Stock (in thousands, except share and per share amounts): Year Ended December 31, 2023 Series A Preferred Stock Series B Preferred Stock Common Stock Net loss per share, basic and diluted: Numerator Allocation of losses $ (239,158) $ (4,749) $ (94,883) Denominator Weighted-average shares outstanding 434,612 8,630 6,201,954 Weighted-average pre-funded warrants outstanding —  —  695,111 Number of shares used in per share computation 434,612 8,630 6,897,065 Net loss per share, basic and diluted $ (550.28) $ (550.29) $ (13.76) Year Ended December 31, 2022 Series A Preferred Stock Series B Preferred Stock Common Stock Net loss per share, basic and diluted: Numerator Allocation of losses $ —  $ —  $ (83,815) Denominator Weighted-average shares outstanding —  —  2,307,668 Weighted-average pre-funded warrants outstanding —  —  1,063,563 Number of shares used in per share computation —  —  3,371,231 Net loss per share, basic and diluted $ —  $ —  $ (24.86) Year Ended December 31, 2021 Series A Preferred Stock Series B Preferred Stock Common Stock Net loss per share, basic and diluted: Numerator Allocation of losses $ —  $ —  $ (65,801) Denominator Weighted-average shares outstanding —  —  1,956,933 Weighted-average pre-funded warrants outstanding —  —  672,851 Number of shares used in per share computation —  —  2,629,784 Net loss per share, basic and diluted $ —  $ —  $ (25.02) The following weighted-average equity instruments were excluded from the calculation of diluted net loss per share because their effect would have been anti-dilutive for the periods presented: Year Ended December 31, 2023 2022 2021 Options to purchase Common Stock 2,583,226 346,331 264,858 Unvested restricted stock units 4,240 6,983 7,975 Outstanding Parapyre Warrants 5,625 —  —

v3.24.3

Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2023
Accounting Policies [Abstract]
Basis of Presentation	The consolidated financial statements have been prepared in conformity with generally accepted accounting principles in the United States (“U.S. GAAP”) as defined by the Financial Accounting Standards Board (“FASB”) and include the accounts of the Company and its wholly owned subsidiaries.
Consolidation	All intercompany balances and transactions have been eliminated in consolidation.
Use of Estimates	The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets, liabilities, and equity and the amount of revenues and expenses. Actual results could differ significantly from those estimates. The most significant estimates and assumptions that management considers in the preparation of the Company's financial statements relate to the valuation of consideration transferred in acquiring in-process research & development ("IPR&D"); the discount rate, probabilities of success, and timing of estimated cash flows in the valuation of the CVR liability; inputs used in the Black-Scholes model for stock-based compensation expense; estimated future cash flows used in calculating the impairment of right-of-use lease assets; and estimated cost to complete performance obligations related to revenue recognition. The consideration transferred in acquiring IPR&D in connection with the acquisition of Pre-Merger Spyre was comprised of shares of the Company’s Common Stock and shares of Series A Preferred Stock. To determine the fair value of the equity transferred, the Company considered the per share value of the Series A PIPE securities, which was a financing event involving a group of accredited investors.
Cash and Cash Equivalents	The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist of money market funds and debt securities and are stated at fair value.
Marketable Securities	All investments have been classified as available-for-sale and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments in debt securities at the time of purchase. The Company may hold securities with stated maturities greater than one year until maturity. All available-for-sale securities are considered available to support current operations and are classified as current assets. The Company presents credit losses as an allowance rather than as a reduction in the amortized cost of the available-for-sale securities. For available-for-sale debt securities in an unrealized loss position, the Company first assesses whether it intends to sell, or it is more likely than not that it will be required to sell the security before recovery of its amortized cost basis. If either of the criteria regarding intent or requirement to sell is met, the security’s amortized cost basis is written down to fair value and recognized in other income (expense) in the results of operations. For available-for-sale debt securities that do not meet the aforementioned criteria, the Company evaluates whether the decline in fair value has resulted from credit losses or other factors. In making this assessment, management considers the extent to which fair value is less than amortized cost, any changes to the rating of the security by a rating agency, and adverse conditions specifically related to the security, among other factors. If this assessment indicates that a credit loss exists, an allowance is recorded for the difference between the present value of cash flows expected to be collected and the amortized cost basis of the security. Impairment losses attributable to credit loss factors are charged against the allowance when management believes an available-for-sale security is uncollectible or when either of the criteria regarding intent or requirement to sell is met. Any unrealized losses from declines in fair value below the amortized cost basis as a result of non-credit loss factors is recognized as a component of accumulated other comprehensive (loss) income, along with unrealized gains. Realized gains and losses and declines in fair value, if any, on available-for-sale securities are included in other income (expense) in the results of operations. The cost of securities sold is based on the specific-identification method.
Restricted Cash	Restricted cash consisted of money market accounts held by financial institutions as collateral for the Company’s obligations under a credit agreement and a facility lease for the Company’s corporate headquarters in Austin, Texas. The lease was terminated in August 2023 and the cash was subsequently unrestricted. Remaining restricted cash balances relate to the Company's operations in the United Kingdom.
Concentration of Credit Risk	Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, marketable securities, and restricted cash. The Company’s investment policy limits investments to high credit quality securities issued by the U.S. government, U.S. government-sponsored agencies, highly rated banks, and corporate issuers, subject to certain concentration limits and restrictions on maturities. The Company’s cash, cash equivalents, marketable securities, and restricted cash are held by financial institutions that management believes are of high credit quality. The financial instruments that potentially subject the Company to a concentration of credit risk consist principally of cash deposits. Accounts at each of the Company's two U.S. banking institutions are insured by the Federal Deposit Insurance Corporation (“FDIC”) up to $250,000 per depositor. As of December 31, 2023 and 2022, balances at the Company's U.S. banking institutions exceeded the FDIC limits. The Company has not experienced any losses on its deposits of cash, cash equivalents, and restricted cash and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash, cash equivalents, and restricted cash, and bond issuers.
Property and Equipment	Property and equipment are stated at cost, net of accumulated depreciation and amortization. Depreciation and amortization are computed using the straight-line method over the estimated useful lives of the assets. Repairs and maintenance that do not extend the life or improve an asset are expensed as incurred. Upon retirement or sale, the cost of disposed assets and their related accumulated depreciation and amortization are removed from the balance sheet. Any gain or loss is credited or charged to operations. The useful lives of the property and equipment are as follows: Laboratory equipment 5 years Furniture and office equipment 5 years Computer equipment 3 years Software 3 years Leasehold improvements Shorter of remaining lease term or estimated useful life
Impairment of Long-Lived Assets	Long-lived assets are reviewed for indications of possible impairment whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable. Recoverability is measured by comparison of the carrying amounts to the future undiscounted cash flows attributable to these assets. An impairment loss is recognized to the extent an asset group is not recoverable, and the carrying amount exceeds the fair value.
Accrued Research and Development Costs	The Company records the costs associated with research nonclinical studies, clinical trials, and manufacturing development as incurred. These costs are a significant component of the Company’s research and development expenses, with a substantial portion of the Company’s on-going research and development activities conducted by third-party service providers, including contract research organizations ("CROs") and contract manufacturing organizations ("CMOs"), and the Company's related-party Paragon. The Company accrues for expenses resulting from obligations under the Paragon Agreement and agreements with CROs, CMOs, and other outside service providers for which payment flows do not match the periods over which materials or services are provided to the Company. Accruals are recorded based on estimates of services received and efforts expended pursuant to agreements established with Paragon, CROs, CMOs, and other outside service providers. These estimates are typically based on contracted amounts applied to the proportion of work performed and determined through analysis with internal personnel and external service providers as to the progress or stage of completion of the services. The Company makes significant judgments and estimates in determining the accrual balance in each reporting period. In the event advance payments are made to Paragon, a CRO, CMO, or outside service provider, the payments will be recorded as a prepaid asset which will be amortized as the contracted services are performed. As actual costs become known, the Company adjusts its accruals. Inputs, such as the services performed, the number of patients enrolled, or the study duration, may vary from the Company’s estimates, resulting in adjustments to research and development expense in future periods. Changes in these estimates that result in material changes to the Company’s accruals could materially affect the Company’s results of operations. Historically, the Company has not experienced any material deviations between accrued and actual research and development expenses.
Leases	The Company determines if an arrangement is a lease at inception. Right-of-use ("ROU") assets represent the Company's right to use an underlying asset for the lease term and lease liabilities represent the Company's obligation to make lease payments arising from the lease. The classification of the Company's leases as operating or finance leases along with the initial measurement and recognition of the associated ROU assets and lease liabilities is performed at the lease commencement date. The measurement of lease liabilities is based on the present value of future lease payments over the lease term. As the Company's leases do not provide an implicit rate, the Company uses its incremental borrowing rate based on the information available at the lease commencement date in determining the present value of future lease payments. To determine the incremental borrowing rate, the Company uses the lease-term appropriate current treasury bond rates adjusted for collateral and inflation risks combined with quoted bank financing rates. The ROU asset is based on the measurement of the lease liability and also includes any lease payments made prior to or on lease commencement and excludes lease incentives and initial direct costs incurred, as applicable. The lease terms may include options to extend or terminate the lease when it is reasonably certain the Company will exercise any such options. Rent expense for the Company's operating leases is recognized on a straight-line basis over the lease term. Amortization expense for the ROU asset associated with its finance leases is recognized on a straight-line basis over the term of the lease and interest expense associated with its finance leases is recognized on the balance of the lease liability using the effective interest method based on the estimated incremental borrowing rate. Prior to the Company's restructuring, as described in Note 17, the Company had lease agreements with lease and non-lease components. As allowed under Topic 842, the Company elected to not separate lease and non-lease components for any leases involving real estate and office equipment classes of assets and, as a result, accounted for the lease and non-lease components as a single lease component. The Company also elected to not apply the recognition requirement of Topic 842 to leases with a term of 12 months or less for all classes of assets.
Fair Value of Financial Instruments	The Company uses fair value measurements to record fair value adjustments to certain financial and non-financial assets and liabilities and to determine fair value disclosures. The accounting standards define fair value, establish a framework for measuring fair value, and require disclosures about fair value measurements. Fair value is defined as the price that would be received from selling an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. When determining the fair value measurements for assets and liabilities required to be recorded at fair value, the principal or most advantageous market in which the Company would transact are considered along with assumptions that market participants would use when pricing the asset or liability, such as inherent risk, transfer restrictions, and risk of nonperformance. The accounting standard for fair value establishes a fair value hierarchy based on three levels of inputs, the first two of which are considered observable and the last unobservable, that requires an entity to maximize the use of observable inputs and minimize the use of unobservable inputs when measuring fair value. A financial instrument’s categorization within the fair value hierarchy is based upon the lowest level of input that is significant to the fair value measurement. The three levels of inputs that may be used to measure fair value are as follows: Level 1: Observable inputs, such as quoted prices in active markets for identical assets or liabilities. Level 2: Observable inputs other than Level 1 prices, such as quoted prices for similar assets or liabilities, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities. Level 3: Valuations based on unobservable inputs to the valuation methodology and including data about assumptions that market participants would use in pricing the asset or liability based on the best information available under the circumstances. Financial instruments carried at fair value include cash equivalents and marketable securities. The carrying amounts of accounts payable and accrued liabilities approximate fair value due to their relatively short maturities.
Revenue Recognition	Under ASC Topic 606, “Revenue from Contracts with Customers” (“Topic 606”), an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration that the entity expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that an entity determines are within the scope of Topic 606, the entity performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price, including variable consideration, if any; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the entity satisfies a performance obligation. The Company assesses its license arrangements within the scope of Topic 606 in accordance with this framework as follows: License revenue The Company assesses whether the goods or services promised within each contract are distinct to identify those that are performance obligations. This assessment involves subjective determinations and requires management to make judgments about the individual promised goods or services and whether such are separable from the other aspects of the contractual relationship. In assessing whether a promised good or service is distinct, and therefore a performance obligation, the Company considers factors such as the research, stage of development of the licensed product, manufacturing and commercialization capabilities of the customer and the availability of the associated expertise in the general marketplace. The Company also considers the intended benefit of the contract in assessing whether a promised good or service is separately identifiable from other promises in the contract. If a promised good or service is not distinct, the Company is required to combine that good or service with other promised goods or services until it identifies a bundle of goods or services that is distinct. Arrangements that include rights to additional goods or services that are exercisable at a customer’s discretion are generally considered options. The Company assesses if these options provide a material right to the customer and if so, they are considered performance obligations. The transaction price is determined and allocated to the identified performance obligations in proportion to their stand-alone selling prices (“SSP”) on a relative SSP basis. SSP is based on observable prices of the performance obligations or, when such prices are not observable, are estimated. The estimation of SSP may include factors such as forecasted revenues or costs, development timelines, discount rates, probabilities of technical and regulatory success, and considerations such as market conditions and entity-specific factors. In certain circumstances, the Company may apply the residual method to determine the SSP of a good or service if the SSP is considered highly variable or uncertain. The Company validates the SSP for performance obligations by evaluating whether changes in the key assumptions used to determine the SSP will have a significant effect on the allocation of arrangement consideration between multiple performance obligations. If the consideration promised in a contract includes a variable amount, the Company estimates the amount of consideration to which it will be entitled in exchange for transferring the promised goods or services to a customer. The Company determines the amount of variable consideration by using the expected value method or the most likely amount method. The Company includes the amount of estimated variable consideration in the transaction price to the extent that it is probable that a significant reversal of cumulative revenue recognized will not occur. At the end of each subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis in the period of adjustment. If an arrangement includes development, regulatory or commercial milestone payments, the Company evaluates whether the milestones are considered likely of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant cumulative revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the Company’s control or the licensee’s control, such as regulatory approvals, are generally not considered likely of being achieved until those approvals are received. In determining the transaction price, the Company adjusts consideration for the effects of the time value of money if the timing of payments provides the Company with a significant benefit of financing. The Company does not assess whether a contract has a significant financing component if the expectation at contract inception is such that the period between payment by the licensee and the transfer of the promised goods or services to the licensees will be one year or less. For arrangements with licenses of intellectual property that include sales-based royalties, including milestone payments based on the level of sales, and if the license is deemed to be the predominant item to which the royalties relate, the Company recognizes royalty revenue and sales-based milestones at the later of (i) when the related sales occur, or (ii) when the performance obligation to which the royalty has been allocated has been satisfied. The Company recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) each performance obligation is satisfied at a point in time or over time, and if over time, recognition is based on the use of an output or input method. The Company’s contracts may be modified for changes in the customer’s requirements. If contract modifications are for additional goods and services that are distinct from the existing contract, the modification will be accounted for as either a separate contract or a termination of the existing contract, depending on whether the additional goods or services reflects the SSP. If the additional goods or services in a contract modification are not distinct from the existing contract, they are accounted for as if they were part of the original contract. The effect of the contract modification on the transaction price and the measure of progress for the performance obligation to which it relates is recognized as an adjustment to revenue on a cumulative catch-up basis. The cumulative catch-up adjustment is calculated using an updated measure of progress applied to the sum of (1) the remaining consideration allocated to the partially satisfied performance obligation and (2) the revenue already recognized on that performance obligation. The revenue recognized for fully satisfied goods or services and distinct from the remaining performance obligations is not altered by the modification. Collaborative arrangements The Company analyzes its license arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, Collaborative Arrangements (“Topic 808”). This assessment is performed throughout the life of the arrangement based on changes in the responsibilities of all parties in the arrangement. For arrangements within the scope of Topic 808 that contain multiple elements, the Company first determines which elements of the collaboration are deemed to be within the scope of Topic 808 and which elements of the collaboration are more reflective of a vendor-customer relationship and therefore within the scope of Topic 606. For elements of collaboration arrangements that are accounted for pursuant to Topic 808, an appropriate recognition method is determined and applied consistently, either by analogy to authoritative accounting literature or by applying a reasonable and rational policy election. For those elements of the arrangement that are accounted for pursuant to Topic 606, the Company applies the five-step model described above.
Research and Development Costs	Research and development costs are expensed as incurred. Research and development costs include, but are not limited to, salaries, benefits, travel, stock-based compensation, consulting costs, contract research service costs, laboratory supplies and facilities, contract manufacturing costs, and costs paid to other third parties that conduct research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense. Advance payments for goods or services to be rendered in the future for use in research and development activities are recorded as a prepaid asset and expensed as the related goods are delivered or the services are performed.
Stock-Based Compensation	The Company recognizes the cost of stock-based awards granted to employees and non-employees based on the estimated grant-date fair values of the awards. The fair values of stock options are estimated on the date of grant using the Black-Scholes option pricing model. The fair values of restricted stock units (“RSUs”) are based on the fair value of the Company’s common stock on the date of the grant. The value of the award is recognized as compensation expense on a straight-line basis over the requisite service period. Forfeitures are recognized when they occur, which may result in the reversal of compensation costs in subsequent periods as the forfeitures arise. Compensation expense for employee and non-employee share-based payment awards with performance conditions is recognized when the performance condition is deemed probable.
Convertible Preferred Stock Issued through PIPE	The Company records shares of convertible preferred stock at their respective fair values on the dates of issuance, net of issuance costs. The Company classified the Series B Preferred Stock outside of stockholders’ equity because, if conversion to Common Stock is not approved by the stockholders, the Series B Preferred Stock will be redeemable at the option of the holders for cash equal to the closing price of the Common Stock on the last trading day prior to the holder’s redemption request. The Company has determined that the conversion and redemption are outside of the Company’s control. Additionally, the Company determined the Series B Preferred Stock did not contain any embedded derivatives and therefore the conversion and redemption features did not require bifurcation.
Contingent Milestone Proceeds	The Company recognizes contingent milestone proceeds associated from the sale of in-process research and development assets in earnings once the achievement of the milestone becomes probable and payment to the Company is contractually required.
Acquisitions	The Company evaluates acquisitions of assets and other similar transactions to assess whether or not the transaction should be accounted for as a business combination or asset acquisition by first applying a screen test to determine whether substantially all of the fair value of the gross assets acquired is concentrated in a single identifiable asset or group of similar identifiable assets. If so, the transaction is accounted for as an asset acquisition. If not, further determination is required as to whether or not the Company has acquired inputs and processes that have the ability to create outputs, which would meet the definition of a business. Significant judgment is required in the application of the test to determine whether an acquisition is a business combination or an acquisition of assets. Acquisitions meeting the definition of business combinations are accounted for using the acquisition method of accounting, which requires that the purchase price be allocated to the net assets acquired at their respective fair values. In a business combination, any excess of the purchase price over the estimated fair values of the net assets acquired is recorded as goodwill. The Company measures and recognizes asset acquisitions that are not deemed to be business combinations based on the cost to acquire the assets, which includes pre-acquisition direct costs recorded in accrued professional and consulting fees. Goodwill is not recognized in asset acquisitions. When a transaction accounted for as an asset acquisition includes an IPR&D asset, the IPR&D asset is only capitalized if it has an alternative future use other than in a particular research and development project. Otherwise, the cost allocated to acquire an IPR&D asset with no alternative future use is charged to expense at the acquisition date.
Contingent Value Rights	The Company evaluates its contracts to determine if those contracts qualify as derivatives under ASC 815, Derivatives and Hedging (“ASC 815”). For derivative financial instruments that are accounted for as liabilities, the derivative instrument is initially recorded at its fair value and is then re-valued at each reporting date. Any changes in fair value are recorded as other income or expense for each reporting period. Derivative instrument liabilities are classified in the balance sheet as current or non-current based on whether or not net-cash settlement of the derivative instrument is probable within the next 12 months from the balance sheet date. The Company determined that certain contingent payments under the CVR Agreement qualified as derivatives under ASC 815, and as such, were recorded as a liability on the balance sheet. This value is then remeasured for future expected payout as well as the increase in fair value due to the time value of money. These gains or losses, if any, are recognized in the consolidated statements of operations and comprehensive loss within Other (expense) income, net. The Company applies a scenario-based method and weighs them based on the possible achievement of certain milestones. The milestone payments are contingent on formal reimbursement decisions by national authorities in key European markets and pegzilarginase approval by the U.S. Food and Drug Administration ("FDA"), among other events. This fair value measurement is based on significant inputs not observable in the market and thus represents a Level 3 measurement as defined in ASC 820, Fair Value Measurement. The key assumptions used include the discount rate, probability of regulatory success, and reimbursement rates from certain government agencies. The estimated value of the CVR consideration is based upon available information and certain assumptions which the Company's management believes are reasonable under the circumstances. The ultimate payout under the CVRs may differ materially from the assumptions used in determining the fair value of the CVR consideration.
Income Taxes	The Company uses the asset and liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are recognized for the expected future tax consequences of temporary differences between the financial statements and the tax bases of assets and liabilities. Additionally, any changes in income tax laws are immediately recognized in the year of enactment. A valuation allowance is established against the deferred tax assets to reduce their carrying value to an amount that is more likely than not to be realized. The deferred tax assets and liabilities are classified as noncurrent along with the related valuation allowance. Due to a lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance. The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on the technical merits, as the largest amount of benefits that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the unrecognized tax benefits as a component of income tax expense, if applicable.
Comprehensive Loss	Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive income (loss) is currently comprised of changes in unrealized losses and gains on available-for-sale securities and foreign currency translation adjustments reflecting the cumulative effect of changes in exchange rates between the foreign entity’s functional currency and the reporting currency.
Net Loss Per Share	The Company computes net loss per share of Common Stock, Series A Preferred Stock, and Series B Preferred Stock using the two-class method required for multiple classes of common stock and other participating securities. The two-class method is an earnings (loss) allocation method under which earnings (loss) per share is calculated for each class of common stock. The Company has determined that the Series A Preferred Stock and Series B Preferred Stock do not have preferential rights when compared to the Company's Common Stock and therefore it must allocate losses to these other classes of common stock, as illustrated in the table below. Basic and diluted net loss per share is computed by dividing the net loss by the weighted-average number of shares and pre-funded warrants outstanding during the period, without consideration of potential dilutive securities. The pre-funded warrants are included in the computation of basic net loss per share as the exercise price is negligible and they are fully vested and exercisable. For periods in which the Company generated a net loss, the Company does not include potential shares of common stock in diluted net loss per share when the impact of these items is anti-dilutive. The Company has generated a net loss for all periods presented, therefore diluted net loss per share is the same as basic net loss per share since the inclusion of potential shares of common stock would be anti-dilutive.
Recently Adopted Accounting Pronouncement/Recently Issued Accounting Pronouncement	The Company early adopted the Financial Accounting Standards Board’s Accounting Standards Update 2020-06, Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity (“ASU 2020-06”), effective as of January 1, 2023 using the modified retrospective method. Among other amendments, ASU 2020-06 eliminates the cash conversion and beneficial conversion feature models in ASC 470-20 that required an issuer of certain convertible debt and preferred stock to separately account for embedded conversion features as a component of equity, as well as changes the accounting for diluted earnings‑per‑share for convertible instruments and contracts that may be settled in cash or stock. Additionally, ASU 2020-06 requires the if‑converted method, which is more dilutive than the treasury stock method, be used for all convertible instruments. The Company applied ASU 2020-06 to all Series A Preferred Stock and Series B Preferred Stock during fiscal year 2023, and, accordingly, the Company did not apply the cash conversion or beneficial conversion feature models in its analysis of the Series A Preferred Stock and Series B Preferred Stock. The adoption of ASU 2020-06 did not have a material impact on the Company's consolidated financial statements. In November 2023, the FASB issued ASU 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures to update reportable segment disclosure requirements, primarily through enhanced disclosures about significant segment expenses and information used to assess segment performance and requires companies to disclose all annual disclosures about segments in interim periods. The ASU also requires companies with a single reportable segment to provide all disclosures required by Topic 280 – Segment Reporting. This update is effective beginning with the Company’s 2024 fiscal year annual reporting period and interim periods beginning thereafter. The Company is currently evaluating the impact that the adoption of this standard will have on its consolidated financial statements. In December 2023, the FASB issued ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures. This ASU expands disclosures in an entity’s income tax rate reconciliation table and disclosures regarding taxes paid both in the U.S. and foreign jurisdictions. This update is effective beginning with the Company’s 2025 fiscal year annual reporting period. This ASU will have no impact on the Company’s consolidated financial condition or results of operations. The Company is currently evaluating the impact to its income tax disclosures.

v3.24.3

Summary of Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2023
Accounting Policies [Abstract]
Useful Lives of Property and Equipment	The useful lives of the property and equipment are as follows: Laboratory equipment 5 years Furniture and office equipment 5 years Computer equipment 3 years Software 3 years Leasehold improvements Shorter of remaining lease term or estimated useful life

v3.24.3

Fair Value Measurement (Tables)	12 Months Ended
	Dec. 31, 2023
Fair Value Disclosures [Abstract]
Financial Assets and Liabilities Measured at Fair Value on Recurring Basis	The following tables sets forth the fair value of the Company’s financial assets and liabilities at fair value on a recurring basis based on the three-tier fair value hierarchy (in thousands):   December 31, 2023   Level 1 Level 2 Level 3 Total Financial Assets Money market funds $ 150,648  $ —  $ —  $ 150,648  U.S. government treasury securities 32,843  —  —  32,843  U.S. government agency securities —  16,257  —  16,257  Commercial paper —  104,141  —  104,141  Corporate bonds —  33,064  —  33,064  Total financial assets $ 183,491  $ 153,462  $ —  $ 336,953  Liabilities: CVR liability $ —  $ —  $ 42,700  $ 42,700  Total liabilities $ —  $ —  $ 42,700  $ 42,700  December 31, 2022 Level 1 Level 2 Level 3 Total Financial Assets Money market funds $ 15,250  $ —  $ —  $ 15,250  Commercial paper —  23,641  —  23,641  U.S. government agency securities —  4,230  4,230  Corporate bonds —  3,732  —  3,732  Total financial assets $ 15,250  $ 31,603  $ —  $ 46,853
Changes in Derivative Liabilities	The following table presents changes in the forward contract liability for the periods presented (in millions): Forward Contract Liability Beginning balance as of June 22, 2023 $ 106.2  Change in fair value 83.5  Issuance of Series A Preferred Stock on July 7, 2023 (189.7) Ending balance as of December 31, 2023 $ —  The following table presents changes in the CVR liability for the periods presented (in thousands):   CVR Liability Beginning balance as of December 31, 2022 $ —  Fair value at CVR issuance 29,500  Changes in the fair value of the CVR liability since issuance 18,986  Payments (5,786) Ending Balance as of December 31, 2023 $ 42,700
Significant Inputs used to Estimate the Fair Value of Derivative Liabilities	The significant inputs used to estimate the fair value of the CVR liability were as follows: December 31, 2023 Estimated cash flow dates 2/28/24 - 06/22/26 Estimated probability of success 39% - 100% Estimated reimbursement rate compared to reimbursement target 81% - 100% Risk-adjusted discount rates 5.91% - 6.32%

v3.24.3

Cash Equivalents and Marketable Securities (Tables)	12 Months Ended
	Dec. 31, 2023
Cash and Cash Equivalents [Abstract]
Estimated Fair Value of Cash Equivalents and Marketable Securities and the Gross Unrealized Gains and Losses	The following tables summarize the estimated fair value of the Company’s cash equivalents and marketable securities and the gross unrealized gains and losses (in thousands): December 31, 2023 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Estimated Fair Value Cash equivalents: Money market funds $ 150,648  $ —  $ —  $ 150,648  Commercial paper 24,950  5  —  24,955  U.S. government treasury securities 10,965  1  —  10,966  Total cash equivalents 186,563  6  —  186,569  Marketable securities: Commercial paper 79,124  62  —  79,186  Corporate bonds 32,984  81  (1) 33,064  U.S. government treasury securities 21,846  31  —  21,877  U.S. government agency securities 16,147  110  —  16,257  Total marketable securities $ 150,101  $ 284  $ (1) $ 150,384  December 31, 2022 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Estimated Fair Value Cash equivalents: Money market funds $ 15,250  $ —  $ —  $ 15,250  Commercial paper 7,021  1  (2) 7,020  U.S. government agency securities 3,736  —  (1) 3,735  Total cash equivalents $ 26,007  $ 1  $ (3) $ 26,005  Marketable securities: Commercial paper $ 16,644  $ 2  $ (25) $ 16,621  Corporate bonds 3,738  —  (6) 3,732  U.S. government agency securities 495  —  —  495  Total marketable securities $ 20,877  $ 2  $ (31) $ 20,848
Available-for-Sale Securities in an Unrealized Loss Position	The following table summarizes the available-for-sale securities in an unrealized loss position for which an allowance for credit losses has not been recorded as of December 31, 2023 and 2022, aggregated by major security type and length of time in a continuous unrealized loss position: December 31, 2023 Less Than 12 Months 12 Months or Longer Total Fair Value Unrealized Losses Fair Value Unrealized Losses Fair Value Unrealized Losses Commercial paper $ —  $ —  $ —  $ —  $ —  $ —  Corporate bonds 9,907  (1) —  —  9,907  (1) U.S. government treasury securities 4,831  —  —  —  4,831  —  Total marketable securities $ 14,738  $ (1) $ —  $ —  $ 14,738  $ (1) December 31, 2022 Less Than 12 Months 12 Months or Longer Total Fair Value Unrealized Losses Fair Value Unrealized Losses Fair Value Unrealized Losses Commercial paper $ 17,699  $ (27) $ —  $ —  $ 17,699  $ (27) Corporate bonds 3,732  (6) —  —  3,732  (6) U.S. government agency securities 3,735  (1) —  —  3,735  (1) Total marketable securities $ 25,166  $ (34) $ —  $ —  $ 25,166  $ (34)
Contractual Maturities of Marketable Securities at Estimated Fair Value	The following table summarizes the contractual maturities of the Company's marketable securities at estimated fair value (in thousands): December 31, 2023 2022 Due in one year or less $ 115,784  $ 20,848  Due in 1 - 2 years 34,600  —  Total marketable securities $ 150,384  $ 20,848

v3.24.3

Property and Equipment, Net (Tables)	12 Months Ended
	Dec. 31, 2023
Property, Plant and Equipment [Abstract]
Schedule of Property and Equipment Net	Property and equipment, net consist of the following (in thousands): December 31, 2023 2022 Laboratory equipment $ —  $ 2,257  Furniture and office equipment —  520  Computer equipment —  73  Software —  121  Leasehold improvements —  4,393  Property and equipment, gross —  7,364  Less: Accumulated depreciation and amortization —  (4,144) Property and equipment, net $ —  $ 3,220

v3.24.3

Accrued and Other Current Liabilities (Tables)	12 Months Ended
	Dec. 31, 2023
Accrued Liabilities and Other Liabilities [Abstract]
Accrued and Other Current Liabilities	Accrued and other current liabilities consist of the following (in thousands): December 31, 2023 2022 Accrued compensation $ 4,054  $ 4,589  Accrued contracted research and development costs 7,092  6,972  Accrued professional and consulting fees 1,474  946  Other 488  330  Total accrued and other current liabilities $ 13,108  $ 12,837

v3.24.3

Related Party Transactions (Tables)	12 Months Ended
	Dec. 31, 2023
Related Party Transactions [Abstract]
Expenses related to Related Party which were Settled in Cash	The following is the summary of expenses related to the Paragon Agreement recognized within research and development expenses, which were ultimately settled in cash (in millions): December 31, 2023 2022 2021 Reimbursable costs under the Paragon Agreement $ 37.1  $ —  $ —
Related Party Accounts Payable	The following is the summary of Related party accounts payable and other current liabilities (in millions): December 31, 2023 December 31, 2022 Reimbursable costs under the Paragon Agreement $ 16.6  $ —  Related party accounts payable and other current liabilities $ 16.6  $ —

v3.24.3

Asset Acquisition (Tables)	12 Months Ended
	Dec. 31, 2023
Business Combination and Asset Acquisition [Abstract]
Asset Acquisition Cost	The Asset Acquisition Costs are shown on the following table (in millions): June 22, 2023 Consideration transferred in Series A Preferred Stock and Common Stock $ 110.0  Transaction costs incurred by the Company 3.2  Total cost to acquire asset $ 113.2  The allocation of the purchase price to net assets acquired is as a follows: June 22, 2023 Acquired in-process research and development $ 130.2  Cash acquired 3.0  Assumed liabilities (20.0) Total cost to acquire asset $ 113.2

v3.24.3

Leases (Tables)	12 Months Ended
	Dec. 31, 2023
Leases [Abstract]
Supplemental Balance Sheet Information	The following table summarizes the Company’s recognition of its operating and finance leases (in thousands): December 31, Classification 2023 2022 Assets Operating Operating lease right-of-use assets $ —  $ 3,430  Finance Other non-current assets —  597  Total leased assets —  4,027  Leases Current Operating Operating lease liabilities —  625  Finance Accrued and other current liabilities —  16  Non-current Operating Non-current operating lease liabilities —  4,004  Total lease liabilities $ —  $ 4,645
Weighted-Average Remaining Lease Term/Discount Rates and Lease Cost	The following table summarizes the weighted-average remaining lease term and discount rates for the Company’s operating and finance leases: December 31, 2023 2022 Lease term (years) Operating leases 0.0 5.3 Finance leases 0.0 0.6 Discount rate Operating leases —  % 10.6  % Finance leases —  % 10.2  % The following table summarizes the lease costs pertaining to the Company’s operating leases (in thousands): Year Ended December 31, 2023 2022 2021 Operating lease cost $ 455  $ 910  $ 991  Variable lease cost 471  472  519  Total lease cost $ 926  $ 1,382  $ 1,510

v3.24.3

Convertible Preferred Stock and Stockholders’ Equity (Tables)	12 Months Ended
	Dec. 31, 2023
Equity [Abstract]
Pre-funded Warrants for Common Stock Issued and Outstanding	As of December 31, 2023, the following pre-funded warrants to purchase Common Stock were issued and outstanding: Issue Date Expiration Date Exercise Price Number of Warrants Outstanding May 2022 None $ 0.0025  250,000 Total pre-funded warrants 250,000

v3.24.3

Strategic License Agreement (Tables)	12 Months Ended
	Dec. 31, 2023
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Changes in Contract Liabilities	The following table presents changes in the Company’s contract liabilities for the periods presented (in thousands): Year Ended December 31, 2022 December 31, 2022 Additions Deductions December 31, 2023 Contract liabilities: Deferred revenue $ 2,696  $ 575  $ (3,271) $ —

v3.24.3

Stock-Based Compensation (Tables)	12 Months Ended
	Dec. 31, 2023
Share-Based Payment Arrangement [Abstract]
Employee and Non-Employee Stock Option Activity	The following table summarizes employee and non-employee stock option activity for the year ended December 31, 2023: Shares Issuable Under Options Weighted Average Exercise Price Weighted Average Remaining Contractual Term Aggregate Intrinsic Value (in years) (in thousands) Outstanding as of December 31, 2022 405,082 $ 113.75  6.72 $ 2  Granted 8,776,245 9.67  Exercised (46,246) 8.22  Forfeited (637,686) 43.00  Outstanding as of December 31, 2023 8,497,395 $ 12.13  8.40 $ 98,928  Options vested and expected to vest as of December 31, 2023 8,497,395 $ 12.13  8.40 $ 98,928  Options exercisable as of December 31, 2023 1,065,700 $ 24.72  5.62 $ 13,328
Employee Restricted Stock Activity	The following table summarizes employee restricted stock activity for the year ended December 31, 2023: Shares Weighted Average Grant Date Fair Value Unvested restricted stock units as of December 31, 2022 5,660 $ 203.25  Granted 153,865 18.17  Vested — —  Forfeited (5,660) 203.25  Unvested restricted stock units as of December 31, 2023 153,865 $ 18.17
Stock-Based Compensation Expense	Total stock-based compensation expense recognized from the Company’s equity incentive plans, 2018 Plan, and the 2016 ESPP for the years ended December 31, 2023, 2022, and 2021 was as follows (in thousands): Year Ended December 31, 2023 2022 2021 Employees Non- Employees Employees Non- Employees Employees Non- Employees Research and development $ 2,910  $ 11,328  $ 2,591  $ —  $ 2,723  $ —  General and administrative 11,327  109  4,520  —  5,315  —  Total stock-based compensation expense $ 14,237  $ 11,437  $ 7,111  $ —  $ 8,038  $ —
Weighted-Average Assumptions Used in Calculating Fair Value of Awards	The following table summarizes the weighted-average assumptions used in calculating the fair value of the awards: Year Ended December 31, 2023 2022 2021 Stock Options Granted Expected term (in years) 5.88 6.00 5.99 Expected volatility 107  % 84  % 83  % Risk-free interest 4.37  % 2.93  % 0.88  % Dividend yield 0  % 0  % 0  % 2016 ESPP Expected term (in years) 0.49 0.49 0.50 Expected volatility 181  % 84  % 86  % Risk-free interest 4.99  % 1.95  % 0.08  % Dividend yield 0  % 0  % 0  %

v3.24.3

Restructuring Charges (Tables)	12 Months Ended
	Dec. 31, 2023
Restructuring and Related Activities [Abstract]
Changes in Accrued Restructuring Balance	The following table summarizes the changes in the Company's accrued restructuring balance (in thousands): Beginning Balance December 31, 2022 Charges Payments Ending Balance December 31, 2023 Severance liability $ —  $ 6,448  $ (5,325) $ 1,123
Charges Related to the Restructuring Activities	A summary of the charges related to the restructuring activities is as follows (in thousands): Severance Related Expenses Stock Compensation Expenses Loss on Disposal of Long Lived Assets Lease Asset Impairment Total Restructuring Costs Research and development $ 3,182  $ 123  $ 749  $ 1,405  $ 5,459  General and administrative 3,266  870  182  1,175  5,493  Total $ 6,448  $ 993  $ 931  $ 2,580  $ 10,952

v3.24.3

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2023
Income Tax Disclosure [Abstract]
(Loss) Income Before Income Tax Expense by Jurisdiction	The following table summarizes the (loss) income before income tax expense by jurisdiction for the periods indicated: Year Ended December 31, 2023 2022 2021 Domestic $ (338,942) $ (84,113) $ (65,940) Foreign 126  162  280  Loss before income tax expense $ (338,816) $ (83,951) $ (65,660)
Effective Income Tax Rate Reconciliation	The difference between the Company’s provision for income taxes and the amounts computed by applying the statutory federal income tax rate to income before income taxes is as follows (in thousands): Year Ended December 31, 2023 2022 2021 Tax provision derived by applying the federal statutory rate to income before income taxes $ (71,151) $ (17,630) $ (13,789) Loss on forward contract valuation 17,541  —  —  Acquired IPR&D 27,340  —  —  Loss on CVR revaluation 3,987  —  —  Other permanent differences 4,472  1,042  1,002  Federal tax credits (1) (3,559) (3,815) State tax credits —  (640) (152) Effect of tax rate on foreign jurisdiction (53) 42  (5) Change in the valuation allowance 17,839  20,609  16,900  Income tax (benefit) expense $ (26) $ (136) $ 141
Components of Deferred Tax Assets and Liabilities	The components of the deferred tax assets and liabilities consist of the following (in thousands): December 31, 2023 2022 Deferred tax assets Net operating loss carryforward $ 74,454  $ 68,917  Capitalized 174 R&D costs 22,532  11,097  Intangible assets 47  52  Deferred revenue —  566  Accrued expense 579  668  Stock-based compensation 4,246  3,293  Federal tax credits 21,914  21,914  State tax credits 1,631  1,631  Other 88  190  Total deferred tax assets 125,491  108,328  Deferred tax liabilities Depreciable assets —  (676) Total deferred tax liabilities —  (676) Less: Valuation allowance (125,491) (107,652) Deferred tax assets, net $ —  $ —

v3.24.3

Net Loss Per Share (as restated) (Tables)	12 Months Ended
	Dec. 31, 2023
Earnings Per Share [Abstract]
Reconciliation of Basic and Diluted Net Loss Per Share	The following table sets forth the computation of basic and diluted net loss per share of Common Stock, Series A Preferred Stock, and Series B Preferred Stock (in thousands, except share and per share amounts): Year Ended December 31, 2023 Series A Preferred Stock Series B Preferred Stock Common Stock Net loss per share, basic and diluted: Numerator Allocation of losses $ (239,158) $ (4,749) $ (94,883) Denominator Weighted-average shares outstanding 434,612 8,630 6,201,954 Weighted-average pre-funded warrants outstanding —  —  695,111 Number of shares used in per share computation 434,612 8,630 6,897,065 Net loss per share, basic and diluted $ (550.28) $ (550.29) $ (13.76) Year Ended December 31, 2022 Series A Preferred Stock Series B Preferred Stock Common Stock Net loss per share, basic and diluted: Numerator Allocation of losses $ —  $ —  $ (83,815) Denominator Weighted-average shares outstanding —  —  2,307,668 Weighted-average pre-funded warrants outstanding —  —  1,063,563 Number of shares used in per share computation —  —  3,371,231 Net loss per share, basic and diluted $ —  $ —  $ (24.86) Year Ended December 31, 2021 Series A Preferred Stock Series B Preferred Stock Common Stock Net loss per share, basic and diluted: Numerator Allocation of losses $ —  $ —  $ (65,801) Denominator Weighted-average shares outstanding —  —  1,956,933 Weighted-average pre-funded warrants outstanding —  —  672,851 Number of shares used in per share computation —  —  2,629,784 Net loss per share, basic and diluted $ —  $ —  $ (25.02)
Weighted-Average Equity Instruments Excluded from Calculation of Diluted Net Loss Per Share	The following weighted-average equity instruments were excluded from the calculation of diluted net loss per share because their effect would have been anti-dilutive for the periods presented: Year Ended December 31, 2023 2022 2021 Options to purchase Common Stock 2,583,226 346,331 264,858 Unvested restricted stock units 4,240 6,983 7,975 Outstanding Parapyre Warrants 5,625 —  —

v3.24.3

The Company and Basis of Presentation (Details) $ / shares in Units, $ in Thousands					1 Months Ended		3 Months Ended	12 Months Ended			106 Months Ended
	Dec. 11, 2023 USD ($) $ / shares shares	Sep. 08, 2023	Jun. 26, 2023 USD ($) shares	Jun. 22, 2023 $ / shares shares	Dec. 31, 2023 USD ($) $ / shares shares	Jun. 30, 2023 USD ($) shares	Jun. 30, 2023	Dec. 31, 2023 USD ($) segment $ / shares shares	Dec. 31, 2022 USD ($) $ / shares	Dec. 31, 2021 USD ($)	Dec. 31, 2023 USD ($) $ / shares	Dec. 08, 2023
Company and Basis of Presentation [Line Items]
Number of operating segments | segment								1
Employee workforce, termination percentage							83.00%
Preferred stock, par value (in dollars per share) | $ / shares					$ 0.0001			$ 0.0001			$ 0.0001
Proceeds from issuance of private placement								$ 84,555	$ 0	$ 0
Series B non-voting convertible preferred stock, par value (in dollars per share) | $ / shares	$ 0.0001				$ 0.0001			$ 0.0001	$ 0.0001		$ 0.0001
Issuance of temporary equity (in shares) | shares	150,000				150,000			150,000
Proceeds from raising capital											$ 896,200
Accumulated deficit					$ 764,414			$ 764,414	$ 425,624		764,414
Cash, cash equivalents, and marketable securities					$ 339,300			$ 339,300			$ 339,300
Spyre Therapeutics, Inc.
Company and Basis of Presentation [Line Items]
Fixed exchange ratio				0.5494488
Asset acquisition, stockholder payment period				3 years
Asset acquisition, cash payment, threshold period				1 year
Spyre 2023 Equity Incentive Plan | Spyre Therapeutics, Inc.
Company and Basis of Presentation [Line Items]
Number of outstanding and unexercised stock options to purchase (in shares) | shares				2,734
Series A Non-Voting Convertible Preferred Stock
Company and Basis of Presentation [Line Items]
Preferred stock, par value (in dollars per share) | $ / shares					$ 0.0001			$ 0.0001	$ 0.0001		$ 0.0001
Conversion basis				40
Series A Non-Voting Convertible Preferred Stock | Spyre Therapeutics, Inc.
Company and Basis of Presentation [Line Items]
Shares transferred as equity interest in asset acquisition (in shares) | shares				364,887
Preferred stock, par value (in dollars per share) | $ / shares				$ 0.0001
Conversion basis				40
Series B Non-Voting Convertible Preferred Stock
Company and Basis of Presentation [Line Items]
Conversion basis	40											40
Private Placement
Company and Basis of Presentation [Line Items]
Sale of stock (in shares) | shares			721,452			721,452
Proceeds from issuance of private placement	$ 180,000		$ 210,000					$ 180,000
Offering costs	10,900		$ 12,700		$ 10,900	$ 12,700
Private Placement | Series B Non-Voting Convertible Preferred Stock
Company and Basis of Presentation [Line Items]
Proceeds from issuance of private placement	$ 90,000
Common Stock
Company and Basis of Presentation [Line Items]
Reverse stock split, conversion ratio		0.04
Common Stock | Spyre Therapeutics, Inc.
Company and Basis of Presentation [Line Items]
Shares transferred as equity interest in asset acquisition (in shares) | shares				517,809
Common Stock | Private Placement
Company and Basis of Presentation [Line Items]
Sale of stock (in shares) | shares	6,000,000				6,000,000

v3.24.3

Summary of Significant Accounting Policies - Narrative (Details)	12 Months Ended
	Dec. 31, 2023 USD ($) bank	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Cash Equivalents And Marketable Securities [Line Items]
Number of domestic banking institutions (in banks) | bank	2
Impairments of long-lived assets	$ 2,600,000	$ 0	$ 0
Impairment, Long-Lived Asset, Held-for-Use, Statement of Income or Comprehensive Income [Extensible Enumeration]	General and administrative, Research and development
Unrecognized tax benefits	$ 0	0
Interest or penalties incurred	0	$ 0	$ 0
Maximum | U.S. Banking Institution
Cash Equivalents And Marketable Securities [Line Items]
Cash, FDIC insured amount	$ 250,000

v3.24.3

Summary of Significant Accounting Policies - Useful Lives of Property and Equipment (Details)	Dec. 31, 2023
Laboratory equipment
Property Plant And Equipment [Line Items]
Useful lives of the property and equipment	5 years
Furniture and office equipment
Property Plant And Equipment [Line Items]
Useful lives of the property and equipment	5 years
Computer equipment
Property Plant And Equipment [Line Items]
Useful lives of the property and equipment	3 years
Software
Property Plant And Equipment [Line Items]
Useful lives of the property and equipment	3 years

v3.24.3

Fair Value Measurements - Financial Assets and Liabilities Measured at Fair Value on Recurring Basis (Details) - Fair Value, Measurements, Recurring - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Financial Assets
Total financial assets	$ 336,953	$ 46,853
Liabilities:
Total liabilities	42,700
U.S. government treasury securities
Financial Assets
Total financial assets	32,843
Commercial paper
Financial Assets
Total financial assets	104,141	23,641
U.S. government agency securities
Financial Assets
Total financial assets	16,257	4,230
Corporate bonds
Financial Assets
Total financial assets	33,064	3,732
CVR liability
Liabilities:
Total liabilities	42,700
Money market funds
Financial Assets
Total financial assets	150,648	15,250
Level 1
Financial Assets
Total financial assets	183,491	15,250
Liabilities:
Total liabilities	0
Level 1 | U.S. government treasury securities
Financial Assets
Total financial assets	32,843
Level 1 | Commercial paper
Financial Assets
Total financial assets	0	0
Level 1 | U.S. government agency securities
Financial Assets
Total financial assets	0	0
Level 1 | Corporate bonds
Financial Assets
Total financial assets	0	0
Level 1 | CVR liability
Liabilities:
Total liabilities	0
Level 1 | Money market funds
Financial Assets
Total financial assets	150,648	15,250
Level 2
Financial Assets
Total financial assets	153,462	31,603
Liabilities:
Total liabilities	0
Level 2 | U.S. government treasury securities
Financial Assets
Total financial assets	0
Level 2 | Commercial paper
Financial Assets
Total financial assets	104,141	23,641
Level 2 | U.S. government agency securities
Financial Assets
Total financial assets	16,257	4,230
Level 2 | Corporate bonds
Financial Assets
Total financial assets	33,064	3,732
Level 2 | CVR liability
Liabilities:
Total liabilities	0
Level 2 | Money market funds
Financial Assets
Total financial assets	0	0
Level 3
Financial Assets
Total financial assets	0	0
Liabilities:
Total liabilities	42,700
Level 3 | U.S. government treasury securities
Financial Assets
Total financial assets	0
Level 3 | Commercial paper
Financial Assets
Total financial assets	0	0
Level 3 | U.S. government agency securities
Financial Assets
Total financial assets	0
Level 3 | Corporate bonds
Financial Assets
Total financial assets	0	0
Level 3 | CVR liability
Liabilities:
Total liabilities	42,700
Level 3 | Money market funds
Financial Assets
Total financial assets	$ 0	$ 0

v3.24.3

Fair Value Measurements - Narrative (Details) - USD ($)			6 Months Ended	12 Months Ended
	Jul. 07, 2023	Jun. 22, 2023	Dec. 31, 2023	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Issuance of Series A non-voting convertible preferred stock				$ 189,741,000
Financial liabilities measured at fair value					$ 0
Forward Contract Liability
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Fair value of liability		$ 106,200,000
Change in fair value of derivative liability				83,530,000	0	$ 0
Change in fair value			$ 83,500,000
CVR liability
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Change in fair value of derivative liability				18,986,000	$ 0	$ 0
Change in fair value				$ 18,986,000
Series A Non-Voting Convertible Preferred Stock
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Issuance of Series A non-voting convertible preferred stock	$ 189,700,000
Spyre Therapeutics, Inc.
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Asset acquisition, stockholder payment period		3 years
Asset acquisition, cash payment, threshold period		1 year
Spyre Therapeutics, Inc. | Series A Non-Voting Convertible Preferred Stock
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Shares transferred as equity interest in asset acquisition (in shares)		364,887

v3.24.3

Fair Value Measurements - Changes in Forward Contract Liability (Details) - Forward Contracts $ in Millions	6 Months Ended
	Dec. 31, 2023 USD ($)
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation, Calculation [Roll Forward]
Beginning balance	$ 106.2
Change in fair value	83.5
Issuance of Series A Preferred Stock on July 7, 2023	(189.7)
Ending balance	$ 0.0

v3.24.3

Fair Value Measurements - Significant Inputs used to Estimate the Fair Value of Derivative Liability (Details) - Level 3	Dec. 31, 2023
Maximum | Risk-adjusted discount rates | CVR liability
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation [Line Items]
Derivative liability, measurement input	0.0632
Maximum | CVR liability | Estimated probability of success
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation [Line Items]
Derivative liability, measurement input	1
Maximum | CVR liability | Estimated reimbursement rate compared to reimbursement target
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation [Line Items]
Derivative liability, measurement input	1
Minimum | Risk-adjusted discount rates | CVR liability
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation [Line Items]
Derivative liability, measurement input	0.0591
Minimum | CVR liability | Estimated probability of success
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation [Line Items]
Derivative liability, measurement input	0.39
Minimum | CVR liability | Estimated reimbursement rate compared to reimbursement target
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation [Line Items]
Derivative liability, measurement input	0.81

v3.24.3

Fair Value Measurements - Changes in CVR Liability (Details) - CVR liability $ in Thousands	12 Months Ended
	Dec. 31, 2023 USD ($)
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation, Calculation [Roll Forward]
Beginning balance	$ 0
Fair value at CVR issuance	29,500
Changes in the fair value of the CVR liability since issuance	18,986
Payments	(5,786)
Ending balance	$ 42,700

v3.24.3

Cash Equivalents and Marketable Securities - Estimated Fair Value of Cash Equivalents and Marketable Securities and the Gross Unrealized Gains and Losses (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Cash equivalents:
Amortized Cost	$ 186,563	$ 26,007
Gross Unrealized Gains	6	1
Gross Unrealized Losses	0	(3)
Estimated Fair Value	186,569	26,005
Marketable securities:
Amortized Cost	150,101	20,877
Gross Unrealized Gains	284	2
Gross Unrealized Losses	(1)	(31)
Estimated Fair Value	150,384	20,848
Money market funds
Cash equivalents:
Amortized Cost	150,648	15,250
Gross Unrealized Gains	0	0
Gross Unrealized Losses	0	0
Estimated Fair Value	150,648	15,250
Commercial paper
Cash equivalents:
Amortized Cost	24,950	7,021
Gross Unrealized Gains	5	1
Gross Unrealized Losses	0	(2)
Estimated Fair Value	24,955	7,020
Marketable securities:
Amortized Cost	79,124	16,644
Gross Unrealized Gains	62	2
Gross Unrealized Losses	0	(25)
Estimated Fair Value	79,186	16,621
Corporate bonds
Marketable securities:
Amortized Cost	32,984	3,738
Gross Unrealized Gains	81	0
Gross Unrealized Losses	(1)	(6)
Estimated Fair Value	33,064	3,732
U.S. government treasury securities
Cash equivalents:
Amortized Cost	10,965
Gross Unrealized Gains	1
Gross Unrealized Losses	0
Estimated Fair Value	10,966
Marketable securities:
Amortized Cost	21,846
Gross Unrealized Gains	31
Gross Unrealized Losses	0
Estimated Fair Value	21,877
U.S. government agency securities
Cash equivalents:
Amortized Cost		3,736
Gross Unrealized Gains		0
Gross Unrealized Losses		(1)
Estimated Fair Value		3,735
Marketable securities:
Amortized Cost	16,147	495
Gross Unrealized Gains	110	0
Gross Unrealized Losses	0	0
Estimated Fair Value	$ 16,257	$ 495

v3.24.3

Cash Equivalents and Marketable Securities - Available-for-Sale Securities in an Unrealized Loss Position (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Fair Value
Less Than 12 Months	$ 14,738	$ 25,166
12 Months or Longer	0	0
Total, fair value	14,738	25,166
Unrealized Losses
Less Than 12 Months	(1)	(34)
12 Months or Longer	0	0
Total	(1)	(34)
Commercial paper
Fair Value
Less Than 12 Months	0	17,699
12 Months or Longer	0	0
Total, fair value	0	17,699
Unrealized Losses
Less Than 12 Months	0	(27)
12 Months or Longer	0	0
Total	0	(27)
Corporate bonds
Fair Value
Less Than 12 Months	9,907	3,732
12 Months or Longer	0	0
Total, fair value	9,907	3,732
Unrealized Losses
Less Than 12 Months	(1)	(6)
12 Months or Longer	0	0
Total	(1)	(6)
U.S. government treasury securities
Fair Value
Less Than 12 Months	4,831
12 Months or Longer	0
Total, fair value	4,831
Unrealized Losses
Less Than 12 Months	0
12 Months or Longer	0
Total	$ 0
U.S. government agency securities
Fair Value
Less Than 12 Months		3,735
12 Months or Longer		0
Total, fair value		3,735
Unrealized Losses
Less Than 12 Months		(1)
12 Months or Longer		0
Total		$ (1)

v3.24.3

Cash Equivalents and Marketable Securities - Narrative (Details) - USD ($)	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Cash Equivalents And Marketable Securities [Line Items]
Debt securities, available-for-sale, allowance for credit loss, excluding accrued interest	$ 0
Unrealized gains or losses on marketable securities	300,000
Realized gains or losses on marketable securities	0	$ 0	$ 0
Accrued interest receivable on available-for-sale debt securities	$ 900,000	100,000
Debt Securities, Available-For-Sale, Accrued Interest, After Allowance For Credit Loss, Statement Of Financial Position, Extensible List, Not Disclosed Flag	Accrued interest receivable on available-for-sale debt securities
US Government Agencies Debt Securities
Cash Equivalents And Marketable Securities [Line Items]
Debt securities, available-for-sale, allowance for credit loss, excluding accrued interest		$ 0

v3.24.3

Cash Equivalents and Marketable Securities - Contractual Maturities of Marketable Securities at Estimated Fair Value (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Cash and Cash Equivalents [Abstract]
Due in one year or less	$ 115,784	$ 20,848
Due in 1 - 2 years	34,600	0
Total marketable securities	$ 150,384	$ 20,848

v3.24.3

Property and Equipment, Net - Schedule of Property and Equipment Net (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Property Plant And Equipment [Line Items]
Property and equipment, gross	$ 0	$ 7,364
Less: Accumulated depreciation and amortization	0	(4,144)
Property and equipment, net	0	3,220
Laboratory equipment
Property Plant And Equipment [Line Items]
Property and equipment, gross	0	2,257
Furniture and office equipment
Property Plant And Equipment [Line Items]
Property and equipment, gross	0	520
Computer equipment
Property Plant And Equipment [Line Items]
Property and equipment, gross	0	73
Software
Property Plant And Equipment [Line Items]
Property and equipment, gross	0	121
Leasehold improvements
Property Plant And Equipment [Line Items]
Property and equipment, gross	$ 0	$ 4,393

v3.24.3

Property and Equipment, Net - Narrative (Details) - USD ($) $ in Thousands	3 Months Ended		12 Months Ended
	Jun. 30, 2023	Jun. 30, 2023	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Property Plant And Equipment [Line Items]
Depreciation and amortization			$ 744	$ 1,567	$ 1,576
Employee workforce, termination percentage	83.00%
Proceeds from the sale of property plant and equipment		$ 500	475	0	0
Loss on disposal of long-lived assets			915	0	0
Research and development
Property Plant And Equipment [Line Items]
Loss on disposal of long-lived assets		700
General and administrative
Property Plant And Equipment [Line Items]
Loss on disposal of long-lived assets		$ 200
Property, Plant and Equipment
Property Plant And Equipment [Line Items]
Depreciation and amortization			$ 700	$ 1,400	$ 1,400

v3.24.3

Accrued and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Accrued Liabilities and Other Liabilities [Abstract]
Accrued compensation	$ 4,054	$ 4,589
Accrued contracted research and development costs	7,092	6,972
Accrued professional and consulting fees	1,474	946
Other	488	330
Total accrued and other current liabilities	$ 13,108	$ 12,837

v3.24.3

Related Party Transactions - Narrative (Details) $ / shares in Units, $ in Thousands					1 Months Ended	12 Months Ended
	Dec. 14, 2023 USD ($)	Nov. 22, 2023 installment $ / shares shares	Jul. 12, 2023 USD ($)	Jun. 22, 2023 USD ($)	May 31, 2023 USD ($)	Dec. 31, 2023 USD ($) seat shares	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Related Party Transaction [Line Items]
Stock compensation expense						$ 25,675	$ 7,111	$ 8,038
Related party accounts payable and other current liabilities						16,584	0
Proceeds from issuance of private placement						$ 84,555	0	0
Granted (in shares) | shares						8,776,245
Related Party
Related Party Transaction [Line Items]
Related party accounts payable and other current liabilities						$ 16,600	0
Appoint Of Board Members
Related Party Transaction [Line Items]
Number of board seats held by related party | seat						2
Paragon Agreement
Related Party Transaction [Line Items]
Related party expenses incurred prior to asset acquisition				$ 19,000
Related party expenses unpaid prior to asset acquisition				19,000
Paragon Agreement | Related Party
Related Party Transaction [Line Items]
Research initiation fees				3,000	$ 3,000
Reimbursable research costs				$ 16,000
Stock compensation expense						$ 11,400
Stock Compensation And Research And Development Expense
Related Party Transaction [Line Items]
Related party transaction amount						48,500
Reimbursable Costs Under Paragon Agreement | Related Party
Related Party Transaction [Line Items]
Related party accounts payable and other current liabilities						16,600	0
Milestone Payments
Related Party Transaction [Line Items]
Related party transaction amount						39,500
SPY001 License Agreement | Related Party
Related Party Transaction [Line Items]
Nomination fee			$ 1,500
Milestone payments			2,500
SPY002 License Agreement | Related Party
Related Party Transaction [Line Items]
Nomination fee	$ 1,500
Milestone payments	2,500
Sale Of Stock, December 2023 PIPE | Related Party
Related Party Transaction [Line Items]
Proceeds from issuance of private placement						10,000
Consulting Agreement | Related Party
Related Party Transaction [Line Items]
Granted (in shares) | shares		477,000
Exercise price (in dollars per share) | $ / shares		$ 10.39
Number of monthly installments | installment		48
Stock-based compensation expense						$ 100	$ 0	$ 0
Consulting Agreement | Related Party | Share-Based Payment Arrangement, Tranche One
Related Party Transaction [Line Items]
Vesting percentage		25.00%
Awards granted, vesting period		1 year
Paragon Therapeutics Inc | Ownership Interest | Maximum | Related Party
Related Party Transaction [Line Items]
Percentage of ownership by noncontrolling owner						5.00%
Paragon Therapeutics Inc | SPY001 License Agreement | Maximum | Related Party
Related Party Transaction [Line Items]
Contingent obligation based on milestones			$ 22,000
Paragon Therapeutics Inc | SPY002 License Agreement | Maximum | Related Party
Related Party Transaction [Line Items]
Contingent obligation based on milestones	$ 22,000
Fairmount Funds Management LLC | Ownership Interest | Minimum | Related Party
Related Party Transaction [Line Items]
Percentage of ownership by noncontrolling owner						5.00%
Percentage of ownership held in third party						5.00%

v3.24.3

Related Party Transactions - Expenses related to Related Party which were Settled in Cash (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Reimbursable Costs Under Paragon Agreement | Research and development
Related Party Transaction [Line Items]
Reimbursable costs	$ 37.1	$ 0.0	$ 0.0

v3.24.3

Related Party Transactions - Related Party Accounts Payable (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Related Party Transaction [Line Items]
Related party accounts payable and other current liabilities	$ 16,584	$ 0
Related Party
Related Party Transaction [Line Items]
Related party accounts payable and other current liabilities	16,600	0
Related Party | Reimbursable Costs Under Paragon Agreement
Related Party Transaction [Line Items]
Related party accounts payable and other current liabilities	$ 16,600	$ 0

v3.24.3

Asset Acquisition - Narrative (Details) - Spyre Therapeutics, Inc. $ / shares in Units, $ in Millions	Jun. 22, 2023 USD ($) $ / shares shares
Asset Acquisition [Line Items]
Cost to acquire asset | $	$ 113.2
Asset acquisition consideration transferred issuable shares of common stock on an as-converted basis	14,595,480
Spyre 2023 Equity Incentive Plan
Asset Acquisition [Line Items]
Number of outstanding and unexercised stock options to purchase (in shares)	2,734
Series A Non-Voting Convertible Preferred Stock
Asset Acquisition [Line Items]
Shares transferred as equity interest in asset acquisition (in shares)	364,887
Shares issued, price per share (in dollars per share) | $ / shares	$ 291.08
Common Stock
Asset Acquisition [Line Items]
Shares transferred as equity interest in asset acquisition (in shares)	517,809
Shares issued, price per share (in dollars per share) | $ / shares	$ 7.277

v3.24.3

Asset Acquisition - Asset Acquisition Cost (Details) - USD ($) $ in Thousands		12 Months Ended
	Jun. 22, 2023	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Asset Acquisition [Line Items]
Acquired in-process research and development		$ 130,188	$ 0	$ 0
Cash acquired		$ 3,035	$ 0	$ 0
Spyre Therapeutics, Inc.
Asset Acquisition [Line Items]
Consideration transferred in Series A Preferred Stock and Common Stock	$ 110,000
Transaction costs incurred by the Company	3,200
Acquired in-process research and development	130,200
Cash acquired	3,000
Assumed liabilities	(20,000)
Total cost to acquire asset	$ 113,200

v3.24.3

Paragon Agreement (Details) $ in Millions			1 Months Ended	12 Months Ended
	Jul. 12, 2023 USD ($)	Jun. 22, 2023 USD ($)	May 31, 2023 USD ($) researchProgram	Dec. 31, 2023 USD ($)
Paragon Therapeutics Inc
Related Party Transaction [Line Items]
Milestone payments				$ 39.5
Parapyre Option Obligation
Related Party Transaction [Line Items]
Percentage of annual equity grant of options			1.00%
Paragon Agreement
Related Party Transaction [Line Items]
Number of research programs | researchProgram			4
Related party expenses incurred prior to asset acquisition		$ 19.0
Related party expenses unpaid prior to asset acquisition		19.0
Stock Compensation And Research And Development Expense
Related Party Transaction [Line Items]
Related party transaction amount				$ 48.5
Related Party | Paragon Agreement
Related Party Transaction [Line Items]
Research initiation fees		3.0	$ 3.0
Reimbursable research costs		16.0
Nonrefundable research initiation fee for one program paid in cash		$ 0.8
Related Party | SPY001 License Agreement
Related Party Transaction [Line Items]
Nomination fee	$ 1.5
Milestone payments	$ 2.5

v3.24.3

Leases - Narrative (Details) ft² in Thousands	12 Months Ended
	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Aug. 31, 2023 USD ($)	Apr. 30, 2019 USD ($) ft²
Lessee, Lease, Description [Line Items]
Area of land | ft²				30
Letter of credit				$ 1,500,000
Termination fee amount			$ 2,000,000
Operating lease, payments	$ 500,000	$ 900,000
Operating and finance lease obligations	$ 0	$ 4,645,000
Minimum
Lessee, Lease, Description [Line Items]
Lessee, operating lease, renewal term	3 years
Maximum
Lessee, Lease, Description [Line Items]
Lessee, operating lease, renewal term	5 years
Tenant improvement allowance (up to)				$ 1,000,000

v3.24.3

Leases - Operating and Financing Leases Presented in Balance Sheet (Details) - USD ($)	Dec. 31, 2023	Dec. 31, 2022
Assets
Operating	$ 0	$ 3,430,000
Finance	$ 0	$ 597,000
Finance Lease, Right-of-Use Asset, Statement of Financial Position [Extensible Enumeration]	Other non-current assets	Other non-current assets
Total leased assets	$ 0	$ 4,027,000
Current
Operating	0	625,000
Finance	$ 0	$ 16,000
Finance Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]	Accrued and other current liabilities	Accrued and other current liabilities
Non-current
Operating	$ 0	$ 4,004,000
Total lease liabilities	$ 0	$ 4,645,000

v3.24.3

Leases - Weighted-Average Remaining Lease Term and Discount Rates for Operating and Finance Leases (Details)	Dec. 31, 2023	Dec. 31, 2022
Lease term (years)
Operating leases	0 years	5 years 3 months 18 days
Finance leases	0 years	7 months 6 days
Discount rate
Operating leases	0.00%	10.60%
Finance leases	0.00%	10.20%

v3.24.3

Leases - Lease Cost (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Leases [Abstract]
Operating lease cost	$ 455	$ 910	$ 991
Variable lease cost	471	472	519
Total lease cost	$ 926	$ 1,382	$ 1,510

v3.24.3

Convertible Preferred Stock and Stockholders’ Equity - Narrative (Details)						1 Months Ended			3 Months Ended	12 Months Ended
	Dec. 11, 2023 USD ($) shares	Dec. 08, 2023	Jul. 07, 2023 shares	Jun. 26, 2023 USD ($) shares	Jun. 22, 2023	Dec. 31, 2023 USD ($) Vote $ / shares shares	Jun. 30, 2023 USD ($) $ / shares shares	May 31, 2022 USD ($) $ / shares shares	Dec. 31, 2023 USD ($) Vote $ / shares shares	Dec. 31, 2023 USD ($) Vote $ / shares shares	Dec. 31, 2022 USD ($) $ / shares shares	Dec. 31, 2021 USD ($) shares	Dec. 31, 2020 shares
Class Of Stock [Line Items]
Shares authorized (in shares)						410,000,000			410,000,000	410,000,000
Common stock, authorized (in shares)						400,000,000			400,000,000	400,000,000	20,000,000
Preferred stock, authorized (in shares)						10,000,000			10,000,000	10,000,000
Common stock, par value (in dollars per share) | $ / shares						$ 0.0001			$ 0.0001	$ 0.0001	$ 0.0001
Preferred stock, par value (in dollars per share) | $ / shares						$ 0.0001			$ 0.0001	$ 0.0001
Number of votes for common stock holders | Vote						1			1	1
Common stock dividends declared | $										$ 0	$ 0
Series B non-voting convertible preferred stock, outstanding (in shares)						150,000			150,000	150,000	0	0	0
Warrants to purchase shares (in shares)								694,892
Offering price of warrant (in dollars per share) | $ / shares								$ 39.9975
Exercise price per warrant (in dollars per share) | $ / shares								$ 0.0025
Net proceeds from sale of common stock | $								$ 42,900,000		$ 84,555,000	$ 0	$ 0
Placement agent fees and offering costs | $								$ 2,100,000
Issuance of temporary equity (in shares)	150,000					150,000				150,000
Maximum ownership percentage of common stock shares for outstanding warrants to be exercised								4.99%
Maximum ownership percentage of common stock shares for outstanding warrants to be exercised upon written notice								19.99%
Ownership percentage for outstanding warrants to purchase shares of common stock to be exercised to certain holders								9.99%
Revised ownership percentage, period to take effect after notice								61 days
Proceeds from issuance of private placement | $										$ 84,555,000	$ 0	$ 0
Temporary equity, redemption value | $						$ 129,100,000			$ 129,100,000	$ 129,100,000
Temporary equity, redemption per share (in dollars per share) | $ / shares						$ 21.52			$ 21.52	$ 21.52
Parapyre Warrants
Class Of Stock [Line Items]
Warrants to purchase shares (in shares)						684,407			684,407	684,407
Exercise price per warrant (in dollars per share) | $ / shares						$ 21.52			$ 21.52	$ 21.52
Series A Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Preferred stock, authorized (in shares)						1,086,341			1,086,341	1,086,341	0
Preferred stock, par value (in dollars per share) | $ / shares						$ 0.0001			$ 0.0001	$ 0.0001	$ 0.0001
Preferred stock, outstanding (in shares)						437,037			437,037	437,037	0
Preferred stock issued and outstanding percentage					30.00%
Conversion basis					40
Series B Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Conversion basis	40	40
Maximum | Series A Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Beneficial holders owned percentage					20.00%
Maximum | Series B Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Beneficial holders owned percentage		19.99%
Minimum | Series A Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Beneficial holders owned percentage					0.00%
Minimum | Series B Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Beneficial holders owned percentage		0.00%
Common Stock
Class Of Stock [Line Items]
Issued (in shares)								430,107
Public offering price (in dollars per share) | $ / shares								$ 40.00
Issuance of common stock upon conversion (in shares)											204,000	40,000
Common Stock | Conversion Of Series A Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Issuance of common stock upon conversion (in shares)									25,972,080	25,972,000
Series A Non-Voting Convertible Preferred Stock | Series A Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Preferred stock, outstanding (in shares)						437,000			437,000	437,000	0	0	0
Issued (in shares)										721,000
Issued as part of consideration transferred in acquisition (in shares)			364,887							365,000
Series A Non-Voting Convertible Preferred Stock | Series A Non-Voting Convertible Preferred Stock | Conversion Of Series A Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Issuance of common stock upon conversion (in shares)									649,302	(649,000)
Private Placement
Class Of Stock [Line Items]
Public offering price (in dollars per share) | $ / shares							$ 291.08
Sale of stock (in shares)				721,452			721,452
Aggregate purchase price for stock sold | $				$ 197,300,000		$ 169,100,000	$ 197,300,000
Offering costs | $	$ 10,900,000			12,700,000		$ 10,900,000	$ 12,700,000
Proceeds from issuance of private placement | $	180,000,000.0			$ 210,000,000.0						$ 180,000,000.0
Private Placement | Series B Non-Voting Convertible Preferred Stock
Class Of Stock [Line Items]
Public offering price (in dollars per share) | $ / shares						$ 600			$ 600	$ 600
Proceeds from issuance of private placement | $	$ 90,000,000.0
Private Placement | Common Stock
Class Of Stock [Line Items]
Issued (in shares)										6,000,000
Public offering price (in dollars per share) | $ / shares						$ 15.00			$ 15.00	$ 15.00
Sale of stock (in shares)	6,000,000					6,000,000

v3.24.3

Convertible Preferred Stock and Stockholders’ Equity - Pre-funded Warrants for Common Stock Issued and Outstanding (Details) - $ / shares	Dec. 31, 2023	May 31, 2022
Equity [Abstract]
Exercise price (in dollars per share)		$ 0.0025
Class of Warrant or Right [Line Items]
Exercise price (in dollars per share)		$ 0.0025
May 2022
Equity [Abstract]
Exercise price (in dollars per share)	$ 0.0025
Number of warrants outstanding (in shares)	250,000
Class of Warrant or Right [Line Items]
Exercise price (in dollars per share)	$ 0.0025
Number of warrants outstanding (in shares)	250,000
Pre-Funded Warrants
Equity [Abstract]
Number of warrants outstanding (in shares)	250,000
Class of Warrant or Right [Line Items]
Number of warrants outstanding (in shares)	250,000

v3.24.3

Strategic License Agreement - Narrative (Details) - USD ($)			1 Months Ended		12 Months Ended
	Jul. 27, 2023	Mar. 21, 2021	Jul. 31, 2021	Jun. 30, 2021	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Revenue recognized					$ 886,000	$ 2,329,000	$ 18,739,000
Deferred revenue					0	2,696,000
Deferred revenue, current					0	517,000
Contract assets					0	0
Proceeds from sale of intangible assets					15,000,000	0	0
Gain on sale of in-process research and development asset					16,449,000	0	0
Disposal Group, Disposed of by Sale, Not Discontinued Operations | Global Rights To Pegzilarginase
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Proceeds from sale of intangible assets	$ 15,000,000.0
Contingent consideration	100,000,000.0
Carrying value of assets	0
Gain on sale of in-process research and development asset	16,400,000
Contingent reimbursement of pre-paid manufacturing costs	1,800,000
Derecognition of nonfinancial assets and liabilities	$ 400,000
Immedica Pharma AB
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Reimbursement			$ 3,000,000.0
Non refundable payment received		$ 21,500,000
Percentage of payment for cost incurred in trial		50.00%
Maximum amount of costs to reimburse		$ 1,800,000
Additional upfront payment to be received		$ 120,800,000
Milestone payments exchange rate		1.07
Rate of revenue share		25.00%
Upfront payment		$ 21,500,000
Estimated amount incurred			3,600,000
Related party transaction amount			25,100,000
Allocation for stand-alone selling prices			12,000,000.0
Deferred revenue						2,700,000
Deferred revenue, current						500,000
Immedica Pharma AB | PEACE Trial and BLA Package
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Allocated amount of modified transaction price			9,600,000
Revenue recognized					$ 900,000	$ 2,300,000	6,700,000
Immedica Pharma AB | PIP Trial
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Allocated amount of modified transaction price			$ 3,500,000
Immedica Pharma AB | License Agreements
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Revenue recognized				$ 12,000,000.0			$ 12,000,000.0

v3.24.3

Strategic License Agreement - Changes in Contract Liabilities (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2023 USD ($)
Change In Contract With Customer, Liability [Roll Forward]
Beginning balance	$ 2,696
Additions	575
Deductions	(3,271)
Ending balance	$ 0

v3.24.3

Sale of Pegzilarginase to Immedica (Details) - USD ($)		12 Months Ended
	Jul. 27, 2023	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Income Statement, Balance Sheet and Additional Disclosures by Disposal Groups, Including Discontinued Operations [Line Items]
Proceeds from sale of intangible assets		$ 15,000,000	$ 0	$ 0
Gain on sale of in-process research and development asset		$ 16,449,000	$ 0	$ 0
Disposal Group, Disposed of by Sale, Not Discontinued Operations | Global Rights To Pegzilarginase
Income Statement, Balance Sheet and Additional Disclosures by Disposal Groups, Including Discontinued Operations [Line Items]
Proceeds from sale of intangible assets	$ 15,000,000.0
Contingent consideration	100,000,000.0
Carrying value of assets	0
Gain on sale of in-process research and development asset	16,400,000
Contingent reimbursement of pre-paid manufacturing costs	1,800,000
Derecognition of nonfinancial assets and liabilities	$ 400,000

v3.24.3

Novation of Manufacturing Agreements (Details)	1 Months Ended
	Apr. 30, 2023 USD ($)
Commitments and Contingencies Disclosure [Abstract]
Right to terminate agreement or work order, prior written notice period	30 days
Right to terminate work order, reasonable cause, prior written notice period	6 months
Right to terminate work order by counterparty, reasonable cause, termination amount payable	$ 0
Right to terminate work order, material breach, uncured period	30 days
Right to terminate work order, unusual or infrequent cause, period	90 days
Non-refundable license fee amount	$ 200,000
Royalty percentage (less than)	1.00%
Right to terminate agreement, prior written notice period	6 months
Right to terminate agreement by counterparty, material breach, uncured period	60 days
Right to terminate agreement by counterparty, payments not received, period	30 days

v3.24.3

Stock-Based Compensation - Narrative (Details) - USD ($)		1 Months Ended								12 Months Ended
	Jun. 22, 2023	Nov. 30, 2023	Feb. 28, 2023	Jul. 31, 2020	Oct. 31, 2018	Jun. 30, 2018	Feb. 28, 2018	Apr. 30, 2016	Mar. 31, 2015	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Sep. 29, 2023	Jan. 01, 2023	Jan. 01, 2022	Jan. 01, 2021	Jan. 01, 2020
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding option awards (in shares)										8,497,395	405,082
Stock compensation expense										$ 25,675,000	$ 7,111,000	$ 8,038,000
Tax benefits recognized										$ 0	$ 0	$ 0
Expected dividend yield										0.00%	0.00%	0.00%
Parapyre Option Obligation
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Percentage of annual grant of common stock outstanding for warrants	1.00%
Warrants term													10 years
Warrant grant date fair value	$ 11,500,000
Liability assumed in asset acquisition related to warrants	$ 100,000
Stock compensation expense										$ 11,400,000	$ 0	$ 0
Warrant unamortized expense										$ 0
Stock Options
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Weighted-average grant date fair value (in dollars per share)										$ 9.67	$ 1.80	$ 4.96
Intrinsic value of options exercised										$ 400,000	$ 0	$ 700,000
Unrecognized stock-based compensation expense for options										$ 64,400,000
Weighted average period over which unrecognized compensation is expected to be recognized										3 years 6 months
Expected dividend yield										0.00%	0.00%	0.00%
Stock Options | Non- Employees
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock option issued (in shares)										477,000	0	0
Stock option vested (in shares)										0	0	0
Restricted Stock Units (RSUs)
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Shares, granted to employees (in shares)										153,865	0	0
Restricted Stock Units (RSUs) | Non- Employees
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Shares, granted to employees (in shares)										0	0	0
Performance Shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expense recognized for unvested employee and non-employee awards										$ 0	$ 0	$ 0
2015 Equity Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Percentage of market value of common stock									100.00%
Grantees with more than five years vesting term, percent									10.00%
Maximum vesting term for more than ten percent grantees									5 years
Shares subject to options outstanding (in shares)										3,029
Available for issuance (in shares)								20,395
2015 Equity Incentive Plan | Stock Options
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Awards granted, expiration period									10 years
2016 Equity Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Initial reserves of common stock (in shares)								44,000
Increase in common stock reserved for issuance (in shares)					70,384
Annual percentage of additional shares		5.00%			4.00%
Additional common stock available for issuance (in shares)														104,561	78,968	76,735
Additional shares authorized (in shares)		4,481,152
Annual limit for non-employee director compensation (in shares)								4,000
Annual limit for non-employee director compensation		$ 750,000
Non-employee director compensation		$ 1,000,000
Shares reserved for issuance (in shares)										5,019,177
Outstanding option awards (in shares)										3,294,962
2016 Equity Incentive Plan | Restricted Stock Units (RSUs)
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Shares, granted to employees (in shares)				9,128
Stock-based compensation expense										$ 0
Equity instruments other than options, vested (in shares)										0
2018 Equity Inducement Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Initial reserves of common stock (in shares)							44,000
Additional shares authorized (in shares)										6,000,000
Shares reserved for issuance (in shares)										6,044,000
Outstanding option awards (in shares)										5,350,595
2018 Plan, 2016 Plan and 2015 Plan | Service Based Awards
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Awards granted, expiration period							10 years
Awards granted, vesting period							4 years
Spyre 2023 Equity Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding option awards (in shares)	2,734
2016 Employee Stock Purchase Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Awards granted, expiration period								10 years
Additional common stock available for issuance (in shares)															26,140	19,742	19,184
Shares reserved for issuance (in shares)								6,600		72,404
Percentage of fair market value of common stock								85.00%
Percentage of discount through payroll deductions to eligible employees to purchase common stock								15.00%
Maximum purchase value per employee under employee stock purchase plan								$ 25,000
Additional annual percentage increase of common stock						1.00%
Maximum shares purchased under employee stock purchase plan (in shares)			400					80
Stock-based compensation expense										$ 0	$ 100,000	$ 200,000
Expected dividend yield										0.00%	0.00%	0.00%

v3.24.3

Stock-Based Compensation - Employee and Non-Employee Stock Option Activity (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Shares Issuable Under Options
Outstanding, beginning balance (in shares)	405,082
Granted (in shares)	8,776,245
Exercised (in shares)	(46,246)
Forfeited (in shares)	(637,686)
Outstanding, ending balance (in shares)	8,497,395	405,082
Options vested and expected to vest (in shares)	8,497,395
Options exercisable (in shares)	1,065,700
Weighted Average Exercise Price
Outstanding, beginning balance (in dollars per share)	$ 113.75
Granted (in dollars per share)	9.67
Exercised (in dollars per share)	8.22
Forfeited (in dollars per share)	43.00
Outstanding, ending balance (in dollars per share)	12.13	$ 113.75
Options vested and expected to vest (in dollars per share)	12.13
Options exercisable (in dollars per share)	$ 24.72
Weighted Average Remaining Contractual Term
Outstanding	8 years 4 months 24 days	6 years 8 months 19 days
Options vested and expected to vest	8 years 4 months 24 days
Options exercisable	5 years 7 months 13 days
Aggregate Intrinsic Value
Outstanding	$ 98,928	$ 2
Options vested and expected to vest	98,928
Options exercisable	$ 13,328

v3.24.3

Stock-Based Compensation - Employee Restricted Stock Activity (Details) - Restricted Common Stock - Employees	12 Months Ended
	Dec. 31, 2023 $ / shares shares
Shares
Unvested (in shares) | shares	5,660
Granted (in shares) | shares	153,865
Vested (in shares) | shares	0
Forfeited (in shares) | shares	(5,660)
Unvested (in shares) | shares	153,865
Weighted Average Grant Date Fair Value
Unvested (in dollars per share) | $ / shares	$ 203.25
Granted (in dollars per share) | $ / shares	18.17
Vested (in dollars per share)) | $ / shares	0
Forfeited (in dollars per share) | $ / shares	203.25
Unvested (in dollars per share) | $ / shares	$ 18.17

v3.24.3

Stock-Based Compensation - Stock-Based Compensation Expense (Details) - 2018 Equity Inducement Plan and 2016 Employee Stock Purchase Plan - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Employees
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Total stock-based compensation expense	$ 14,237	$ 7,111	$ 8,038
Non- Employees
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Total stock-based compensation expense	11,437	0	0
Research and development | Employees
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Total stock-based compensation expense	2,910	2,591	2,723
Research and development | Non- Employees
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Total stock-based compensation expense	11,328	0	0
General and administrative | Employees
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Total stock-based compensation expense	11,327	4,520	5,315
General and administrative | Non- Employees
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Total stock-based compensation expense	$ 109	$ 0	$ 0

v3.24.3

Stock-Based Compensation - Weighted-Average Assumptions Used in Calculating Fair Value of Awards (Details)	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Dividend yield	0.00%	0.00%	0.00%
Stock Options
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Expected term (in years)	5 years 10 months 17 days	6 years	5 years 11 months 26 days
Expected volatility	107.00%	84.00%	83.00%
Risk-free interest	4.37%	2.93%	0.88%
Dividend yield	0.00%	0.00%	0.00%
2016 Employee Stock Purchase Plan
Employee Service Share Based Compensation Allocation of Recognized Period Costs [Line Items]
Expected term (in years)	5 months 26 days	5 months 26 days	6 months
Expected volatility	181.00%	84.00%	86.00%
Risk-free interest	4.99%	1.95%	0.08%
Dividend yield	0.00%	0.00%	0.00%

v3.24.3

Defined Contribution Plan (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Retirement Benefits [Abstract]
Defined contribution plan, contribution amount	$ 0.2	$ 0.6	$ 0.6

v3.24.3

Restructuring Charges - Narrative (Details) - USD ($) $ in Thousands		3 Months Ended		12 Months Ended
	Jun. 30, 2023	Jun. 30, 2023	Jun. 30, 2023	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Aug. 31, 2023
Restructuring Cost and Reserve [Line Items]
Employee workforce, termination percentage		83.00%
Cash severance payments and other employee-related costs				$ 6,400
Cash payments for employee related restructuring charges				5,300
Non-cash stock-based compensation expense related to accelerated vesting of stock-based awards				1,000
Total consideration from disposal of long lived assets	$ 500	$ 500	$ 500
Loss on disposal of long-lived assets				$ 915	$ 0	$ 0
Lease asset impairment	900
Impairment on leasehold improvements	$ 1,700
Termination fee amount							$ 2,000
Research and development
Restructuring Cost and Reserve [Line Items]
Loss on disposal of long-lived assets			700
General and administrative
Restructuring Cost and Reserve [Line Items]
Loss on disposal of long-lived assets			$ 200

v3.24.3

Restructuring Charges - Changes in Accrued Restructuring Balance (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2023 USD ($)
Restructuring Cost and Reserve [Line Items]
Payments	$ (5,300)
Severance Liability
Restructuring Cost and Reserve [Line Items]
Beginning Balance December 31, 2022	0
Charges	6,448
Payments	(5,325)
Ending Balance December 31, 2023	$ 1,123

v3.24.3

Restructuring Charges - Charges Related to the Restructuring Activities (Details) - USD ($) $ in Thousands		3 Months Ended	12 Months Ended
	Jun. 30, 2023	Jun. 30, 2023	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Restructuring Cost and Reserve [Line Items]
Severance Related Expenses			$ 6,400
Loss on disposal of long-lived assets			$ 915	$ 0	$ 0
Lease Asset Impairment	$ 900
Research and development
Restructuring Cost and Reserve [Line Items]
Loss on disposal of long-lived assets		$ 700
General and administrative
Restructuring Cost and Reserve [Line Items]
Loss on disposal of long-lived assets		200
Restructuring Activities
Restructuring Cost and Reserve [Line Items]
Severance Related Expenses		6,448
Stock-based compensation expense		993
Loss on disposal of long-lived assets		931
Lease Asset Impairment		2,580
Total Restructuring Costs		10,952
Restructuring Activities | Research and development
Restructuring Cost and Reserve [Line Items]
Severance Related Expenses		3,182
Stock-based compensation expense		123
Loss on disposal of long-lived assets		749
Lease Asset Impairment		1,405
Total Restructuring Costs		5,459
Restructuring Activities | General and administrative
Restructuring Cost and Reserve [Line Items]
Severance Related Expenses		3,266
Stock-based compensation expense		870
Loss on disposal of long-lived assets		182
Lease Asset Impairment		1,175
Total Restructuring Costs		$ 5,493

v3.24.3

Income Taxes - (Loss) Income Before Income Tax Expense by Jurisdiction (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Domestic	$ (338,942)	$ (84,113)	$ (65,940)
Foreign	126	162	280
Loss before income tax expense	$ (338,816)	$ (83,951)	$ (65,660)

v3.24.3

Income Taxes - Narrative (Details)	12 Months Ended
	Dec. 31, 2023 USD ($) subsidiary	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Income Tax Contingency [Line Items]
Provision or benefit from income taxes	$ (26,000)	$ (136,000)	$ 141,000
Increase in valuation primarily due to operation losses	17,800,000	20,600,000	16,900,000
Net operating loss carryforwards	354,500,000	328,200,000
Net operating loss carryforwards, set to expire if not utilized	58,400,000
Tax credit carryforwards, set to expire if not utilized	$ 21,900,000
Number of domestic subsidiaries | subsidiary	8
Unrecognized tax benefits	$ 0	0
Foreign subsidiaries
Income Tax Contingency [Line Items]
Provision or benefit from income taxes	0	100,000	$ 100,000
U.S
Income Tax Contingency [Line Items]
Tax credit carryforwards	21,900,000	21,900,000
State
Income Tax Contingency [Line Items]
Tax credit carryforwards	$ 1,600,000	$ 1,600,000

v3.24.3

Income Taxes - Effective Income Tax Rate Reconciliation (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Income Taxes [Line Items]
Tax provision derived by applying the federal statutory rate to income before income taxes	$ (71,151)	$ (17,630)	$ (13,789)
Loss on forward contract valuation	17,541	0	0
Acquired IPR&D	27,340	0	0
Loss on CVR revaluation	3,987	0	0
Other permanent differences	4,472	1,042	1,002
Effect of tax rate on foreign jurisdiction	(53)	42	(5)
Change in the valuation allowance	17,839	20,609	16,900
Income tax (benefit) expense	(26)	(136)	141
Federal tax credits
Income Taxes [Line Items]
Tax credits	(1)	(3,559)	(3,815)
State tax credits
Income Taxes [Line Items]
Tax credits	$ 0	$ (640)	$ (152)

v3.24.3

Income Taxes - Components of Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Deferred tax assets
Net operating loss carryforward	$ 74,454	$ 68,917
Capitalized 174 R&D costs	22,532	11,097
Intangible assets	47	52
Deferred revenue	0	566
Accrued expense	579	668
Stock-based compensation	4,246	3,293
Other	88	190
Total deferred tax assets	125,491	108,328
Deferred tax liabilities
Depreciable assets	0	(676)
Total deferred tax liabilities	0	(676)
Less: Valuation allowance	(125,491)	(107,652)
Deferred tax assets, net	0	0
Federal tax credits
Deferred tax assets
Tax credits	21,914	21,914
State tax credits
Deferred tax assets
Tax credits	$ 1,631	$ 1,631

v3.24.3

Net Loss Per Share (as restated) - Narrative (Details)	12 Months Ended
	Dec. 31, 2023 $ / shares
Error Corrections and Prior Period Adjustments Restatement [Line Items]
Net loss per share, basic (in dollars per share)	$ 13.76
Net loss per share, diluted (in dollars per share)	13.76
Previously Reported
Error Corrections and Prior Period Adjustments Restatement [Line Items]
Net loss per share, basic (in dollars per share)	49.12
Net loss per share, diluted (in dollars per share)	$ 49.12

v3.24.3

Net Loss Per Share (as restated) - Reconciliation of Basic and Diluted Net Loss Per Share (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]
Allocation of losses	$ (338,790)	$ (83,815)	$ (65,801)
Weighted-average shares outstanding (in shares)	6,897,065	3,371,231	2,629,784
Number of shares used in per share computation (in shares)	6,897,065	3,371,231	2,629,784
Net loss per share, basic (in dollars per share)	$ 13.76
Net loss per share, diluted (in dollars per share)	$ 13.76
Series A Preferred Stock
Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]
Allocation of losses	$ (239,158)	$ 0	$ 0
Weighted-average shares outstanding (in shares)	434,612	0	0
Weighted average pre-funded warrants outstanding (in shares)	0	0	0
Number of shares used in per share computation (in shares)	434,612	0	0
Net loss per share, basic (in dollars per share)	$ (550.28)	$ 0	$ 0
Net loss per share, diluted (in dollars per share)	$ (550.28)	$ 0	$ 0
Series B Preferred Stock
Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]
Allocation of losses	$ (4,749)	$ 0	$ 0
Weighted-average shares outstanding (in shares)	8,630	0	0
Weighted average pre-funded warrants outstanding (in shares)	0	0	0
Number of shares used in per share computation (in shares)	8,630	0	0
Net loss per share, basic (in dollars per share)	$ (550.29)	$ 0	$ 0
Net loss per share, diluted (in dollars per share)	$ (550.29)	$ 0	$ 0
Common Stock
Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]
Allocation of losses	$ (94,883)	$ (83,815)	$ (65,801)
Weighted-average shares outstanding (in shares)	6,201,954	2,307,668	1,956,933
Weighted average pre-funded warrants outstanding (in shares)	695,111	1,063,563	672,851
Number of shares used in per share computation (in shares)	6,897,065	3,371,231	2,629,784
Net loss per share, basic (in dollars per share)	$ (13.76)	$ (24.86)	$ (25.02)
Net loss per share, diluted (in dollars per share)	$ (13.76)	$ (24.86)	$ (25.02)

v3.24.3

Net Loss Per Share (as restated) - Weighted-Average Equity Instruments Excluded from Calculation of Diluted Net Loss Per Share (Details) - shares	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Options to purchase Common Stock
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	2,583,226	346,331	264,858
Unvested restricted stock units
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	4,240	6,983	7,975
Outstanding Parapyre Warrants
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	5,625	0	0

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