Exhibit 99.2
MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS
This management’s discussion and analysis is designed to provide you with a narrative explanation of our financial condition and results of operations. You should read this discussion and analysis in conjunction with
our unaudited condensed consolidated interim financial statements, including the notes thereto, as of and for the three and nine months ended September 30, 2024. You should also read this discussion and analysis in conjunction with our audited
consolidated financial statements, including the notes thereto, and the section in our annual report on Form 20-F for the year ended December 31, 2023 titled “Item 3. Key Information—D. Risk Factors.”
Our unaudited condensed consolidated interim financial statements for the three and nine months ended September 30, 2024, were prepared in accordance with International Accounting Standard 34, Interim Financial
Reporting. The terms “dollar,” “USD” or “$” refer to U.S. dollars. We have made rounding adjustments to some of the figures included in this discussion. Accordingly, any numerical discrepancies in any table between totals and sums of the amounts
listed are due to rounding.
Unless otherwise indicated or the context otherwise requires, all references in this discussion and analysis to “GH Research” or “GH,” the “Company,” “we,” “our,” “ours,” “us” or similar terms refer to GH Research PLC
and its consolidated subsidiary.
Overview
We are a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders. Our initial focus is on developing our novel and proprietary mebufotenin
(5-methoxy-N,N-dimethyltryptamine, or 5-MeO-DMT) therapies for the treatment of patients with treatment-resistant depression, or TRD. Mebufotenin was selected as the International Nonproprietary Name (INN) for 5-MeO-DMT by the World Health
Organization (WHO) Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations.
Our portfolio currently includes GH001, our proprietary inhalable mebufotenin product candidate, GH002, our proprietary intravenous mebufotenin product candidate, and GH003, our proprietary intranasal mebufotenin
product candidate. While GH001 is currently delivered via a vaporization device produced by a third party, we are developing a proprietary aerosol delivery device. We have completed two Phase 1 healthy volunteer clinical trials for GH001
(GH001-HV-101 and GH001-HV-103), in which administration of GH001 via inhalation was observed to be well tolerated at the investigated single dose levels and in an individualized dosing regimen, or IDR, with intra-subject dose escalation within a
single day. We have also completed a Phase 1/2 clinical trial in patients with TRD (GH001-TRD-102). Based on observed clinical activity in the Phase 1 part of the clinical trial, we believe that administration of a single dose of GH001 has the
potential to induce ultra-rapid remissions as measured by the Montgomery-Åsberg Depression Rating Scale, or MADRS, in certain patients, driven by the ultra-rapid onset of psychoactive effects (commonly within seconds) and an intense and short-lived
(commonly five to 30 minutes) psychoactive experience. Based on observed clinical activity in the Phase 2 part of the trial, we believe that administration of GH001 in an IDR with intra-subject dose escalation within a single day can further increase
the MADRS remission rate as compared to a single dose of GH001.
We have incurred losses since inception, including losses of $30.2 million for the nine months ended September 30, 2024, and losses of $35.6 million and $22.5 million for the years ended December 31, 2023 and 2022,
respectively. As of September 30, 2024, we had an accumulated deficit of $97.6 million. We expect to incur significant expenses and operating losses for the foreseeable future as we expand our research and development activities. In addition, our
losses from operations may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our clinical trials, our expenditures on other research and development activities and based on foreign currency translation
differences. We anticipate that our expenses will increase significantly in connection with our ongoing activities, if and as we:
|
• |
continue to develop and conduct clinical trials, including in expanded geographies such as the United States, for GH001, our inhalable mebufotenin product candidate, GH002, our intravenous mebufotenin product candidate, and GH003, our
intranasal mebufotenin product candidate for our initial indications and additional indications;
|
|
• |
continue both the technical development and expansion of our external manufacturing capabilities for our current product candidates GH001, GH002 and GH003 and of the medical devices required to deliver these product candidates, such as our
proprietary aerosol delivery device for GH001;
|
|
• |
initiate and continue research and development, including nonclinical, clinical, and discovery efforts for any future product candidates;
|
|
• |
seek to identify additional product candidates;
|
|
• |
seek regulatory approvals for our product candidates GH001, GH002 and GH003, including the medical devices required to deliver these product candidates, such as our proprietary aerosol delivery device, or any other product candidates that
successfully complete clinical development;
|
|
• |
progress any nonclinical programs and any other work that may be required to lift the clinical hold on the study we proposed in our IND for GH001;
|
|
• |
add operational, financial and management information systems and personnel, including personnel to support our product candidate and device development and help us comply with our obligations as a public company;
|
|
• |
hire and retain additional personnel, such as clinical, quality control, scientific, commercial, sales, marketing and administrative personnel;
|
|
• |
continue to prepare, file, prosecute, maintain, protect and enforce our intellectual property rights and claims;
|
|
• |
establish sales, marketing, distribution, manufacturing, supply chain and other commercial infrastructure in the future to commercialize various products for which we may obtain regulatory approval;
|
|
• |
comply with ongoing regulatory requirements for products approved for commercial sale, if ever;
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|
• |
acquire or in-license other product candidates, medical devices to deliver our product candidates, and other technologies; and
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|
• |
incur increased costs as a result of operating as a public company.
|
In addition, as we progress toward marketing approval for any of our product candidates, we also expect to incur significant commercialization expenses related to product manufacturing, marketing, sales, and
distribution.
As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy. Until such time as we can generate significant revenue from product sales, if ever, we
expect to finance our operations through the sale of equity, debt financings or other capital sources, including potential collaborations with other companies or other strategic transactions. We cannot be certain that additional funding will be
available on acceptable terms, or at all. If we fail to raise capital or enter into such agreements as and when needed, we may have to significantly delay, scale back, or discontinue the development and commercialization of one or more of our product
candidates or other research and development initiatives, which could have a material adverse effect on our business, results of operations, and financial condition. We will need to generate significant revenue to achieve profitability, and we may
never do so.
We are subject to a number of risks comparable to those of other similar companies, including dependence on key individuals; the need to develop product candidates with the required safety and efficacy profile and
which support regulatory approval and are commercially viable; competition from other companies, many of which are larger and better capitalized; and the need to obtain adequate additional financing to fund the development of our product candidates.
Business Updates
GH001 in Patients with TRD
GH001, our proprietary inhaled mebufotenin (5-MeO-DMT) product candidate, is currently being investigated in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in approximately 80 patients with
treatment-resistant depression (TRD) (GH001-TRD-201). GH001 is administered on a single dosing day, without mandated in-trial psychotherapeutic intervention, consistent with our previously completed trials.
We completed enrolment of the double-blind phase in the third quarter of 2024, with top-line data expected to be available in the fourth quarter of 2024 or the first quarter of 2025. This trial includes a 6-month
open-label extension which is on track for completion in the first quarter of 2025.
GH001 Administered with Proprietary Aerosol Delivery Device
Our Phase 1 clinical pharmacology trial to evaluate our proprietary aerosol delivery device for administration of GH001 in healthy volunteers (GH001-HV-106) is ongoing in the United Kingdom. This trial is designed to
support our global program for GH001, by bridging to the clinical data generated with the commercially available device that we have used in our clinical trials to date.
Update on IND for GH001
As previously announced, our investigational new drug application (IND) for GH001 administered using our proprietary aerosol delivery device was placed on clinical hold by the U.S. Food and Drug Administration (FDA).
Based on interactions with the FDA, we believe we have a path to respond on the device element of the hold. The nonclinical studies to address the inhalation toxicology aspect are ongoing.
Proof-of-Concept Trials with GH001
GH001 is being investigated in a proof-of-concept clinical trial in bipolar II disorder in patients with a current depressive episode (BDII) (GH001-BD-202). While
increasing the number of sites has improved enrolment, recruitment has continued to be difficult and, for these reasons, the trial will end in the fourth quarter of 2024.
GH001 is also being investigated in a proof-of-concept clinical trial in patients with postpartum depression (PPD) (GH001-PPD-203). We continue to expect GH001-PPD-203
completion in the fourth quarter of 2024.
Results of Operations
Comparison of the three months ended September 30, 2024 and 2023
The following table summarizes our results of operations for the three months ended September 30, 2024 and 2023:
|
|
|
Three months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
Operating Expenses:
|
|
|
|
|
|
|
|
|
|
|
Research and development
|
|
|
(8,397
|
)
|
|
|
(7,088
|
)
|
|
|
(1,309
|
)
|
|
General and administrative
|
|
|
(4,224
|
)
|
|
|
(2,631
|
)
|
|
|
(1,593
|
)
|
|
Loss from operations
|
|
|
(12,621
|
)
|
|
|
(9,719
|
)
|
|
|
(2,902
|
)
|
|
Net finance income1
|
|
|
2,352
|
|
|
|
2,237
|
|
|
|
115
|
|
|
Foreign exchange (loss)/gain
|
|
|
(1,845
|
)
|
|
|
1,833
|
|
|
|
(3,678
|
)
|
|
Loss for the period
|
|
|
(12,114
|
)
|
|
|
(5,649
|
)
|
|
|
(6,465
|
)
|
1Net finance income for the three months ended September 30, 2024 and 2023, comprises finance income, finance expense and
expected credit losses.
Research and Development Expenses
The following table summarizes our research and development expenses for the three months ended September 30, 2024 and 2023:
|
|
|
Three months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
External research and development expenses
|
|
|
(6,728
|
)
|
|
|
(5,207
|
)
|
|
|
(1,521
|
)
|
|
Employee expenses1
|
|
|
(1,606
|
)
|
|
|
(1,812
|
)
|
|
|
206
|
|
|
Depreciation
|
|
|
(5
|
)
|
|
|
(8
|
)
|
|
|
3
|
|
|
Other expenses
|
|
|
(58
|
)
|
|
|
(61
|
)
|
|
|
3
|
|
|
Research and development
|
|
|
(8,397
|
)
|
|
|
(7,088
|
)
|
|
|
(1,309
|
)
|
1 Includes a share-based compensation expense of $0.1 million and a share-based compensation expense of $0.4 million for
the three months ended September 30, 2024 and 2023, respectively.
The following table summarizes our research and development expenses for our product candidates for the three months ended September 30, 2024 and 2023:
|
|
|
Three months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
GH001
|
|
|
(6,551
|
)
|
|
|
(4,298
|
)
|
|
|
(2,253
|
)
|
|
GH002
|
|
|
(316
|
)
|
|
|
(400
|
)
|
|
|
84
|
|
|
GH003
|
|
|
-
|
|
|
|
(19
|
)
|
|
|
19
|
|
|
Related to multiple product candidates (GH001, GH002 and GH003) and exploratory work for potential future product candidates 1
|
|
|
(1,530
|
)
|
|
|
(2,371
|
)
|
|
|
841
|
|
|
Research and development
|
|
|
(8,397
|
)
|
|
|
(7,088
|
)
|
|
|
(1,309
|
)
|
1 Includes expenses that relate to any combination of GH001, GH002 and/or GH003 and exploratory work for potential future product
candidates.
Research and development expenses increased by $1.3 million to $8.4 million for the three months ended September 30, 2024, from $7.1 million for the three months ended September 30, 2023. The increase is primarily due
to increased expenses relating to our clinical development activities including clinical trials and nonclinical activities, partly offset by the recognition of a research and development tax credit.
Our research and development expenses for our product candidates have fluctuated from period to period, and are likely to fluctuate, primarily due to the nature and timing associated with the various lifecycle stages
of each candidate.
Research and development expenses relating to GH001 increased by $2.3 million in the three months ended September 30, 2024, primarily due to an increase in our clinical development activities including clinical trials,
and nonclinical activities .
Research and development expenses relating to multiple product candidates decreased by $0.8 million in the three months ended September 30, 2024, primarily due to the recognition of a research and development tax
credit.
General and Administrative Expenses
The following table summarizes our general and administrative expenses for the three months ended September 30, 2024 and 2023:
|
|
|
Three months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
External costs
|
|
|
|
) |
|
|
|
) |
|
|
(1,291
|
)
|
|
Employee expenses1
|
|
|
(1,134
|
)
|
|
|
(834
|
)
|
|
(300
|
) |
|
Depreciation
|
|
|
(74
|
)
|
|
|
(72
|
)
|
|
|
(2
|
)
|
|
General and administrative
|
|
|
(4,224
|
)
|
|
|
(2,631
|
)
|
|
(1,593
|
)
|
1 Includes a share-based compensation expense of $0.1 million and $0.2 million for the three months ended September 30,
2024 and 2023, respectively.
General and administrative expenses increased by $1.6 million to $4.2 million for the three months ended September 30, 2024, from $2.6 million for the three months ended September 30, 2023. The increase is primarily
due to an increase in professional fees and employee expenses in our general and administrative functions to support our growth initiatives.
Foreign Exchange Loss/Gain
Foreign exchange loss is $1.8 million for the three months ended September 30, 2024, a movement of $3.7 million from a gain of $1.8 million for the three months ended September 30, 2023. This movement is primarily
because of the translation of the U.S. dollar cash and other financial assets balances in the accounts of our subsidiary into its functional currency, which is the euro. During the three months ended September 30, 2024, the U.S. dollar weakened
compared to the euro, which resulted in the foreign exchange loss.
Comparison of the nine months ended September 30, 2024 and 2023
The following table summarizes our results of operations for the nine months ended September 30, 2024 and 2023:
|
|
|
Nine months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
Operating Expenses:
|
|
|
|
|
|
|
|
|
|
|
Research and development
|
|
|
(26,810
|
)
|
|
|
(21,570
|
)
|
|
|
(5,240
|
)
|
|
General and administrative
|
|
|
(10,558
|
)
|
|
|
(8,493
|
)
|
|
|
(2,065
|
)
|
|
Loss from operations
|
|
|
(37,368
|
)
|
|
|
(30,063
|
)
|
|
|
(7,305
|
)
|
|
Net finance income1
|
|
|
7,267
|
|
|
|
5,516
|
|
|
|
1,751
|
|
|
Foreign exchange (loss)/gain
|
|
|
(58
|
)
|
|
|
232
|
|
|
|
(290
|
)
|
|
Loss for the period
|
|
|
(30,159
|
)
|
|
|
(24,315
|
)
|
|
|
(5,844
|
)
|
1Net finance income for the nine months ended September 30, 2024 and 2023, comprises finance income, finance expense and
expected credit losses.
Research and Development Expenses
The following table summarizes our research and development expenses for the nine months ended September 30, 2024 and 2023:
|
|
|
Nine months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
External research and development expenses
|
|
|
(21,651
|
)
|
|
|
(16,521
|
)
|
|
|
(5,130
|
)
|
|
Employee expenses1
|
|
|
(4,964
|
)
|
|
|
(4,857
|
)
|
|
|
(107
|
)
|
|
Depreciation
|
|
|
(16
|
)
|
|
|
(28
|
)
|
|
|
12
|
|
|
Other expenses
|
|
|
(179
|
)
|
|
|
(164
|
)
|
|
|
(15
|
)
|
|
Research and development
|
|
|
(26,810
|
)
|
|
|
(21,570
|
)
|
|
|
(5,240
|
)
|
1 Includes share-based compensation expense of $0.2 million and $1.0 million for the nine months ended September 30, 2024
and 2023, respectively.
The following table summarizes our research and development expenses for our product candidates for the nine months ended September 30, 2024 and 2023:
|
|
|
Nine months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
GH001
|
|
|
(18,867
|
)
|
|
|
(12,913
|
)
|
|
|
(5,954
|
)
|
|
GH002
|
|
|
(1,472
|
)
|
|
|
(1,528
|
)
|
|
|
56
|
|
|
GH003
|
|
|
(18
|
)
|
|
|
(161
|
)
|
|
|
143
|
|
|
Related to multiple product candidates (GH001, GH002 and GH003) and exploratory work for potential future product candidates 1
|
|
|
(6,453
|
)
|
|
|
(6,968
|
)
|
|
|
515
|
|
|
Research and development
|
|
|
(26,810
|
)
|
|
|
(21,570
|
)
|
|
|
(5,240
|
)
|
1 Includes expenses that relate to any combination of GH001, GH002 and/or GH003 and exploratory work for potential future product
candidates.
Research and development expenses increased by $5.2 million to $26.8 million for the nine months ended September 30, 2024, from $21.6 million for the nine months ended September 30, 2023. The increase is primarily due
to increased expenses relating to our clinical development activities including clinical trials and nonclinical activities, partly offset by a decrease in technical development expenses and the recognition of a research and development tax credit.
Employee expenses also increased primarily due to the hiring of personnel to support our research and development activities.
Our research and development expenses for our product candidates have fluctuated from period to period, and are likely to continue to fluctuate, primarily due to the nature and timing associated with the various
lifecycle stages of each candidate.
Research and development expenses relating to GH001 increased by $6.0 million in the nine months ended September 30, 2024, primarily due to an increase in our clinical development activities including clinical trials
and nonclinical activities, partly offset by a decrease in technical development expenses.
Research and development expenses which relate to multiple product candidates decreased by $0.5 million in the nine months ended September 30, 2024, primarily due to a decrease in technical development expenses and the
recognition of a research and development tax credit. These costs have been partly offset by an increase in our clinical development activities, including nonclinical activities and increased employee expenses.
General and Administrative Expenses
The following table summarizes our general and administrative expenses for the nine months ended September 30, 2024, and 2023:
|
|
|
Nine months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
External costs
|
|
|
(7,253
|
)
|
|
|
(5,834
|
)
|
|
|
(1,419
|
)
|
|
Employee expenses1
|
|
|
(3,084
|
)
|
|
|
(2,450
|
)
|
|
|
(634
|
)
|
|
Depreciation
|
|
|
(221
|
)
|
|
|
(209
|
)
|
|
|
(12
|
)
|
|
General and administrative
|
|
|
(10,558
|
)
|
|
|
(8,493
|
)
|
|
|
(2,065
|
)
|
1 Includes share-based compensation expense of $0.2 million and $0.7 million for the nine months ended September 30, 2024 and 2023,
respectively.
General and administrative expenses increased by $2.1 million to $10.6 million for the nine months ended September 30, 2024, from $8.5 million for the nine months ended September 30, 2023. The increase is primarily due
to an increase in professional fees and employee expenses in our general and administrative functions to support our growth initiatives.
Net Finance Income
Our net finance income increased by $1.8 million for the nine months ended September 30, 2024, from $5.5 million for the nine months ended September 30, 2023. The increase is primarily due to an increase in finance
income of $1.5 million on cash, cash equivalents and other financial assets, as well as an increase in the fair value gain on cash equivalents and other financial assets.
Foreign Exchange Gain/Loss
Foreign exchange loss is $0.1 million for the nine months ended September 30, 2024, a movement of $0.3 million from a gain of $0.2 million for the nine months ended September 30, 2023. This movement is primarily
because of the translation of the U.S. dollar cash and other financial assets balance in the accounts of our subsidiary into its functional currency, which is the euro. During the nine months ended September 30, 2024, the U.S. dollar weakened
compared to the euro, which resulted in the foreign exchange loss.
Liquidity and Capital Resources
Sources of Liquidity
We have incurred operating losses since inception, and we have not generated any revenue from any product sales or any other sources. We have not yet commercialized any of our product candidates, which are in various
phases of technical and clinical development, and we do not expect to generate revenue from sales of any products for several years, if at all. Until such time as we can generate significant revenue from product sales, if ever, we expect to finance
our operations through the sale of equity, debt financings or other capital sources, including potential collaborations with other companies or other strategic transactions. We have funded our operations to date primarily through equity financings,
including our initial public offering. As of September 30, 2024, we had cash, cash equivalents, other financial assets and marketable securities of $193.8 million, compared to cash, cash equivalents, other financial assets and marketable securities
of $222.7 million as of December 31, 2023.
We plan to continue to fund our operating and capital funding needs through sales of additional equity or other forms of financing. We may also consider pursuing strategic partnerships for clinical development and
commercialization of our product candidates. The sale of additional equity would result in additional dilution to our shareholders.
Cash Flows
The following table provides information regarding our cash flows for the nine months ended September 30, 2024 and 2023:
|
|
|
Nine months ended
September 30
|
|
|
|
|
2024
|
|
|
2023
|
|
|
Change
|
|
| |
|
(in USD thousands)
|
|
|
Net cash flows used in operating activities
|
|
|
(31,839
|
)
|
|
|
(25,251
|
)
|
|
|
(6,588
|
)
|
|
Net cash flows from/(used in) investing activities
|
|
|
43,804
|
|
|
|
(54,076
|
)
|
|
|
97,880
|
|
|
Net cash flows used in financing activities
|
|
|
(245
|
)
|
|
|
(163
|
)
|
|
|
(82
|
)
|
|
Net increase/(decrease) in cash and cash equivalents
|
|
|
11,720
|
|
|
|
(79,490
|
)
|
|
|
91,210
|
|
Net Cash Flows Used in Operating Activities
Net cash flows used in operating activities increased by $6.6 million to $31.8 million for the nine months ended September 30, 2024, from $25.3 million for the nine months ended September 30, 2023, primarily due to an
increase in loss from operations for the period and movement in working capital.
Net Cash Flows From/(Used in) Investing Activities
Net cash flows from investing activities for the nine months ended September 30, 2024, is $43.8 million, a movement of $97.9 million from net cash flows used in investing activities of $54.1 million for the nine months
ended September 30, 2023. The net cash from investing activities during the nine months ended September 30, 2024, comprised the receipt of proceeds from the sale of financial assets of $25.0 million and the redemption of marketable securities of
$18.8 million. The net cash used in investing activities during the nine months ended September 30, 2023, was primarily due to an investment in a money market fund of $54.0 million.
Funding Requirements
We expect our expenses to continue to increase substantially in connection with our ongoing research and development activities, particularly as we advance the technical development work, nonclinical studies and
clinical trials of our product candidates and the medical devices required to deliver such product candidates, such as our proprietary aerosol delivery device for GH001. In addition, if we obtain regulatory approval for any of our product candidates,
we expect to incur significant commercialization expenses related to sales, marketing, manufacturing and distribution. Furthermore, we have incurred and expect to continue to incur additional costs associated with operating as a public company. Until
such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of public or private equity offerings, debt financings, convertible debt financings, strategic collaborations and licensing
arrangements. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and
market product candidates that we would otherwise prefer to develop and market ourselves. Our future capital requirements will depend on many factors, which are outlined in our annual report on Form 20-F for the year ended December 31, 2023 and this
discussion and analysis. We believe that we have sufficient financial resources available to cover our planned cash outflows for at least the next twelve months.
Critical Accounting Estimates
There have been no material changes to the significant accounting policies and significant judgments and estimates from those referred to in the section in our annual report on Form 20-F for the year ended December 31,
2023, titled “Item 5. Operating and Financial Review and Prospects—E. Critical Accounting Estimates.”
Emerging Growth Company Status
On April 5, 2012, the Jumpstart our Business Act of 2012 (“JOBS Act”) was enacted. As an emerging growth company, or EGC, we rely on exemptions and reduced reporting requirements under the JOBS Act including exemptions
from (i) providing an auditor’s attestation report on our system of internal controls over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act and (ii) complying with any requirement that may be adopted by the Public Company
Accounting Oversight Board, regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements, known as the auditor discussion and analysis.
We will remain classified as an EGC until the earlier of (1) the last day of the fiscal year (i) in which we have total annual gross revenue of $1.235 billion; (ii) following the fifth anniversary of the completion of
our initial public offering; or (iii) in which we are deemed to be a “large accelerated filer,” which requires the market value of our ordinary shares that is held by non-affiliates to exceed $700 million as of the prior September 30th, and (2) the date on which we have issued more than $1 billion in nonconvertible debt during the previous three-year period.
Recently Issued Accounting Pronouncements
As disclosed in note 2 to our unaudited condensed consolidated interim financial statements, there are no standards that are mandatory for the financial year beginning on January 1, 2024, that are relevant to and have
had any material impact on our unaudited condensed consolidated interim financial statements. The review of the impact of new standards on our unaudited condensed consolidated interim financial statements, including the recently issued IFRS 18
“Presentation and Disclosure in Financial Statements”, which is not yet effective and which has not been early adopted by us is ongoing.
Risk Factors
There have been no material changes in our risk factors from those disclosed in our annual report on Form 20-F for the year ended December 31, 2023.
Cautionary Statement Regarding Forward-Looking Statements
This discussion contains statements that are, or may be deemed to be, forward-looking. All statements other than statements of historical fact included in this discussion, including statements regarding our future
results of operations and financial position, business strategy, product candidates, medical devices required to deliver these product candidates, research pipeline, ongoing and currently planned preclinical studies and clinical trials, regulatory
submissions and approvals, research and development costs, cash runway, timing and likelihood of success, as well as plans and objectives of management for future operations are forward-looking statements. Many of the forward-looking statements
contained in this discussion can be identified by the use of forward-looking words such as “may,” “anticipate,” “believe,” “could,” “expect,” “should,” “plan,” “intend,” “estimate,” “will,” “potential” and “ongoing,” among others.
Forward-looking statements appear in a number of places in this discussion and include, but are not limited to, statements regarding our intent, belief or current expectations. Forward-looking statements are based on
our management’s beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking
statements due to various factors, including, but not limited to, those identified under the section in our annual report on Form 20-F for the year ended December 31, 2023 titled “Item 3. Key Information—D. Risk Factors.” These risks and
uncertainties include, among others, factors relating to:
|
• |
the commencement, timing, progress and results of our research and development programs, preclinical studies and clinical trials;
|
|
• |
the timing, progress and results of developing and conducting clinical trials for our GH001, GH002 and GH003 product candidates and the medical devices required to deliver these product candidates, such as our proprietary aerosol delivery
device for GH001, for our initial and any additional indications;
|
|
• |
our efforts to expand into other jurisdictions such as the United States and in the European Union;
|
|
• |
our expectations related to the technical development and expansion of our external manufacturing capabilities for our GH001, GH002 and GH003 product candidates as well as the medical devices required to deliver these product candidates,
such as our proprietary aerosol delivery device for GH001;
|
|
• |
our reliance on the success of our GH001, GH002 and GH003 product candidates;
|
|
• |
the timing, scope or likelihood of regulatory filings and approvals by the U.S. Food and Drug Administration, or the FDA, the European Medicines Agency, or the EMA, or other comparable foreign regulatory authorities, for our GH001, GH002
and GH003 product candidates and our initial and any additional indications;
|
|
• |
our expectations related to the clinical hold imposed by the FDA on the study we proposed in our IND for GH001, including our plans and expectations for progressing any nonclinical programs and any other work to lift the clinical hold, the
timing required to lift such clinical hold and for discussions with the FDA and the outcomes and resolution of such discussions;
|
|
• |
our expectations regarding the size of the eligible patient populations for our GH001, GH002 and GH003 product candidates, if approved for commercial use;
|
|
• |
our ability to identify third-party clinical trial sites to conduct trials and our ability to identify and train appropriately qualified therapists to administer our investigational therapy;
|
|
• |
the effect of pandemics, such as the COVID-19 pandemic, epidemics, outbreaks of an infectious disease or similar events on aspects of our business operations, including delays in the regulatory approval process, contracting with clinical
trial sites and engaging in clinical trials;
|
|
• |
our ability to implement our business model and our strategic plans for our business and GH001, GH002 and GH003 product candidates;
|
|
• |
our ability to identify, develop or acquire and obtain approval by the FDA, EMA or other comparable foreign regulatory authorities of medical devices required to deliver our GH001, GH002 and GH003 product candidates, such as our
proprietary aerosol delivery device for GH001;
|
|
• |
our commercialization and marketing capabilities and strategy;
|
|
• |
the effects of undesirable clinical trial outcomes and potential adverse public perception regarding the use of mebufotenin (5-MeO-DMT) and psychedelics generally on the regulatory approval process and future development of our product;
|
|
• |
the pricing, coverage and reimbursement of our GH001, GH002 and GH003 product candidates, if approved;
|
|
• |
the scalability and commercial viability of our manufacturing methods and processes;
|
|
• |
the rate and degree of market acceptance and clinical utility of our GH001, GH002 and GH003 product candidates;
|
|
• |
our reliance on third-party suppliers for our nonclinical study and clinical trial drug substance and product candidate supplies, as well as key raw materials used in our manufacturing processes;
|
|
• |
our ability to establish or maintain collaborations or strategic relationships or obtain additional funding;
|
|
• |
our expectations regarding potential benefits of our GH001, GH002 and GH003 product candidates and our approach generally;
|
|
• |
our expectations around regulatory development paths and with respect to Controlled Substances Act, or CSA, classification;
|
|
• |
the scope of protection we and any current or future licensors or collaboration partners are able to establish and maintain for intellectual property rights covering our GH001, GH002 and GH003 product candidates;
|
|
• |
our ability to operate our business without infringing, misappropriating, or otherwise violating the intellectual property rights and proprietary technology of third parties;
|
|
• |
our ability to protect our intellectual property rights, including enforcing and defending intellectual property-related claims;
|
|
• |
regulatory developments in the United States, under the laws and regulations of the European Union and other jurisdictions;
|
|
• |
continuing inflation, interest rates and foreign currency exchange rates, disruptions in global supply chains and labor markets, volatility and stress within the banking sector and the measures governments and financial services companies
have taken in response, and geopolitical risks and global hostilities, including any direct or indirect economic impacts resulting from Russia’s invasion of Ukraine, the ongoing military conflict between Israel and Hamas and any resulting
conflicts in the region, or increased tensions between China and Taiwan;
|
|
• |
developments and projections relating to our competitors and our industry;
|
|
• |
our ability to remediate our material weaknesses in our internal control over financial reporting;
|
|
• |
the amount of time that our existing cash, cash equivalents, other financial assets and marketable securities will be sufficient to fund our operations and capital expenditures;
|
|
• |
our estimates regarding expenses, capital requirements and needs for additional financing;
|
|
• |
our ability to effectively manage our anticipated growth;
|
|
• |
our ability to attract and retain qualified employees and key personnel;
|
|
• |
whether we are classified as a passive foreign investment company for current and future periods;
|
|
• |
our expectations regarding the time during which we will be an EGC under the JOBS Act and as a foreign private issuer;
|
|
• |
the future trading price of the ordinary shares and impact of securities analysts’ reports on these prices; and
|
|
• |
other risks and uncertainties, including those listed under “Item 3. Key Information—D. Risk Factors.”
|
These forward-looking statements speak only as of the date of this discussion and are subject to a number of risks, uncertainties and assumptions described under the sections in our annual report on Form 20-F for the
year ended December 31, 2023, titled “Item 3. Key Information—D. Risk Factors” and “Item 5. Operating and Financial Review and Prospects” and elsewhere in our annual report and this discussion. Because forward-looking statements are inherently
subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances
reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in an evolving environment. New risk factors and
uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements
contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this discussion,
and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all
potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.
Exhibit 99.3
GH Research Reports Third Quarter 2024 Financial Results and Provides Business Updates
November 14, 2024
|
• |
Phase 2b clinical trial of GH001 in patients with treatment-resistant depression completed enrolment of the double-blind phase in Q3 2024
|
|
• |
Phase 1 clinical trial to evaluate proprietary aerosol delivery device in healthy volunteers is ongoing in the UK
|
|
• |
Cash, cash equivalents, other financial assets and marketable securities of $193.8 million
|
DUBLIN, November 14, 2024 (GLOBE NEWSWIRE) -- GH Research PLC (Nasdaq: GHRS), a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological
disorders, today reported financial results for the third quarter ended September 30, 2024, and provided updates on its business.
Business Updates
GH001 in Patients with TRD
GH001, our proprietary inhaled mebufotenin (5-MeO-DMT) product candidate, is currently being investigated in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial in
approximately 80 patients with treatment-resistant depression (TRD) (GH001-TRD-201). GH001 is administered on a single dosing day, without mandated in-trial psychotherapeutic intervention, consistent with our previously completed trials.
We completed enrolment of the double-blind phase in the third quarter of 2024, with top-line data expected to be available in the fourth quarter of 2024 or the first quarter of 2025. This trial
includes a 6-month open-label extension which is on track for completion in the first quarter of 2025.
GH001 Administered with Proprietary Aerosol Delivery Device
Our Phase 1 clinical pharmacology trial to evaluate our proprietary aerosol delivery device for administration of GH001 in healthy volunteers (GH001-HV-106) is ongoing in the United
Kingdom. This trial is designed to support our global program for GH001, by bridging to the clinical data generated with the commercially available device that we have used in our clinical trials to date.
Update on IND for GH001
As previously announced, our investigational new drug application (IND) for GH001 administered using our proprietary aerosol delivery device was placed on clinical hold by the U.S.
Food and Drug Administration (FDA). Based on interactions with the FDA, we believe we have a path to respond on the device element of the hold. The nonclinical studies to address the inhalation toxicology aspect are ongoing.
Proof-of-Concept Trials with GH001
GH001 is being investigated in a proof-of-concept clinical trial in bipolar II disorder in patients with a current depressive episode (BDII) (GH001-BD-202). While increasing the number
of sites has improved enrolment, recruitment has continued to be difficult and, for these reasons, the trial will end in the fourth quarter of 2024.
GH001 is also being investigated in a proof-of-concept clinical trial in patients with postpartum depression (PPD) (GH001-PPD-203). We continue to expect GH001-PPD-203 completion in
the fourth quarter of 2024.
Third Quarter 2024 Financial Highlights
Cash position
Cash, cash equivalents, other financial assets and marketable securities were $193.8 million as of September 30, 2024, compared to cash, cash equivalents, other financial assets and marketable
securities of $222.7 million as of December 31, 2023. Other financial assets are comprised of money market funds, and marketable securities are comprised of investment grade bonds.
Research and development expenses
R&D expenses were $8.4 million for the quarter ended September 30, 2024, compared to $7.1 million for same quarter in 2023. The increase is primarily due to increased expenses relating to our
clinical development activities including clinical trials and nonclinical activities.
General and administrative expenses
G&A expenses were $4.2 million for the quarter ended September 30, 2024, compared to $2.6 million for the same quarter in 2023. The increase is primarily due to an increase in professional
fees and employee expenses in our general and administrative functions to support our growth initiatives.
Net loss
Net loss was $12.1 million, or $0.23 loss per share, for the quarter ended September 30, 2024, compared to $5.6 million, or $0.11 loss per share, for the same quarter in 2023.
About GH Research PLC
GH Research PLC is a clinical-stage biopharmaceutical company dedicated to transforming the treatment of psychiatric and neurological disorders. GH Research PLC's initial focus is on developing
its novel and proprietary mebufotenin (5-MeO-DMT) therapies for the treatment of patients with treatment-resistant depression (TRD).
GH Research PLC's annual report on Form 20-F filed with the U.S. Securities and Exchange Commission for the year ended December 31, 2023 is available at www.ghres.com and shareholders may receive a hard copy free of charge upon request.
About GH001
Our lead product candidate, GH001, is formulated for mebufotenin (5-MeO-DMT) administration via a proprietary inhalation approach. With GH001, we have completed two Phase 1 healthy volunteer
clinical trials and a Phase 1/2 clinical trial in patients with TRD. Based on the observed clinical activity, where 87.5% of patients with TRD achieved ultra-rapid remission with our GH001 individualized single-day dosing regimen in the Phase 2 part
of the trial, we believe that GH001 has the potential to change the way TRD is treated today.
About GH002 and GH003
GH002 is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intravenous approach. We have completed a Phase 1 trial of GH002 in healthy volunteers. GH003
is our mebufotenin (5-MeO-DMT) product candidate formulated for administration via a proprietary intranasal administration approach. GH003 is currently in preclinical development. We anticipate developing GH002 and GH003 within our focus areas of
psychiatric and neurological disorders.
Forward-Looking Statements
This press release contains statements that are, or may be deemed to be, forward-looking statements. All statements other than statements of historical fact included in this press release, including
statements regarding our future results of operations and financial position, business strategy, product candidates, medical devices required to deliver these product candidates, research pipeline, ongoing and currently planned preclinical studies
and clinical trials, regulatory submissions and approvals and their effects on our business strategy, including our plans and expectations related to addressing the clinical hold on the GH001 IND, research and development costs, cash runway, timing
and likelihood of success, as well as plans and objectives of management for future operations, are forward-looking statements. Forward-looking statements appear in a number of places in this press release and include, but are not limited to,
statements regarding our intent, belief or current expectations. Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and
uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including, but not limited to, those described in our filings with the U.S. Securities and Exchange
Commission. No assurance can be given that such future results will be achieved. Such forward-looking statements contained in this press release speak only as of the date hereof. We expressly disclaim any obligation or undertaking to update these
forward-looking statements contained in this press release to reflect any change in our expectations or any change in events, conditions, or circumstances on which such statements are based unless required to do so by applicable law. No
representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Investor Relations:
Julie Ryan
GH Research PLC
investors@ghres.com
GH RESEARCH PLC
Condensed Consolidated Interim Statement of Comprehensive Income (Unaudited)
(in thousands, except share and per share amounts)
| |
|
Three months ended
September 30,
|
|
|
Nine months ended
September 30,
|
|
| |
|
2024
|
|
|
2023
|
|
|
2024
|
|
|
2023
|
|
| |
|
$’000
|
|
|
$’000
|
|
|
$’000
|
|
|
$’000
|
|
|
Operating expenses
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development
|
|
|
(8,397
|
)
|
|
|
(7,088
|
)
|
|
|
(26,810
|
)
|
|
|
(21,570
|
)
|
|
General and administration
|
|
|
(4,224
|
)
|
|
|
(2,631
|
)
|
|
|
(10,558
|
)
|
|
|
(8,493
|
)
|
|
Loss from operations
|
|
|
(12,621
|
)
|
|
|
(9,719
|
)
|
|
|
(37,368
|
)
|
|
|
(30,063
|
)
|
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Finance income
|
|
|
2,535
|
|
|
|
2,438
|
|
|
|
7,760
|
|
|
|
6,049
|
|
|
Finance expense
|
|
|
(181
|
)
|
|
|
(184
|
)
|
|
|
(538
|
)
|
|
|
(534
|
)
|
|
Movement of expected credit loss
|
|
|
(2
|
)
|
|
|
(17
|
)
|
|
|
45
|
|
|
|
1
|
|
|
Foreign exchange (loss)/gain
|
|
|
(1,845
|
)
|
|
|
1,833
|
|
|
|
(58
|
)
|
|
|
232
|
|
|
Total other income
|
|
|
507
|
|
|
|
4,070
|
|
|
|
7,209
|
|
|
|
5,748
|
|
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Loss before tax
|
|
|
(12,114
|
)
|
|
|
(5,649
|
)
|
|
|
(30,159
|
)
|
|
|
(24,315
|
)
|
|
Tax charge/(credit)
|
|
|
-
|
|
|
|
-
|
|
|
|
-
|
|
|
|
-
|
|
|
Loss for the period
|
|
|
(12,114
|
)
|
|
|
(5,649
|
)
|
|
|
(30,159
|
)
|
|
|
(24,315
|
)
|
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Other comprehensive income/(expense)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Items that may be reclassified to profit or loss
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Fair value movement on marketable securities
|
|
|
908
|
|
|
|
(428
|
)
|
|
|
258
|
|
|
|
(1,216
|
)
|
|
Currency translation adjustment
|
|
|
1,622
|
|
|
|
(1,780
|
)
|
|
|
(113
|
)
|
|
|
(161
|
)
|
|
Total comprehensive loss for the period
|
|
|
(9,584
|
)
|
|
|
(7,857
|
)
|
|
|
(30,014
|
)
|
|
|
(25,692
|
)
|
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Attributable to owners:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Loss for the period
|
|
|
(12,114
|
)
|
|
|
(5,649
|
)
|
|
|
(30,159
|
)
|
|
|
(24,315
|
)
|
|
Total comprehensive loss for the period
|
|
|
(9,584
|
)
|
|
|
(7,857
|
)
|
|
|
(30,014
|
)
|
|
|
(25,692
|
)
|
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Loss per share
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic and diluted loss per share (in USD)
|
|
|
(0.23
|
)
|
|
|
(0.11
|
)
|
|
|
(0.58
|
)
|
|
|
(0.47
|
)
|
GH RESEARCH PLC
Condensed Consolidated Interim Balance Sheet (Unaudited)
(in thousands)
| |
|
At September 30,
|
|
|
At December 31,
|
|
| |
|
2024
|
|
|
2023
|
|
| |
|
|
|
|
|
|
|
ASSETS
|
|
|
|
|
|
|
|
|
|
Current assets
|
|
|
|
|
|
|
|
|
|
Cash and cash equivalents
|
|
|
90,059
|
|
|
|
78,420
|
|
|
Other financial assets
|
|
|
32,517
|
|
|
|
55,615
|
|
|
Marketable securities
|
|
|
27,461
|
|
|
|
27,525
|
|
|
Other current assets
|
|
|
4,909
|
|
|
|
2,529
|
|
|
Total current assets
|
|
|
154,946
|
|
|
|
164,089
|
|
|
Non-current assets
|
|
|
|
|
|
|
|
|
|
Marketable securities
|
|
|
43,806
|
|
|
|
61,142
|
|
|
Property, plant and equipment
|
|
|
859
|
|
|
|
1,069
|
|
|
Total non-current assets
|
|
|
44,665
|
|
|
|
62,211
|
|
|
Total assets
|
|
|
199,611
|
|
|
|
226,300
|
|
| |
|
|
|
|
|
|
|
|
|
LIABILITIES AND EQUITY
|
|
|
|
|
|
|
|
|
|
Current liabilities
|
|
|
|
|
|
|
|
|
|
Trade payables
|
|
|
2,946
|
|
|
|
3,490
|
|
|
Lease liability
|
|
|
275
|
|
|
|
343
|
|
|
Other current liabilities
|
|
|
6,566
|
|
|
|
2,868
|
|
|
Total current liabilities
|
|
|
9,787
|
|
|
|
6,701
|
|
|
Non-current liabilities
|
|
|
|
|
|
|
|
|
|
Lease liability
|
|
|
458
|
|
|
|
631
|
|
|
Total non-current liabilities
|
|
|
458
|
|
|
|
631
|
|
|
Total liabilities
|
|
|
10,245
|
|
|
|
7,332
|
|
| |
|
|
|
|
|
|
|
|
|
Equity attributable to owners
|
|
|
|
|
|
|
|
|
|
Share capital
|
|
|
1,301
|
|
|
|
1,301
|
|
|
Additional paid-in capital
|
|
|
291,463
|
|
|
|
291,463
|
|
|
Other reserves
|
|
|
4,866
|
|
|
|
4,651
|
|
|
Foreign currency translation reserve
|
|
|
(10,620
|
)
|
|
|
(10,507
|
)
|
|
Accumulated deficit
|
|
|
(97,644
|
)
|
|
|
(67,940
|
)
|
|
Total equity
|
|
|
189,366
|
|
|
|
218,968
|
|
|
Total liabilities and equity
|
|
|
199,611
|
|
|
|
226,300
|
|
