Form 8-K - Current report

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

    Date of Report (Date of earliest event reported): November 21, 2024

   

Perspective Therapeutics, Inc.

(Exact name of Registrant as Specified in Its Charter)


Delaware	001-33407	41-1458152
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)

2401 Elliott Avenue, Suite 320
Seattle, Washington		98121
(Address of Principal Executive Offices)		(Zip Code)

    Registrant’s Telephone Number, Including Area Code: (206) 676-0900

   

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:


Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.001 par value	CATX	NYSE American LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 8.01 Other Events.

On November 21, 2024, Perspective Therapeutics, Inc. issued a press release and posted to its website a presentation announcing certain initial results from its Phase 1/2a study of [212Pb]VMT-α-NET for the treatment and diagnosis of patients with somatostatin receptor subtype 2-expressing neuroendocrine tumors (NETs) that are being presented at the 2024 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium taking place from November 21-23, 2024 in Chicago, Illinois. A copy of the press release is filed herewith as Exhibit 99.1, and a copy of the presentation is filed herewith as Exhibit 99.2, and each is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits


Exhibit No.		Description
99.1		Press Release dated November 21, 2024.
99.2		Investor Presentation.
104		Cover Page Interactive Data File (embedded within the Inline XBRL document).

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.


			PERSPECTIVE THERAPEUTICS, INC.

Date:	November 21, 2024	By:	/s/ Johan (Thijs) Spoor
			Johan (Thijs) Spoor Chief Executive Officer

Perspective Therapeutics to Pursue Dose Escalation of [212Pb]VMT-α-NET in its Ongoing

Phase 1/2a Clinical Trial Based on Data Presented at the 2024 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium

•

[212Pb]VMT-α-NET continued to have a favorable safety profile, with no dose-limiting toxicities observed at the two doses tested (2.5 and 5.0 mCi)

•

Eight of nine patients had durable control of disease. Six of nine patients had a measurable reduction of tumor volume, one of whom had a confirmed response as defined by RECIST v1.1. Signal of anti-tumor activity was generally more pronounced in patients with lower body weight

•

Perspective is continuing all required activities to pursue dose escalation according to Safety Monitoring Committee recommendations; recruitment is ongoing at 5.0 mCi

SEATTLE, WASHINGTON – November 21, 2024 – Perspective Therapeutics, Inc. (“Perspective” or the “Company”) (NYSE AMERICAN: CATX), a radiopharmaceutical company that is pioneering advanced treatment applications for cancers throughout the body, announced initial results from its ongoing Phase 1/2a clinical trial of [212Pb]VMT-α-NET that are being presented at the 2024 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium taking place November 21-23, 2024 in Chicago.

VMT-α-NET is a somatostatin receptor type 2 (SSTR2)-targeted radiopharmaceutical therapy (RPT) that can be radiolabeled with either 203Pb for patient selection and dosimetry assessments, or 212Pb for alpha-particle therapy. Perspective received Fast Track Designation for this program from the U.S. Food and Drug Administration (FDA) based on preclinical data for SSTR2-positive neuroendocrine tumors (NETs) regardless of prior treatment response.

This Phase 1/2a clinical trial is a multi-center open-label dose escalation, dose expansion study (clinicaltrials.gov identifier NCT05636618) of [212Pb]VMT-α-NET in patients with unresectable or metastatic SSTR2-positive NETs who have not received prior RPTs and have shown radiological evidence of disease progression in the 12 months prior to enrollment.

Two patients were enrolled in Cohort 1, while seven patients were enrolled in Cohort 2. As of the data cut-off date for the NANETS presentation of October 31, 2024, eight patients had completed all four doses of treatment per the study protocol, while the remaining patient had completed three doses of treatment and will be scheduled to receive a fourth dose. As of the data cut-off

date, scans were available to the study team for four patients after their fourth treatment, and post-final treatment scans were pending for the remaining five patients.

Per the study protocol, two patients in Cohort 1 received administered activity of 2.5 mCi per dose regardless of body weight. Based on their respective body weights, the median administered activity per kilogram of weight was 45.5 µCi/kg per dose. Seven patients in Cohort 2 received administered activity of 5.0 mCi per dose regardless of body weight. Based on their respective body weights, the median administered activity per kilogram of weight was 62.1 µCi/kg per dose, ranging from 31.8 µCi/kg to 84.6 µCi/kg per dose. One patient in Cohort 2 received two doses of 84.6 µCi/kg per dose, then received the third and fourth doses at a reduced activity level of 42.4 µCi/kg per dose due to an adverse event that was determined by the investigator to be unrelated.

•

Safety findings: No dose limiting toxicities (DLTs) were observed among any patients. No grade 4 or 5 treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) were observed. Two grade 3 adverse events (AEs) – one case of diarrhea and one case of syncope – were observed. No decline in renal function was observed. Hematologic AEs such as decreased lymphocyte count and anemia were all grades 1 and 2. No treatment discontinuations due to AEs have occurred.

•

Activity has been observed with treatment. Eight of nine patients had durable control of disease. Six of nine patients had measurable reduction of tumor volume, one of whom had a confirmed response as defined by RECIST v1.1. The patient who experienced an objective response received the first two doses at 84.6 µCi/kg per dose, then received the remaining two doses at a reduced activity level of 42.4 µCi/kg. One patient was deemed to have progressive disease after one dose under RECIST v1.1, by unambiguous progression of non-target lesions.

The Safety Monitoring Committee (SMC) determined that safety observations during the DLT observation period supported proceeding with dose escalation to Cohort 3 and expanding the number of patients dosed at 5 mCi (up to 40 more patients). Based on FDA interactions prior to trial initiation, the decision to open Cohort 3 will follow consultation and alignment with the agency.

“I am excited to see that [212Pb]VMT-α-NET has demonstrated well-tolerated safety and appreciable activity at an early stage in this study,” said Richard L. Wahl, MD, Professor of Radiology, Mallinckrodt Institute of Radiology at Washington University School of Medicine. “These early clinical results support continuation of the dose escalation of [212Pb]VMT-α-NET.”

Markus Puhlmann, Chief Medical Officer of Perspective, commented, “Based on the safety profile and observed anti-tumor activities at this early stage, we believe the appropriate next step for patients is to continue treatment optimization for VMT-α-NET and to explore higher administered activities. In keeping with the commitment we made to the FDA prior to the start

of dosing in this study, we expect to engage with the FDA in the coming weeks to pursue dose escalation, and an update will be provided in due course.”

Thijs Spoor, Chief Executive Officer of Perspective, added, “VMT-α-NET is the second investigational product from our proprietary platform to have delivered initial clinical results from a Company-sponsored dose finding study, both of which began in 2023. We are excited about our plans to file an IND by the end of this year for the third investigational product, PSV359, an internally discovered molecule that targets fibroblast activation protein-α, or FAP-α, associated with a variety of solid tumors. We look forward to seeing more data from our existing clinical programs and making progress on our plans to leverage our platform to help more patients in need in 2025.”

About VMT-α-NET

VMT-α-NET is a clinical-stage, targeted alpha-particle therapy (TAT) radiopharmaceutical being developed for the treatment and diagnosis of patients with somatostatin receptor subtype 2 (SSTR2) expressing neuroendocrine tumors (NETs), which are a rare and difficult-to-treat type of cancer. VMT-α-NET incorporates Perspective's proprietary lead-specific chelator (PSC) to bind 203Pb for SPECT imaging, and 212Pb for alpha particle therapy. Perspective is conducting a multi-center open-label dose escalation, dose expansion study (clinicaltrials.gov identifier NCT05636618) of [212Pb]VMT-α-NET in patients with unresectable or metastatic SSTR2-positive NETs who have not received prior radiopharmaceutical therapies (RPT). Perspective received Fast Track Designation for this program from the U.S. Food and Drug Administration (FDA) based on preclinical data for SSTR2-positive NETs regardless of prior treatment response. Perspective is also collaborating with a number of thought leaders to further elucidate the clinical profile of [212Pb]VMT-α-NET through investigator-initiated studies in the U.S. as well as overseas.

About Neuroendocrine Tumors

Neuroendocrine tumors form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. Neuroendocrine tumors are typically classified as pancreatic neuroendocrine tumors or non-pancreatic neuroendocrine tumors. According to cancer.net, it is estimated that more than 12,000 people in the United States are diagnosed with a NET each year. Importantly, neuroendocrine tumors are associated with a relatively long duration of survival compared to other tumors and as a result, there are over 170,000 people living with this diagnosis.

About Perspective Therapeutics, Inc.

Perspective Therapeutics, Inc. is a radiopharmaceutical development company that is pioneering advanced treatment applications for cancers throughout the body. The Company has proprietary technology that utilizes the alpha emitting isotope 212Pb to deliver powerful radiation specifically to cancer cells via specialized targeting peptides. The Company is also developing complementary imaging diagnostics that incorporate the same targeting peptides which provide the opportunity to personalize treatment and optimize patient outcomes. This "theranostic" approach enables

the ability to see the specific tumor and then treat it to potentially improve efficacy and minimize toxicity.

The Company's melanoma ([212Pb]VMT01) and neuroendocrine tumor ([212Pb]VMT-α-NET) programs have entered Phase 1/2a imaging and therapy trials for the treatment of metastatic melanoma and neuroendocrine tumors at several leading academic institutions. The Company has also developed a proprietary 212Pb generator to secure key isotopes for clinical trial and commercial operations.

For more information, please visit the Company's website at www.perspectivetherapeutics.com.

Safe Harbor Statement

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Statements in this press release that are not statements of historical fact are forward-looking statements. Words such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "estimate," "believe," "predict," "potential," or "continue" or the negative of these terms or other similar expressions are intended to identify forward-looking statements, though not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include statements concerning, among other things, the Company’s ability to pioneer advanced treatment applications for cancers throughout the body; the Company’s ability to make progress in developing treatments for neuroendocrine tumors; the Company’s anticipated timing and expectations regarding regulatory communications, requests, interactions, submissions, and approvals; the Company’s activities and plans to pursue dose escalation for its Phase 1/2a clinical trial of [212Pb]VMT-α-NET; the Company’s expected timing for the receipt and disclosure of additional data regarding the Company’s Phase 1/2a clinical trial of [212Pb]VMT-α-NET; the Company’s plans to file an investigational new drug filing by the end of 2024 for PSV359; the Company’s plans to leverage its platform to help more cancer patients in 2025; the Company’s ability to provide targeted and effective treatment options for cancer patients; the ability of the Company’s proprietary technology utilizing the alpha emitting isotope 212Pb to deliver powerful radiation specifically to cancer cells via specialized targeting peptides; the Company’s prediction that complementary imaging diagnostics that incorporate certain targeting peptides provide the opportunity to personalize treatment and optimize patient outcomes; the Company’s belief that its "theranostic" approach enables the ability to see a specific tumor and then treat it to potentially improve efficacy and minimize toxicity; the Company’s ability to develop a proprietary 212Pb generator to secure key isotopes for clinical trial and commercial operations; the Company’s clinical development plans and the expected timing thereof; the expected timing for availability and release of data in connection with its clinical trials; expectations regarding the potential market opportunities for the Company’s product candidates; the potential functionality, capabilities, and benefits of the Company’s product candidates and the potential application of these product candidates for other disease indications; the Company’s expectations, beliefs, intentions, and strategies regarding the future; the Company’s intentions to improve important aspects of care in cancer treatment; and other statements that are not historical fact.

The Company may not actually achieve the plans, intentions, or expectations disclosed in the forward-looking statements, and you should not place undue reliance on the forward-looking statements. These forward-looking statements involve risks and uncertainties that could cause the Company’s actual results to differ materially from the results described in or implied by the forward-looking statements. Certain factors that may cause the Company’s actual results to differ materially from those expressed or implied in the forward-looking statements in this press release are described under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (the "SEC"), in the Company's other filings with the SEC, and in the Company's future reports to be filed with the SEC and available at www.sec.gov. Forward-looking statements contained in this news release are made as of this date. Unless required to do so by law, we undertake no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

Media and Investor Relations Contacts:

Perspective Therapeutics IR:

Annie Cheng

ir@perspectivetherapeutics.com

Russo Partners, LLC

Nic Johnson

PerspectiveIR@russopr.com

Investor CallNANETS 2024 Presentation November 21, 2024 NYSE AMERICAN: CATX

This presentation contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Statements in this presentation that are not statements of historical fact are forward-looking statements. Words such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, though not all forward-looking statements contain these identifying words. Forward-looking statements in this presentation include statements concerning, among other things, the Company's clinical development plans and the expected timing thereof; the expected timing for availability and release of data; the Company’s timing and expectations regarding regulatory communications, interactions, submissions and approvals; expectations regarding the potential market opportunities for the Company’s product candidates; the Company’s expected cash runway; the potential functionality, capabilities and benefits of the Company’s product candidates; the potential size of the commercial market for the Company’s product candidates; the Company’s expectations, beliefs, intentions, and strategies regarding the future; and other statements that are not historical fact. The Company may not actually achieve the plans, intentions or expectations disclosed in the forward-looking statements and you should not place undue reliance on the forward-looking statements. These forward-looking statements involve risks and uncertainties that could cause the Company’s actual results to differ materially from the results described in or implied by the forward-looking statements, including, without limitation, the potential that regulatory authorities may not grant or may delay approval for the Company’s product candidates; uncertainties and delays relating to the design, enrollment, completion and results of clinical trials; unanticipated costs and expenses; early clinical trials may not be indicative of the results in later clinical trials; clinical trial results may not support regulatory approval or further development in a specified indication or at all; actions or advice of regulatory authorities may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company may not be able to maintain regulatory approval for the Company’s product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s expectations, projections and estimates regarding expenses, future revenue, capital requirements and the availability of and the need for additional financing; the Company’s ability to obtain additional funding to support its clinical development programs; the availability or potential availability of alternative products or treatments for conditions targeted by the Company that could affect the availability or commercial potential of its product candidates; the ability of the Company to manage growth; whether the Company can maintain its key employees; whether there is sufficient training and use of the Company’s products and product candidates; the market acceptance and recognition of the Company’s products and product candidates; the Company’s ability to maintain and enforce its intellectual property rights; whether the Company can maintain its therapeutic isotope supply agreement with the DOE; whether the Company will continue to comply with the procedures and regulatory requirements mandated by the FDA for additional trials, Phase 1 and 2 approvals, Fast Track approvals, and 510(k) approval and reimbursement codes; and any changes in applicable laws and regulations. Other factors that may cause the Company’s actual results to differ materially from those expressed or implied in the forward-looking statements in this presentation are described under the heading “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and the Company’s most recent Quarterly Report on Form 10-Q, each filed with the Securities and Exchange Commission (the “SEC”), in the Company’s other filings with the SEC, and in the Company’s future reports to be filed with the SEC and available at www.sec.gov. Forward-looking statements contained in this presentation are made as of this date, and the Company undertakes no duty to update such information whether as a result of new information, future events or otherwise, except as required under applicable law. Legal Disclaimers

Despite multiple treatment modalities, cancer remains the 2nd leading cause of death in the US1 Targeted therapiese.g., TKIs, mAbs Surgery Bone marrow transplantation External beam radiation Chemotherapy Immunotherapy Hormone therapy Antibody-drug conjugates Radiopharmaceuticals Physical removal or destruction of tumors 1U.S. Centers for Disease Control and Prevention; 2Bryant et al, Cancer Epidemiol Biomarkers Prev (2017), DOI: 10.1158/1055-9965.EPI-16-1023; 3Wilson et al, The Lancet Oncology (2019), DOI: 10.1016/S1470-2045(19)30163-9 Systemic treatments Radiopharmaceutical Therapy Poised to Revolutionize Oncology Treatment Technology Developments Enable Higher Potency Payloads with Cancer-Specific Targeting “Next Generation Therapies” combining cytotoxicity with cancer-specific targeting Radiopharmaceuticals Targeted molecules deliver radioactive isotopes to cancer Therapeutic window: limited by radiation dose to healthy tissues The number of U.S. cancer survivors treated with radiation is projected to be 4.2 million in 20302 ADCs Antibody-based targeting delivers chemotherapy to cancer Therapeutic window: limited by unstable linker/toxin The number of patients in high income countries treated with chemotherapy drugs is projected to be 4.7 million per year in 20403

Targeting Peptide Engineered for cancer-specific receptors to ensure highly directed uptake Linker Selected to assist peptide binding and optimize clearance from blood and healthy tissues Isotope 203Pb for SPECT imaging Chelator Perspective’s proprietary platform technology enabling stable radiolabeling with Pb isotopes or 212Pb for alpha particle therapy Perspective’s Radiopharmaceutical Optimization Process Unique Payload Delivery Technology Offers Pan-Cancer Opportunities

Designed to Deliver a Potent Payload + Optimized Therapeutic Window 1”Pb-Specific Chelator”; 2Mirzadeh et al., Radiochimica Acta, 1993 Perspective’s proprietary technology integrates a chelator optimized for 212/203Pb DOTA TCMC PSC1 Perspective’s PSC Chelator Proprietary Designed specifically for Pb isotopes Optimized for rapid renal clearance through neutralized formal charge Improves radiolabeling, receptor binding & internalization Generic chelators leak the 212Bi alpha-emitting daughter up to 36%2 Retention of alpha-emitting 212Bi can direct higher radiation dose to tumors and less radiation in off-target organs NET 2- NET 2+ NET 0 Commercially Available Perspective’s Chelator

Lee D, Li M, Liu D, et al. Structural modifications toward improved lead-203/lead-212 peptide-based image-guided alpha-particle radiopharmaceutical therapies for neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2024;51(4):1147-1162. doi:10.1007/s00259-023-06494-9 Preclinical Results: Evidence of a Differentiated Biodistribution Profile Estimated cumulative tumor and kidney doses over time Tumor to kidney ratio at select time points Radiopeptide Estimated dose (Gy/MBq) Tumor Kidney T/K [212Pb]Pb-DOTATOC 2.43 7.03 0.35 [212Pb]Pb-PSCTOC 9.19 5.41 1.70 [212Pb]Pb-PSC-PEG2-TOC 12.70 6.22 2.04 [212Pb]Pb-PSC-PEG2-TOC (+ Lysine) 8.65 3.24 2.67 Comparative biodistributions of constructs with different chelators

Construct Target Disease Discovery Human Clinical Imaging First in Human Therapy Phase 1/2 Phase 3 VMT-⍺-NET Neuroendocrine tumors Other SSTR2 expressing tumors VMT01/02 Melanoma (MC1R imaging & therapy) PSV359 (FAP) Multiple solid tumors PSV40X (Small Molecule) Prostate (PSMA imaging & therapy) Other Programs (Novel Peptides) Solid and hematological tumors Pre-targeting Platform Antibodies & Proteins Multiple solid and hematological tumors Initial results at NANETS 2024 Monotherapy initial results at SMR 2024 Broad Proprietary Pipeline Combination with nivolumab open

Neuroendocrine Tumors: VMT-⍺-NET Targeting the somatostatin receptor to treat rare neuroendocrine-type cancers

Image Panel: Whole body SPECT scan of NETs patient imaged with [203Pb]VMT-𝛼-NET Fast Track Designation for first line therapy received October 2022 Therapeutic trial in PRRT naïve setting currently recruiting throughout the US Initiated therapy (2022) investigator led study in India – data on 10 NETs patients presented at EANM in October 2024 Fast Track Designation for received October 2022 Phase 1/2a Therapeutic trial in PRRT naïve setting currently recruiting throughout the US US Phase 1 study in PRRT refractory patients recruiting at the University of Iowa VMT-⍺-NET will potentially expand into this population as well as PRRT naïve patients Targeting somatostatin receptor type 2 (SSTR2) for the imaging and treatment of neuroendocrine tumors with possible expansion into other SSTR2+ tumor types Neuroendocrine tumors (NETs) Neuroendocrine cells are specialized cells that secrete hormones and other bioactive substances Neuroendocrine cells are found throughout the body. Often grow in the pancreas or other areas of the gut, such as the stomach, small intestine, rectum, colon or appendix SSTR2 is expressed widely in various tumors Small cell lung cancer Breast cancer Meningioma Nasopharyngeal carcinoma Thyroid cancer Merkel cell carcinoma Neuroblastoma Neuroendocrine Tumors: VMT-⍺-NET Targeting the Somatostatin Receptor to Treat Neuroendocrine and Other Cancers

Abbreviations: APC, antigen-presenting cell; DAMPs, damage-associated molecular patterns; dsDNA, double-stranded DNA; RPT, radiopharmaceutical therapy. RPT injection Targeting peptide 212Pb isotope 1. Targeted cell death RPT binds to receptors on cancer cells and releases α particles, resulting in double-stranded DNA breaks, cell membrane and organelle disruption in the bound cell and neighboring cells. 2. Bystander effect 3. Immune activation Dying cancer cells release neoantigens, which are taken up by APCs. APCs activate T cells which further attack cancer cells and can convert into memory T cells, providing a durable and widespread response throughout the body. α radiation dsDNA breaks; repair mechanisms overwhelmed Neoantigens Tumor Dying cancer cell DAMPs Cancer cell APC Naïve T cell Naïve T cell Memory T cell Active T cell Cytokines Vaccine-like effect Cytoreductive Immunostimulatory In NETs, the Desired Primary Activity is Direct Cell Death, Requiring a Potent Payload Dying cancer cells release DAMPs, causing nearby cells to die as well.

Lee D, Li M, Liu D, et al. Structural modifications toward improved lead-203/lead-212 peptide-based image-guided alpha-particle radiopharmaceutical therapies for neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2024;51(4):1147-1162. doi:10.1007/s00259-023-06494-9 Liu D, et al. European Association of Nuclear Medicine EANM, 15-19 Oct 2022, Barcelona, Spain. Preclinical Results: Linear Dose-Response Spider plots of AR42J NET tumor volumes over time post treatment with [212Pb] VMT-alpha-NET Single ascending doses from 0 – 4.4 MBq Red dashed line indicates tumor growth beyond limits for compassionate animal sacrifice Bottom right graph of animal body weights per treatment group is a surrogate for general health 0.37 MBq 1.85 MBq 3.70 MBq 0 MBq 4.44 MBq Tumor growth inhibition or regression correlates with increasing administered activity. All doses were well tolerated. 4.44 MBq

Preclinical Time to Progression and Survival By Administered Dose More than 20% increase to the initial tumor volume has been assumed to be progressive Study plan of 90 days duration Lee D, Li M, Liu D, et al. Structural modifications toward improved lead-203/lead-212 peptide-based image-guided alpha-particle radiopharmaceutical therapies for neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2024;51(4):1147-1162. doi:10.1007/s00259-023-06494-9 Liu D, et al. European Association of Nuclear Medicine EANM, 15-19 Oct 2022, Barcelona, Spain. 90 90 90

(1) US prescribing information; (2) DOI: 10.1056/NEJMoa1607427; (3) NANETS 2021; (4) DOI: 10.1016/S0140-6736(24)00701-3; (5) ASCO 2024; (6) ASCO 2024; (7) SNMMI 2024. No head-to-head studies between the products have been conducted. Given the different study designs and methods, cross-trial comparisons cannot be made. The information on this slide is not intended to promote the products referenced herein or otherwise influence healthcare prescribing decisions. The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the investigational agents will receive regulatory approval or become commercially available for the uses being investigated. 177Lu-DOTATATE 177Lu-DOTATATE 212Pb-DOTAMTATE 225Ac-DOTATATE VMT-α-NET Study NETTER-1 (1) (2) RCT; randomized 2:1 N = 229 NETTER-2 (4) RCT; randomized 2:1 N = 226 Phase I/II (5) Single arm N=44 ACTION-1 Phase Ib/III (6) Phase Ib: Single arm N=17 Investigator led research (7) N=13 Dose Level (administered) 4 x Q8W 200 mCi 4 x Q8W 200 mCi 4 x Q8W 67 µCi/kg  4.7 mCi/70 kg 4 x Q8W 3.2 uCi/kg  0.23 mCi/70 kg 4 x Q8W 67 µCi/kg  median 2.9 mCi Patient Population SSTR2+, GEP-NETs SSTR2+, GEP-NETs SSTR2+, GEP-NETs SSTR2+, GEP-NETS SSTR2+ GEP-NETs, B-NETs, MTCs Prior PRRT 0% 0% 0% 100% 62% Median time from dx 3.8 years 1.9 months 5 years 5 years N/A Performance Status Karnofsky Performance Scale Median was 90 Karnofsky Performance Scale 83% at 90-100 N/A ECOG 0 (59%), 1 (41%) ECOG 0 (38%), 1( 31%), 2 (31%) Histology Well differentiated G1 (66%), G2 (35%) Well differentiated G2 (73%), G3 (27%) Well differentiated G1 (18%), G2 (68%), G3 (7%) Well differentiated G1 (47%), G2 (53%) Well differentiated G1 (15%), G2 (85%) PFS Median 28.4 vs 8.5 months (3) Median 22.8 vs 8.5 months 74.3% at 24 months NE (95% CI: 12 months, NE) Median 16.4 months ORR (CR/PR) 13% (1%/12%) vs. 4% (0%/4%) 43% (5%/38%) vs. 9% (0%/9%) 56% 29.4% confirmed 41.2% (6%/35%) w/ unconfirmed 62% (0%/62%) confirmed AEs (>20%) Nausea, vomiting, fatigue, diarrhea, abdominal pain, multiple laboratory abnormalities Nausea, diarrhea Alopecia, nausea, fatigue, appetite↓, diarrhea, dysphagia, lymphocyte count↓, abdominal pain, vomiting, weight↓, blood glucose↑ Nausea, fatigue, weight↓, hyperglycemia, abdominal pain, constipation, vomiting, multiple laboratory abnormalities >10 events: alopecia, anemia, fatigue, nausea Grade 3+ (>10%) Lymphopenia (44%), GGT↑ (20%) TEAE: 35% TEAE: 52% Lymphocyte count↓ (25%) TEAE: 53% Anemia (18%), lymphocyte count↓ (18%), creatinine clearance↓ (12%) Anemia (2 events) Other notes 5 Lu-177 treated patients withdrew due to renal-related events Nephrotoxicities 13 (8.8%) vs. (2.0%) Dysphagia treated with Botox injection Transient dysphagia resolved without intervention Competitive Landscape: NET Radiopharmaceutical Trials Rationale for testing higher doses of VMT-⍺-NET

Preliminary Safety and Efficacy Data of [212Pb]VMT-α-NET in Somatostatin Receptor 2 (SSTR2) Expressing Neuroendocrine tumors (NETs) Richard L Wahl MD, Lowell Anthony MD, Lilja B Solnes MD, Samuel H Mehr MD, Lucia Baratto MD, Alaa Hanna MD, Wenjing Yang PhD, Stephen Keefe MD, Thorvardur R Halfdanarson MD

Disclosures for Dr. Richard Wahl and FDA Status Abdera: consultant Molecular Targeting Technologies, Inc.: consultant, stock options Siemens Healthineers: consultant Voximetry: consultant, stock options Techspert: consultant Clarity Pharmaceuticals: stockholder Perspective Therapeutics: consultant, research Fusion Pharmaceuticals: research contract Rayze Pharmaceuticals: research contract White Rabbit AI: research contract [212Pb]VMT-α-NET is not FDA approved. It is being used under an FDA IND in a clinical trial

Trial Design: [212Pb]VMT-α-NET mTPI-2 Phase 1/2a For Neuroendocrine Tumors 1 mTPI-2: Modified toxicity probability index | https://clinicaltrials.gov/study/NCT05636618 Expansion phase Expansion into non-NET indications (e.g., SCLC) also possible Expansion Cohort [212Pb]VMT-⍺-NET RP2D mCi x 4 Escalation phase Recommended Phase 2 Dose Cohort 2 Recruited [212Pb]VMT-⍺-NET n = 7 / 5 mCi x 4 Cohort 1 Recruitment Complete [212Pb]VMT-⍺-NET n = 2 /2.5 mCi x 4 Cohort 3 [212Pb]VMT-⍺-NET n = 3 – 8 / 7.5 mCi x 4 Cohort 4 [212Pb]VMT-⍺-NET n = 3 – 8 / 10 mCi x 4 Intermediate doses or de-escalation possible for Cohort 2 – 4 Added slots for addl safety & efficacy observation (≤47) Trial Parameters Bayesian mTPI-2 design based on iterative toxicity probability monitoring Dosimetry to be assessed during screening period for cohorts 1 & 2 using 5-7 mCi [203Pb]VMT-α-NET Key Study Features Advanced/unresectable or metastatic NETs Progressive disease on prior therapy PRRT naïve FDA approved SSTR2 PET/CT avid disease Escalation Stage Population Primary: To measure incidence of DLTs following a single administration of [212Pb]VMT-α-NET in order to determine the MTD and/or MFD, and RP2D Secondary / exploratory: ORR, DOR and PFS by RECIST v1.1, OS Using dosimetry, estimate selected organ and whole body absorbed radiation doses for [212Pb]VMT-α-NET Study Endpoints

Patient Characteristics (all patients as treated) Data cutoff 10/31/24 All Treated (N = 9 ) Time since diagnosis (months) Mean 70 Median 37 Range 12, 181 Number of prior systemic therapies Median 1 Range 0, 2 Prior systemic therapies (patients with each) Somatostatin analogues 7 Capecitabine, temozolomide 1 Small molecule (sunitinib, everolimus) 2 ECOG Performance Status, n (%) 0 8 (89) 1 1 (11) Disease at Baseline, median (range) RECIST median sum of target lesions (cm) 6.7 (2.9, 8.7) SUV max SUV mean 41.5 (18, 162) 30 (12, 102) All Treated (N = 9 ) Age (years) Median 63 Range 37,78 Sex, n (%) Female 4 (44) Male 5 (56) Race, n (%) White 8 (89) Asian 1 (11) Tumor Type, n (%) Pancreatic NET 3 (33) Non-pancreatic NET 6 (66) Grade, n (%) G1 3 (33) G2 6 (66)

Patient Disposition and Exposure (all patients as treated) 1 Patient experienced syncope and dose was reduced for cycle 3 and cycle 4 to 2.5 mCi of administered activity Additional notes: (1) 17 patients screened, (2) one patient (102-102) experienced a decline in renal function prior to administration of [212Pb]VMT-α-NET and was not treated. Data cutoff 10/31/24 Cohort Subject Subject Status Weight (kg) Adm Activity (mCi) Adm Activity per Weight (µCi/kg) C1D1 C2D1 C3D1 C4D1 1 103-101 Follow-Up 53 2.5 50.1     1 103-102 Follow-Up 61 2.5 40.8     2 103-103 Follow-Up 157 5 31.7     2 109-103 Progressive disease 78 5 63.9  2 102-101 Follow-Up 91 5 54.5     2 103-104 Follow-Up1 59 5/2.5 84.5/42.3     2 102-103 Follow-Up 80 5 62.1    scheduled 2 112-101 Follow-up 101 5 49.1     2 103-105 Follow-up 73 5 68.7     Green line denotes timepoint through which all post-cycle scans are available to the study team.

Incidence of TEAEs [212Pb]-VMT-a-NET 92.5 MBq (2.5 mCi) (N=2) [212Pb-VMT-a-NET 185 MBq (5.0 mCi) (N=7) Total (n=9) Grade Grade 1 Grade 2 Grade 3 Grade 1 Grade 2 Grade 3 Grade 1 Grade 2 Grade 3 AEs by Preferred Term and Grade Reported by Patient [Number patients with AE (% of pts treated per cohort)] Most Common (Occurring in ≥ 2 patients and/or grade ≥ 2 Fatigue 1 (50) 1 (50) - 3 (43) 2 (28) - 4 (44) 3 (33) - Alopecia 2 (100) - - 4 (57) - - 6 (66) - - Lymphocyte count decreased - 1 (50) - 2 (29) 3 (42) - 2 (22) 4 (44) - Nausea - 1 (50) - 4 (57) 1 (14) - 4 (44) 2 (22) - Anaemia - 2 (100) - 3 (43) - - 3 (33) 2 (22) - Diarrhoea 2 (100) - - 2 (29) 1 (14) 1 (14) 4 (44) 1 (11) 1 (11) Haematocrit decreased 1 (50) 1 (50) - 2 (29) - - 3 (33) 1 (11) - Red blood cell count decreased 1 (50) 1 (50) - 2 (29) - - 3 (33) 1 (11) - White blood cell count decreased 2 (100) - - - - - 2 (22) - - Abdominal pain - - - 2 (29) - - 2 (22) - - Haemoglobin decreased - - - 2 (29) - - 2 (22) - - Hyperglycaemia - - - 2 (29) - - 2 (22) - - Blood alkaline phosphatase - - - 2 (29) - - 2 (22) - - Constipation - - - 2 (29) - - 2 (22) - - Haematuria - - - 2 (29) - - 2 (22) - - Headache 1 (50) - - 1 (14) - - 2(22) - - Lethargy 1 (50) - - 1 (14) - - 2(22) - - Aspartate aminotransferase incr’d 1 (50) - - 1 (14) - - 2(22) - - Dizziness 1 (50) - - 1 (14) - - 2(22) - - Treatment Emergent Adverse Events (occurring in ≥ 2 patients and/or Grade ≥ 2) (1/2) All patients as treated Data cutoff 10/31/24

Treatment Emergent Adverse Events (Occurring in ≥ 2 patients and/or Grade ≥ 2) (2/2) All patients as treated Data cutoff 10/31/24 Incidence of TEAEs [212Pb]-VMT-a-NET 92.5 MBq (2.5 mCi) (N=2) [212Pb-VMT-a-NET 185 MBq (5.0 mCi) (N=7) Total (n=9) Grade Grade 1 Grade 2 Grade 3 Grade 1 Grade 2 Grade 3 Grade 1 Grade 2 Grade 3 AEs by Preferred Term and Grade Reported by Patient [No patients with AE (% of pts treated per cohort)] Grade ≥ 2 Presyncope - - - - 1 (14) - 1 (11) Syncope - - - - - 1 (14) - - 1 (11) Amylase increased - 1 (50) - - - - - 1 (11) - Hypercalcemia - 1 (50) - - - - - 1 (11) - Weight decreased - - - - 1 (14) - - 1 (11) - Note: No renal insufficiency or dysphagia were observed.

Estimated Glomerular Filtration Rate (eGFR), Most Recent versus Baseline 212Pb-VMT-a-NET 92.5 MBq (2.5 mCi) 212Pb-VMT-a-NET 185 MBq (5.0 mCi) Data cutoff 10/31/24 eGFR eligibility cut-off eGFR eligibility cut-off

Safety Summary No DLTs were observed in either cohort No grade 4, grade 5 or serious AEs were observed No decline in renal function was observed Hematologic AEs were few in number and low grade No dysphagia was observed No treatment discontinuations due to AE have occurred Data cutoff 10/31/24

Predicted Tumor to Kidney Activity of [212Pb]VMT-α-NET Over Time(Based on Pre-Treatment [203Pb]VMT-α-NET SPECT Imaging and Dosimetry Analysis) Time activity curves for [212Pb]VMT-α-NET are derived from pre-treatment SPECT imaging using 5-7 mCi [203Pb]VMT-α-NET at 1, 4, and 24 hours (n=6). The bold line represents the average across all samples in the dataset for tumors (magenta) and kidney (blue). Measurements of %IA/L in tumors and kidneys has been corrected for partial volume effects. However, SPECT imaging may still underestimate the true tumor to kidney ratio of absorption. Data cutoff 10/31/24 Average Tumor-to-Kidney Ratio vs Time

Preliminary Response Assessment by RECIST v1.1 by Patient Dose Level * * * * * The full sets of scans following cycle 4 are not yet available to the study team for five patients. Note: Patient 109-103 experienced progressive disease by unambiguous progression of non-target lesions Data cutoff 10/31/24 *

Kinetics of Treatment Response * The full sets of scans following cycle 4 are not yet available to the study team for five patients. Notes: Patients had progressive disease prior to enrollment on study, and patient 109-103 experienced progressive disease by unambiguous progression of non-target lesions Data cutoff 10/31/24 VMT-a-NET-T101 Spider Plot 212Pb-VMT-a-NET 92.5 MBq (2.5 mCi) 212Pb-VMT-a-NET 185 MBq (5.0 mCi) Post Cycle 4 efficacy assessment period 103-101 (50.1 µCi/kg) 103-102 (40.8 µCi/kg) 103-103 (31.7 µCi/kg) 109-103 (63.9 µCi/kg) 102-103 (62.1 µCi/kg) 112-101 (49.1 µCi/kg) 102-101 (54.5 µCi/kg) 103-105 (68.7 µCi/kg) 103-104 (84.5, 42.3 µCi/kg) Cycle 1 Cycle 2 Cycle 3 Cycle 4 * * * * *

Preliminary Assessment of Disease Control Durability Death Disease Progression RECIST v1.1 Response Cohort Cycle 1 Cycle 2 Cycle 3 Cycle 4 Scan 4 completed Scan 4 completed Scan 4 completed Post final treatment scan pending Post final treatment scan pending Post final treatment scan pending Post final treatment scan pending Post final treatment scan pending Data cutoff 10/31/24

Patient 103-104 – 212Pb VMT alpha NET Rx 5 mCi x 2, 2.5 mCi x 2 March 2023 Oct 2024 May 2023 June 2023

Patient 103-104 – 212Pb VMT alpha NET Rx 5 mCi x 2, 2.5 mCi x 2 Pre-Rx 3/2024 Post Rx 10/2024

Conclusions No DLTs were observed No grade 4, grade 5 AEs or SAEs were observed No decline in renal function was observed Hematologic AEs were low in number and low grade No treatment discontinuations due to AE have occurred [203Pb]VMT-α-NET and [212Pb]VMT-α-NET were well-tolerated 8 of 9 (89%) patients had durable control of disease Analysis of cohort 1 and 2 at this early stage already shows clear signs of clinical activity The study will continue to define the RP2D with further dose escalation cohorts Appreciable activity was been observed with treatment at this early timepoint in the study The Safety Monitoring Committee has recommended dose escalation which will be considered with FDA

Acknowledgements Multi Center trial thanking all investigators and the patients who participated. Special thanks to Doctors Vikas Prasad and Nikos Trikalinos, Lauren Sandner and the CCTR (Center for Clinical Theranostics Research) staff from Washington University for their major contributions, and also Markus Puhlmann, MD, MBA and Ian Marsh, PhD, from Perspective Therapeutics, Inc.

Next steps and concluding remarks

Trial Design: [212Pb]VMT-α-NET mTPI-2 Phase 1/2a For Neuroendocrine Tumors 1mTPI-2: Modified toxicity probability index | https://clinicaltrials.gov/study/NCT05636618 Trial Parameters Escalation Stage Population Key Study Features Study Endpoints Advanced/unresectable or metastatic NETs Progressive disease on prior therapy PRRT naïve FDA approved SSTR2 PET/CT avid disease Bayesian mTPI-2 design based on iterative toxicity probability monitoring Dosimetry to be assessed during screening period for cohorts 1 & 2 using 5-7 mCi [203Pb]VMT-α-NET Primary: to measure incidence of DLTs following a single administration of [212Pb]VMT-α-NET in order to determine the MTD and/or MFD, and RP2D Secondary / exploratory: ORR, DOR, PFS, OS by RECIST v1.1 Using dosimetry, estimate selected organ and whole body absorbed radiation doses for [212Pb]VMT-α-NET Expansion Cohort [212Pb]VMT-⍺-NET RP2D mCi x 4 Escalation phase Expansion phase Expansion into non-NET indications (eg SCLC) also possible Recommended Phase 2 Dose Recruitment Complete Cohort 1 [212Pb]VMT-⍺-NET n = 2 / 2.5 mCi x 4 Recruited Cohort 2 [212Pb]VMT-⍺-NET n = 7 / 5 mCi x 4 Cohort 3 [212Pb]VMT-⍺-NET n = 3 – 8 / 7.5 mCi x 4 Cohort 4 [212Pb]VMT-⍺-NET n = 3 – 8 / 10 mCi x 4 Intermediate doses or de-escalation possible for Cohort 2 – 4 Added slots: total of up to 47

Data cutoff 10/31/24 Deeper RECIST Responses Occur with Higher Administered Activity per Kg Body Weight

1 Investigator led research in India in patients with neuroendocrine tumor and medullary thyroid carcinomas. 2 RP2D = recommended Phase 2 dose; ICI = immune check point inhibitor. Program Target Tumor Types Nominate Candidate IND Filing Initiate Cohort 1 Enrolled Cohort 2 Preliminary Update RP2D2 Status Key future milestones & expected timelines VMT-α-NET SSTR2 Neuro-endocrine Tumors      Pending Cohort 3 outcome Cohorts 1&2 Duration of results: 2025 Cohort 3: Pending FDA interaction VMT01/ VMT02 MC1R Metastatic Melanoma      Society of Melanoma Research 2024 ICI combo study with nivolumab results expected 2025 Cohorts 1&2 Duration of results: 2025 Combination cohorts Initial dosing: 2H 2024 Initial results: 2025 PSV359 FAP-α Multiple solid tumors  Expected late 2024 Expected 2025 Various Discovery Programs PSMA Prostate Expected late 2024 Undisclosed Breast Undisclosed Lung North American Neuroendocrine Tumor Society (NANETS) 2024 Delivering Momentum Across Solid Tumor ProgramsPlatform for consistent generation and development of new assets

Q & A

Document And Entity Information	Nov. 21, 2024
Cover [Abstract]
Document Type	8-K
Amendment Flag	false
Document Period End Date	Nov. 21, 2024
Entity Registrant Name	Perspective Therapeutics, Inc.
Entity Central Index Key	0000728387
Entity Emerging Growth Company	false
Entity File Number	001-33407
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	41-1458152
Entity Address, Address Line One	2401 Elliott Avenue, Suite 320
Entity Address, City or Town	Seattle
Entity Address, State or Province	WA
Entity Address, Postal Zip Code	98121
City Area Code	(206)
Local Phone Number	676-0900
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false
Title of 12(b) Security	Common Stock, $0.001 par value
Trading Symbol	CATX
Security Exchange Name	NYSEAMER