Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(D) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(D) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File No. 001-33407 PERSPECTIVE THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) | Delaware | 41-1458152 | | --- | --- ...

Clinical Development and Pipeline - The company has three clinical-stage programs with multiple read-outs and milestones expected in the next 12-18 months[9]. - The proprietary pipeline includes VMT01/02 targeting melanoma, with the next cohort open for enrollment, and PSV359 for multiple solid tumors, with IND filed in late 2024 and dosing to initiate in mid-2025[10]. - The ongoing clinical trial for [212Pb]VMT-α-NET is designed to measure the incidence of dose-limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD) in patients with advanced neuroendocrine tumors[45]. - The company is currently recruiting for a therapeutic dose-finding trial in a PRRT-naïve setting throughout the US, indicating strong progress in clinical development[39]. - Recruitment is ongoing for the combination cohort with nivolumab, with an estimated time to primary completion of approximately 18 months[68]. - The first-in-human therapeutic studies for PSV359 are anticipated by mid-2025[94]. Safety and Efficacy - Preliminary results show that [212Pb]VMT-α-NET was well tolerated, with treatment-emergent adverse events occurring in 44% of patients treated[48]. - No decline in renal function has been observed in patients treated with [212Pb]VMT-α-NET, suggesting a favorable safety profile[49]. - [212Pb]VMT-α-NET was well tolerated, supporting rationale for dose escalation, with no dose-limiting toxicities (DLTs) reported[52]. - An objective response and prolonged progression-free survival (PFS) were observed at the 3 mCi activity level[73]. - 89% of patients (8 out of 9) achieved durable disease control, with 67% showing molecular imaging decline in SUVs[52]. - The combination of [212Pb]VMT01 with immune checkpoint inhibitors showed superior efficacy in preclinical studies[58]. Manufacturing and Supply Chain - The company has developed a robust manufacturing infrastructure to ensure patient coverage via distributed manufacturing, providing ready-to-administer products on the day of scheduled treatment[8]. - The company has established a long-term supply contract with the Department of Energy (DoE) to ensure a reliable supply of radioisotopes for therapeutic products[34]. - The regional manufacturing strategy aims to cover over 90% of the US population within an 11-hour delivery radius, enhancing the commercialization of 212Pb-labeled finished products[36]. - The company is advancing multiple pre-IND assets towards clinical trials and developing regional manufacturing sites[99]. Intellectual Property and Regulatory - The company emphasizes the importance of maintaining and enforcing its intellectual property rights to support its innovative therapies[4]. - The company has a robust intellectual property portfolio with 7 issued patents and 54 pending applications, covering various aspects of radiopharmaceuticals[97][98]. - The expected cash runway and market opportunities for the company's product candidates are under evaluation, with a focus on maintaining regulatory approvals[4]. Research and Development - The ideal isotope used is 212Pb, which provides potent tumor cell killing with reduced off-target effects, enhancing safety and efficacy[21]. - The proprietary chelator has been optimized for lead-based RPTs, improving radiolabeling and reducing off-target toxicity[24]. - The platform's theranostics approach allows for imaging pre-treatment, which de-risks clinical trials and optimizes patient selection[14]. - Imaging studies indicate strong tumor retention and low accumulation in normal organs, enhancing the therapeutic profile of FAP-targeted agents[91]. - Preclinical data supports the potential of the optimized peptide developed by the in-house discovery team as a best-in-class candidate[93]. - PSV359 shows anti-tumor activity in mice with U87MG xenografts, achieving a 50% complete response rate[82]. - Imaging with [68Ga]PSV377 demonstrates excellent tumor uptake and fast clearance, indicating favorable characteristics for diagnostic applications[86]. Market and Unmet Needs - The overall response rate (ORR) for existing treatments like LUTATHERA is only 13-17%, highlighting the unmet need for more effective targeted alpha therapies[39]. - The company aims to expand the breadth of tumors addressed by RPT, with a focus on SSTR2+ tumors and potential first-in-class therapies[11]. - The melanoma program targets high melanocortin 1 receptor (MC1R) expression, with approximately 100,000 new diagnoses and 8,000 deaths annually in the US[57]. - The company is evaluating expansion into other SSTR2+ tumor types, including breast cancer and small cell lung cancer (SCLC)[52].

Core Insights - Perspective Therapeutics, Inc. is advancing its clinical-stage proprietary medicines based on a next-generation targeted radiopharmaceutical technology platform, with multiple clinical updates expected through mid-2026 [2][6][41] Clinical Programs - The company is conducting a Phase 1/2a trial of [212Pb]VMT-α-NET for patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2)-positive neuroendocrine tumors, having received Fast Track Designation from the FDA [3][4][6] - As of February 2025, 30 patients have been enrolled in Cohort 2 of the trial, with no dose-limiting toxicities observed [6][14] - The company has achieved first-in-human combination dosing of a PD-1 inhibitor with its potential new medicine, VMT01, and has cleared an IND for PSV359, targeting FAP-α in solid tumors, with first patient dosing expected in mid-2025 [6][18][19] Financial Performance - For the year ended December 31, 2024, the company reported a net loss of $79.3 million, or $1.23 per share, compared to a net loss of $46.5 million, or $1.74 per share, for 2023 [40][49] - Research and development expenses increased by approximately 95% to $41.6 million in 2024, reflecting ongoing investments in clinical trials and manufacturing capabilities [36] - Cash, cash equivalents, and short-term investments totaled approximately $227 million as of December 31, 2024, expected to fund operations into late 2026 [31][32] Manufacturing and Operations - The company is expanding its manufacturing capabilities by establishing a regional network of drug-product finishing facilities, with a second facility in Somerset, New Jersey, commencing shipments in Q4 2024 [21][23] - The company has procured three buildings for manufacturing program candidates, with ongoing modifications and equipment installations [30] Strategic Developments - The company divested its brachytherapy business in Q2 2024, which included radioactive Cesium-131 seed assets, to focus on its core radiopharmaceutical development [28] - The patent portfolio was strengthened in 2024 with the issuance of two patents related to key assets, expiring in 2037 and 2039 [27]

Core Insights - Perspective Therapeutics, Inc. has initiated dosing for the first patient in a new cohort of a Phase 1/2a trial for [212Pb]VMT01, a targeted alpha-particle therapy for melanoma patients with positive MC1R imaging scans [1][2] - The trial is evaluating the safety of [212Pb]VMT01 in combination with nivolumab, a PD-1 blocking antibody, following encouraging initial results from earlier cohorts [2][3] - The FDA has granted Fast Track Designation for [212Pb]VMT01, which aims to expedite its development for patients with unresectable or metastatic melanoma [4] Company Overview - Perspective Therapeutics is focused on developing radiopharmaceuticals, utilizing the alpha-emitting isotope 212Pb to target cancer cells specifically [6] - The company is also working on complementary imaging diagnostics to personalize treatment and optimize patient outcomes through a "theranostic" approach [6] - The company is expanding its regional network of drug product finishing facilities to support clinical trials and commercial operations [7] Industry Context - Melanoma is a serious skin cancer with approximately 100,000 new diagnoses and 8,300 deaths annually in the U.S. [5] - Metastatic melanoma has a poor prognosis, with a one-year survival rate of 50% and a five-year survival rate of 29%-35% [5] - Current second-line therapies have limited median progression-free survival (mPFS) of 2-5 months, indicating a high unmet need for effective treatments [5]

Core Insights - Perspective Therapeutics, Inc. is a radiopharmaceutical development company focused on advanced cancer treatment applications [3][4] - The company utilizes proprietary technology with the alpha-emitting isotope Pb to target cancer cells specifically [3][4] - Perspective is developing a "theranostic" approach that combines imaging diagnostics with treatment to enhance patient outcomes [3][4] Company Events - The company will present at the TD Cowen 45th Annual Health Care Conference on March 3, 2025, from 11:10 a.m. to 11:40 a.m. ET in Boston, MA [2] - A fireside chat is scheduled at the Barclays 27th Annual Global Healthcare Conference on March 11, 2025, from 3:30 p.m. to 3:55 p.m. ET in Miami, FL [2] - Webcast events will be available live and archived for 90 days on the company's investor page [2] Product Development - The company's melanoma (VMT01) and neuroendocrine tumor (VMT-α-NET) programs are currently in Phase 1/2a trials in the U.S. [4] - Perspective is expanding its network of drug product finishing facilities using its proprietary Pb generator to support clinical trials and commercial operations [4]

Company Overview - Perspective Therapeutics, Inc. is a radiopharmaceutical development company focused on advanced treatment applications for cancers throughout the body [2] - The company utilizes proprietary technology with the alpha-emitting isotope Pb to deliver targeted radiation specifically to cancer cells [2] - Perspective is also developing complementary imaging diagnostics that enhance treatment personalization and optimize patient outcomes through a "theranostic" approach [2] Current Developments - The company's melanoma (VMT01) and neuroendocrine tumor (VMT-α-NET) programs are currently in Phase 1/2a imaging and therapy trials in the U.S. [3] - Perspective is expanding its regional network of drug product finishing facilities, supported by its proprietary Pb generator, to provide patient-ready products for clinical trials and commercial operations [3] Upcoming Events - The company will report its full year 2024 financial results and provide a business update on March 26, 2025, after market close [1]

Company Overview - Perspective Therapeutics, Inc. is a radiopharmaceutical development company focused on advanced treatment applications for cancers throughout the body [3] - The company utilizes proprietary technology with the alpha-emitting isotope Pb to deliver targeted radiation specifically to cancer cells [3] - Perspective is developing complementary imaging diagnostics that enhance the personalization of treatment and optimize patient outcomes through a "theranostic" approach [3] Clinical Development - The company's melanoma program (VMT01) and neuroendocrine tumor program (VMT-α-NET) are currently in Phase 1/2a imaging and therapy trials for metastatic melanoma and neuroendocrine tumors at leading academic institutions [4] - Perspective has developed a proprietary Pb generator to secure key isotopes necessary for clinical trials and commercial operations [4] Investor Engagement - Members of the senior leadership team will participate in upcoming investor conferences, including Oppenheimer's 35th Annual Healthcare Life Sciences Conference on February 12, 2025, and B. Riley Securities Precision Oncology & Radiopharma Investor Conference on February 28, 2025 [2]

Core Insights - Perspective Therapeutics, Inc. announced updated interim results from its ongoing Phase 1/2a clinical trial of [212Pb]VMT-α-NET, presented at the 2025 ASCO-GI symposium, indicating promising anti-tumor activity and a favorable safety profile [1][11] Clinical Trial Overview - The Phase 1/2a clinical trial is a multi-center open-label dose escalation and expansion study targeting patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2) expressing neuroendocrine tumors (NETs) who have not received prior radiopharmaceutical therapy [2] - As of January 10, 2025, all nine patients in the trial had completed treatments, with at least one post-treatment scan available for each [4] Treatment Efficacy - One patient experienced a confirmed objective response lasting 17 weeks, while two additional patients showed initial unconfirmed responses after treatment [5][6][7] - Three out of seven patients in Cohort 2 had investigator-assessed objective responses, with two responses occurring after the treatment period [7][8] Safety Profile - The treatment demonstrated a favorable safety profile, with no dose-limiting toxicities or serious adverse events reported since the study's initiation [8] - Adverse events observed were primarily grade 1 and 2, with no significant decline in renal function noted [8] Future Directions - The company plans to continue dose-finding studies for [212Pb]VMT-α-NET and is engaging with the FDA regarding dose escalation and further patient enrollment [11][13] - Perspective aims to leverage insights from this clinical program to enhance its pipeline and develop new targeted radiopharmaceutical therapies [11][15]

Core Viewpoint - Perspective Therapeutics, Inc. announced the acceptance of an abstract on updated interim results from its Phase 1/2a trial of [Pb]VMT-α-NET for neuroendocrine tumors, to be presented at the ASCO Gastrointestinal Cancers Symposium in January 2025 [1][2] Company Overview - Perspective Therapeutics is a radiopharmaceutical development company focused on advanced treatment applications for various cancers [5] - The company utilizes proprietary technology with the alpha-emitting isotope Pb to target cancer cells specifically, aiming to improve treatment efficacy and minimize toxicity through a "theranostic" approach [5][6] Clinical Trials and Presentations - The interim safety and efficacy data of [Pb]VMT-α-NET will be presented during the "Poster Session B" at the ASCO-GI symposium on January 24, 2025 [2] - A conference call will be held on January 24, 2025, to discuss the data presented, featuring the lead investigator and members of the management team [3] Research and Development - The company is conducting Phase 1/2a imaging and therapy trials for its melanoma (VMT01) and neuroendocrine tumor (VMT-α-NET) programs at leading academic institutions [6] - Perspective has developed a proprietary Pb generator to secure key isotopes for clinical trials and commercial operations [6]

Core Insights - Perspective Therapeutics is focusing on advancing its clinical pipeline and expanding its manufacturing capabilities over the next 12-18 months [2][6][18] Clinical Pipeline Advancements - The company is conducting a multi-center open-label dose escalation study of [212Pb]VMT-α-NET for patients with unresectable or metastatic SSTR2-positive neuroendocrine tumors [3] - Initial results from the study indicated no dose-limiting toxicities and two grade 3 adverse events, with eight of nine patients showing durable disease control [5][8][16] - The VMT01 program is also in a dose escalation study for previously treated melanoma patients, with initial results presented at a recent conference [9][10] Financial Position - As of December 31, 2024, the company reported preliminary unaudited cash, cash equivalents, and short-term investments of approximately $227.8 million, expected to fund operations into late 2026 [6][14][15] Manufacturing and Infrastructure - The company is working on expanding its manufacturing capabilities by improving existing facilities and evaluating additional capacity expansion opportunities [6][22] - Plans include building out recently acquired sites to enhance the availability of its medicines [6][22] Upcoming Events - The company will present updates at the 43rd Annual J.P. Morgan Healthcare Conference on January 15, 2025 [17]