isr20210630_10k.htm

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United States

Securities and Exchange Commission

Washington, D.C. 20549

FORM 10-K

For the fiscal year ended December 31, 2023

For the transition period from to

Commission File No. 001-33407

Perspective Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

(State of incorporation) (I.R.S. Employer Identification No.)

(Address of principal executive offices) (Zip code)

Registrant’s telephone number, including area code: (206) 676-0900

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

Title of each class Trading Symbol(s) Name of exchange on which registered

Common Stock, $0.001 par value CATX NYSE American

Securities registered pursuant to Section 12(g) of the Act: None

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐

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Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer ☐ Accelerated filer ☐

Non-accelerated filer ☒ Smaller reporting company ☒

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. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to § 240.10D-1(b). ☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act): Yes ☐ No ☒

As of June 30, 2023, the last business day of the registrant’s most recently completed second fiscal quarter, the approximate aggregate market value of voting and non-voting common equity held by non-affiliates of the registrant was $186,423,142 based on the closing price of the registrant’s common stock on June 30, 2023.

As of March 22, 2024, the number of shares outstanding of the registrant’s common stock, $0.001 par value per share, was 586,915,977.

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PERSPECTIVE THERAPEUTICS, INC.

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Page

PART I

ITEM 1 – BUSINESS 4

ITEM 1A – RISK FACTORS 34

ITEM 1B – UNRESOLVED STAFF COMMENTS 53

ITEM 1C – CYBERSECURITY 53

ITEM 2 – PROPERTIES 54

ITEM 3 – LEGAL PROCEEDINGS 54

ITEM 4 – MINE SAFETY DISCLOSURES 55

PART II

ITEM 6 – [RESERVED] 55

ITEM 7A – QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 64

ITEM 8 – FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 64

ITEM 9A – CONTROLS AND PROCEDURES 64

ITEM 9B – OTHER INFORMATION 65

ITEM 9C – DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 65

PART III

ITEM 10 – DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 65

ITEM 11 – EXECUTIVE COMPENSATION 68

ITEM 14 – PRINCIPAL ACCOUNTANT FEES AND SERVICES 77

PART IV

ITEM 15 – EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 78

SIGNATURES 80

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NOTE REGARDING COMPANY REFERENCES

Unless the context requires otherwise, references to “Perspective,” "the Company,” “our company,” “we,” “us” and “our” refer to Perspective Therapeutics, Inc., and, as the context requires, its subsidiaries. References to “Viewpoint” refer to Viewpoint Molecular Targeting, Inc., a wholly owned subsidiary, and references to “Isoray” refer to Isoray Medical, Inc., a wholly owned subsidiary.

CAUTION REGARDING FORWARD-LOOKING INFORMATION

In addition to historical information, this Form 10-K contains certain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 ("PSLRA"). This statement is included for the express purpose of availing Perspective Therapeutics, Inc., of the protections of the safe harbor provisions of the PSLRA.

All statements contained in this Form 10-K, other than statements of historical facts, regarding our future financial condition, results of operations, business strategy and plans and objectives of management for future operations, industry trends and other future events are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “believe,” “expect,” “anticipate,” “intend,” “estimate,” “forecast,” “project,” “may,” “could,” “might,” “plan,” “project,” “should,” “will,” “would” or the negative of these terms and other similar expressions, although not all forward-looking statements contain these identifying terms. Forward-looking statements in this Form 10-K include, among other things:

● the potential size of the commercial market for our program candidates;

● our ability to successfully commercialize our program candidates;

● expectations, beliefs, intentions and strategies regarding the future.

These statements are based on certain assumptions and analyses made by us in light of our experience and our assessment of historical trends, current conditions and expected future developments as well as other factors we believe are appropriate under the circumstances. However, whether actual results will conform to the expectations and predictions of management is subject to a number of risks and uncertainties as updated in this Form 10-K in Item 1A under the heading “Risk Factors” beginning on page 34 below that may cause actual results to differ materially.

Consequently, all of the forward-looking statements made in this Form 10-K are qualified by these cautionary statements and there can be no assurance that the actual results anticipated by management will be realized or, even if substantially realized, that they will have the expected consequences to or effects on our business operations. Readers are cautioned not to place undue reliance on such forward-looking statements as they speak only of the Company’s views as of the date the statement was made (or any earlier date indicated in such statement). While we may update certain forward-looking statements from time to time, we undertake no obligation to do so, whether as a result of new information, future events or otherwise, except as required by applicable law.

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Summary of Risk Factors

Investing in our common stock involves significant risks. Some of the principal risks related to our business include the following. These risks are discussed more fully under “Item 1A - Risk Factors” of this Annual Report.

Risks Related to Our Business, Financial Results and Need for Additional Capital

Risks Related to Our Business and Industry

● We obtain our supply of Thorium-228 from a single supplier.

● We will face intense competition and may not be able to compete successfully.

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Risks Related to Our Discontinued Brachytherapy Industry and Operations

● Continuing regulatory liability may exist from our discontinued operations.

Legal and Regulatory Risks Related to the Our Operations

● Healthcare reform measures could hinder our programs’ commercial success.

● The value of our granted patents, and our patents pending, is uncertain.

● Failure to comply with government regulations could harm our business.

● Our business exposes us to product liability claims.

● Our business involves environmental risks.

Risks Related to Ownership of Shares of Common Stock and Public Company Status

● Our reporting obligations as a public company are costly.

● We do not expect to pay any dividends for the foreseeable future.

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PART I

ITEM 1 – BUSINESS

Change in Fiscal Year

As previously reported, on February 6, 2023, we changed our fiscal year end from June 30 to December 31, effective December 31, 2022. This Annual Report on Form 10-K ("Annual Report" or "Form 10-K") is for the 12-month period from January 1, 2023 through December 31, 2023.

Overview

Perspective is developing the next generation of precision-targeted alpha therapies (“TAT”) for oncology that have the potential to treat a large population of cancer patients across multiple tumor types, including those with metastatic disease. By leveraging its proprietary TAT platform, Perspective aims to develop alpha-emitting radiopharmaceuticals that can be attached to targeting peptides to deliver the radioactive payload directly to difficult-to-treat tumors. The foundation of Perspective’s TAT platform is its Pb-specific chelator ("PSC") and peptide linker technology, which is designed to enable Perspective to connect Perspective’s alpha-emitting isotope of choice, Lead-212 (“212Pb” or “Pb-212”), to a desired targeting peptide to deliver radiation directly to cancer cells. Unlike commercially available chelators and linkers, Perspective’s proprietary PSC and peptide linker have shown in preclinical studies the differentiated ability to promote enhanced clearance of the non-tumor localized 212Pb payload without sacrificing the uptake of the alpha particle into the tumor. Rapid clearance of the alpha-emitting isotope from normal tissues is important to enhance tolerability and widen the therapeutic window of Perspective’s program candidates. Perspective is also developing complementary diagnostics that utilize the same targeting peptide and imaging isotopes such as Lead-203 (“203Pb” or “Pb-203”), Gallium-68 (“68Ga” or “Ga-68”), or Copper-64 (“64Cu” or “Cu-64”) to provide the opportunity to understand which patients may respond to its targeted therapy.

Perspective’s platform generates TATs that are comprised of three components: (i) a targeting peptide that is designed to selectively target ligands that are unique to, or preferentially expressed on, cancer cells throughout the body; (ii) the alpha-emitting medical isotope 212Pb designed to kill cancer cells; and (iii) Perspective’s proprietary linker that attaches the targeting molecule to the radioactive payload.

Perspective utilized its TAT platform to discover, design and develop its initial programs, VMT-α-NET and VMT01, which are currently in ongoing Phase 1 clinical trials, and Perspective plans to continue to leverage its platform to assess the potential of, and develop, multiple additional pipeline programs. Using our proprietary platform technology, VMT-α-NET and VMT01 are engineered to target cancer-specific receptors on tumor cells. [212Pb]VMT-α-NET is a TAT in development for patients with unresectable or metastatic somatostatin receptor type 2 ("SSTR2")-expressing tumors who have not previously received peptide-targeted radiopharmaceutical therapy, such as Lutathera, a beta-emitting therapy marketed by Novartis. [212Pb]VMT01 is a TAT in development for second-line or later treatment of patients with progressive melanocortin 1 receptor ("MC1R")-positive metastatic melanoma.

Our Strategy

Perspective’s goal is to advance innovative precision medicines for the treatment of cancer by developing and commercializing its TATs. The key elements of its strategy are to:

Advance its initial drug candidate, VMT-α-NET, through clinical development for the treatment of neuroendocrine tumors expressing SSTR2. [203Pb]VMT-α-NET is in an ongoing diagnostic Phase 1 clinical trial in patients with SSTR2-positive neuroendocrine tumors ("NETs"). Perspective has received FDA's permission to enter into an open label Phase 1 therapeutic trial to assess [212Pb]VMT-α-NET safety, tolerability and pharmacokinetics as well as to identify the maximum tolerated dose and the recommended Phase 2 dose in patients with SSTR2-positive NETs who have not received prior radiotherapy. Secondary endpoints assess efficacy using imaging criteria, best and overall response, progression-free survival and overall survival. This trial includes patients with NETs of gastrointestinal, pancreatic and lung origin, as well as pheochromocytoma and paraganglioma. Perspective has received a Fast Track designation from the FDA under this investigational new drug ("IND") application. Perspective intends to leverage this accelerated approval pathway to design and seek approval for an adaptive registrational trial as data becomes available in the dose escalation study. This strategy, which is commonly employed for drugs showing effectiveness in life-threatening oncological disease states, has the opportunity to provide a path to a new drug application and commercial approval in one more NET cancer subtypes without first executing a traditional Phase 3, double-blind, randomized and placebo-controlled clinical trial. As information on the tolerability and radiation exposure to normal tissues is defined in its Phase 1/2a study, Perspective intends to seek approval for expanding its indication to patients who have received prior radiotherapy and are experiencing recurrence.

Advance its second drug candidate,[203/212Pb]VMT01, through clinical development for the treatment of melanoma tumors expressing MC1R. [203Pb]VMT01 and [68Ga]VMT02 imaging tracers are in an ongoing diagnostic Phase 1 clinical trial in patients with stage IV metastatic melanoma. Perspective has received an IND "safe to proceed" letter from the FDA to evaluate the therapeutic [212Pb]VMT01 in patients with advanced and progressive melanoma. Perspective has begun enrollment and has completed the first cohort in October 2023. The second cohort is currently enrolling. The opening study under this IND is a Phase 1/2a trial utilizing a modified 3+3 dose-ranging design to evaluate approximately 30 subjects with previously treated inoperable stage III and stage IV melanoma. The primary endpoints of this study are safety and tolerability, determination of a recommended dose for subsequent study and tumor targeting as determined by imaging. Secondary endpoints assess efficacy using imaging criteria, best and overall response, progression-free survival and overall survival. Perspective may design and seek approval for an adaptive registrational trial in refractory or uveal melanoma as data becomes available in the dose escalation study. However, [212Pb]VMT01 has shown strong synergy with immune-oncology drugs including PD-1 and CTLA-4 inhibitors in preclinical studies. Perspective intends to present this information to the FDA in a Fast Track Application for use of [212Pb]VMT01 in combination with one or more immune oncology drugs as first-line therapy of inoperable stage III or stage IV melanoma, thus creating opportunity for parallel paths to approval.

Continue to leverage its TAT platform to expand its pipeline of program candidates. Perspective’s technology allows it to create novel TATs by combining 212Pb encased within its Pb-specific chelator ("PSC") with a wide variety of targeting peptides and other delivery vehicles. Targeting molecules can come from discontinued programs, novel molecules currently in development, approved molecules or other proprietary targeting agents. As such, Perspective is continuously evaluating opportunities to acquire or in-license additional new targeting molecules such as those recently licensed from the Mayo Foundation for Medical Education and Research ("Mayo Clinic") and Stony Brook University that Perspective believes can be utilized with its platform to create a potent alpha therapeutic agent. Perspective is leveraging its platform to progress its existing program candidates into clinical development for additional indications, including breast and pancreatic cancers, as well as the development of new program candidates.

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Expand the potential of its program candidates in additional indications and as combination therapies in current and additional indications. SSTR2, the molecular target of [212Pb]VMT-α-NET, is overexpressed in a number of cancers that are not classified as NETs, including meningioma and neuroblastoma. Both of these cancers can be difficult to treat when advanced and inoperable, but this is especially true for advanced neuroblastoma, a rare and orphan pediatric disease that is one of the most morbid of pediatric cancers. Perspective intends to prioritize seeking regulatory approval to test [212Pb]VMT-α-NET in advanced pediatric neuroblastoma as soon as adult experience in NETs provides a basis for determining safety and tolerability. Perspective will leverage the unique capability of [203Pb]VMT-α-NET quantitative imaging to arrive at individualized [212Pb]VMT-α-NET starting doses for the children by calculating the expected radiation delivery to the tumors and normal tissues before treatment begins.

In preclinical studies, Perspective also observed a synergistic effect on anti-tumor activity when its TATs are used in combination with approved checkpoint inhibitors. Perspective believes that the synergies it has observed could expand the addressable patient populations for [212Pb]VMT01 and allow for potential use in earlier lines of treatment, if approved, after completing the initial evaluation of [212Pb]VMT01 in a relapsed or refractory patient population. Perspective is currently evaluating [212Pb]VMT01 in preclinical studies in combination with approved checkpoint inhibitors and deoxyribonucleic acid ("DNA") damage response inhibitors, such as poly-ADP ribose polymerase inhibitors. Perspective may also explore other combination therapies that it believes may improve response rates in immune oncology-responsive tumors as compared to monotherapies of approved oncology therapeutics across Perspective's development pipeline.

Utilize a precision medicine approach by leveraging its imaging diagnostics. In order to enrich the patient population for its trials, Perspective created an imaging analogue of each of its program candidates by replacing 212Pb with the radioactive imaging isotope 203Pb while retaining the same targeting peptide. This allows Perspective to assess the uptake of the imaging isotope into the targeted tumor and radiation doses to key organs. Using this data, Perspective is able to enroll only those patients who meet predefined tumor uptake and dosimetry standards and are, therefore, more likely to respond to treatment. Perspective believes this strategy will allow it to enrich the patient population of its clinical trials and enable the use of a precision medicine approach for the treatment of multiple tumor types.

Continue to strengthen and scale its internal manufacturing capabilities. Perspective believes the quality, reliability and scalability of the manufacturing process for its program candidates will be a core competitive advantage and better enable its long-term success. Perspective has developed its proprietary VMT-α-GEN isotope delivery system (generator) to deliver its therapeutic isotope 212Pb for supply to patients. Perspective has a license to possess radioactive materials and distribute our radiopharmaceuticals from the Iowa Department of Health and Human Services, Radioactive Materials Program at our Coralville, IA site. In January 2021, we entered into a 10-year feedstock contract with the National Isotope Development Center of the Department of Energy's ("DoE") Isotope Program. Perspective has scaled manufacturing of the supply of VMT-α-GEN systems for research purposes and is developing its supply capabilities in an effort to support the clinical development of its drug candidates. Perspective believes that by controlling its own therapeutic isotope supply, Perspective can solve the many supply chain risks that have slowed alpha-particle therapy clinical adoption to date. In March 2024, Perspective acquired the assets and associated lease of Lantheus Holdings, Inc.'s ("Lantheus") radiopharmaceutical manufacturing facility in Somerset, NJ. This site has three production suites that Perspective intends to utilize to supply drug product for the northeastern half of the United States. Perspective plans to continue to invest resources to further develop its internal manufacturing process and capabilities in addition to collaborating with contract drug manufacturers.

Background of Radiation-Based Therapies and Radiopharmaceuticals

External beam radiation, or ExB, is one of the most widely used treatments for cancer, with approximately 50% of all cancer patients receiving radiation therapy during the course of treatment. To deliver ExB, a radiation therapy device is used to aim a beam of ionizing radiation into the tumor to kill cancer cells. Based on advances in radiation technology, ExB is highly effective in killing cancer cells and this treatment modality contributes towards approximately 40% of curative treatment for cancer. However, despite the successes of ExB treatment, only a limited number of sites in the body can be irradiated at any time by this treatment due to the off-target effects of radiation that can damage normal tissues. In addition, not all types of cancers can be treated with ExB, as certain organs or tumor types may be difficult to access with radiation beams. As a result, ExB use has generally been restricted to treating localized tumors and is not typically used as a monotherapy to treat patients who have metastatic disease.

Radiopharmaceuticals have been developed to precisely apply the tumor-killing power of radiation to a wider array of cancers, including for patients who have metastatic disease. Radiopharmaceuticals are drugs that contain medical isotopes, which are unstable elements that emit radiation and can be used to diagnose and treat cancers. To create radiopharmaceuticals, radiation-emitting medical isotopes are typically attached to targeting molecules and administered via intravenous injection. Once administered, the radiopharmaceuticals selectively target tumor antigens that are unique to, or preferentially expressed on, cancer cells throughout the body. Currently available targeted radiopharmaceuticals have demonstrated the ability to simultaneously bind to and kill multiple tumors. By precisely delivering alpha radiation directly to cancer cells, Perspective believes the power of radiotherapy can be realized while reducing the off-target effects.

Targeted radiopharmaceuticals are drugs that contain a radionuclide payload and a targeting moiety, which are unstable elements that emit radiation and can be used to diagnose and treat cancers. To create targeted radiopharmaceuticals, radiation-emitting medical isotopes are typically attached to targeting molecules, which are then administered via intravenous injection. Once administered, the radiopharmaceuticals selectively target tumor receptors that are unique to, or preferentially expressed on, cancer cells throughout the body. There are two main classes of therapeutic radiopharmaceuticals, which differ based on the types of particles that are emitted - beta-emitting isotopes and alpha-emitting isotopes. Beta-emitting isotopes kill cancer cells primarily by creating free radicals that damage cellular machinery and cause single-stranded DNA breaks, which can be repaired by the cell. In contrast, alpha particles cause greater physical damage to cancer cells than beta particles, including multiple double-stranded DNA breaks, which are highly lethal. Alpha particles are larger (over 7,000-fold greater atomic mass) and have higher energy transfer rates than beta particles. This higher energy transfer rate allows alpha particles to deposit a greater amount of tumor-killing energy over a short distance of one to five cells (<0.1 mm), compared to the relatively long distance of up to 200 cells (12 mm) for beta particles, allowing alpha particles to cause damage only to cancer cells in close proximity while reducing off-target radiation risk.

Targeted radiopharmaceuticals as a class have achieved clear clinical benefit over non-radioactive standard-of-care agents in the treatment of gastroenteropancreatic neuroendocrine tumors and castration-resistant metastatic prostate cancer and they possess characteristics that many believe may improve upon the profiles of current antibody-drug conjugates ("ADCs").

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Perspective is leveraging its proprietary TAT platform to build on the successes of currently available radiation therapies and create the next generation of precision oncology alpha radiopharmaceuticals. Perspective’s TATs are comprised of three components: (i) a targeting peptide, that is designed to selectively target receptors that are unique to, or preferentially expressed on, cancer cells throughout the body; (ii) the alpha-emitting medical isotope 212Pb, designed to kill cancer cells, that is encased in its proprietary lead-specific chelator; and (iii) its proprietary linker that attaches the targeting molecule to the radioactive payload.

Perspective believes that its TAT platform and program candidates, if approved, could provide several potential advantages over currently available radiopharmaceuticals, including:

● ability to use multiple targets and classes of targeting molecules;

Perspective believes the multiple mechanisms of action of its TATs may give them the ability to treat hard-to-treat tumors and the potential to work synergistically with other approved oncology therapies. The primary mechanism of action of 212Pb is direct cell damage through the induction of multiple double-stranded DNA breaks. A secondary mechanism, which would likely expand the effective direct cell kill range of the alpha particles, is referred to as the Bystander Effect. This effect has been shown to be as significant to the overall efficacy in killing cancer cells as the direct DNA breaks. The Bystander Effect has been shown to propagate alpha particle-induced cell death from irradiated dying cells to kill adjacent non-irradiated cells up to 1,000 μm away in a three-dimensional solid tumor model.

Alpha vs Beta Radiopharmaceuticals

There are two main classes of therapeutic radiopharmaceuticals, which differ based on the types of particles that are emitted - beta-emitting isotopes and alpha-emitting isotopes. Historically, due to the readily available supply of beta-emitting isotopes and the better understanding of their chemistry and biology, they were more widely used than alpha-emitting isotopes. As a result, first-generation-targeted therapeutic radiopharmaceuticals were based on beta-emitting isotopes, which kill cancer cells primarily by creating free radicals that damage cellular machinery and cause single-stranded DNA breaks, which can be repaired by the cell. As a result, certain cancers are refractory to beta particle-based radiopharmaceutical treatment. Products based on beta-emitting isotopes have been developed successfully, but as the development of radiopharmaceuticals continued to evolve, a deeper understanding of the potential of alpha-emitting isotopes for treating cancer has emerged.

Compared to beta particles, alpha particles cause greater physical damage to cancer cells, including multiple double-stranded DNA breaks, for which there is no viable resistance mechanism, unlike in the case of single-stranded DNA breaks. Rather, double-stranded DNA breaks are highly lethal, with even a single double-stranded break being sufficient to cause cancer cell death. Alpha particles are over 7,000 times more massive than beta particles with an approximately 4,000-fold higher energy transfer rate, providing alpha particles the advantage of depositing a high amount of tumor-killing energy over a short distance of one to two cells, compared to the relatively long distance of up to 12 mm for beta particles. The amount of energy produced by alpha particles is high enough such that only a small number of alpha particles are required to cause cell death. This feature, when combined with their short path length, enables alpha particles to cause damage only to cancer cells in close proximity, reducing the risk of off-target radiation and normal cell damage that can occur with beta particles. However, because of the short travel distance, alpha particles need to be delivered into or on the surface of tumor cells to achieve the desired therapeutic effect.

The graphic below is management’s illustration of the comparison of the key differences between beta particles and alpha particles.

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Commercially Available Radiopharmaceuticals

Two of the earliest antibody-targeted radiopharmaceuticals, Bexxar, marketed by GlaxoSmithKline, and Zevalin, marketed by Acrotech Biopharma, LLC, are beta-emitting therapies whose market acceptance was hampered by several issues, including handling and administration difficulties, supply chain challenges and reimbursement complications. Next-generation radiopharmaceuticals that have overcome the challenges faced by first-generation radiopharmaceuticals have since been developed and approved. One such approved, next-generation targeted radiopharmaceutical therapy is Lutathera, a beta-emitting therapy marketed by Novartis. Novartis reported that fiscal year 2023 sales revenue from Lutathera was $605 million, up 28% from fiscal year 2022, despite only being approved for a subset of neuroendocrine cancers that affect the pancreas or gastrointestinal tract, known as GEP-NETs. Recently, in March 2022, Pluvicto, a beta-emitting radioligand therapy marketed by Novartis, was approved to treat progressive, prostate-specific membrane antigen ("PSMA") positive metastatic castration-resistant prostate cancer. Pluvicto is being further developed by Novartis for other prostate cancer indications. Novartis reported that fiscal year 2023 sales revenue for Pluvicto were $980 million, up 262% from fiscal year 2022.

Over the past decade the global radiopharmaceutical market has been growing rapidly. Radiotherapeutics have been projected to grow at a compound annual growth rate ("CAGR") of 39.0% from 2022-2032, and radiodiagnostics have been projected to grow at CAGR of 7.2% from 2022-2032 (Source: 2023 MEDraysintell Nuclear Medicine Report).

Perspective's TAT Platform

Through the use of proprietary, specialized targeting peptides, Perspective is able to diagnose and then deliver a powerful alpha-particle radiotherapy directly to the tumor, while potentially limiting damage to healthy tissue. Utilizing a radioactive imaging agent that emits gamma rays, 203Pb, connected to a specific targeting peptide, Perspective has the ability to diagnose the tumor. Following diagnosis, Perspective links its alpha-particle radioactive isotope, 212Pb, to the same targeting peptide to treat and potentially kill the tumor. This two-step, personalized medicine approach, as depicted below, offers the ability to understand which patients may respond to its therapy and potentially improve efficacy while minimizing toxicity associated with many other types of cancer treatments.

Perspective’s image-guided TAT leverages a specialized targeting peptide to deliver cancer-killing 212Pb directly to the tumor. Targets are carefully selected to ensure they are overexpressed in cancer cells and minimally expressed on normal healthy cells. When the peptide is radiolabeled with 203Pb, the patient can be imaged (i.e., single-photon emission computed tomography ("SPECT") and computed tomography ("CT")) to reveal cancer cells in the body. When the peptide is radiolabeled with 212Pb, the target-peptide binding delivers powerful, yet locally deposited, cancer-killing alpha-particle radiation directly to cancer cells. This targeting mechanism allows for maximized therapeutic effects while minimizing off-target toxicities and may be used as a monotherapy or in combination with other precision treatments, such as targeted intracellular pathway inhibitors and immune checkpoint inhibitors.

Perspective’s TAT platform is highlighted by research and insights into the underlying biology of alpha-emitting radiopharmaceuticals as well as its differentiated capabilities in target identification, candidate generation, manufacturing and supply chain, and the development of imaging diagnostics. Perspective’s TAT platform was primarily developed over 15 years at the University of Iowa. Perspective believes that its TATs have the potential to be broadly applicable across multiple targets and tumor types and transform the treatment landscape of radiopharmaceuticals for the treatment of cancer.

Perspective’s next-generation radiopharmaceutical technology has been recognized by many prestigious organizations and has received numerous awards and grants. Over the past 10 years, through December 2023, approximately $13 million has been awarded to Perspective and over $4 million to Co-Founder Michael Schultz’s laboratory at the University of Iowa. Grant support has been for the Company’s TAT development activities, including the advancement of preclinical diagnostic and therapeutic studies for both VMT-α-NET and VMT01, Phase 1 diagnostic clinical trials for both VMT-α-NET and VMT01, and its VMT-α-GEN in-house radioisotope production technologies. These grants have been received primarily from the National Institutes of Health ("NIH"), National Cancer Institute ("NCI") and state-funded programs.

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212Pb (Lead-212)

Although there are many alpha-emitting isotopes, Perspective believes that the ideal therapeutic isotope should emit alpha particles in rapid succession in order to maximize damage to cancer cells and increase efficacy. Alpha particles kill tumors through multiple mechanisms. The primary mechanism of action is direct cell damage through the induction of multiple double-stranded DNA breaks. As alpha particles traverse the nucleus of a cell, they create a linear track of direct chromosomal damage, leaving behind multiple clusters of double-stranded DNA breaks. These direct alpha particles can kill cells up to a distance of 100 μm, which is equal to a depth of a few cells. A secondary mechanism, which would expand effective direct cell kill range of the alpha particle, is referred to as the Bystander Effect. This effect has been shown to be as significant to the overall efficacy in killing cancer cells as the direct DNA breaks. The Bystander Effect has been shown to propagate alpha particle-induced cell death from irradiated dying cells to kill adjacent non-irradiated cells up to 1,000 μm away in a three-dimensional solid tumor model. A third mechanism by which alpha-particle therapy enhances the body’s own anti-tumor immune response is less well understood but has been widely observed and reported. In Perspective’s own preclinical studies, Perspective has observed a vaccine-like effect that prevented the regrowth of tumors upon re-challenge. This is an area of ongoing investigation by Perspective and the international scientific community. Our findings are reported by Perspective senior scientist Dr. Mengshi Li, et.al. in the peer-reviewed journal Cancers 2021, 13: 3676, 2021.

Perspective believes 212Pb is an optimal therapeutic isotope as compared to currently commercially available radiopharmaceuticals as well as other alpha therapies in development. With a half-life of 10.6 hours, 212Pb is ideally suited to deliver powerful alpha-particle therapy to cancerous tumors, while representing a lower risk for off-target unintended effects. The decay properties of the 212Pb isotope and the rapid excretion of drug that has not bound to the tumor target provide the potential for treatment on an outpatient basis.

212Pb is an alpha-emitting nuclide that acts as the therapeutic in Perspective’s innovative theranostic approach. The higher linear-energy transfer of alpha particles, compared to beta particles, results in an increased incidence of double-stranded DNA breaks and improved localized cancer-cell damage. Perspective believes 212Pb half-life of 10.6 hours provides many significant advantages over other radiotherapies, including faster clearance and the potential for reduced off-site toxicity. Its decay chain includes the short-lived isotopes bismuth-212, polonium-212 and thallium-208, which all emit either alpha or beta during decay over about another hour. The end of the decay chain is the stable element lead-208.

In order to maximize the potential clinical benefit of radiopharmaceuticals to patients and minimize potential toxicity issues, Perspective believes that TATs must selectively localize and remain within the tumor while the portions of the TAT that are not localized within the tumor are rapidly cleared from the body. Nearly 15 years of work by Perspective’s co-founder, Dr. Michael Schultz, and colleagues at the University of Iowa and Perspective resulted in Perspective’s proprietary TAT, PSC and peptide linker technology to enable the delivery of isotopes to tumor cells while simultaneously promoting enhanced clearance of the non-tumor localized isotopes.

Due to the short half-life of 212Pb and the small size of the compounds, when Perspective’s TATs are not bound to targeted cancer cells, they rapidly clear from the body through the urinary system, along with any isotopes bound to the linker. This results in lower total body radiation exposure when compared to radiopharmaceuticals designed with longer lived isotopes or larger molecular weight targeting moieties such as antibodies or antibody fragments. Perspective believes that its TAT's ability to promote clearance without compromising the tumor’s uptake of the alpha particle overcomes a longstanding challenge of radiopharmaceutical drug development.

Perspective’s Chemistry and Biology Expertise with 212Pb

Perspective believes that its experience working with alpha-emitting radiopharmaceuticals positions it to build on the success of currently approved radiopharmaceuticals. By utilizing the advantages of 212Pb and its proprietary chelator, Perspective has the ability to develop next-generation radiopharmaceutical therapies. 212Pb has complex chemistry and requires extensive experience and expertise to develop and properly characterize 212Pb radiopharmaceuticals with regard to the required tumor targeting, shelf-life, in vivo stability and potential for commercial-scale manufacturing. For example, the high energy emitted from 212Pb can cause program candidates to prematurely degrade. Perspective believes it has the experience and know-how to develop molecules and formulations of 212Pb to maximize the shelf-life of its program candidates and allow for regional production and distribution. In addition to a deep understanding of the chemistry of 212Pb, Perspective has differentiated knowledge of the underlying biology of 212Pb and its mechanisms of directly damaging the DNA of tumors through single- and double-stranded DNA breaks, causing the Bystander Effect and using the immune system’s adaptive response to attack non-target expressing tumors in order to stimulate a vaccine effect.

Imaging Diagnostics – 203Pb (Lead-203)

For each of its program candidates, Perspective creates an imaging analogue that utilizes the same linker and targeting molecule but replaces 212Pb with the radioactive imaging isotope 203Pb. This allows Perspective to assess uptake of the imaging analogue into the targeted tumor and to determine radiation doses to key organs. The imaging analogue versions of Perspective’s program candidates are leveraged in both preclinical and clinical development and are used to enrich the patient population in its clinical trials by identifying the patients and tumor types more likely to respond to therapy.

203Pb is a gamma-emitting nuclide that acts as the diagnostic in Perspective’s innovative theranostic approach. 203Pb has a long enough half-life to facilitate radiopharmaceutical preparation and gamma-ray imaging (e.g., SPECT or planar gamma camera) at time points up to 24 hours and, potentially, 48 hours post administration. The ability to collect data on the biodistribution of 203Pb over this period allows for a more detailed understanding of tumor and other organ accumulation, retention and clearance that can be used as part of a treatment planning process for determining appropriately administered radioactivity levels of 212Pb for alpha-particle therapy.

Perspective’s Pipeline

Perspective is leveraging its TAT platform to advance a pipeline of alpha-based therapeutic programs to treat various cancers. The figure below details its current pipeline of TATs. To date, Perspective has retained global development and commercialization rights to all its program candidates. In January 2024, Perspective announced it had entered into a strategic agreement with Lantheus whereby in exchange for an upfront payment of $28 million (less certain withholding amounts), Lantheus obtained an exclusive option to negotiate for an exclusive license to Perspective's [212Pb]VMT-α-NET and a right to co-fund the IND-enabling studies for early-stage therapeutic candidates targeting PSMA and gastrin-releasing peptide receptor and, prior to IND filing, a right to negotiate for an exclusive license to such candidates.

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The table below shows Perspective’s two lead programs in clinic and its broad proprietary pipeline:

Perspective anticipates multiple near-term data readouts on its clinical and preclinical assets as follows:

Programs

VMT-α-NET: A Targeted Alpha Therapy Targeting SSTR2

Overview

Perspective is leveraging its TAT platform with one of its two initial program candidates, VMT-α-NET, that is currently in Phase 1/2a clinical trials. Perspective designed VMT-α-NET to target and deliver 212Pb to tumor sites expressing somatostatin receptor subtype 2 ("SSTR2"), a protein that is overexpressed in neuroendocrine tumors ("NETs") and other cancers. Using our proprietary platform technology, VMT-α-NET and VMT01 are engineered to target cancer-specific receptors on tumor cells. [212Pb]VMT-α-NET is a TAT in development for patients with unresectable or metastatic SSTR2-expressing tumors who have not previously received peptide-targeted radiopharmaceutical therapy, such as Lutathera. [212Pb]VMT01 is a TAT in development for second-line or later treatment of patients with progressive MC1R-positive metastatic melanoma.

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NETs are a group of rare, heterogeneous tumors that develop in different organs of the body and arise from specialized cells in the neuroendocrine system. Both the incidence and prevalence of NETs have continued to rise globally over several decades, primarily due to improvements in the diagnosis and surveillance of disease. The worldwide incidence of NETs is projected to reach 118,475 new cases in 2024 (source: Global Data). In the U.S. alone, the incidence of NETs has increased more than 6-fold over the last four decades to an anticipated 34,592 new cases in 2024 (source: Dasari A, Shen C, Halperin D, et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States. JAMA Oncol. 2017;3(10):1335-1342. doi:10.1001/jamaoncol.2017.0589). Earlier detection has not only given rise to an increase in localized disease diagnoses but also improvements in staging, disease classification, management and survival. Despite these advancements, delayed diagnosis is still common due to asymptomatic presentation or nonspecific symptoms. Gastroenteropancreatic NETs, or GEP NETs, represent the most common NET subtype, comprising 55–70% of all NETs followed by lung (22-27%) (source: Patel N, Benipal B. Incidence of Neuroendocrine Tumors in the United States from 2001-2015: A United States Cancer Statistics Analysis of 50 States. Cureus. 2019;11(3):e4322. Published 2019 Mar 26. doi:10.7759/cureus.4322). Current prevalence of NETs in the U.S approximates at 170,000 patients per year. As NETs display a wide variety of biologic behavior, the prognosis differs immensely between indolent limited disease grade 1 tumors and widely spread grade 3 carcinomas.

The median overall survival also varies widely in the highly heterogeneous NET populations and is based on site, stage and grade of disease. It is estimated that 80% of NETs over-express SSRT2. For this reason, somatostatin analogues are a cornerstone of the treatment of most NETs. In addition to SSTR2 analogs, low-grade and/or localized disease is amenable to surgical intervention and carries a good prognosis in terms of five-year overall survival (>90%), but there remains recurrence risk (source: Chan H, Zhang L, Choti MA, et al. Recurrence Patterns After Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: Analysis From the National Comprehensive Cancer Network Oncology Outcomes Database. Pancreas. 2021;50(4):506-512. doi:10.1097/MPA.0000000000001791). High-grade and/or distant disease is more difficult to treat and carries lower median survival rates typically measured in months (source: Das S, Dasari A. Epidemiology, Incidence, and Prevalence of Neuroendocrine Neoplasms: Are There Global Differences?. Curr Oncol Rep. 2021;23(4):43. Published 2021 Mar 14. doi:10.1007/s11912-021-01029-7). Radioligand therapy has emerged as a promising therapeutic option for GEP NETs in late stage and is being evaluated for earlier lines of treatment. Perspective believes there is additional opportunity for radioligand therapy in earlier lines of treatment and other somatostatin-expressing NET indications, such as lung and pheochromocytoma/paraganglioma NETs, where there remains significant unmet medical need. Worldwide sales for systemic NET treatments are estimated to reach $3.2 billion by end of 2025, of which the U.S. sales represents over 60% (source: Global Data).

Using a specialized peptide, VMT-α-NET is designed to target and bind to the SSTR2 on tumor cells. As a diagnostic, Perspective links 203Pb, a radioactive imaging agent that emits gamma rays, to its SSTR2-targeting peptide. Through the use of imaging scans, Perspective is able to characterize the tumor to confirm the patient’s cancer expresses SSTR2. This confirms the patient may be a candidate for treatment. As a therapeutic, Perspective links 212Pb, its alpha-particle radioactive isotope, to the same SSTR2 targeting peptide which has been shown to bind to the cancerous cell, to treat and potentially kill the tumor.

In August 2022 Perspective received a “safe to proceed” decision on an Investigational New Drug (“IND”) application with the U.S. Food and Drug Administration (“FDA”) to evaluate [212Pb]VMT-α-NET therapy under IND #160357. The indication of the opening study is treatment of advanced SSTR2-positive NETs patients who are progressing on, symptomatic on, or intolerant of approved non-radiological therapies. On September 29, 2022, Perspective received Fast Track Designation for this program based on preclinical data for the indication of SSTR2-positive NETs regardless of prior treatment response.

Additionally, Perspective believes there is an opportunity for Orphan Drug Designations for VMT-α-NET for NET subtype indications. There is also potential for a priority review voucher if Perspective pursues the rare pediatric disease of advanced neuroblastoma as Perspective’s best path for drug approval after review of Phase 1 trial data.

Clinical Studies of 212Pb-VMT-α-NET

Perspective has a multi-center open-label study (clinicaltrials.gov identifier NCT05636618) of [212Pb]VMT-α-NET, a targeted alpha-particle therapy, for patients with advanced SSTR2-positive neuroendocrine tumors. This study is intended to utilize a mTPI-2, or modified toxicity probability interval 2, dose-ranging design to evaluate approximately 10 - 32 adult subjects with unresectable or metastatic NETs of gastrointestinal, lung, adrenal or neural tissue origin. The primary endpoints of this study are safety and tolerability, determination of a recommended dose for subsequent study and determination of pharmacokinetic ("PK") properties. Secondary endpoints are overall response rate by RECIST v.1.1, progression-free survival by RECIST v.1.1 and overall survival. The first part of the study involves dose escalation, designed to determine the maximum tolerated dose ("MTD") or maximum feasible dose ("MFD") following a single administration of [212Pb]VMT-α-NET. The first patient cohort received 111 MBq (3mCi) per dose. The second cohort, which is currently being recruited, will receive administered activities of 185 MBq (5mCi), with cohorts 3 and 4 receiving 370 MBq (10 mCi) and 555 MBq (15 mCi), respectively, if the MTD or MFD is not reached during escalation. According to the mTPI-2 study design, intermediate de-escalation doses are also possible to allow selection of the optimal activity dose to take forward into the dose expansion part of the study.

The second part of the study is a dose expansion phase based on the identified MTD/MFD. Patients with positive uptake on FDA-approved SSTR2 PET/CT will receive a fixed dose of [212Pb]VMT-α-NET IV administered at the recommended Phase 2 dose and schedule determined in the Phase 1 dose escalation.

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In March 2024, Perspective provided the following update on the ongoing clinical trial (all data is as of March 7, 2024):

Preclinical Studies of 212Pb-VMT-α-NET

Perspective’s therapeutic [212Pb]VMT-α-NET has demonstrated positive clinical activity in preclinical studies using a mouse model of NETs, whereby [212Pb]VMT-α-NET significantly inhibited tumor growth and significantly improved survival compared to untreated mice controls.

Perspective’s diagnostic [203Pb]VMT-α-NET has produced strong SPECT/CT imaging and tumor contrast in multiple preclinical studies using mouse models of tumors expressing SSTR2, whereby [203Pb]VMT-α-NET has shown an 8-fold improved tumor uptake with decreased kidney retention as compared to 203Pb radiolabeled DOTATOC. DOTATOC is an established targeting compound for imaging SSTR2-expressing NETs when radiolabeled to positron emission tomography ("PET") isotopes.

The Company also presented mouse model data highlighting the efficacy of [203/212Pb]VMT-α-NET in treating metastatic neuroblastoma tumors. The study showed successful tumor uptake via sequential SPECT imaging and demonstrated a maximum tolerated dose of [212Pb]VMT-α-NET as 2.22 MBq without acute toxicity, with a 100% overall survival rate at 90 days observed in the group receiving three fractionated doses of 740 kBq of [212Pb]VMT-α-NET.

At the World Molecular Imaging Congress, the Company presented data highlighting the effectiveness of [212Pb]VMT-α-NET in treating neuroendocrine tumors in a tumor xenograft mouse model. The results highlighted the significant therapeutic efficacy of treatment with three fractionated doses of [212Pb]VMT-α-NET, which resulted in a 70% complete response rate and 80% survival at 120 days.

Perspective’s first-in-human experience with [203Pb]VMT-α-NET imaging occurred as an investigator-initiated trial ("IIT") at the University of Ulm in Dresden, Germany in 2021 in a patient with metastatic and refractory gastrointestinal NET. Imaging from this study using [203Pb]VMT-α-NET revealed favorable properties, including rapid tumor accumulation, rapid renal clearance and excellent tumor retention as seen by SPECT/CT imaging at 22 hours with high tumor conspicuity. There were no adverse signs or symptoms attributed to the imaging tracer. The pharmacokinetic and biodistribution properties of the imaging agent, based on medical physics analysis, suggest the potential for the chemically identical therapeutic agent, [212Pb]VMT-α-NET, to be administered without concurrent renal protective amino acid infusion in radiotherapy naïve patients. This would be a clinically relevant point of differentiation from the current practice using approved radiopharmaceutical products for NETs.

Investigator-Initiated Studies of 212Pb/203Pb-VMT-α-NET

An investigator-initiated Phase 1 imaging trial of [203Pb]VMT-α-NET is expected to begin at the University of Iowa to investigate the feasibility of using the agent to enable personalized, image-guided therapy dose calculations for [212Pb]VMT-α-NET therapy in patients with recurrent NETs after treatment with approved radiopharmaceutical therapy. An Imaging IND is open for this trial and IRB approval has been obtained. Perspective is uncertain when the provisional results will be available.

In December 2023, Perspective announced that the first patient was dosed at the University of Iowa in an investigator-initiated Phase 1 trial evaluating the safety of [212Pb]VMT-α-NET, in patients with unresectable or metastatic SSTR2-expressing neuroendocrine tumors. The patients being enrolled in the study have either progressed or relapsed after previous therapies, including currently approved peptide receptor radionuclide therapies ("PRRT"). This is a single site safety study (clinicaltrials.gov identifier NCT06148636) of [212Pb]VMT-α-NET targeted alpha-particle therapy for patients with refractory or relapsed SSTR2-positive neuroendocrine tumors. The first part of this Phase 1 trial is imaging with a surrogate tracer, [203Pb]VMT-α-NET, using SPECT/CT imaging. Each participant is assigned a radiation dose to the kidneys that cannot be exceeded. The second part of the study is a sequential 3 + 3 dose escalation phase of four cohorts based on the maximum allowed injected dose for an individual while keeping kidney exposure to less than a predetermined threshold. The study involves two treatments, about eight to ten weeks apart. The drug will be given by infusion once per treatment. Participants will also receive an infusion of amino acids to help protect the kidneys as well as medications to help protect against nausea. A participant who is administered [212Pb]VMT-α-NET will be monitored for at least six months for safety assessments. Participants will also have imaging at six months post-treatment to measure how their tumors responded to therapy and will have lifelong follow-up for this study. The preliminary data readout is expected in the second half of 2024.

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In November 2023, Perspective announced the publication of the first human SPECT images utilizing the alpha-emitting isotope of 212Pb, which was labeled to the Company's proprietary theranostic VMT-α-NET program. The imaging was conducted as part of a series of four neuroendocrine tumor patients who were administered VMT-α-NET at a clinical study site in Germany. The patient received 90 MBq (2.4mCi) of [212Pb]VMT-α-NET intravenously, and whole-body scintigraphy and SPECT/CT images were acquired 2 hours, 5 hours, and 19 hours after injection. Images were collected on a Symbia Intevo T6 (Siemens Healthineers) using a high-energy collimator. The SPECT/CT images showed high accumulation of [212Pb]VMT-α-NET in liver metastases and were consistent with the previously acquired [68Ga]DOTATATE PET/CT. High tumor retention was observed in the planar and SPECT/CT images over time. Due to the short half-life of 212Pb (10.6 hours), the images acquired after 19 hours showed a high level of noise due to the low count statistics. The patient showed no early or acute side effects.

In September 2023, the Company announced the presentation of encouraging early clinical results from an open-label, single-arm, investigator-initiated study in India investigating the safety and efficacy of [212Pb]VMT-α-NET in patients with NETs and medullary thyroid carcinomas. The early clinical findings were presented at the 36th Annual Congress of the European Association of Nuclear Medicine ("EANM") for the Phase 2a study of [212Pb]VMT-α-NET in pre- and post-Lutathera GEP-NET patients, being conducted at Fortis Healthcare, India. Ten adult patients with histologically confirmed NETs and metastatic medullary thyroid carcinomas who failed at least one prior line of treatment were treated as part of an IIT. All patients were planned to receive [212Pb]VMT-α-NET peptide at intervals of eight weeks up to four doses or until evidence of radiographic progression, unacceptable toxicity or the patient’s decision to discontinue. All patients were to be co-infused with an amino acid solution for renal protection. The primary objective of the study is to evaluate the safety of low doses of [212Pb]VMT-α-NET in this patient population. Secondary assessments will include objective response rate measured by RECIST 1.1 or PERCIST criteria, and the number of patients with treatment-related adverse events as assessed by CTCAE v.4.0. Both will be measured at 24 months after the last administered dose of [212Pb]VMT-α-NET. The isotope was supplied via the Company’s proprietary VMT-α-GEN isotope delivery system.

Highlights of the presented results at EANM included:

Three additional patients were enrolled in the second half of 2023 for a total of ten GEP-NET patients and two medullary thyroid cancer patients. All ongoing patients are expected to complete their fourth treatment cycle by end of March 2024. The updated results from the investigator-initiated study are expected to be presented at the Society of Nuclear Medicine and Molecular Imaging, or SNMMI, meeting in Toronto at the end of the second quarter in 2024.

Three patients were screened in 2023 in the IIT in post-Lutathera GEP-NET, and all three patients were located at the University of Iowa. All three patients received treatment in December 2023 for the completion of the first cohort. If all patients complete four cycles, then the end of fourth cycle of treatment is expected in June 2024.

The IIT for patients with advanced NETs and lack of further treatment options is underway at the University Dresden in Germany. Four patients were treated with [212Pb]VMT-α-NET and eight patients were imaged with [203Pb]VMT-α-NET during the second half of 2023, and investigators may plan additional treatments in 2024.

VMT01: A Targeted Alpha Therapy Targeting MC1R

Overview of VMT01and VMT02

Perspective is also leveraging its TAT platform with its second program candidate, VMT01, which is currently in Phase 1/2a clinical trials. Perspective designed VMT01 to target and deliver 212Pb to tumor sites expressing MC1R, a protein that is overexpressed in melanoma cancers. Review of market research by Grandview Research, Inc., and ForeSight Niche Assessment indicates metastatic melanoma represents over an $8.0 billion market opportunity.

Using a specialized peptide, VMT01 is designed to target MC1R on tumor cells. As a diagnostic, Perspective either links 203Pb or Gallium-68 to its MC1R-targeting peptide. MC1R is a G-protein coupled receptor that has been investigated as a target for metastatic melanoma drug delivery due to its overexpression on the surface of melanoma cells and relative absence in normal cells. MC1R-targeted radiolabeled peptides have been used as delivery vehicles for delivering radiometals to melanoma tumors in preclinical models for diagnostic imaging and therapy, as well as in clinical imaging studies that demonstrated the ability to identify MC1R-positive tumors by PET imaging.

Perspective also designed two imaging surrogates, the chemically identical [203Pb]VMT01 for SPECT imaging and dosimetric calculations and [68Ga]VMT02, a PET imaging tracer, for patient selection. [68Ga]VMT02 utilizes the same targeting peptide as VMT01 but differs in having a chelator optimized for PET radiotracers (DOTA). Through the use of the imaging scans, Perspective is able to characterize whether the patient’s cancer expresses MC1R. This confirms the patient may be a candidate for treatment. As a therapeutic, Perspective links 212Pb to the same MC1R targeting peptide which has been shown to bind to the cancerous cell, to treat and potentially kill the tumor. The melanoma program focuses primarily on development of the therapeutic compound. The rationale for the development of two imaging tracers is to provide flexibility in imaging a molecular target for which a validated and approved imaging tracer does not exist. Further commercialization of one or both of these imaging tracers will follow a separate regulatory path from the therapeutic compound and will proceed based on the potential for utility after a therapeutic efficacy signal is identified.

VMT01 and VMT02 peptides bind with high affinity and specificity to melanoma tumors (where MC1R is present) and do not bind to healthy cells (where MC1R is absent). Thus, the radioactive nuclide carried by the peptide is delivered primarily to tumor cells, while nonspecific binding to healthy cells is minimal. Treatment is carried out in two stages. In the first stage (i.e., the diagnostic stage), [203Pb]VMT01 or [68Ga]VMT02 is administered for SPECT or PET imaging, respectively. The decay of radionuclides 203Pb and 68Ga result in gamma radiation that can be detected by the imaging device. This detection can be used to pinpoint the presence of cancerous tumors expressing MC1R and illuminate the pharmacokinetic properties and biodistribution of the radiopharmaceutical. This information can be used to guide the second stage (i.e., the therapeutic stage) with [212Pb]VMT01, in which radionuclide 212Pb replaces 203Pb and 68Ga. [212Pb]VMT01 is designed to deliver alpha (α) radiation efficiently to melanoma tumors that express the MC1R receptor. This two-stage process is commonly referred to as image-guided receptor-targeted alpha-particle radionuclide therapy for cancer and is also referred to as a “theranostic” approach.

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Nonclinical pharmacology, pharmacokinetics and toxicology studies utilizing in vitro and in vivo assays, SPECT and PET imaging and histopathology were conducted by the sponsor to support the first-in-human Phase 1/2a clinical development of [212Pb]VMT01 per recommendations in the United States Food and Drug Administration Guidance document titled “Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations Guidance for Industry.” Promising results have demonstrated an increase in progression-free survival, improvement in overall survival and, in some cases, complete remission in mice bearing murine and human melanoma tumors. Perspective has also observed significant synergy with checkpoint inhibitors in animal models that are resistant to immunotherapy alone and a subset of animals receiving the combination therapy demonstrate resistance to re-inoculation with naive melanoma cells.

Management believes that there are currently no FDA approved peptide-based receptor targeting approaches for the treatment of metastatic melanoma. The goal of the theranostic approach with [203Pb]VMT01 or [68Ga]VMT02 (diagnosis) and [212Pb]VMT01 (therapy) is to establish a new methodology to treat patients with MC1R-expressing tumors that has the potential to improve long-term outcomes.

Role of VMT01 in Advanced Melanoma Treatment

Melanoma is a cancer of the skin arising from uncontrollable growth of melanocytes, the melanin producing cells of the body. Melanoma generally originates on the epidermis (the outermost layer of skin). In rare instances, melanoma can originate in the eyes or mucosal membranes, as these are other locations where melanocytes are present. Metastatic melanoma is the result of melanoma that has progressed through the layers of skin, infiltrated the blood stream or lymphatic system and traveled to other areas of the body to metastasize.

The worldwide melanoma incidence is estimated to reach 335,160 new cases in 2024 (source: GlobalData) and the risk of melanoma increases as people age, with the average age of diagnosis being early to mid 60s. Melanoma is a global disease affecting all populations around the world. The risk of developing melanoma increases significantly in areas of high ultraviolet exposure and for people with fair complexion. Particularly high incidences are observed in North America, Northern Europe and New Zealand. The highest occurs in Australia, where annual rates are more than twice that of North America. In the U.S., there will be an estimated 107,879 new diagnoses of melanoma by 2025 (representing one-third of all cases worldwide) and approximately 7,868 deaths annually from metastatic melanoma (source: GloboCan). In most cases, metastatic melanoma cannot be cured but treatment can support a longer life.

The National Cancer Institute’s Surveillance, Epidemiology, and End Results ("SEER") Program estimates 77% of all melanoma cases in the United States are local disease, receiving surgical treatment followed by watchful waiting. Melanoma that has regional spread (stage III) indicates spreading to nearby lymph nodes and accounts for 9% of cases, with a five-year survival ranging from 93% for stage IIIA to 32% for stage IIID reported in 2021 (source: Tonella L, Pala V, Ponti R, Rubatto M, Gallo G, Mastorino L, Avallone G, Merli M, Agostini A, Fava P, Bertero L, Senetta R, Osella-Abate S, Ribero S, Fierro MT, Quaglino P. Prognostic and Predictive Biomarkers in Stage III Melanoma: Current Insights and Clinical Implications. Int J Mol Sci. 2021 Apr 27;22(9):4561. doi: 10.3390/ijms22094561. PMID: 33925387; PMCID: PMC8123895). Metastatic melanoma is classified as stage IV, where melanoma metastasizes to distant organs, such as the brain, lungs or liver, and contains any T or N value in the TNM staging system. Metastatic melanoma accounts for 4% of cases and carries a poor prognosis with a five-year survival of 30% (source: SEER). The majority of metastatic melanoma patients will receive some form of immunotherapy; however, more than 50% ultimately progress. Patients with tumors positive for the BRAF mutation who progress on immunotherapy can receive targeted therapy; however, these patients ultimately acquire resistance. Thus, the majority of metastatic melanoma patients who eventually progress on immunotherapy (and targeted therapy if BRAF positive) are left with very limited options and represent the patient population with the greatest unmet need in melanoma (source: Global Data). This segment of the melanoma population is the intended entry market for VMT01. Worldwide sales for the systemic treatment of advanced melanoma are expected to reach $6.7 billion by 2025 with the U.S. accounting for over 60% of the market, or approximately $4.0 billion in sales (source: Global Data).

Leading treatments for metastatic melanoma are typically not curative. Treatments include immunotherapy to help the immune system recognize evading cancer cells, targeted therapy to interfere with known cancer processes, radiation therapy to kill cancer cells via high-energy X-ray or proton beams and chemotherapy to attack rapidly dividing cancer cells. Immunotherapies and targeted mitogen-activated protein kinase inhibitor ("MAPKi") cell therapies have improved outcomes, but low response rates, acquired drug resistance and adverse side effects have limited quality of life for metastatic melanoma patients. The most dramatic improvements in response (combination therapies; up to 61%) have often been reported to lead to grade 3/4 adverse events and therapy discontinuation. Recurrence is common, with complex mechanisms of resistance that include altered oncogenic pathways, tumor heterogeneity and enhanced DNA repair. Perspective’s TAT platform using [212Pb]VMT01 has the potential to overcome many of these resistance pathways. Perspective’s intent is to test the safety and tolerability of [212Pb]VMT01in previously treated patients who are experiencing progression or recurrence of disease as monotherapy and seek approval for testing in combination with first-line immunotherapies as soon as a preliminary safety profile is established and regulatory approval is obtained.

Clinical Studies of 212Pb–VMT01

In 2020, Perspective filed an IND application with the FDA to evaluate [203Pb]VMT01 and [68Ga]VMT01 imaging in adults with advanced stage melanoma under IND #152145, which was given a "safe to proceed" designation on August 21, 2020. Perspective completed evaluating [203Pb]VMT01 and [68Ga]VMT01 in a first-in-human Phase 1 imaging study conducted at the Mayo Clinic in Rochester, MN. This study utilized a cross-over design where six subjects with stage IV unresectable melanoma were imaged. The primary endpoints of this study are safety and biodistribution and secondary endpoints are molecular target validation and image quality. Perspective has finished enrolling subjects in the study and is nearing completion of analysis of the dosimetry portion of the trial. Perspective is working on the clinical study report and anticipates it will be released in the first half of 2024. Positive imaging of MC1R was seen in a subset of patients using both agents, and no treatment-related adverse events have been observed to date.

On January 21, 2022, Perspective received an IND "safe to proceed" letter from the FDA to evaluate [212Pb]VMT01 in patients with advanced and progressive melanoma. Perspective’s ongoing trial of [212Pb]VMT01 (clinicaltrials.gov identifier NCT05655312) is a multi-center, open-label dose escalation, dose expansion study in subjects with histologically confirmed melanoma and MC1R-positive imaging scans. The first part of the study is a dose escalation phase to determine the MTD or MFD following a single administration of [212Pb]VMT01. In October 2023, Perspective announced that recruitment for the first patient cohort was complete, and those patients received 111 MBq (3mCi) per dose. The second cohort, which is currently being recruited, will receive administered activities of 185 MBq (5mCi), with cohorts 3 and 4 receiving 370 MBq (10 mCi) and 555 MBq (15 mCi), respectively, if the MTD or MFD is not reached during escalation. According to the mTPI-2 study design, intermediate de-escalation doses are also possible to allow selection of the optimal activity dose to take forward into the dose expansion part of the study.

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The second part of the study is a dose expansion phase based on the identified MTD/MFD. Patients may be eligible to receive up to three administrations of [212Pb]VMT01 approximately eight weeks apart. A dosimetry sub-study is included to assess biodistribution, tumor uptake and correlation of uptake with observed toxicities and efficacy.

In March 2024, Perspective provided the following update on the ongoing clinical trial (all data is as of March 7, 2024):

In March 2024, Perspective announced a clinical trial collaboration agreement with Bristol Myers Squibb to evaluate the safety and tolerability of [212Pb]VMT01 in combination with Bristol Myers Squibb’s nivolumab in patients with histologically confirmed melanoma and positive MC1R imaging scans. This combination study is an amendment to the Company’s ongoing Phase1/2a study of [212Pb]VMT01 in patients with metastatic melanoma.

PSV40X: A Differentiated PSMA-Targeted Alpha Therapy

On December 31, 2023, Perspective entered into an exclusive patent license agreement with the Mayo Clinic for the rights to the PSMA Alpha-PET DoubLET platform technology for the treatment of PSMA-expressing cancers, with an initial focus on prostate. The PSMA Alpha-PET DoubLET platform technology represents a potential leap forward in the field of prostate cancer diagnostics and treatment. This leading radiopharmaceutical platform provides detailed PET imaging-based diagnosis and dosimetry using long-lived copper-64 (64Cu) for imaging and alpha-particle-targeted radiopharmaceutical therapy ("RPT") using 212Pb. It can also be used for beta-particle-targeted RPT using copper isotopes. Prostate cancer is the second-most prevalent form of cancer affecting men worldwide, emphasizing the critical need for advanced technologies to improve early detection and treatment outcomes. For 2023, the Cancer Institute estimated 88,300 new cases of prostate cancer in the U.S. and around 34,700 deaths from the disease.

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Preclinical studies demonstrated a high degree of radiation delivered to tumors while minimizing exposure to critical organs and tissues, particularly a reduction in salivary gland uptake and kidney retention (Johnson et al., RPT Interest Group June 7 2023 https://rrp.cancer.gov/working_groups/AlphaPET-RPT_Int_group_lecture.pdf) as noted in the graphic below.

1 indicates p < 0.05 [64Cu]PSV401 vs [68Ga]PSMA-11 (all data sets as indicated)

2 Johnson et al., RPT Interest Group June 7 2023 https://rrp.cancer.gov/working_groups/AlphaPET-RPT_Int_group_lecture.pdf;

3 SUV = Standardized Uptake Variable

Pre-Targeting Theranostic Targeting Platform - The Next Generation of TAT

In February 2024, Perspective announced that it has executed an exclusive, worldwide license agreement with Stony Brook University for the global intellectual property rights to its Cuburbit[7]uril-admantane ("CB7-Adma") pre-targeting platform and has applied for the Phase 1 tranche of a 2.5-year Fastrack Small Business Innovation Research grant (Phase 1 $400 thousand; total $2.4 million) from the National Institutes of Health's ("NIH") National Cancer Institute ("NCI") in support of Perspective's CB7-Adma host-guest pre-targeting program for the diagnosis and treatment of cancer.

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Pre-targeting using the CB7-Adma platform involves two steps. First, an antibody that binds with high specificity to a cancer-specific protein is administered via intravenous injection. This antibody is chemically modified to include the CB7 chemical entity and accumulates over time at the tumor site. Then, a radionuclide held tightly by Perspective's proprietary chelator attached to an Adma group is administered. The Adma group binds to the CB7 group that was previously attached to the cancerous cells with remarkable specificity, delivering radiation dose selectively to the tumor sites.

Central to this innovation is CB7-Adma (host-guest) complex formation, driving the interaction between the antibody and radioligand. The chosen host-guest pair, CB7-Adma, demonstrates promising in vivo stability, modularity and low immunogenicity. The platform's potential was validated through in vivo profiling of ligands, employing a CB7-modified carcinoembryonic antigen ("CEA") targeting antibody.

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PSV359 – A Targeted Alpha Therapy Targeting Fiber Activation Protein

Tumor stroma cells do not typically express cancer-specific markers like SSTR2 or MC1R. Fiber Activation Protein ("FAP") is primarily expressed on tumor stroma cells, but also on some cancer cells. FAP-α is a pan-cancer target that is highly expressed in many cancers. Perspective’s in-house discovery team has developed an optimized peptide with potential best-in-class characteristics that has been demonstrated in preclinical models. In March 2024, Perspective released the first in human clinical SPECT/CT imaging which suggests the tumor targeting and retention of the PSV359 compound is excellent, while clearing from normal organs rapidly and completely. The FAP-α PSV359 program is a significant addition to Perspective’s clinical pipeline of targeted alpha therapeutic assets and Perspective is working to file an IND application in late 2024 for this new program.

Images courtesy of Dr. Ishita B. Sen, Director & Head Department of Nuclear Medicine & Molecular Imaging at Fortis Memorial Research Institute, Gurgaon, India.

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Manufacturing and Supply

Perspective has developed a proprietary isotope delivery system, colloquially called a “generator,” VMT-α-GEN, to allow for delivery of its preferred therapeutic isotope 212Pb for supply to patients. Perspective has a license to possess radioactive materials and distribute our radiopharmaceuticals from the Iowa Department of Health and Human Services, Radioactive Materials Program at our Coralville, IA site. In January 2021, we entered into a 10-year feedstock contract with the National Isotope Development Center ("NIDC") of the Department of Energy's ("DoE") Isotope Program. Perspective receives feedstock shipments of Thorium-228 from the NIDC. Perspective also has contracts with various manufacturers to produce certain components of its VMT-α-GEN system. This has allowed Perspective to scale manufacturing of VMT-α-GEN for research purposes that Perspective believes will facilitate its alpha therapy clinical trials. Perspective believes that by controlling its own therapeutic isotope supply, it can solve the many supply chain risks that have slowed alpha-particle therapy clinical adoption to date.

Perspective assembles and manufactures its finished radiopharmaceutical candidates by chelating or trapping an atom of 212Pb within a specialized chemical “cage” and connecting the 212Pb within its cage to the targeting peptide with its proprietary linker technology. For clinical supply, Perspective intends to use a combination of third-party contract manufacturing organizations, or CMOs, and its own manufacturing sites, which comply with the FDA’s current good manufacturing practices, or cGMP, for the manufacture and distribution of its drug substance.

For the drug precursors and isotopes that comprise Perspective’s TAT platform, a variety of cGMP manufacturers have been engaged and qualified. Perspective procures chelator-modified peptide precursors from peptide manufacturers who are capable of producing cGMP precursor material. The imaging isotope 203Pb is procured from manufacturers with appropriate radiation handling licensing and shipped to its production site in Coralville, IA, or to CMOs, while 68Ga, is produced on site at PET radiopharmacies that have access to this isotope and are capable of producing finished product. Therapeutic isotope 212Pb is supplied via Perspective’s proprietary 224Ra/212Pb isotope delivery systems (“generators”), which are manufactured by a CMO. These isotope delivery systems can be shipped globally to enable final finished radiopharmaceutical production. Perspective has received "safe to proceed" designations for two therapeutic IND applications in which its isotope delivery system was presented to the FDA for use in clinical trial manufacturing. Quality and stability testing for all of Perspective’s precursors is an ongoing process, and there have been no quality or stability issues in its supply chain to date.

For discovery activities and early phase clinical testing, Perspective has established a clinical drug manufacturing facility at its laboratories in Coralville, IA, to assemble the precursors into ready-to-use drug products. These facilities comprise approximately 2,000 square feet of wet laboratory facilities and a small finished product facility equipped with appropriate air and temperature handling and monitoring to comply with applicable clinical drug regulatory requirements. Perspective has staff experienced in finished radiopharmaceutical manufacturing and shipping who will not only supply drug product for its near-term activities but will also perform technology transfer to any CMOs where the finished production radiopharmaceuticals will be accomplished. Perspective has obtained all appropriate radiation handling licensing to provide clinical doses for its Phase 1/2 clinical trials. In addition, Perspective is capable of synthesizing peptides, chelators and linkers in its facilities in Coralville, and this capability enables it to perform research independently for pipeline development.

Short-list CMOs have locations that are strategically placed locally to major metropolitan areas that are within reach for delivery of Perspective’s radiopharmaceuticals for trials and ultimately for commercialization. Perspective is currently establishing a network of CMOs across the United States and is transferring know-how and technology to these CMOs to allow broader potential geographic coverage of radioactive products across its potential clinical trial sites. As noted in the graphic below showing a heat map of population in the United States, Perspective will be able to service a majority of cancer centers by strategically locating facilities throughout the United States.

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In March 2024, Perspective acquired the assets and associated lease of Lantheus’ radiopharmaceutical manufacturing facility in Somerset, New Jersey. Perspective believes it will be able to convert the facility, which has three production suites, to manufacture finished radiopharmaceutical product using previously validated precursors. As a cGMP compliant facility, Perspective intends to utilize the facility to manufacture clinical supply of high quality 203Pb-labeled tumor-specific peptides to visualize and diagnose tumors, and 212Pb-labeled radiopharmaceuticals to treat target tumors with TAT. Moreover, with its three cGMP suites at the facility, Perspective expects to have the capacity to meet future clinical trial and commercial demands at major cancer treatment centers throughout the Northeastern U.S.

Perspective intends to continue to expand its manufacturing and supply network during 2024 as it anticipates increasing its clinical trial activities.

Commercialization

None of Perspective’s current program candidates have received the regulatory approvals required to begin commercialization.

Competition

The life sciences and pharmaceutical industries are known to have rapid advancement of novel technologies, intense competition and a strong emphasis on intellectual property. While Perspective believes that its technology and intellectual property provide us with competitive advantages, we face potential competition from multiple sources, including large pharmaceutical companies, specialty pharmaceutical and biotechnology companies, academic institutions, government agencies and public and private research organizations.

Commercial and academic clinical trials are being pursued by a number of parties in the field of radiopharmaceuticals. Early results from these trials have fueled continued interest in radiopharmaceuticals, which is being pursued by several biotechnology companies, as well as by large pharmaceutical companies, including both commercial and academic clinical trials. Results from these trials, combined with recent product approvals, have garnered continued interest in the space by both large pharmaceutical companies and specialized biotechnology companies, which are developing both early-stage and later-stage candidates.

There are also several companies developing alpha-based radiopharmaceuticals for the treatment of cancer, including Bayer, Novartis, Bristol-Myers Squibb (with their recent acquisition of RayzeBio), Eli Lilly (with their recent acquisition of POINT Biopharma), Telix Pharmaceuticals Limited, Actinium Pharmaceuticals, Inc., RadioMedix, Inc., Orano Med, Aktis Oncology, Fusion Pharmaceuticals, Inc. (which announced on March 19, 2024 that they are being acquired by AstraZeneca), Aktis Oncology, Inc., Convergent Therapeutics, Janssen, ARTBIO and Curie Therapeutics, Inc. These companies use various alpha-emitting isotopes such as 223Ra, 225Ac, 212Pb and 227Th. Most alpha-based radiopharmaceuticals are in clinical development, with Bayer’s Xofigo® being the only approved alpha particle-based therapy. Xofigo® was approved in 2013 for the treatment of symptomatic bone metastases in people with castration-resistant prostate cancer.

There are also companies with beta-based radiopharmaceuticals, both in development and already approved. There are multiple companies, including Lantheus, Novartis and Q BioMed Inc., with approved beta-based radiopharmaceutical products using isotopes such as 131I, 177Lu, 89Sr and 90Y. Novartis’ Lutathera® and Pluvicto® are prominent beta-based radioligands, and other beta-based radiopharmaceuticals are in various stages of clinical development by companies including Novartis, Curium SAS, Nordic Nanovector, Cellectar Biosciences, ITM Isotope Technologies Munich SE, Clovis Oncology and Y-mAbs Therapeutics, Inc., Actinium Pharmaceuticals, Inc., Lantheus, Blue Earth Therapeutics and Clarity Pharmaceuticals.

For Perspective's program candidate [212Pb]VMT-α-NET, the company is aware of several competing therapies targeting neuroendocrine tumors. Novartis’ Lutathera®, which was approved in 2018, uses 177Lu for the treatment of individuals with somatostatin receptor-positive gastroenteropancreatic neuroendocrine cancers. The Company is aware of the following companies with neuroendocrine tumor, radioligand preclinical and clinical development programs: ITM, Bristol-Myers Squibb (through their recent acquisition of RayzeBio), Eli Lilly (through their recent acquisition of POINT Biopharma) and Radiomedix. Perspective also faces potential competition from other treatments targeting neuroendocrine tumors such as Sandostatin® and Afinitor® (Novartis), Somatuline® (Ipsen) and Sutent® (Pfizer). While Perspective believes [212Pb]VMT-α-NET has significant advantages compared to conventional approaches to neuroendocrine tumors, the Company may still face competition from these more established treatments.

Many of our current or potential competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

We could see a reduction or elimination in our commercial opportunity if our competitors develop and commercialize drugs that are safer, more effective, have fewer or less severe side effects, are more convenient to administer, are less expensive or with a more favorable label than our drug candidates. Our competitors also may obtain FDA or other regulatory approval for their drugs more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. The key competitive factors affecting the success of all of our drug candidates, if approved, are likely to be efficacy, safety, convenience, price, availability of the relevant isotope, the effectiveness of imaging diagnostics, the level of generic competition and the availability of reimbursement from government and other third-party payors.

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Grants and Awards

Perspective’s next-generation radiopharmaceutical technology has been recognized by many prestigious organizations and has received numerous awards and grants in support of the development of its technology and programs.

Perspective has benefited from Small Business Innovation Research ("SBIR") awards of approximately $17 million through September 2022 from the National Institutes of Health and National Cancer Institute to Michael K. Schultz, PhD, Perspective’s co-founder and the Company’s Chief Science Officer, Frances L. Johnson, M.D., Perspective’s co-founder and the Company’s Chief Innovation Officer and to Perspective’s principal collaborators at the University of Iowa. The table below summarizes key grant awards that have been peer-reviewed by expert panels at the National Cancer Institute.

Date Type Amount ($) Principal Investigator Summary Use

* Ongoing Grant

Intellectual Property

Perspective’s success depends, in part, on its ability to obtain and maintain intellectual property protection for its platform technology, program candidates and know-how, to defend and enforce its intellectual property rights, in particular, its patent rights, to preserve the confidentiality of its know-how and trade secrets and to operate without infringing the proprietary rights of others. Perspective seeks to protect its program candidates and technologies by, among other methods, filing U.S. and foreign patent applications related to its proprietary technology, inventions and improvements that are important to the development of its business. Perspective also relies on trade secrets, know-how, continuing technological innovation and in-licensing of third-party intellectual property to develop and maintain its proprietary position. Perspective, or its collaborators and licensors, file patent applications directed to its key program candidates in an effort to establish intellectual property positions to protect its program candidates as well as uses of its program candidates for the prevention and/or treatment of diseases.

As of December 31, 2023, Perspective exclusively licenses five issued U.S. patents, 20 pending foreign patent applications and one pending international Patent Cooperation Treaty, or PCT, applications from the University of Iowa and currently has filed two pending provisional U.S. patent applications relating to its continuous new program development.

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Perspective in-licensed a patent family with composition of matter and method claims directed to radiopharmaceutical cancer-targeted compositions comprising chelating moieties, linkers and targeting moieties. Patent applications are pending in the United States and various foreign jurisdictions and regions including China, Canada, South Korea, India, Europe and Australia.

From the University of Iowa, Perspective in-licenses patent applications with composition of matter and methods of use claims covering VMT-α-NET and its therapeutic and diagnostic use, along with structural claims for Perspective’s PSC with patent applications in the United States and various other foreign jurisdictions and regions including Europe, Australia, Canada, India and China. Patent applications in this family, if issued, are expected to expire in approximately 10 to 17 years, without taking potential patent term extensions into account.

Additionally, from the University of Iowa, Perspective in-licenses one issued U.S. patent (US 11,179,484 B2) and one provisional pending U.S. patent application with composition of matter and methods of use claims covering VMT01 and its therapeutic and diagnostic use for treating melanoma, which are expected to expire in approximately 13 years, without taking potential patent term extensions into account.

The issuance of the VMT01 patent coincided with the completion of a clinical imaging trial which allowed Perspective to evaluate VMT01 against the value of a portfolio of patents in-licensed from the University of New Mexico ("UNM"). Positive results of its clinical trial in comparison to previously published clinical data on the use of the UNM-patented compound allowed Perspective to issue a Notice of Termination for the portfolio in 2022, which represented a significant cost to the company, and the IND for the use of VMT01 for clinical therapy of melanoma patients has received a "safe to proceed" designation (i.e., approval to conduct the trial) from the FDA. The issued U.S. patent with composition-of-matter and methods-of use-claims covering VMT01 and its therapeutic and diagnostic use for melanoma or other MCR1-expressing tumors are expected to expire in approximately 13 years, without taking potential patent term extensions into account.

In December 2023, Perspective entered into a patent license agreement with Mayo Clinic for the rights to the PSMA Alpha-PET DoubLET platform technology for the treatment of PSMA-expressing cancers, with an initial focus on prostate. The PSMA Alpha-PET DoubLET platform technology represents a potential leap forward in the field of prostate cancer diagnostics and treatment. This leading radiopharmaceutical platform provides detailed PET imaging-based diagnosis and dosimetry using long-lived copper-64 (64Cu) for imaging and alpha-particle-targeted radiopharmaceutical therapy ("RPT") using 212Pb. It can also be used for beta-particle-targeted RPT using copper isotopes. Preclinical studies demonstrated a high degree of radiation delivered to tumors while minimizing exposure to critical organs and tissues. The agreement with Mayo Clinic will expire upon the later of the expiration date of the last-to-expire patent rights or the date of discontinuation of sales of the licensed product.

In January 2024, Perspective entered into an exclusive in-licensing of Stony Brook University’s Cuburbit[7]uril-admantane ("CB7-Adma") pre-targeting platform which covers the global intellectual property rights. Pre-targeting using the CB7-Adma platform involves two steps. First, an antibody that binds with high specificity to a cancer-specific protein is administered via intravenous injection. This antibody is chemically modified to include the CB7 chemical entity and accumulates over time at the tumor site. Then, a radionuclide held tightly by Perspective's proprietary chelator attached to an Adma group is administered. The Adma group binds to the CB7 group that was previously attached to the cancerous cells with remarkable specificity, delivering radiation dose selectively to the tumor sites. Central to this innovation is CB7-Adma (host-guest) complex formation, driving the interaction between the antibody and radioligand. The chosen host-guest pair, CB7-Adma, demonstrates promising in vivo stability, modularity and low immunogenicity. The platform's potential was validated through in vivo profiling of ligands, employing a CB7-modified CEA targeting antibody. The agreement with Stony Brook University will expire on the later of the expiration date of the last to expire licensed patents or 20 years from the date of the first sale of a product utilizing the intellectual property.

Perspective has an active pipeline development program, resulting in additional intellectual property developments within the company. Perspective submitted two provisional applications in 2022 to support its programs and submitted applications for the next peptide-based radiopharmaceutical (compositions and methods patent applications) in 2023. Perspective anticipates new peptide-based radiopharmaceuticals provisional applications from its discovery laboratory on a rolling basis of approximately 18- to 24-month schedules, depending on the complexity of the target and molecular construct. Perspective intends to supplement this effort with in-licensing supported by an active collaborative grant program with academic centers around the globe. Perspective has added a collaboration with Seoul National University and Technical University Munich to expand the reach of the discovery program. All collaborations include appropriate confidentiality arrangements and material transfer agreements and documentation to protect Perspective’s intellectual property assets as well as establish a relationship to enable it to license intellectual property it identifies as valuable to it. These activities leverage a strong collaborative network established by Perspective to drive innovation and generate new intellectual property.

Agreements and Collaborations

Lantheus Agreements

Investment Agreement

On January 8, 2024, Perspective entered into an investment agreement (the “Lantheus Investment Agreement”) with Lantheus Alpha Therapy, LLC, a Delaware limited liability company and wholly owned subsidiary of Lantheus Holdings, Inc. (“Lantheus”), pursuant to which Perspective agreed to sell and issue to Lantheus in a private placement transaction (the “Lantheus Private Placement”) certain shares (the “Lantheus Shares”) of Perspective’s Common Stock. The closing of the purchase and sale of the Lantheus Shares to Lantheus by Perspective (the “Lantheus Closing”) were subject to Perspective raising at least $50.0 million of gross proceeds (excluding Lantheus’ investment) in a qualifying third-party financing transaction, which occurred on January 22, 2024.

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The number of Lantheus Shares sold was 56,342,355, representing 19.99% of the outstanding shares of Common Stock as of January 8, 2024. The Lantheus Shares were sold at a price of $0.37 per share, for gross proceeds to Perspective of approximately $20.8 million. Pursuant to the Lantheus Investment Agreement, Perspective agreed to cooperate in good faith to negotiate and enter into a registration rights agreement with Lantheus, obligating Perspective to file a registration statement on Form S-3 with the U.S. Securities and Exchange Commission to register for resale the Lantheus Shares issued at the Lantheus Closing. The Lantheus Investment Agreement also contains agreements of Perspective and Lantheus whereby Lantheus is provided certain board observer and information rights of Perspective, as well as standstill provisions prohibiting Lantheus from taking certain actions for a specified period of time, subject to certain exceptions.

The Lantheus Investment Agreement also provides Lantheus with certain pro rata participation rights to maintain its ownership position in Perspective in the event that Perspective makes any public or non-public offering of any equity or voting interests in Perspective or any securities that are convertible or exchangeable into (or exercisable for) equity or voting interests in Perspective, subject to certain exceptions.

Pursuant to the Lantheus Investment Agreement, Perspective is required to notify Lantheus within 10 business days of the end of a fiscal quarter in which Perspective issued shares of Common Stock pursuant to that certain At Market Issuance Sales Agreement among Perspective, Oppenheimer & Co. Inc., B. Riley Securities, Inc., and JonesTrading Institutional Services LLC dated November 17, 2023 (the “ATM Agreement”), of (i) the number of shares of Common Stock issued during such fiscal quarter pursuant to the ATM Agreement and (ii) the average price per share received by Perspective before commissions (the “ATM Average Price”). Upon receipt of such notice, Lantheus may elect, at its option, to purchase all or a portion of its Pro Rata Portion (as defined in the Lantheus Investment Agreement) of such shares at an aggregate price equal to the number of shares purchased multiplied by the ATM Average Price for such quarter (the “ATM Participation Right”). Pursuant to the Lantheus Investment Agreement, Lantheus may not exercise the ATM Participation Right more than two times per calendar year.

Asset Purchase Agreement

On January 8, 2024, Perspective entered into an Asset Purchase Agreement (the “Progenics APA”) with Progenics Pharmaceuticals, Inc., a Delaware corporation (“Progenics”) and affiliate of Lantheus, pursuant to which Perspective will acquire certain assets and the associated lease of Progenics’ radiopharmaceutical manufacturing facility in Somerset, New Jersey for a purchase price of $8.0 million in cash. The closing of the transactions pursuant to the Progenics APA was subject to customary closing conditions, including regulatory approval. The transactions contemplated by the Progenics' APA closed on March 1, 2024.

Option Agreement

On January 8, 2024, Perspective entered into that certain Option Agreement (the “Option Agreement”) and together with the Lantheus Investment Agreement and the Progenics APA, the “Agreements”) with Lantheus whereby Lantheus was granted an exclusive option to negotiate an exclusive, worldwide, royalty- and milestone-bearing right and license to [212Pb]VMT-α-NET, the Company’s clinical-stage alpha therapy developed for the treatment of neuroendocrine tumors and a right to co-fund the Investigational New Drug ("IND") application, enabling studies for early-stage therapeutic candidates targeting prostate-specific membrane antigen and gastrin-releasing peptide receptor and, prior to IND filing, a right to negotiate for an exclusive license to such candidates. In consideration of the rights granted by the Company to Lantheus pursuant to the Option Agreement, Lantheus will pay to Perspective a one-time payment of $28.0 million, subject to certain withholding provisions related to the closing contemplated by the Progenics APA.

Under the terms of the Option Agreement, Lantheus also has a right of first offer and last look protections for any third-party merger and acquisition transactions involving the Company for a 12-month period beginning on January 8, 2024.

The Agreements contain customary representations, warranties and covenants that were made solely for the benefit of the parties to the Agreements. Such representations, warranties and covenants (i) are intended as a way of allocating risk between the parties to the Agreements and not as statements of fact and (ii) may apply standards of materiality in a way that is different from what may be viewed as material by stockholders of, or other investors in, Perspective. Accordingly, the Agreements are being disclosed only to provide investors with information regarding the terms of the transaction and not to provide investors with any other factual information regarding Perspective. Moreover, information concerning the subject matter of the representations and warranties may change after the date of the Agreements, which subsequent information may or may not be fully reflected in public disclosures.

Equity Financings

March 2024 Private Placement with Institutional Investors

On March 4, 2024, Perspective entered into an investment agreement (the "March 2024 Investment Agreement”) with certain accredited institutional investors (“Institutional Investors”) pursuant to which Perspective agreed to issue and sell, in a private placement (the “March 2024 Private Placement”), 92,009,981 shares (“March 2024 Shares”) of Perspective’s common stock, par value $0.001 per share (the “Common Stock”), for a purchase price of $0.95 per share, representing the closing price of the Common Stock on March 1, 2024. The closing of the March 2024 Private Placement occurred on March 6, 2024 (the "March 2024 Closing").

The gross proceeds to the Company from the March 2024 Private Placement were approximately $87.4 million, before deducting fees payable to the Placement Agents (as defined below) and other estimated transaction expenses. Perspective intends to use the net proceeds from the March 2024 Private Placement for general corporate and working capital purposes, which may include research and development expenditures, preclinical study and clinical trial expenditures, manufacturing expenditures, commercialization expenditures, capital expenditures, acquisitions of new technologies, products or businesses and investments.

The March 2024 Investment Agreement contains customary representations, warranties and agreements by the Company and the Institutional Investors, indemnification obligations of the Company and the Institutional Investors, other obligations of the parties and termination provisions.

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The March 2024 Private Placement was conducted pursuant to a Placement Agency Agreement, dated March 4, 2024 (the “Placement Agency Agreement”), by and between Perspective and Oppenheimer & Co. Inc., as representative of the placement agents named therein (the “Placement Agents”). Per the Placement Agency Agreement, Perspective agreed to: (i) pay the Placement Agents a cash fee equal to 5.85% of the gross proceeds received by the Company from the sale of the Shares; and (ii) reimburse the Placement Agents for certain fees and expenses. The Placement Agency Agreement also contains representations, warranties, indemnification and other provisions customary for transactions of this nature.

In connection with the Private Placement, Perspective also entered into a registration rights agreement, dated March 6, 2024 (the “Registration Rights Agreement”), with the Institutional Investors obligating the Company to register the resale of the March 2024 Shares within a specified period of time after the March 2024 Closing.

January 2024 Public Offering

On January 17, 2024, Perspective entered into an underwriting agreement (the “Underwriting Agreement”) with Oppenheimer & Co. Inc., as representative of the underwriters named therein (the “Underwriters”), in connection with its previously announced underwritten public offering (the “Public Offering”) of 132,075,218 shares (the “Public Shares”) of Perspective's Common Stock and, in lieu of Public Shares to certain investors, pre-funded warrants (the “Pre-funded Warrants”) to purchase 30,086,944 shares of Common Stock. The price to the public for the Public Shares was $0.37 per Public Share, and the price to the public for the Pre-funded Warrants was $0.369 per Pre-funded Warrant, which represents the per share price for the Public Shares less the $0.001 per share exercise price for each such Pre-funded Warrant. Under the terms of the Underwriting Agreement, Perspective granted the Underwriters an option, exercisable for 30 days, to purchase up to an additional 24,324,324 shares of Common Stock at the same price per share as the Public Shares, which such option was fully exercised by the Underwriters on January 18, 2024. The Public Offering closed on January 22, 2024.

The gross proceeds to Perspective from the Public Offering were approximately $69.0 million, before underwriting discounts and commissions and estimated expenses of the Public Offering.

Perspective intends to use the net proceeds from the Public Offering for general corporate purposes, which may include research and development expenditures, preclinical study and clinical trial expenditures, manufacturing expenditures, commercialization expenditures, working capital, capital expenditures, acquisitions of new technologies, products or businesses and investments.

The Public Offering was made pursuant to Perspective’s shelf registration statement on Form S-3 (File No. 333-275638), declared effective by the Securities and Exchange Commission on December 14, 2023, a base prospectus dated December 14, 2023, and the related prospectus supplement dated January 17, 2024.

The Pre-funded Warrants are exercisable at any time after the date of issuance. The exercise price and the number of shares of Common Stock issuable upon exercise of each Pre-funded Warrant (the “Warrant Shares”) are subject to appropriate adjustment in the event of certain stock dividends and distributions, stock splits, stock combinations, reclassifications or similar events affecting the Common Stock as well as upon any distribution of assets, including cash, stock or other property, to Perspective’s stockholders. The Pre-funded Warrants will not expire and are exercisable in cash or by means of a cashless exercise. A holder of Pre-funded Warrants may not exercise such Pre-funded Warrants if the aggregate number of shares of Common Stock beneficially owned by such holder, together with its affiliates, would beneficially own more than 4.99% of the issued and outstanding shares of Common Stock following such exercise, as such percentage ownership is determined in accordance with the terms of the Pre-funded Warrants. A holder of Pre-funded Warrants may increase or decrease this percentage not in excess of 19.99% by providing at least 61 days’ prior notice to Perspective.

The Underwriting Agreement contains customary representations, warranties and agreements by Perspective, customary conditions to closing, indemnification obligations of Perspective and the Underwriters, including for liabilities under the Securities Act of 1933, as amended, other obligations of the parties and termination provisions. The representations, warranties and covenants contained in the Underwriting Agreement were made only for purposes of such agreement and as of specific dates, were solely for the benefit of the parties to such agreement and may be subject to limitations agreed upon by the contracting parties.

Brachytherapy Divestiture

On December 7, 2023, Isoray entered into an Asset Purchase Agreement (the “GT Medical APA”) by and among Isoray, Perspective, and GT Medical Technologies, Inc., a Delaware corporation (“GT Medical”). Perspective entered into the GT Medical APA as sole stockholder of Isoray and as Seller Parent as that term is defined in the GT Medical APA.

Subject to the satisfaction or waiver of the conditions set forth in the GT Medical APA, Isoray will sell to GT Medical, and GT Medical will purchase from Isoray, all of Isoray’s right, title and interest in and to substantially all of the assets of Isoray related to Isoray’s commercial Cesium-131 business (the “Business”) including equipment, certain contracts, inventory and intellectual property (the “GT Medical Asset Purchase”). Subject to limited exceptions set forth in the GT Medical APA, GT Medical is not assuming the liabilities of Isoray.

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Pursuant to the terms of, and subject to the conditions specified in, the GT Medical APA, upon consummation of the GT Medical Asset Purchase (the “GT Medical Closing”), (i) GT Medical will issue to Isoray shares of GT Medical’s common stock, par value $0.0001 per share, representing 0.5% of GT Medical’s issued and outstanding capital stock on a fully diluted basis as of the GT Medical Closing (the “GT Medical Stock Consideration”) and (ii) Isoray will have the right to receive, and GT Medical will be obligated to pay, certain cash royalty payments during each of the first four years beginning upon the date of the GT Medical Closing (each such year, a “Measurement Period”), as summarized below:

The GT Medical Stock Consideration has no registration rights and transfers of the GT Medical Stock Consideration are subject to a right of first refusal on behalf of the other stockholders of GT Medical and GT Medical as further described in the GT Medical Asset Purchase Agreement.

The consummation of the GT Medical APA is subject to the parties mutually obtaining the necessary operating permits and licenses to operate the Business after the GT Medical Closing, at least one Key Employee, as defined in the GT Medical APA, entering into an employment offer letter and not expressing prior to the GT Medical Closing any intention to rescind or repudiate such offer letter or terminate employment with GT Medical or its affiliates following the GT Medical Closing and certain other customary closing conditions to the GT Medical Closing.

Isoray also has agreed that, for the period commencing on the date of the GT Medical Closing and continuing until the third anniversary thereof, neither it nor any of its affiliates will, directly or indirectly, operate, perform or have any ownership interest in any business that designs, develops, manufactures, markets, sells, installs or distributes products that are competitive with the activities of the Cesium-131 business, which is defined as the manufacturing, refinement, commercialization, use, marketing, sale and distribution of Cesium-131 and brachytherapy seeds containing Cesium-131.

The GT Medical APA also includes customary termination provisions, including that, in general, either party may terminate the GT Medical APA if the transaction has not been consummated by March 31, 2024, or if any governmental authority issues any order that restrains, enjoins or otherwise prohibits or prevents the transaction. Likewise, either party may terminate the GT Medical APA if the other party has breached any representation, warranty, covenant, obligation or agreement which would reasonably be expected to cause any of the conditions to closing to not be satisfied prior to the GT Medical Closing, subject, in some cases, to the opportunity of the breaching party to cure such breach.

The respective Board of Directors of Isoray, Perspective and GT Medical have approved the GT Medical APA and the transactions contemplated therein.

The GT Medical Closing is anticipated to be completed in the first half of 2024 and the assets and operations of the Business are presented as a discontinued operation in accordance with Accounting Standards Codification ("ASC") 205-20, Presentation of Financial Statements – Discontinued Operations, and prior year amounts have been reclassified in accordance with this accounting pronouncement. As a result of the transaction, the Company has effectively exited the brachytherapy segment and will now focus exclusively on its radiopharmaceutical development segment.

Viewpoint Merger

On February 3, 2023, Perspective completed the merger of Isoray Acquisition Corp., a Delaware corporation and wholly owned subsidiary of Perspective, with Viewpoint Molecular Targeting, Inc. (“Viewpoint”) (such transaction being the “Merger”). Pursuant to the Merger, the Company issued 136,545,075 shares of common stock, representing approximately 49% of its fully diluted outstanding capital stock. Viewpoint is an alpha-particle radiopharmaceutical company in the alpha-emitter market developing oncology therapeutics and complementary imaging agents.

Upon the closing of the Merger, Perspective Therapeutics increased the size of its Board of Directors from four members to five members. Alan Hoffmann and Dr. Philip Vitale resigned from the board and Michael McCormick resigned as Chairman of the Board but remained a director of the Company. Lori Woods was appointed as Chairperson of the Board and Johan (Thijs) Spoor, Robert Froman Williamson, III and Dr. Frank Morich were appointed as directors of the Company. In addition, Ms. Woods resigned as Chief Executive Officer of the Company and Mr. Spoor was appointed as Chief Executive Officer of the Company. On May 9, 2023, Michael McCormick resigned from the board and on June 1, 2023, Heidi Henson was appointed to the board.

For a more detailed summary of the Merger, see our Forms 8-K filed with the Securities and Exchange Commission (“SEC”) on September 28, 2022, and on February 6, 2023, and our Form 8-K/A filed with the SEC on April 21, 2023.

Collaborations

License Agreement with the University of Iowa

On June 5, 2018, Perspective entered into a license agreement, as amended on August 1, 2018, November 1, 2019, January 30, 2020, and June 12, 2020, with the University of Iowa Research Foundation ("UIRF"), for certain patent rights relating to: (i) the composition and use of peptide radiopharmaceutical drugs for the treatment of cancer alone or in combination with approved therapies (collectively, the “Patent Rights”). Perspective holds a worldwide exclusive license, with the right to sublicense, import, make, have made, use, provide, offer to sell and sell all products derived from technology covered by the Patent Rights (the “Licensed Products and/or Process(es)”).

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The UIRF License is a royalty-bearing license obligating Perspective to pay a percentage of proceeds received from sales of Licensed Products and/or Licensed Process(es) at a rate that Perspective believes is within market parameters for a newly organized preclinical development stage company. Perspective has also agreed to share a percentage of its proceeds that it derives from other agreements, like sublicense agreements, relating to Licensed Products and/or Licensed Process(es) that Perspective may enter into in amounts that it also believes are within market parameters for a newly organized preclinical development stage company. In addition to its obligation to pay royalties, Perspective has also agreed to pay UIRF a success fee on the execution of a liquidity event (or an initial public offering of its equity) in lieu of milestone payments. Perspective paid the success fee to UIRF in 2023 following the completion of the merger between Perspective and Viewpoint. Perspective is also obligated to pay for past and ongoing intellectual property expenses.

The UIRF License commenced on June 5, 2018 and expires on the date of the last-to-expire Patent Rights, unless terminated earlier under the provisions thereof. Perspective has the right to terminate the UIRF License at any time upon 90 days’ written notice to UIRF and the payment of a $10,000 termination fee. Each party has the right to terminate the UIRF License if the other party is in default or breach of any condition of the UIRF License with a right to cure any such breach within 90 days from receipt of notice of such default or breach. Either party can also terminate the UIRF License if the other party voluntarily files for bankruptcy or other similar insolvency proceedings, makes a general assignment for the benefit of creditors, or is the subject of an involuntary bankruptcy petition. If Perspective fails to pay any sum that is due and payable to UIRF within 90 days after receiving written notice of its default from UIRF, then UIRF has the option of terminating the UIRF License. UIRF may also terminate the UIRF License in the event Perspective, or any sublicensee, brings any action against UIRF, unless such suit is for an uncured material breach or imminent threatened breach of the UIRF License Agreement.

Perspective was required to procure liability insurance, naming UIRF as an additional insured, before it initiated any human testing or clinical trials and to maintain such insurance at least 15 years beyond the term of the UIRF License.

The UIRF License also obligates Perspective to meet certain performance and financial milestones.

If Perspective fails to meet these milestones, UIRF will have the right to terminate the UIRF License upon notice as provided in the UIRF License.

License Agreement with Mayo Clinic

License Agreement with Stony Brook University

Facilities

Perspective’s corporate headquarters are located at 2401 Elliott Avenue, Suite 320, Seattle, WA 98121. In addition, the Company leases laboratory and office space at 2500 Crosspark Road, Coralville, IA 52241 ("BioVentures Center") in the University of Iowa Research Park. In December 2022, Perspective completed the purchase of a 20,000 square-foot building located at 4125 Westcor Court, Coralville, IA, that has office and laboratory space which is currently used only for office space and will be built out to accommodate laboratory and manufacturing facilities.

Perspective’s facilities include a radiopharmaceutical manufacturing laboratory (750 square feet) for finished product, clinical use radiopharmaceutical production. The wet labs have appropriate bench, hood and radiochemistry equipment and a separate cell-culture room for all discovery lab pipeline development. The facilities at the BioVentures Center include wifi, internet connections and shared data archive space on the University system as well as data integrity storage and backup provided by the University of Iowa Research Park. In addition, the lease at the BioVentures Center grants 24/7 access for Perspective employees to the University of Iowa core laboratories including the vivarium, small animal imaging facilities, pathology, microscopy, mass spectrometry, nuclear magnetic resonance and other molecular characterization facilities. Perspective also maintains a separate secure network data storage.

In March 2024, Perspective acquired the lease of Lantheus' radiopharmaceutical manufacturing facility located at 110 Clyde Road, Somerset, NJ and Perspective has subsequently agreed to acquire Lantheus’ office lease in at 270 Davidson Avenue, Suite 320, Somerset, NJ. The Davidson Avenue office lease was acquired in February 2024, and Perspective closed on the Clyde Road facility in March 2024.

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In December 2023, Perspective announced the divestiture of the brachytherapy division which includes the leased production facility located at Applied Process Engineering Laboratory in Richland, WA. Subject to satisfaction of customary closing conditions the facility lease is expected to transfer to GT Medical in the first half of 2024.

Perspective believes that its current facilities and CMO relationships are adequate to meet its existing needs.

Other Agreements

For information related to in-licensing and patent licensing agreements, see the section entitled "Intellectual Property."

Overview of the Discontinued Operations

In 2003, Isoray, our wholly owned subsidiary, obtained clearance from the Food and Drug Administration ("FDA") for the use of Cesium-131 radioisotope in the treatment of all malignant tumors. The FDA's clearance granted in August 2009 permits loading Cesium-131 seeds into bio-absorbable braided sutures or “braided strands,” giving the Company the ability to treat brain, lung, head and neck, colorectal and chest wall cancers. As of the date of this Report, such applications include prostate cancer, brain cancer, colorectal cancer, gynecological cancer, lung cancer, ocular melanoma and pancreatic cancer. The brachytherapy seed form (a sealed source) of Cesium-131 may be used in surface, interstitial and intra-cavity applications for tumors with known radio-sensitivity.

Isoray’s core product is its Cesium-131 sealed source brachytherapy “seed.” These seeds can be inserted individually or in combination into various locations in the body until the physician is satisfied with the radiation dose delivered and are used to treat prostate, brain, lung, head and neck, gynecological and certain other solid tumors.

Financial Information About Segments

The Company has previously presented its results in two segments: Drug Operations and Brachytherapy. Due to the divestiture of all of the brachytherapy segment to GT Medical and the classification of the assets and operations of the brachytherapy segment as discontinued operations in Perspective’s financial statements, Perspective has now determined that it operates in only one segment, as it only reports profit and loss information on an aggregate basis to its chief operating decision maker.

Financial Information About Geographic Areas

All of the Company’s long-lived assets are located in the United States.

Government Regulation

The Company’s present and future intended activities in the development, manufacture and sale of cancer therapy programs are subject to extensive laws, regulations, regulatory approvals and guidelines. In the United States, the Company must comply with laws, such as the U.S. Federal Food, Drug and Cosmetic Act ("FFDCA"), regulations, guidance documents and standards promulgated by the FDA, which govern, among other things, the testing, development, manufacturing, quality control, safety, purity, potency, efficacy, approval, labeling, packaging, storage, record keeping, distribution, marketing, sales, import, export, post-approval monitoring and reporting, advertising and other promotional practices involving pharmaceutical programs. We cannot market a program candidate in the United States until the pharmaceutical program has received FDA approval or licensure.

The FFDCA provides several distinct pathways for the approval of new drugs. A new drug application (“NDA”) under Section 505(b)(1) of the FFDCA is a comprehensive application to support approval of a product candidate that includes, among other things, data and information to demonstrate that the proposed drug is safe and effective for its proposed uses, that production methods are adequate to ensure the identity, strength, quality and purity of the drug, and that proposed labeling is appropriate and contains all necessary information. A 505(b)(1) NDA generally contains results of the full set of pre-clinical studies and clinical trials conducted by or on behalf of the applicant to characterize and evaluate the product candidate. Alternatively, Section 505(b)(2) of the FFDCA permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. The applicant may rely to some extent upon the FDA’s findings of safety and effectiveness for an approved product that acts as the reference drug and submit its own product-specific data, which may include data from pre-clinical studies or clinical trials conducted by or on behalf of the applicant, to address differences between the product candidate and the reference drug. Drug manufacturers may also submit an abbreviated new drug application ("ANDA") under section 505(j) of the FFDCA to market a generic version of an approved branded drug product if the manufacturer shows the generic version is “therapeutically equivalent” or expected to have the same clinical effect and safety profile as the branded drug product when administered to patients under the conditions specified in the labeling.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. In addition, the laws, rules and regulations that apply to our business are subject to change and it is difficult to foresee whether, how or when such changes may affect our business.

Development and Approval

Drug development process. The process to develop and obtain approval for pharmaceutical products for commercialization in the United States and many other countries is lengthy, complex and expensive, and the outcome is far from certain. Although foreign requirements for conducting clinical trials and obtaining approval may differ in certain respects from those in the United States, there are many similarities, and they often are equally rigorous, and the outcome cannot be predicted with confidence.

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The process required before a pharmaceutical product may be marketed in the United States generally include the following:

● Consideration by an FDA Advisory Committee, if applicable;

● Payment of applicable user fees;

Prior to initiating human testing of any pharmaceutical product, the product undergoes preclinical testing. Nonclinical tests include laboratory evaluations of product chemistry, pharmacology, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the product candidate. Adherence to federal regulations, such as GLPs and the Animal Welfare Act enforced by the Department of Agriculture, is required during the conduct of these tests.

The sponsor of a clinical study is required to submit the results of nonclinical tests, along with manufacturing details, analytical data, any available clinical data or literature, and a proposed clinical protocol, to the FDA as part of an IND application before clinical testing may begin. Some nonclinical testing typically continues even after IND submission. An IND provides an exemption from the FFDCA, allowing the shipment of an unapproved product for investigational use in clinical trials, subject to FDA authorization. The IND becomes effective 30 days after FDA receipt, unless concerns are raised by the FDA about the proposed clinical trial, including whether subjects will be exposed to unreasonable risks, within that period, in which case outstanding issues must be resolved before the clinical trial can proceed.

Clinical trials may involve the administration of the program candidate to healthy volunteers or subjects under the supervision of qualified investigators, generally physicians not employed by or under the study sponsor’s control. Clinical trials involving some products for certain diseases may begin with testing in patients with the disease. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur. Each protocol and any amendments to the protocol must be submitted to the FDA as part of the IND. Clinical trials must be conducted and monitored in accordance with the FDA’s regulations comprising the GCP requirements, including the requirement that all research subjects or his or her legal representative provide informed consent. Further, each clinical trial must be reviewed and approved by an independent IRB at, or servicing, each institution at which the clinical trial will be conducted. IRBs are charged with protecting the welfare and rights of study participants and consider such items as whether the risks to individuals participating in clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the form and content of the informed consent that must be signed by each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed. Additionally, some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee.

A sponsor who wishes to conduct a clinical trial outside the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. Foreign study conducted under an IND must meet the same requirements that apply to studies being conducted in the United States. If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of an application if the clinical trial is conducted in compliance with GCP, including review and approval by an independent ethics committee and compliance with informed consent principles, and FDA is able to validate the data from the study through an onsite inspection if deemed necessary.

Clinical trials are typically conducted in sequential phases, although they may overlap or be combined. The four phases are as follows:

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During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data and clinical trial investigators. Annual progress reports detailing the results of the clinical trials must be submitted to the FDA. Written IND safety reports must be promptly submitted to the FDA and the investigators for serious and unexpected adverse events, any findings from other studies, tests in laboratory animals or in vitro testing and other sources that suggest a significant risk for human subjects, or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.

Clinical trials may not be completed successfully within a specified period of time, if at all. The decision to terminate development of an investigational product may be made by a health authority (such as the FDA), an IRB/ethics committee, or by a company for various reasons. At any time before or during clinical trials, the FDA may order the temporary or permanent discontinuation of a clinical trial, which is referred to as a clinical hold, or impose other sanctions, if the agency believes the clinical trial is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. If the FDA imposes a clinical hold, trials may not recommence without FDA authorization and then only under terms authorized by the FDA. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the investigational product has been associated with unexpected serious harm to patients.

There are requirements for the registration of ongoing clinical trials of program candidates on public registries and the disclosure of certain clinical trial results and other trial information after completion within timeframes to the NIH for public dissemination on its clinicaltrials.gov website. In addition, sponsors or distributors of investigational products for the diagnosis, monitoring or treatment of one or more serious diseases or conditions must have a publicly available policy on evaluating and responding to requests for expanded access requests.

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, detailed investigational product candidate information is submitted to the FDA in the form of a marketing application to request market approval for the product in specified indications.

Marketing Application. After completing the clinical studies, a sponsor seeking approval to market a product candidate in the United States submits to the FDA a new drug application ("NDA"). The NDA is a comprehensive application intended to demonstrate the product candidate’s safety and effectiveness and includes, among other things, pre-clinical and clinical data, information about the product candidate’s composition, the sponsor’s plans for manufacturing and packaging and proposed labeling. When an application is submitted, the FDA makes an initial determination as to whether the application is sufficiently complete to be accepted for review. If the application is not, the FDA may refuse to accept the application for filing and request additional information. A refusal to file, which requires resubmission of the application with the requested additional information, delays review of the application.

The FDA reviews the application to determine, among other things, whether the proposed product is safe and effective for its intended use, and whether the product is being manufactured in accordance with cGMP. Before approving an application, the FDA often will inspect the facilities at which the product is manufactured for cGMP compliance and may inspect one or more clinical sites to assure compliance with GCP. FDA Advisory Committee meetings are often held for New Chemical Entities, novel indications, or for applications that otherwise present scientific, technical or policy questions on which the agency believes it would benefit from the perspectives of outside experts. An advisory committee meeting includes a panel of independent experts, including clinicians and other scientific experts, who review, evaluate and make a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

After review of an NDA, the FDA may grant marketing approval, request additional information, or issue a complete response letter (“CRL”) communicating the reasons for the agency’s decision not to approve the application. The CRL may request additional information, including additional preclinical or clinical data, for the FDA to reconsider the application. An application may be resubmitted with the deficiencies addressed, but resubmission does not guarantee approval. Data from clinical trials are not always conclusive, and the FDA’s interpretation of data may differ from the sponsor’s. Obtaining approval can take years, requires substantial resources and depends on a number of factors, including the severity of the targeted disease or condition, the availability of alternative treatments, and the risks and benefits demonstrated in clinical trials. Additionally, as a condition of approval, the FDA may impose restrictions that could affect the commercial prospects of a product and increase costs, such as a REMS, and/or post-approval commitments to conduct additional clinical trials or non-clinical studies or to conduct surveillance programs to monitor the product’s effects. Under the Pediatric Research Equity Act (“PREA”), certain applications for approval must also include an assessment, generally based on clinical study data, of the safety and effectiveness of the subject product in relevant pediatric populations, unless a waiver or deferral is granted.

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Expedited Programs. The FDA maintains certain expedited programs to facilitate the development and review processes for certain qualifying pharmaceutical program candidates, including Fast Track designation, breakthrough therapy designation, priority review and accelerated approval. A pharmaceutical product candidate may be granted Fast Track designation if it is intended for the treatment of a serious or life-threatening condition and demonstrates the potential to address unmet medical needs for such condition. With Fast Track designation, the sponsor may be eligible for more frequent opportunities to obtain the FDA’s feedback, and the FDA may initiate review of sections of an application before the application is complete. This rolling review is available if the applicant provides, and the FDA approves, a schedule for the remaining information. Even if a product receives Fast Track designation, the designation can be rescinded and provides no assurance that a product will be reviewed or approved more expeditiously than would otherwise have been the case, or that the product will be approved at all.

The FDA may designate a product candidate as a breakthrough therapy if it finds that the product candidate is intended, alone or in combination with one or more other program candidates or approved products, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the product candidate may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. For program candidates with Breakthrough Therapy Designation, more frequent interaction and communication between the FDA and the sponsor can help to identify the most efficient path for clinical development. Program candidates designated as breakthrough therapies by the FDA may also be eligible for priority review. Even if a product receives Breakthrough Therapy Designation, the designation can be rescinded if the FDA determines the program no longer meets the qualifying criteria for breakthrough therapy and provides no assurance that a product will be reviewed or approved more expeditiously than would otherwise have been the case, or that the product will be approved at all.

Accelerated approval under FDA regulations allows a product designed to treat a serious or life-threatening disease or condition that provides a meaningful therapeutic advantage over available therapies to be approved on the basis of either an intermediate clinical endpoint or a surrogate endpoint that is reasonably likely to predict clinical benefit. As a condition of accelerated approval, the FDA will require that a sponsor of a drug product subject to accelerated approval perform an adequate and well-controlled post-marketing clinical trial to confirm clinical benefit. If a sponsor fails to conduct any required post-approval trial with due diligence, the FDA may withdraw the drug from the market. In addition, the FDA currently requires as a condition for accelerated approval that promotional materials be submitted in advance of initial dissemination, which could adversely impact the timing of the commercial launch of the product.

The FDA may also grant priority review designation to a product candidate, which sets the target date for FDA action on the application at six months from FDA filing, or eight months from the sponsor’s submission. Priority review may be granted where a product is intended to treat a serious or life-threatening disease or condition and, if approved, has the potential to provide a safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in safety or efficacy compared to available therapy. If criteria are not met for priority review, the standard FDA review period is 10 months from FDA filing or 12 months from sponsor submission. Priority review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval. Priority review may be available also for sponsors with a priority review voucher (“PRV”). FDA awards PRVs to drug sponsors that develop drugs for tropical diseases or rare pediatric diseases or to use as medical countermeasures. The PRV is transferable and may be sold to another drug sponsor.

Orphan Drug Designation. Under the Orphan Drug Act, the FDA may grant orphan designation to a drug product intended to treat a “rare disease or condition,” which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States, but for which there is no reasonable expectation that the cost of developing and making a drug product available in the United States for this type of disease or condition will be recovered from sales of the product. If orphan product designation is sought, it must be requested before submitting an NDA for the drug product for the proposed rare disease or condition. If the FDA grants orphan drug designation, the common name of the therapeutic agent and its designated orphan use are disclosed publicly by the FDA. Orphan product designation does not, by itself, convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which the FDA has interpreted to preclude approving for seven years any other sponsor’s application to market the same drug for the same use for which the drug has been granted orphan drug designation, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity. Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition. Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA application user fee.

As in the United States, designation as an orphan drug for the treatment of a specific indication in the European Union, must be made before the application for marketing authorization is made. Orphan drugs in Europe enjoy economic and marketing benefits, including up to 10 years of market exclusivity for the approved indication unless another applicant can show that its product is safer, more effective or otherwise clinically superior to the orphan designated product.

Exclusivity and Patent Restoration. In the United States and elsewhere, certain regulatory exclusivities and patent rights can provide an approved drug product with protection from certain competitors’ products for a period of time and within a certain scope. In the United States, those protections include regulatory exclusivity under the Hatch-Waxman Act, which provides periods of exclusivity for a branded drug product that would serve as a reference listed drug for a generic drug applicant filing and an ANDA under section 505(j) of the FFDCA or as a listed drug for an applicant filing an NDA under section 505(b)(2) of the FFDCA. If such a product is a “new chemical entity” (“NCE”) generally meaning that the active moiety has never before been approved in any drug, there is a period of five years from the product’s approval during which the FDA may not accept for filing any ANDA or 505(b)(2) application for a drug with the same active moiety. (An application that contains a challenge to a patent associated with the reference product may be submitted at four years after reference product approval.) Certain changes to an approved drug, such as the approval of a new indication, may qualify for a three-year period of exclusivity during which the FDA cannot approve an ANDA or 505(b)(2) NDA for a similar drug that includes the change.

In addition, the Hatch-Waxman Act also provides for the restoration of a portion of the patent term lost during product development and FDA review of a marketing application if approval of the application is the first permitted commercial marketing of a drug containing the active ingredient. The patent term restoration period is generally one-half the time between the effective date of the IND or the date of patent grant (whichever is later) and the date of submission of the application, plus the time between the date of submission of the application and the date of FDA approval of the product. The maximum period of restoration is five years, and the patent cannot be extended to more than 14 years from the date of FDA approval of the product. Only one patent claiming each approved product is eligible for restoration and the patent holder must apply for restoration within 60 days of approval. The United States Patent and Trademark Office, in consultation with the FDA, reviews and approves the application for patent term restoration.

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Post-Approval Regulation

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