10-K
Table of Contents
United States
Securities and Exchange Commission
Washington, D.C. 20549
FORM 10-K
For the fiscal year ended December 31, 2024
OR
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. EmployerIdentification 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 ☐
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 28, 2024, 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 $551,716,041 based on the closing price of the registrant’s common stock on June 28, 2024.
As of March 21, 2025, the number of shares outstanding of the registrant’s common stock, $0.001 par value per share, was 74,051,841.
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INCORPORATION BY REFERENCE
Part III of this Annual Report on Form 10-K incorporates certain information by reference from the registrant's proxy statement for the 2025 annual meeting of stockholders to be filed no later than 120 days after the end of the registrant's fiscal year ended December 31, 2024.
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PERSPECTIVE THERAPEUTICS, INC.
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PART I
ITEM 1 – BUSINESS 4
ITEM 1A – RISK FACTORS 36
ITEM 1B – UNRESOLVED STAFF COMMENTS 61
ITEM 1C – CYBERSECURITY 61
ITEM 2 – PROPERTIES 62
ITEM 3 – LEGAL PROCEEDINGS 62
ITEM 4 – MINE SAFETY DISCLOSURES 63
PART II
ITEM 6 – [RESERVED] 64
ITEM 7A – QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 79
ITEM 8 – FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 79
ITEM 9A – CONTROLS AND PROCEDURES 79
ITEM 9B – OTHER INFORMATION 79
ITEM 9C – DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 79
PART III
ITEM 10 – DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 80
ITEM 11 – EXECUTIVE COMPENSATION 80
ITEM 14 – PRINCIPAL ACCOUNTANT FEES AND SERVICES 80
PART IV
ITEM 15 – EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 81
SIGNATURES 84
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CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
In addition to historical information, this Annual Report on Form 10-K (“Annual Report” or “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.
This Form 10-K, including Management’s Discussion and Analysis of Financial Condition and Results of Operations in Part II, Item 7, contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act). All statements contained in this Form 10-K other than statements of historical fact, including, without limitation, statements 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,” “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:
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the timing, progress and results of our preclinical studies and clinical trials of our current and future program candidates, including statements regarding the timing of our planned regulatory communications, submissions and approvals, initiation and completion of studies or trials and related preparatory work and the period during which the results of the trials will become available, and our research and development programs;
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our ability to obtain and maintain regulatory approvals for our future program candidates, including our ability to obtain Fast Track designation from the U.S. Food and Drug Administration (FDA) under our Investigational New Drug (IND) application for our novel asset, PSV359;
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our manufacturing capabilities and strategy, including the scalability and commercial viability of our manufacturing methods and processes;
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our ability to identify patients with the diseases treated by our program candidates and to enroll these patients in our clinical trials;
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our expectations regarding the potential functionality, capabilities and benefits of our program candidates, if approved, for commercial use;
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the potential size of the commercial market for our program candidates;
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our expectations regarding the scope of any approved indication for any program candidate;
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our ability to successfully commercialize our program candidates;
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our ability to leverage technology to identify and develop future program candidates;
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our estimates of our expenses, ongoing losses, future revenue, capital requirements and our need for or ability to obtain additional funding before we can expect to generate any revenue from product sales;
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our belief regarding the sufficiency of our cash resources to fund our current planned operating expenses and capital expenditure requirements into late 2026;
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our competitive position and expectations regarding developments and projections relating to our competitors or our industry; and
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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. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond our control) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. 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” 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 risks and uncertainties, 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 our 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. Our U.S. Securities and Exchange Commission (SEC) filings are available publicly on the SEC’s website at www.sec.gov.
AVAILABLE INFORMATION
As soon as reasonably practicable after they are filed electronically with the SEC, our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, other SEC filings and amendments to those reports are available without charge on our website, www.perspectivetherapeutics.com, which we also use to announce material information to the public. We are providing the address to our website solely for the information of investors. We do not intend the address to be an active link or to otherwise incorporate the contents of the website into this Form 10-K.
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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.
BASIS OF PRESENTATION
On June 14, 2024, we filed a Certificate of Amendment to our Certificate of Incorporation with the Secretary of State of the State of Delaware to effect a 1-for-10 reverse stock split of our issued and outstanding shares of common stock, par value $0.001 per share (Reverse Split), which became effective on that date. All historical share and per share amounts reflected throughout this Annual Report on Form 10-K have been adjusted to reflect the Reverse Split. However, our periodic and current reports, and all other documents that were filed prior to June 14, 2024, do not give effect to the Reverse Split.
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
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We are a clinical-stage biopharmaceutical company and have a limited operating history upon which to base an investment decision.
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We will require substantial additional capital to fund our operations. Additional funds may be dilutive to shareholders or impose operational restrictions. Further, if additional capital is not available, we may need to delay, limit or eliminate our research, development and commercialization programs and modify our business strategy.
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We have incurred losses in nearly every year since our inception, and we anticipate that we will not achieve profits for the foreseeable future.
Risks Related to Our Business and Industry
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Our program candidates are in early stages of development and must go through clinical trials, which are very expensive, time consuming and difficult to design and implement. The outcomes of clinical trials are uncertain, and delays in the completion of or the termination of any clinical trial of our program candidates could harm our business, financial condition and prospects.
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We rely on single vendors to provide supplies and services used in the development and production of our alpha-particle therapies.
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If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected.
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Because the results of preclinical studies and early clinical trials are not necessarily predictive of future results, any program candidate we advance into clinical trials may not have favorable results in later clinical trials, if any, or receive regulatory approval.
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Delays in the commencement, execution or completion of our clinical trials could result in increased costs and delay our ability to pursue regulatory approval and commercialization of our program candidates.
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We may be required to suspend, repeat or terminate our clinical trials if they are not conducted in accordance with regulatory requirements, the results are negative or inconclusive, or the trials are not well designed.
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The approval processes of regulatory authorities are lengthy, time consuming, expensive and inherently unpredictable; if we experience unanticipated delays or are unable to obtain approval for our program candidates from applicable regulatory authorities, we will not be able to market and sell those program candidates in those countries or regions and our business will be substantially harmed.
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Disruptions at the FDA, including due a reduction in the FDA’s workforce and/or decreased funding for the FDA, could prevent the FDA from performing functions on which our business relies, which could negatively impact our business.
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We rely on federal funding for conducting certain research on our products or product candidates, and recent federal policy changes could disrupt that funding.
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Our program candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial profile of the approved labeling, or result in significant negative consequences following marketing approval, if any.
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If we are unable to execute our sales and marketing strategy for our programs and are unable to gain market acceptance, we may be unable to generate sufficient revenue to sustain our business.
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Because we license technology underlying some of our program candidates from third parties, any dispute with our licensors or non-performance by us or by our licensors may adversely affect our ability to develop and commercialize the applicable program candidates.
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We may form or seek strategic alliances or enter into additional licensing arrangements in the future, and we may not realize the benefits of such alliances or licensing arrangements.
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We may rely partially on third parties to manufacture our clinical pharmaceutical supplies and could continue to rely on third parties to produce commercial supplies of any approved program candidate, and our dependence on third party suppliers could adversely impact our business.
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We may not be successful in managing the build-out of our manufacturing facilities and associated costs or satisfying manufacturing-related regulatory requirements.
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We rely on third parties to conduct our clinical trials, and if these third parties do not meet their deadlines or otherwise conduct the trials as required, our clinical development programs could be delayed or unsuccessful, and we may not be able to obtain regulatory approval for or commercialize our program candidates when expected or at all.
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We have in-sourced part of the research, development and clinical operations functions previously assigned to clinical research organizations (CROs), and we may not be able to efficiently execute those operations, or the cost savings expected from this transition may not materialize, which may adversely affect the financial performance of our business and our ability to advance our pipeline.
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We may seek orphan drug designation, rare pediatric disease designation or other FDA designations but may not receive such designation. Even if the FDA grants the designation, we may not receive orphan drug exclusivity or a priority review voucher, if the program candidate does not meet the FDA requirements at the time of approval or licensure.
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We have received Fast Track designation for VMT-α-NET and VMT01, but such designation may not actually lead to a faster development or regulatory review or approval process. Additionally, the FDA may rescind the designation if it determines the applicable program candidate no longer meets the qualifying criteria for Fast Track.
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We will face intense competition and may not be able to compete successfully.
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We may rely on market exclusivity periods that may not be or remain available to us.
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If any program candidate that we successfully develop does not achieve broad market acceptance among physicians, patients, healthcare payors and the medical community, the revenues that it generates from their sales will be limited.
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Coverage and adequate reimbursement may not be available for our products, if commercialized, which could make it difficult for us to sell our products profitably.
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Due to the significant resources required for the development of our drug candidates, we must prioritize development of certain drug candidates and/or certain disease indications and may expend our limited resources on candidates or indications that do not yield a successful program and fail to capitalize on drug candidates or indications that may be more profitable or for which there is a greater likelihood of success.
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If we fail to attract and retain key management, scientific and clinical development personnel, we may be unable to successfully develop or commercialize our program candidates.
Legal and Regulatory Risks Related to Our Operations
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Significant disruptions of information technology systems or breaches of data security could materially adversely affect our business, results of operations and financial condition.
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Our employees and independent contractors, including principal investigators, consultants, commercial collaborators, service providers and other vendors may engage in misconduct or other improper activities, including noncompliance with regulatory pricing standards and requirements, which could have an adverse effect on our results of operations.
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If we fail to comply with applicable healthcare regulations, we could face substantial penalties, and our business, operations and financial condition could be adversely affected.
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Healthcare reform measures could hinder our programs’ commercial success.
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Failure to comply with government regulations could harm our business.
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Our business exposes us to product liability claims.
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Our business involves environmental risks.
Risks Related to Intellectual Property Matters
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Our success will depend upon intellectual property, proprietary technologies and regulatory market exclusivity periods, and we may be unable to protect our intellectual property.
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Our ability to compete may decline if we do not adequately protect our proprietary rights.
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Potential patent litigation could be costly and disruptive and may have an adverse effect on our financial condition and results of operations.
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The value of our granted patents, and our patents pending, is uncertain.
Risks Related to Ownership of Shares of Common Stock and Public Company Status
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The concentration of our common share ownership will likely limit the ability of other shareholders to influence corporate matters.
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Our stock price has been and may continue to be volatile.
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Our common stock price is likely to be volatile and may be adversely affected by the future issuance and sale of shares of our stock or other equity interests.
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The price of our common stock may be adversely affected by the future issuance and sale of shares of our common stock or other equity securities.
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PART I
ITEM 1 – BUSINESS
Overview
We are a radiopharmaceutical development company that is pioneering advanced treatment applications for cancers throughout the body. We have proprietary technology that utilizes the alpha-emitting isotope Lead-212 (212Pb) to deliver powerful radiation specifically to cancer cells via specialized targeting moieties. We are also developing complementary imaging diagnostics that incorporate the same targeting moieties, which provides the opportunity to personalize treatment and optimize patient outcomes. This theranostic approach enables the ability to see the specific tumor and then treat it to potentially improve efficacy and minimize toxicity.
Our melanoma (VMT01) and neuroendocrine tumor (VMT-α-NET) programs are in Phase 1/2a imaging and therapy trials for the treatment of metastatic melanoma and neuroendocrine tumors in the U.S. We are growing our regional network of drug product finishing facilities, enabled by our proprietary 212Pb generator, to deliver patient-ready products for clinical trial and commercial operations.
Our Strategy
Our goal is to advance innovative precision medicines for the treatment of cancer by developing and commercializing our precision targeted alpha therapies (TATs). The key elements of our strategy are to:
Discover and Develop a Broad Oncology Pipeline
Advance our initial drug candidate, VMT-α-NET, through clinical development for the treatment of neuroendocrine tumors expressing SSTR2. In 2024, we continued dosing in Cohort 1 and initiated dosing in Cohort 2 of our Phase 1/2a study of [212Pb]VMT-α-NET in patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2)-expressing neuroendocrine tumors (NETs) who have not received prior radiotherapy (clinicaltrials.gov identifier NCT05636618). Subsequently, the safety monitoring committee (SMC) determined that the safety data observations during the dose-limiting toxicity period supported proceeding with dose escalation to Cohort 3 and increasing the number of patients dosed at 5 mCi. Based on interactions with the U.S. Food and Drug Administration (FDA) prior to the initiation of patient dosing in this study, which occurred in late 2023, the decision to open Cohort 3 will follow consultation and alignment with the agency. FDA interactions are ongoing with regards to the initiation of the next dosing cohort.
Expand the potential of our 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. We intend to prioritize seeking regulatory approval to test [212Pb]VMT-α-NET in other cancers.
Advance our second drug candidate, VMT01, through clinical development for the treatment of melanoma tumors expressing melanocortin 1 receptor (MC1R). VMT01 can be radiolabeled with either Lead-203 (203Pb) for patient selection and dosimetry assessments, or 212Pb for alpha-particle therapy. In preclinical experiments [212Pb]VMT01 demonstrated efficacy via two distinct mechanisms of action: direct cell killing at high radiation doses and through immunostimulatory low-dose induction of immune-mediated cell death. Efficacy was augmented by immune checkpoint inhibitors. In September 2024, we announced that on the basis of these results, the FDA granted Fast Track Designation for the clinical development of [212Pb]VMT01. This study is a multi-center, open-label dose escalation, dose expansion study (clinicaltrials.gov identifier NCT05655312) in patients with histologically confirmed melanoma and MC1R-positive imaging scans. In 2024, we continued dosing in Cohort 1 and initiated dosing in Cohort 2 of our Phase 1/2a study. We released the results of the patients dosed in the first two cohorts in October 2024 and announced that we would deescalate the dose in Cohort 3 to 1.5mCi. In addition, in July 2024 we submitted an amendment to the Phase 1/2a trial to explore the combination of the checkpoint inhibitor nivolumab with [212Pb]VMT01 which was subsequently approved. We are currently enrolling patients in both the monotherapy and combination therapy cohorts.
Obtain Fast Track designation from the FDA under our Investigational New Drug (IND) application for our novel asset, PSV359. In June 2024, at the Society of Nuclear Medicine and Molecular Imaging 2024 Annual Meeting (SNMMI), researchers presented on a novel cyclic peptide targeting fibroblast activation protein alpha (FAP-α), which is a protein abundantly expressed in certain cancer cells as well as cancer-associated fibroblasts in tumor lesions and involved in promoting disease progression. To target FAP-α, we created the novel radiotherapeutic, PSV359, comprising a peptide directed against FAP-α conjugated to the chelator-bound radioisotope 212Pb or 203Pb. [203/212Pb]PSV359 was evaluated in vitro and in preclinical xenograft models. Overall, strong anti-tumor clinical activity of [212Pb]PSV359 was found in both FAP-α on cancer cells and in stromal tissues xenograft models. In September 2024, research was presented on the preclinical evaluation of [203/212Pb]PSV359 for imaging and alpha-particle therapy of cancers expressing FAP-α, in which our team of researchers found that in vitro, [203/212Pb]PSV359 demonstrated superior FAP-α-binding affinity and specificity as compared to other FAP-targeted drugs, and that [203Pb]PSV359 showed strong tumor uptake and clearance from the blood via the renal system. In the study, [212Pb]PSV359 also showed strong anti-tumor effects in xenograft models in which FAP-α was either on cancer cells or in stromal tissues. In January 2025, we received approval from the FDA to proceed and anticipate dosing our first patients with this compound in mid 2025. We plan to seek to obtain Fast Track designation from the FDA for this compound.
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Deploy Our Innovative Platform Technology
Continue to leverage our TAT platform to expand our pipeline of program candidates. Our technology allows us to create novel TATs by combining 212Pb encased within its 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, we continuously evaluate opportunities to acquire or in-license additional new targeting molecules such as those licensed from the Mayo Foundation for Medical Education and Research (Mayo Clinic) and Stony Brook University that we believe can be utilized with our platform to create a potent alpha therapeutic agent. We are leveraging our platform to progress our existing program candidates into clinical development for additional indications, including breast and pancreatic cancers, as well as the development of new program candidates.
Utilize a precision medicine approach by leveraging imaging diagnostics. To enrich the patient population for our trials, we created an imaging analogue of each of our program candidates by replacing 212Pb with the radioactive imaging isotope 203Pb while retaining the same targeting peptide. This allows us to assess the uptake of the imaging isotope into the targeted tumor and radiation doses to key organs. Using this data, we have the ability to enroll only those patients who meet predefined tumor uptake and dosimetry standards and are, therefore, more likely to respond to treatment. We believe this strategy will allow us to enrich the patient population of our clinical trials and enable the use of a precision medicine approach for the treatment of multiple tumor types.
Build and Strengthen Our Manufacturing and Supply Infrastructure
Continue to strengthen and scale our internal manufacturing capabilities. We believe the quality, reliability and scalability of the manufacturing process for our program candidates will be a core competitive advantage and better enable our long-term success. We have developed our proprietary VMT-α-GEN isotope delivery system (generator) to deliver our therapeutic isotope 212Pb for supply to patients. 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. We scaled manufacturing of the supply of VMT-α-GEN systems for research purposes and are developing our supply capabilities in an effort to be able to support the clinical development of our drug candidates. We believe that by controlling our own therapeutic isotope supply, we can solve the many supply chain risks that have slowed alpha-particle therapy clinical adoption to date.
In March 2024, we acquired the assets and associated lease of Lantheus Holdings, Inc.’s (Lantheus) radiopharmaceutical manufacturing facility in Somerset, NJ. In October 2024, we completed our first shipment and patient dosing of 212Pb-labeled radiopharmaceuticals from the Somerset facility, which has three production suites. We intend to utilize this location to supply drug product for the northeastern portion of the United States. During 2024, we also purchased buildings located in the Houston, TX, Chicago, IL, and Los Angeles, CA metropolitan areas, which we intend to use for the manufacture of our program candidates upon completion of modifications and installation of equipment.
In September 2024, we entered into a Master Equipment and Services Agreement and statements of work with Comecer SpA (Comecer), pursuant to which we agreed to purchase from Comecer manufacturing equipment for the production of our radiopharmaceutical products including, but not limited to, isotope processing hot cells and production suites and related equipment (collectively, the Deliverables) and services for installation and validation of the Deliverables at several of our production facilities in the United States.
Background of Radiopharmaceuticals
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, we believe 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. 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.
We are leveraging our proprietary TAT platform to build on the successes of currently available radiation therapies and create the next generation of precision oncology targeted radiopharmaceuticals. Our 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)
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the alpha-emitting medical isotope 212Pb, designed to kill cancer cells, that is encased in our proprietary lead-specific chelator; and (iii) our optimized proprietary chelator.
We believe that our TAT platform and program candidates, if approved, could provide several potential advantages over currently available radiopharmaceuticals, including:
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enhanced tumor-killing power by using 212Pb alpha-particle radiation in an outpatient setting;
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ability to use multiple targets and classes of targeting molecules;
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broad applicability across multiple tumor types, including neuroendocrine, metastatic melanomas and other cancers;
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increased tolerability and therapeutic window associated with our lead-based TATs;
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exploitation of multiple mechanisms of action, including direct DNA damage through double-stranded DNA breaks, and an alpha particle-mediated enhanced anti-tumor immune response;
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a scalable manufacturing process and supply chain using our proprietary generator; and
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ability to use our 203Pb imaging diagnostics to enrich targeted patient populations and determine treatment therapeutic suitability.
We believe the multiple mechanisms of action of our 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, which involves the propagation of 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. The Bystander Effect has been shown to be as significant to the overall efficacy in killing cancer cells as the direct DNA breaks.
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 has continued to evolve, a deeper understanding of the potential of alpha-emitting isotopes for treating cancer has emerged.
Compared to beta particles, alpha particles can 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.
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. However, next-generation radiopharmaceuticals that have overcome the challenges faced by first-generation radiopharmaceuticals have since been developed and approved, and over the past decade the global radiopharmaceutical market has been growing rapidly. One such approved, next-generation targeted radiopharmaceutical therapy is Lutathera, a beta-emitting therapy marketed by Novartis. Novartis reported that fiscal year 2024 sales revenue from Lutathera was $724 million, up 20% from fiscal year 2023, despite only being approved for a subset of neuroendocrine cancers that affect the pancreas or gastrointestinal tract, known as GEP-NETs. Another radiopharmaceutical therapy, Pluvicto, a beta-emitting radioligand therapy marketed by Novartis, was initially approved to treat progressive prostate-specific membrane antigen (PSMA) positive metastatic castration-resistant prostate cancer and is being further developed by Novartis for other prostate cancer indications. Novartis reported that fiscal year 2024 sales revenue for Pluvicto were $1.4 billion, up 42% from fiscal year 2023.
Our TAT Platform
Through the use of proprietary, specialized targeting peptides, we are 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
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gamma rays, 203Pb, connected to a specific targeting peptide, we have the ability to diagnose the tumor. Following diagnosis, we can link our alpha-particle radioactive isotope, 212Pb, to the same targeting peptide to treat and potentially kill cancerous cells. This two-step, personalized medicine approach, as depicted below, offers the ability to understand which patients may respond to our therapy and potentially improve efficacy while minimizing toxicity associated with many other types of cancer treatments.
Human Image: Cagle et al. European Association of Nuclear Medicine 2024, Presentation Number: OP-473
Our image-guided TAT leverages a specialized targeting peptide to deliver cancer-killing 212Pb directly to the tumor. Our process for selecting cancer targets is designed to ensure that such targets 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 can deliver 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.
Our TAT platform is highlighted by research and insights into the underlying biology of alpha-emitting radiopharmaceuticals as well as our differentiated capabilities in target identification, candidate generation, manufacturing and supply chain, and the development of imaging diagnostics. Our TAT platform was primarily developed over 15 years at the University of Iowa. We believe that our 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.
Our next-generation radiopharmaceutical technology has been recognized by many prestigious organizations and has received numerous awards and grants. Over the past 11 years, through December 2024, more than $17.0 million has been awarded to us and Co-Founder Michael Schultz’s laboratory at the University of Iowa in the form of Small Business Innovation Research (SBIR), Small Business Technology Transfer (STTR) and National Institutes of Health (NIH) research project grants. Grant support has been for our 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 our VMT-α-GEN in-house radioisotope production technologies.
212Pb (Lead-212)
Although there are many beta- and alpha-emitting isotopes, we believe 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
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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 our own preclinical studies, we have observed a vaccine-like effect that prevented the regrowth of tumors upon re-challenge. This is an area of ongoing investigation by us and the international scientific community. Our findings were reported by our senior scientist, Dr. Mengshi Li, et.al. in the peer-reviewed journal Cancers 2021, 13: 3676, 2021. New findings were published in 2024 at SNMMI, which showed that the cooperative effect between [212Pb]VMT01 and immune checkpoint inhibitors were also observed in a heterogeneous preclinical melanoma model. Induction of this cooperative effect was found even with 2 Gy of alpha-ration in tumor.
We believe 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.
The graphic below provides our illustration of the comparison of the key differences between beta particles and alpha emitters.
1USPI for 177Lu vipivotide tetraxetan
2Sgouros G. Alpha-particles for targeted therapy. Adv Drug Deliv Rev. 2008;60(12):1402-1406. doi:10.1016/j.addr.2008.04.007
212Pb is an alpha-emitting nuclide that acts as the therapeutic in our 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. We believe 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.
To maximize the potential clinical benefit of radiopharmaceuticals to patients and minimize potential toxicity issues, we believe 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 our co-founder, Dr. Michael Schultz, colleagues at the University of Iowa and our team members resulted in the development of our 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 our 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. We believe that our TATs’ ability to promote clearance without compromising the tumor’s uptake of the alpha particle overcomes a longstanding challenge of radiopharmaceutical drug development.
Our Chemistry and Biology Expertise with 212Pb
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We believe that our experience working with alpha-emitting radiopharmaceuticals positions us to build on the success of currently approved radiopharmaceuticals. By utilizing the advantages of 212Pb and our proprietary chelator, we have 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. We believe we have the experience and know-how to develop molecules and formulations of 212Pb to maximize the shelf-life of our program candidates and allow for regional production and distribution. In addition to a deep understanding of the chemistry of 212Pb, we believe we have 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, the Bystander Effect and use of the immune system’s adaptive response to attack non-target expressing tumors in order to stimulate a vaccine effect.
Imaging Diagnostics – 203Pb
For each of our program candidates, we create an imaging analogue that utilizes the same linker and targeting molecule but replaces 212Pb with the radioactive imaging isotope 203Pb. This allows us to assess uptake of the imaging analogue into the targeted tumor and to determine radiation doses to key organs. The imaging analogue versions of our program candidates are leveraged in both preclinical and clinical development and are used to enrich the patient population in our 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 our 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.
Our Pipeline
We are leveraging our TAT platform to advance a pipeline of alpha-based therapeutic programs to treat various cancers. The table below details our current pipeline of TATs, indicating the status of each of our three lead programs in clinic within our broad proprietary pipeline at March 21, 2025.
To date, we have retained global development and commercialization rights to all our program candidates. In January 2024, we announced we 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 our [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 (GRPR) and, prior to IND filing, a right to negotiate for an exclusive license to such candidates.
Programs
VMT-α-NET: A Targeted Alpha Therapy Targeting SSTR2
Overview
We designed VMT-α-NET to target and deliver 212Pb to target cancer-specific receptors on tumor cells expressing SSTR2, a protein that is overexpressed in NETs and other cancers. [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.
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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. 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. As noted by N. Patel and B. Benipal in Incidence of Neuroendocrine Tumors in the United States from 2001-2015: A United States Cancer Statistics Analysis of 50 States, gastroenteropancreatic NETs, or GEP NETs, represent the most common NET subtype, comprising 55–70% of all NETs, followed by lung (22-27%). In Epidemiologic trends of and factors associated with overall survival in patients with neuroendocrine tumors over the last two decades in the USA., P. Wu, D. He, H. Chang, and X. Zhang estimated that more than 12,000 people in the U.S. are diagnosed with a NET each year, and current prevalence of NETs in the U.S is approximately 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 rate 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 rate (>90%), but there remains recurrence risk. High-grade and/or distant disease is more difficult to treat and carries lower median survival rates, typically measured in months. Radioligand therapy has emerged as a promising therapeutic option for GEP NETs in late stage and is being evaluated for earlier lines of treatment. We believe 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. In October 2024, GlobeNewswire.com reported worldwide sales for systemic NET treatments were valued at $3.6 billion in 2023 and are estimated to reach $6.9 billion by the end of 2030.
Using a specialized peptide, VMT-α-NET is designed to target and bind to the SSTR2 on tumor cells. As a diagnostic, we link 203Pb, a radioactive imaging agent that emits gamma rays, to its SSTR2-targeting peptide. Through the use of imaging scans, we are 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, we link 212Pb, its alpha-particle radioactive isotope, to the same SSTR2 targeting peptide which has been shown to bind and kill cancerous cells.
In 2022, we received a “safe to proceed” decision on an IND application with the 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. Later in 2022, we received Fast Track Designation for this program based on preclinical data for the indication of SSTR2-positive NETs regardless of prior treatment response.
Additionally, we believe 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 we pursue the rare pediatric disease of advanced neuroblastoma as our best path for drug approval after review of Phase 1 trial data.
Preclinical Studies of [212Pb]VMT-α-NET
Our 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.
Our 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 PET isotopes.
At the Annual Congress of the European Association of Nuclear Medicine in September 2023, we 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 in September 2023, 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.
Our first-in-human experience with [203Pb]VMT-α-NET imaging occurred under the supervision of the attending physician at the University of Ulm in Dresden, Germany in 2021 in a patient with metastatic and refractory gastrointestinal NET. Imaging from this
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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 semi-quantitative medical physics analysis by the team at the University of Ulm, 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.
Clinical Studies of [212Pb]VMT-α-NET
We have 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 to 32 adult patients 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 properties. Secondary endpoints are overall response rate by response evaluation criteria in solid tumors (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. According to the mTPI-2 study design, intermediate 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 positron emission tomography (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.
In November 2024, at the North American Tumor Society’s NANETS Multidisciplinary NET Medical Symposium, we announced initial results from this study and, in January 2025, we announced an update to these initial results at the 2025 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
Company-Sponsored Trials of [212Pb/203Pb]VMT-α-NET
In June 2024, we announced multiple updates featuring our alpha-particle radiopharmaceuticals at SNMMI. The data presentations highlighted favorable safety profiles and potential benefits of our lead clinical candidates. Specifically, we reported on a Phase 0 imaging trial that is evaluating the optimal imaging timepoint(s) for diagnostic/dosimetric performance of [203Pb]VMT-α-NET in neuroendocrine tumors. Investigators analyzed 48 lesions across nine patients, and the results showed that tumor uptake of [203Pb]VMT-α-NET peaked at approximately four hours post-injection, with 98% of maximum uptake observed at one hour. The results suggest that imaging with [203Pb]VMT-α-NET at four hours post-injection has the best overall diagnostic performance, followed closely by imaging at one hour.
In November 2024, we announced initial results from our multi-center open-label dose escalation, dose expansion study (clinicaltrials.gov identifier NCT05636618) of [212Pb]VMT-α-NET in patients with unresectable or metastatic SSTR2-positive NETs who have not received prior radiopharmaceutical therapy and have shown radiological evidence of disease progression in the 12 months prior to enrollment. The data cut-off date for the presentation was October 31, 2024.
Per the study protocol, the two patients who made up Cohort 1 received administered activity of 2.5 mCi per dose regardless of body weight. Based on their respective body weights, the median administered activity per kilogram of weight was 45.5 μCi/kg per dose. The seven patients who made up Cohort 2 received administered activity of 5.0 mCi per dose regardless of body weight. Based on their respective body weights, the median administered activity per kilogram of weight was 62.1 μCi/kg per dose, ranging from 31.8 μCi/kg to 84.6 μCi/kg per dose. One patient in Cohort 2 received two doses of 84.6 μCi/kg per dose, then received the third and fourth doses at a reduced activity level of 42.4 μCi/kg per dose due to an adverse event that was determined by the investigator to be unrelated.
No dose limiting toxicities (DLTs) were observed among any patients. No grade 4 or 5 treatment emergent or serious adverse events (AEs) were observed. Two grade 3 AEs – one case of diarrhea and one case of syncope – were observed. No decline in renal function was observed. Hematologic AEs, such as decreased lymphocyte count and anemia, were all grades 1 and 2. No treatment discontinuations due to AEs occurred.
Eight of nine patients had durable control of disease. Six of nine patients had measurable reduction of tumor volume, one of whom had a confirmed response as defined by RECIST v1.1. The patient who experienced an objective response received the first two doses at 84.6 μCi/kg per dose, then received the remaining two doses at a reduced activity level of 42.4 μCi/kg. One patient was deemed to have progressive disease after one dose under RECIST v1.1, by unambiguous progression of non-target lesions.
The SMC determined that safety observations during the DLT observation period supported proceeding with dose escalation to Cohort 3 and expanding the number of patients dosed at 5 mCi. Based on interactions with the FDA prior to the initiation of patient dosing in this study, which occurred in late 2023, the decision to open Cohort 3 will follow consultation and alignment with the agency. FDA interactions are ongoing with regards to the initiation of the next dosing cohort.
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In January 2025, we announced updated interim results from this same clinical trial with a data cut-off date of January 10, 2025. All nine patients in Cohort 1 and Cohort 2 had completed treatments per the study protocol, and the study team had at least one scan for all patients after their final treatments. No DLTs, grade 4 or 5 treatment emergent or serious AEs were reported since the start of the study. No new grade 3 AEs were observed aside from the two events discussed earlier. No decline in renal function was observed. Hematologic AEs, such as decreased lymphocyte count and anemia, were all grades 1 and 2. No treatment discontinuations due to AEs occurred.
Further anti-tumor activities have been observed with longer follow-up, and there were two unconfirmed responses and one confirmed response as defined by RECIST v1.1 in Cohort 2. As of the January 10, 2025, data cut-off date, the patient who experienced a confirmed objective response has been in response for 17 weeks and remains in the study. This patient received the first two [212Pb]VMT-α-NET doses at administered dose of 5.0 mCi (equivalent to 84.6 μCi/kg), then received the remaining two doses at the next lower activity level of 2.5 mCi (equivalent to 42.4 μCi/kg) due to an adverse event that was determined by the investigator to be unrelated to [212Pb]VMT-α-NET.
One patient was observed to experience an initial (unconfirmed (as of January 10, 2025)) response in the fifth scan after their first dose, which was the first scan conducted after the end of their treatment period. This patient experienced gradual tumor regression throughout the study, with the magnitude of change meeting the criteria for response on their most recent scan. This patient received four doses of 5.0 mCi (equivalent to 68.7 μCi/kg) of [212Pb]VMT-α-NET.
A third patient was observed to experience an initial (unconfirmed (as of January 10, 2025)) response in the seventh scan after their first dose, which was the third scan conducted after the end of their treatment period. This patient received four doses of 5.0 mCi (equivalent to 31.7 μCi/kg) of [212Pb]VMT-α-NET. Gradual tumor regression was first observed in the fifth scan after their first dose, with the magnitude of change meeting the criteria for response on their most recent scan.
Five patients continued to have stable disease. One patient was deemed to have progressive disease after one dose under RECIST v1.1, by unambiguous progression of non-target lesions.
As noted below, the preliminary response assessment by RECIST v1.1 showed three responses in seven patients from Cohort 2.
Note: Patient 109-103 experienced progressive disease by unambiguous progression of non-target lesions.
Wahl RL et al. Data cutoff date January 10, 2025.
After Cohort 2 reopened for enrollment in August 2024 and through year-end 2024, an additional 11 patients were dosed. Thus, a total of 18 patients received treatment in Cohort 2 through December 31, 2024. Since the start of 2025 through the end of February 2025, an incremental 12 patients have been dosed. Thus, a total of 30 patients have received treatment in Cohort 2 as of February 28, 2025. Cohort 2 remains open for recruitment.
Investigator-Initiated Clinical Research and Section 13-2(B) Usage of [212Pb/203Pb]VMT-α-NET
Also at SNMMI, an investigator reported on [212Pb]VMT-α-NET planning based on [203Pb]VMT-α-NET predictive dosimetry in an investigator-sponsored trial. The investigators applied patient-specific dosimetry in a Phase 0 imaging trial (NCT05111509) of [203Pb]VMT-a-NET and in the first cohort of a Phase 1 absorbed-dose escalation study (NCT06148636) of [212Pb]VMT-α-NET. Ten
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patients with β-peptide receptor radionuclide therapy (PRRT)-relapsed or refractory GEP-NETs received [203Pb]VMT-α-NET (5 mCi) followed by sequential blood sampling, planar imaging and qSPECT/CT imaging at 1 hour, 4 hours, 24 hours and 48 hours post-administration. Three of 10 patients received amino acid infusions while seven patients did not receive amino acids.
The dosimetry showed that the average renal doses for patients who received amino acids was 0.46±0.20 Gy/mCi, as compared to 0.56±0.16 Gy/mCi for patients who did not receive amino acids; the difference was not statistically significant. For the three patients who received [212Pb]VMT-α-NET treatment, based upon their individual dosimetry results, they were prescribed 5.3, 7.3, and 13.3 mCi cumulative activity (delivered over two cycles), respectively, to reach the cohort target renal dose of 3.5 Gy. Higher levels of targeted renal-absorbed doses are in the protocol for subsequent cohorts.
Additionally at SNMMI, the lead investigator reported on an exploratory first-in-human use of [212Pb]VMT-α-NET in adult patients with histologically confirmed metastatic NETs and medullary thyroid carcinomas in an investigator-led research study in India. A total of 13 patients were enrolled: 10 patients with GEP-NETs, one patient with breast NETs and two patients with medullary thyroid carcinomas. The investigator reported updated safety and anti-tumor activity of [212Pb]VMT-α-NET administered at 67 μCi/kg (2.5 MBq/kg) every eight weeks in the 13 patients as of the data cut-off date of May 31, 2024. All patients had received prior treatments, eight of whom received prior PRRT treatment. Six patients remained eligible for further treatments as of the data cut-off date.
The investigator concluded that the toxicity profile suggested the potential for dose escalation to achieve optimal treatment responses. Confirmed tumor response per RECIST 1.1 was reported to be observed in eight of the 13 patients, while unconfirmed responses were observed in two additional patients who eventually had progressive disease and died. Median progression free survival was reported to be 16.4 months (95% confidence interval: 3.5 to NA). The investigator also reported higher absorbed doses in the tumors compared to select other tissues.
Subsequently, in October 2024, at the 37th Annual Congress of the European Association of Nuclear Medicine (EANM) in Hamburg, Germany, the investigator presented an update on a subset of the previously reported investigator-led research study in India. The cut-off date was September 15, 2024, and the study focused on 10 patients with well-differentiated GEP-NETs. These patients were treated with [212Pb]VMT-α-NET at a dosage of 67 μCi/kg (2.5 MBq/kg), with an interval of eight weeks for up to six cycles. Treatment was well tolerated with a modest and manageable adverse effect profile. Confirmed tumor response per RECIST 1.1 was observed in six of the 10 GEP-NETs patients. The investigator again concluded that the toxicity profile suggested the potential for dose escalation to achieve optimal treatment responses.
Additionally, dosimetry estimates were collected from five of the 10 GEP-NETs patients discussed above. The results demonstrated that SPECT/CT imaging with [212Pb]VMT-α-NET showed prompt tumor accumulation, high tumor retention and rapid renal excretion in all patients. Overall, the findings suggested that post-treatment imaging of [212Pb]VMT-α-NET is feasible and can potentially serve as a valuable tool to evaluate and monitor patients through a full course of treatment.
The University of Iowa is conducting an investigator-initiated Phase 1 trial (clinicaltrials.gov identifier NCT05111509) to investigate the feasibility of using [203Pb]VMT-α-NET 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 (RPT). In addition, in December 2023, we 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 enrolled in the study had either progressed or relapsed after previous therapies, including currently approved 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 10 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. Preliminary results from Cohort 1 were presented at SNMMI. Enrollment is ongoing.
We supported diagnostic and therapeutic dosing of [203/212Pb]VMT-α-NET at the Technical University of Dresden under provisions in Section 13-2(B) of Germany’s Medicinal Products Act supporting patients that lack further treatment options. This is a single-site retrospective evaluation of imaging with [203Pb]VMT-α-NET and subsequent single administration of [212Pb]VMT-α-NET in patients with progressive metastatic GEP-NET after exhausting all current therapies, including radiopharmaceuticals. The investigator has informed us that a manuscript of this study is in submission. Eight patients were treated with a single dose of [212Pb]VMT-α-NET at mean activity level of 2.7 mCi (100 MBq). Progression was defined by new SSTR-positive tumor lesions on Gallium-68 (68Ga) DOTATATE-PET/CT imaging or by increasing blood tumor markers, namely Chromogranin A. The investigators have informed us that certain preliminary results were presented at the 2025 Society of Nuclear Medicine and Molecular Imaging Mid-Winter Meeting. A manuscript of this study is in submission.
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VMT01: A Targeted Alpha Therapy Targeting MC1R
Overview of VMT01and VMT02
We are also leveraging our TAT platform with our second program candidate, VMT01, which is currently in Phase 1/2a clinical trials. We designed VMT01 to target and deliver 212Pb to tumor sites expressing MC1R, a protein that is overexpressed in melanoma cancers. [212Pb]VMT01 is a TAT in development for second-line or later treatment of patients with progressive MC1R-positive metastatic melanoma. Review of market research prepared by Global Newswire in March 2024 indicates metastatic melanoma could represent over a $12.0 billion market opportunity by 2028.
Using a specialized peptide, VMT01 is designed to target MC1R on tumor cells. As a diagnostic, we either link 203Pb or 68Ga 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.
We 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. Through the use of the imaging scans, we are able to characterize whether the patient’s cancer expresses MC1R and thus be a candidate for treatment. As a therapeutic, we link 212Pb to the same MC1R targeting peptide which has been shown to bind and kill cancerous cells. 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 would follow a separate regulatory path from the therapeutic compound and would proceed based on the potential for utility after a therapeutic efficacy signal is identified.
VMT01 and VMT02 bind with high affinity and specificity to MC1R-expressing melanoma tumors 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 therapeutic stage with [212Pb]VMT01, in which the 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.
We conducted nonclinical pharmacology, pharmacokinetics and toxicology studies utilizing in vitro and in vivo assays, SPECT and PET imaging and histopathology to support the first-in-human Phase 1/2a clinical development of [212Pb]VMT01 per recommendations in the FDA’s 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. We have 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 demonstrated resistance to re-inoculation with naive melanoma cells.
Management believes that there are currently no FDA-approved radiopharmaceutical 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 International Agency for Research on Cancer disclosed that the worldwide melanoma incidence is estimated to reach 353,000 new cases in 2025, 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. The American Cancer
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Society reported that, in the U.S., there will be an estimated 104,960 new diagnoses of melanoma in 2025 and approximately 8,430 deaths annually from metastatic melanoma.
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 10% of cases, with a five-year survival rate of approximately 70%. 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. SEER also noted that metastatic melanoma accounts for 5% of cases and carries a poor prognosis with a one-year survival rate of 50% and five-year survival rate of 29%-35%. 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: https://www.sciencedirect.com/science/article/pii/S1040842824000192). This segment of the melanoma population is the intended entry market for VMT01. In 2021, worldwide sales for the systemic treatment of advanced melanoma were 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, 2021).
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. Immune checkpoint inhibitors, targeted mitogen-activated protein kinase inhibitors (MAPKi) and cell therapies have improved outcomes but also low response rates and acquired drug resistance, and adverse side effects have limited quality of life for metastatic melanoma patients. The most dramatic improvements in response 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. We believe [212Pb]VMT01 has the potential to overcome many of these resistance pathways. Our intent is to test the safety and tolerability of [212Pb]VMT01 in previously treated patients who are experiencing progression or recurrence of disease as monotherapy as well as in combination with first-line immunotherapies.
Clinical Studies of [203/212Pb]VMT01
In 2020, we 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 later given a “safe to proceed” designation in 2020. We 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 patients with stage IV unresectable melanoma were imaged. The primary endpoints of this study were safety and biodistribution and secondary endpoints were molecular target validation and image quality. We have submitted the clinical study report to the FDA. The results of this study were presented at the Society of Nuclear Medicine and Molecular Imaging Annual Meeting in 2023.
In 2022, we received an IND “safe to proceed” letter from the FDA to evaluate [212Pb]VMT01 in patients with advanced and progressive melanoma and, in September 2024, we received Fast Track designation for the development of [212Pb]VMT01 for the diagnosis and treatment of patients with unresectable or metastatic melanoma who have demonstrated MC1R tumor expression. Our ongoing trial of [212Pb]VMT01 (clinicaltrials.gov identifier NCT05655312) is a multi-center, open-label dose escalation, dose expansion study in patients with histologically confirmed melanoma and MC1R-positive imaging scans. The first part of the study is a dose finding phase to determine the MTD, MFD or optimal biologic dose following a single administration of [212Pb]VMT01. In July 2024, we submitted a protocol amendment to explore the combination of the checkpoint inhibitor nivolumab with [212Pb]VMT01 in patients with histologically confirmed melanoma and positive MC1R imaging scans in our ongoing Phase 1/2a study of [212Pb]VMT01. The supply of nivolumab was secured in March 2024, when we entered into a clinical trial collaboration agreement with Bristol Myers Squibb. As such, another part of the study is a combination therapy dose finding in which [212Pb]VMT01 and nivolumab are administered in escalating doses to determine MTD, MFD or optimal biologic dose. The third part of the study is expected to entail the enrollment of patients in monotherapy and combination therapy expansion cohorts based on the identified MTD, MFD or optimal biologic dose. Patients may be eligible to receive up to three administrations of [212Pb]VMT01 approximately eight weeks apart or they may be eligible to receive nivolumab every four weeks for up to 24 months. A dosimetry sub-study is included to assess biodistribution, tumor uptake and correlation of uptake with observed toxicities and efficacy.
In October 2024, we announced initial results from the first two dosing cohorts of the Phase 1/2a clinical study of [212Pb]VMT01 in patients with progressive MC1R-positive metastatic melanoma. Three patients were enrolled in Cohort 1 (who received 3 mCi of [212Pb]VMT01), while seven patients were enrolled in Cohort 2 (who received 5 mCi of [212Pb]VMT01). Patients in each cohort received a median of five prior lines of systematic therapy, including a median of three prior lines of immunotherapy. No DLTs were observed among any patients, and no AEs led to treatment discontinuation. Treatment emergent AEs were mostly grades 1 and 2. None of the four cases of grade 3 treatment emergent AEs were deemed to be treatment related. There were no grade 4 or 5 treatment emergent AEs. No renal toxicities had been reported as of October 11, 2024 (there were no clinically significant changes in blood urea nitrogen or serum creatinine) in spite of dosimetry estimated renal radiation that approached the higher end of conventional dosing.
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All patients in Cohort 1 completed three treatments, with one patient experiencing an unconfirmed RECIST version 1.1 objective response after completion of treatment, and two patients experiencing stable disease at 9 and 11 months from the start of treatment, respectively, as reported in October 2024 at the 21st International Congress of the Society of Melanoma Research (SMR). In Cohort 2, patients progressed after either the first cycle (three patients) or the second cycle (four patients). These findings are consistent with published and ongoing preclinical studies showing immunostimulatory effects at lower radiation doses.
The SMC reviewed these findings and recommended exploring a lower dose level of 1.5 mCi per dose, both as a single agent and in combination with the anti-PD-1 antibody, nivolumab. The SMC’s recommendation would allow for the monotherapy and combination cohorts to proceed concurrently. An amendment to further explore lower dose levels for monotherapy has been approved, and cohort 3 at 1.5 mCi per dose is active and open for enrollment. The combination cohort at 1.5 mCi per dose with nivolumab is also active and open for enrollment. On March 17, 2025, we announced that the first patient was dosed in the combination cohort.
In October 2024, at SMR, we provided the following update on the ongoing clinical trial with a data cut-off date of September 4, 2024:
Lighter portions of each line in the above slide signify transition of the patient to follow-up periods, which began at approximately 24 weeks after first dose. Patient 03-104 discontinued follow up without progressive disease. Patients 04-113, 03-114 and 01-116 experienced progressive disease after the data cut-off date of September 4, 2024. (Morris ZS et al, Poster Presentation at Society of Melanoma Research, New Orleans 2024.)
PSV359 – A Targeted Alpha Therapy Targeting Fibroblast Activation Protein alpha
Tumor stroma cells do not typically express cancer-specific markers like SSTR2 or MC1R. FAP-α 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. Our in-house discovery team discovered PSV359, a novel cyclic peptide targeting human FAP-α, via phage display methods. We believe PSV359 is an optimized peptide with potential best-in-class characteristics that has been demonstrated in preclinical models. In March 2024, we released the first-in-human clinical SPECT/CT imaging which suggested very favorable tumor targeting and retention by the PSV359 compound, while clearing from normal organs rapidly and completely.
In October 2024, we announced first-in-human SPECT/CT images of [203Pb]PSV359 from an independent investigator revealed strong tumor uptake, fast clearance through the renal system, low accumulation in normal organs, and long tumor retention in three patients with FAP-α expressing cancers.
Preclinical results for PSV359 were presented during the SNMMI and the EANM meetings in June and October 2024, respectively. Researchers presented a novel cyclic peptide targeting human FAP-α, which was discovered by us via phage display methods. FAP-α is a protein abundantly expressed in certain cancer cells as well as cancer-associated fibroblasts in tumor lesions and involved in promoting disease progression. The peptide was conjugated to a lead (Pb)-specific chelator via a molecular linker to form a novel construct, PSV359. The purpose of this study was to evaluate the in vitro and in vivo performance of [203/212Pb]PSV359 in preclinical xenograft models. As depicted below, PSV359 demonstrated superior binding affinity and specificity against human FAP-α (Kd=1.8 nM, Ki=0.4 nM) as compared to other FAP-targeted drugs and remained stable in serum for 96 hours. Overall, strong anti-tumor clinical
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activity of [212Pb]PSV359 was found in both HT1080-human FAP-α (FAP-α on cancer cells) and U87MG (FAP-α in stromal tissues) xenograft models.
Source: Cagle et al. European Association of Nuclear Medicine 2024, Presentation Number: OP-473.
The FAP-α PSV359 program is a significant addition to our clinical pipeline of targeted alpha therapeutics. We filed an IND application for this asset in December 2024, and we received a “study may proceed” letter (i.e., approval to conduct the trial) from the FDA in the first quarter of 2025. We expect to initiate dosing in mid 2025.
PSV4XX: A Differentiated PSMA-Targeted Alpha Therapy
On December 31, 2023, we 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. It can also be used for beta-particle-targeted RPT using copper isotopes. In September 2024, the American Cancer Society reported that prostate cancer is the second most prevalent form of cancer affecting men worldwide and the number one cancer in men for 66% of the world, emphasizing the critical need for advanced technologies to improve early detection and treatment outcomes. In 2024, the Prostate Cancer Foundation cited a report from the Lancet Commission that projected annual prostate cancers will rise from 1.4 million in 2020 to 2.9 million by 2040 with annual deaths increasing by 85%, to almost 700,000, during this same timeframe.
In June 2023, 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.
Pre-Targeting Theranostic Targeting Platform - The Next Generation of TAT
In February 2024, we announced that we 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 were awarded the Phase 1 tranche of a 2.5-year Fastrack Small Business Innovation Research grant (Phase 1 $0.4 million; total $2.4 million) from the NIH’s National Cancer Institute (NCI) in support of our CB7-Adma host-guest pre-targeting program for the diagnosis and treatment of cancer.
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 our 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 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, has demonstrated promising in vivo stability, modularity and low immunogenicity. The
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platform’s potential was validated through in vivo profiling of ligands, employing a CB7-modified carcinoembryonic antigen targeting antibody.
We are currently working through preclinical optimization of this platform and working to identify initial targeting antibodies for further investigation.
1. Pre-targeting platform currently in preclinical development.
Manufacturing and Supply
We have developed a proprietary isotope delivery system, colloquially called a “generator,” VMT-α-GEN, to allow for delivery of our preferred therapeutic isotope 212Pb for supply to patients. In January 2021, we entered into a 10-year feedstock contract with the NIDC of the DoE Isotope Program. We receive feedstock shipments of Thorium-228 from the NIDC. We also have contracts with various manufacturers to produce certain components of our VMT-α-GEN system. This has allowed us to scale manufacturing of VMT-α-GEN for research purposes that we believe will facilitate our alpha therapy clinical trials. We believe that by controlling our own therapeutic isotope supply, we can solve the many supply chain risks that have slowed alpha-particle therapy clinical adoption to date.
We assemble and manufacture our finished radiopharmaceutical candidates by chelating or trapping an atom of 212Pb within a specialized chelator or chemical “cage” and connecting the 212Pb within its cage to the targeting peptide with our linker technology. For clinical supply, we intend to use a combination of third-party contract manufacturing organizations, or CMOs, and our own manufacturing sites complying with the FDA’s current good manufacturing practices, or CGMP, to manufacture and distribute our doses.
For the drug precursors and isotopes that comprise our TAT platform, a variety of clinical phase manufacturers have been engaged and utilized. We procure chelator-modified peptide precursors from peptide manufacturers who are capable of producing clinical phase precursor material. The imaging isotope 203Pb is procured from manufacturers with appropriate radiation handling licensing and shipped to our production sites, such as our facility 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. The therapeutic isotope 212Pb is supplied via our proprietary 224Ra/212Pb generators, which are manufactured by a CMO. These isotope delivery systems can be shipped globally to enable final finished radiopharmaceutical production for clinical trials. We have received “safe to proceed” designations for three therapeutic IND applications in which our isotope delivery system was presented to the FDA for use in clinical trial manufacturing. Quality and stability testing for all of our precursors is an ongoing process, and we are focused on continuing to enhance the robustness and reliability of our supply chain to date.
In September 2024, we entered into a Master Equipment and Services Agreement (MESA) and statements of work (SOWs) thereunder with Comecer SpA (Comecer), pursuant to which we agreed to purchase from Comecer manufacturing equipment for the production of our radiopharmaceutical products including, but not limited to, isotope processing hot cells and production suites and related equipment (collectively, the Deliverables) and services for installation and validation of the Deliverables at several of our production facilities in the United States.
For discovery activities and early phase clinical testing, we have established a clinical drug manufacturing facility at our laboratories in Coralville, IA, and Somerset, NJ, to assemble the precursors into ready-to-use drug products. The Coralville facilities comprise approximately 4,000 square feet of wet laboratory facilities and a small, finished product facility equipped with air and temperature
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handling and monitoring designed to comply with applicable clinical drug regulatory requirements. Additionally, we have built a second production suite that we anticipate will be operational by mid 2025. We have staff experienced in finished radiopharmaceutical manufacturing and shipping who will not only supply drug product for our near-term activities but will also perform technology transfer to any CMOs where the finished production of radiopharmaceuticals will be accomplished. We have obtained radiation handling licenses to enable us to provide clinical doses for our Phase 1/2 clinical trials. In addition, we are capable of synthesizing peptides, chelators and linkers in our Coralville facilities, and this capability enables us to independently perform research for pipeline development.
In March 2024, we acquired the assets and associated lease of Lantheus’ radiopharmaceutical manufacturing facility in Somerset, NJ. Soon after the acquisition, we began the onboarding and operationalization processes and, in October 2024, we achieved the first shipment and patient dosing from our Somerset facility. With three manufacturing suites that can meet CGMP requirements, the Somerset facility is expected to have the capacity to meet future clinical trial and commercial demands at major cancer treatment centers throughout the Northeastern U.S.
We are currently successfully shipping products long distances and meeting patient demands from both our Coralville, IA, and Somerset, NJ sites.
On July 15, 2024, August 2, 2024 and October 31, 2024, we purchased a building in the Houston, TX, metropolitan area for $4.7 million, a building in the Chicago, IL, metropolitan area for $5.0 million, and a building in the Los Angeles, CA, metropolitan area for $11.0 million, respectively, which we intend to use for the manufacture of our program candidates upon completion of modifications and installation of equipment. We intend to continue to expand our manufacturing and supply network in the future as we anticipate increasing our clinical trial activities.
In addition, CMOs have locations that are strategically placed locally to major metropolitan areas that are within reach for delivery of our radiopharmaceuticals for trials and ultimately for commercialization. We are currently reviewing various CMOs across the United States to determine the potential to transfer know-how and technology to these CMOs to allow broader potential geographic coverage of radioactive products across our potential clinical trial sites. As noted in the graphic below showing a heat map of population distribution in the United States, we believe we will be able to service a majority of cancer centers by strategically locating facilities throughout the United States.
1Based on current Company plans and estimates;
2Company estimates based on data from https://www.statsamerica.org/radius/big.aspx; products can also be driven further or flown as necessary.
Commercialization
None of our 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 we believe that our technology and intellectual property provide us with competitive
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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 are 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 (through its acquisition of RayzeBio), Eli Lilly (through its acquisition of POINT Biopharma), Lantheus (through its acquisition of Evergreen), Telix Pharmaceuticals Limited, Actinium Pharmaceuticals, Inc., RadioMedix, Inc., AdvanCell, Orano Med, Aktis Oncology, Inc., AstraZeneca (through its acquisition of Fusion Pharmaceuticals, Inc.), Convergent Therapeutics, Johnson & Johnson, ARTBIO and Abdera. These companies use various alpha-emitting isotopes such as 223Ra, 225Ac, 212Pb and 211At. 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, Cellectar Biosciences, ITM Isotope Technologies Munich SE, Y-mAbs Therapeutics, Inc., Actinium Pharmaceuticals, Inc., Lantheus, Blue Earth Therapeutics and Clarity Pharmaceuticals.
For our program candidate [212Pb]VMT-α-NET, we are 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 tumors. We are aware of the following companies with neuroendocrine tumor, radioligand preclinical and clinical development programs: ITM Isotope Technologies Munich SE, Bristol Myers Squibb (through its acquisition of RayzeBio), Eli Lilly (through its acquisition of POINT Biopharma) and RadioMedix. We also face potential competition from other treatments targeting neuroendocrine tumors such as Sandostatin® and Afinitor® (Novartis), Somatuline® (Ipsen) and Sutent® (Pfizer). While we believe [212Pb]VMT-α-NET has significant advantages compared to conventional approaches to neuroendocrine tumors, we 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.
Grants and Awards
Our next-generation radiopharmaceutical technology has been recognized by many organizations and has received numerous awards and grants in support of the development of our technology and programs.
As discussed above, we have benefited from awards from the SBIR and STTR awards from the National Cancer Institute of the National Institutes of Health to Michael K. Schultz, PhD, our co-founder and Chief Science Officer, to Frances L. Johnson, M.D., our co-founder and former Chief Innovation Officer, and research grants in collaboration with our collaborators at the University of Iowa. These grants and contracts have been awarded to Dr. Schultz and Dr. Johnson as principal investigators as well as co-investigators in collaboration
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with several academic institutions in the U.S. The table below summarizes key grant awards that have been peer reviewed by expert panels at the National Cancer Institute.
Date Type Amount ($) PrincipalInvestigator Summary Use
* Ongoing Grant
** Grants awarded to Dr. Schultz’s laboratory at the University of Iowa
*** The total grant amount was $10,250,000, of which $1,250,000 was granted to Dr. Schultz as Project 3 Leader.
Intellectual Property
Our success depends, in part, on our ability to obtain and maintain intellectual property protection for our platform technology, program candidates and know-how, to defend and enforce our intellectual property rights, in particular, our patent rights, to preserve the confidentiality of our know-how and trade secrets and to operate without infringing the proprietary rights of others. We seek to protect our program candidates and technologies by, among other methods, filing U.S. and foreign patent applications related to our proprietary technology, inventions and improvements that are important to the development of our business. We also rely on trade secrets, know-how, continuing technological innovation and in-licensing of third-party intellectual property to develop and maintain our proprietary position. We, or our collaborators and licensors, file patent applications directed to our key program candidates in an effort to establish intellectual property positions to protect our program candidates as well as uses of our program candidates for the prevention, diagnosis and/or treatment of diseases.
As of December 31, 2024, as the sole applicant, we have filed 19 patent applications on radionuclide (lead and radium) generation technologies, FAP-α-targeting compounds and uses, antibody-conjugated radiopharmaceutical compounds, and lead poisoning treatment technologies. The earliest expiration date for these patents, if granted, is expected to occur in 2043. As a co-applicant, we have
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filed two patent applications on epidermal growth factor receptor-targeting radiopharmaceutical compounds and 203Pb/212Pb clinical imaging protocols. The earliest expiration date for these patents, if granted, is expected to occur in 2045.
As of December 31, 2024, we licensed technology covered by several patents and patent applications from the University of Iowa, Mayo Clinic and Stony Brook University, including six issued U.S. patents, one issued Australian patent, one allowed Australian patent application, and 34 pending U.S. and foreign patent applications. Two patents have recently been granted on key assets for which we have exclusive licenses from the University of Iowa. US 12,128,115, granted by the United States Patent and Trademark Office in October 2024, relates to the use of compounds comprising a lead-specific chelator (PSC) for performing chelating reactions with divalent metals, including Pb2+, and the use of such compounds for diagnosing and treating diseases. The full term of this patent expires in June 2037. AU 2017281940, granted by IP Australia in October 2024, relates to melanoma-targeting radiopharmaceutical compounds and their use for treating melanoma. The full term of this patent expires in June 2037. We believe that both of these patents further strengthen our IP portfolio.
From the University of Iowa, we have in-licensed patents and patent applications with composition of matter and methods of use claims on VMT01, VMT-α-NET, PSC for therapeutic and diagnostic uses, and methods for cancer treatment in the United States and various other foreign jurisdictions and regions including Europe, Australia, Canada, Japan, South Korea, India and China. Among these patents, the earliest patent expiry is expected to occur in 2036, without taking potential patent term extensions into account.
From Mayo Clinic, we have in-licensed a technology related to PSMA-targeting radiopharmaceutical compounds and their use for treating cancers, which includes one patent cooperation treaty (PCT) patent application (PSMA family #1) and eight pending national-phase patent applications (PSMA family #2). Mayo Clinic leads the prosecution and maintenance of these patent applications. If allowed, these patents are expected to expire in 2042 (PSMA family #1) and 2043 (PSMA family #2), without taking potential patent term adjustments into account.
From Stony Brook University (the Research Foundation of the State University of New York), we have in-licensed a pre-targeting radiopharmaceutical technology platform, which includes one PCT patent application (pre-targeting family #1) and one U.S. provisional patent application (pre-targeting family #2). Stony Brook University leads the prosecution and maintenance of these patent applications. If allowed, these patents are expected to expire in 2043 (pre-targeting family #1) and 2045 (pre-targeting family #2), without taking potential patent term adjustments into account.
As the patent claims related to the intellectual property described above may be amended or deleted during prosecution, we cannot guarantee the allowance of all or any of the claims recited in the patent applications for technologies that we either in-licensed or developed in-house.
The issuance of the VMT01 patents coincided with the completion of a clinical imaging trial which allowed us to evaluate VMT01 against the value of a portfolio of patents in-licensed from the University of New Mexico (UNM). Positive results of our clinical trial in comparison to previously published clinical data on the use of the UNM-patented compound allowed us to issue a Notice of Termination for the UNM portfolio in 2022, which represented a significant cost to us, 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 full term of the issued U.S. and Australian patents with composition-of-matter claims covering VMT01 and its therapeutic use for melanoma is expected to expire in 2037, without taking potential patent term extensions into account.
In December 2023, we 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 cancer. The term of 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, unless terminated earlier pursuant to the terms of the agreement.
In January 2024, we entered into an exclusive in-licensing of Stony Brook University’s CB7-Adma pre-targeting platform which covers global intellectual property rights. The term of 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.
We have an active pipeline development program, resulting in additional intellectual property developments within the company. We anticipate filing provisional patent applications on new peptide-based radiopharmaceuticals being developed by our discovery laboratory on a rolling basis of approximately 18- to 24-month schedules, depending on the complexity of the target and molecular construct. We intend to supplement this effort with in-licensing supported by an active collaborative grant program with academic centers around the globe. Our collaborations are governed by agreements designed to protect our intellectual property assets as well as establish a relationship to enable us to license intellectual property we identify as valuable to us. These activities leverage a strong collaborative network we have established to drive innovation and generate new intellectual property.
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Agreements and Collaborations
Lantheus Agreements
Investment Agreement
On January 8, 2024, we entered into an investment agreement (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 we agreed to sell and issue to Lantheus in a private placement transaction certain shares (Lantheus Shares) of our outstanding common stock, par value $0.001 per share (Common Stock). The closing of the purchase and sale of the Lantheus Shares to Lantheus by us (Lantheus Closing) was subject to us 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. The number of Lantheus Shares sold was 5,634,235, representing 19.99% of the outstanding shares of Common Stock as of January 8, 2024. Pursuant to the Lantheus Investment Agreement, we agreed to cooperate in good faith to negotiate and enter into a registration rights agreement with Lantheus, obligating us to file a registration statement on Form S-3 with the U.S. Securities and Exchange Commission (SEC) to register for resale the Lantheus Shares issued at the Lantheus Closing. We filed such Form S-3 on March 29, 2024, and the SEC declared it effective on April 9, 2024 (File No. 333-278362). The Lantheus Investment Agreement also contains agreements between us and Lantheus whereby Lantheus is provided certain board observer and information rights, subject to certain exceptions.
The Lantheus Investment Agreement also provides Lantheus with certain pro rata participation rights to maintain its ownership position in us in the event that we make any public or non-public offering of any equity or voting interests in us or any securities that are convertible or exchangeable into (or exercisable for) equity or voting interests in us, subject to certain exceptions.
Pursuant to the Lantheus Investment Agreement, we are required to notify Lantheus within 10 business days of the end of a fiscal quarter in which we issued shares of Common Stock pursuant to “at the market” sales programs, including the 2024 ATM Agreement (as defined below), of (i) the number of shares of Common Stock issued during such fiscal quarter pursuant to such agreement and (ii) the average price per share received by us before commissions (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 (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, we entered into an Asset Purchase Agreement (Progenics APA) with Progenics Pharmaceuticals, Inc., a Delaware corporation (Progenics) and affiliate of Lantheus, pursuant to which we acquired certain assets and the associated lease of Progenics’ radiopharmaceutical manufacturing facility in Somerset, NJ, for a purchase price of $8.0 million in cash. The transactions contemplated by the Progenics’ APA closed on March 1, 2024.
Option Agreement
On January 8, 2024, we entered into an option agreement (Option Agreement) 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, our clinical-stage alpha therapy developed for the treatment of neuroendocrine tumors, and a right to co-fund the IND application, enabling studies for early-stage therapeutic candidates targeting PSMA and GRPR and, prior to IND filing, a right to negotiate for an exclusive license to such candidates. In consideration of the rights granted by us to Lantheus pursuant to the Option Agreement, Lantheus paid to us a one-time payment of $28.0 million, subject to certain withholding provisions associated with the closing of the Progenics APA.
Under the terms of the Option Agreement, Lantheus also had a right of first offer and last look protections for any third-party merger and acquisition transactions involving us for a 12-month period, which expired on January 8, 2025.
Equity Financings
2024 At-the-Market (ATM) Agreement
On August 13, 2024, we entered into a Controlled Equity OfferingSM Sales Agreement (2024 ATM Agreement) with Cantor Fitzgerald & Co. and RBC Capital Markets, LLC (each, an ATM Agent, and together, the ATM Agents) pursuant to which we, from time to time, may offer and sell shares (2024 ATM Shares) of our Common Stock, through or to the ATM Agents having an aggregate sales price of up to $250.0 million.
Subject to the terms and conditions of the 2024 ATM Agreement, each ATM Agent is required to use its commercially reasonable efforts to sell the ATM Shares from time to time, based upon our instructions. We have provided the ATM Agents with customary indemnification rights, and the ATM Agents will be entitled to a commission of up to 3.0% of the gross proceeds from each sale of the ATM Shares effectuated through or to the applicable ATM Agent selling the ATM Shares.
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Sales of the 2024 ATM Shares, if any, under the 2024 ATM Agreement may be made in transactions that are deemed to be “at the market offerings” as defined in Rule 415 under the Securities Act of 1933, as amended. We have no obligation to sell any of the 2024 ATM Shares and may at any time suspend offers under the 2024 ATM Agreement or terminate the 2024 ATM Agreement.
The Common Stock to be sold under the 2024 ATM Agreement, if any, will be issued and sold pursuant to our shelf registration statement on Form S-3 (File No. 333-279692) (the May 2024 Registration Statement), which became effective upon filing with the SEC on May 24, 2024, as amended from time to time. On August 13, 2024, we filed a prospectus supplement to the May 2024 Registration Statement with the SEC in connection with the offer and sale of the 2024 ATM Shares pursuant to the 2024 ATM Agreement.
As of December 31, 2024, we had not completed any transactions pursuant to the 2024 ATM Agreement. On February 18, 2025, we sold 3,379,377 shares of our common stock under the 2024 ATM Agreement at an average price of approximately $3.02 per common share, resulting in gross proceeds of approximately $10.2 million.
May 2024 Registered Offering
On May 24, 2024, we entered into an underwriting agreement with BofA Securities, Inc., as representative of the underwriters named therein, in connection with our previously announced underwritten offering (Registered Offering) of 5,151,588 shares (Registered Offering Shares) of our Common Stock and, in lieu of Registered Offering Shares to certain investors, pre-funded warrants (May 2024 Pre-funded Warrants) to purchase 146,425 shares of Common Stock. The price to the investors for the Registered Offering Shares was $15.10 per Registered Offering Share, and the price to the investors for the May 2024 Pre-funded Warrants was $15.09 per May 2024 Pre-funded Warrant, which represents the per share price for the Registered Offering Shares less the $0.01 per share exercise price for each such May 2024 Pre-funded Warrant. The Registered Offering closed on May 29, 2024. BofA Securities, Inc., Oppenheimer & Co. Inc. and RBC Capital Markets, LLC acted as joint book-running managers for the Registered Offering and B. Riley Securities, Inc. acted as a co-manager for the Registered Offering. JonesTrading Institutional Services LLC acted as a financial advisor for the Registered Offering.
Our gross proceeds from the Registered Offering were approximately $80.0 million, before underwriting discounts and commissions and estimated expenses of the Offering.
The May 2024 Pre-funded Warrants became exercisable subsequent to the filing and effectiveness of an amendment to our Amended and Restated Certificate of Incorporation with the Secretary of State of the State of Delaware on June 14, 2024. The exercise price and the number of shares of Common Stock issuable upon exercise of each May 2024 Pre-funded Warrant 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 our stockholders. The May 2024 Pre-funded Warrants will not expire and are exercisable in cash or by means of a cashless exercise. A holder of May 2024 Pre-funded Warrants may not exercise such May 2024 Pre-funded Warrants if the aggregate number of shares of Common Stock beneficially owned by such holder, together with its affiliates, would be more than 4.99% or 9.99%, as elected by such holder, 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 May 2024 Pre-funded Warrants. A holder of May 2024 Pre-funded Warrants may increase or decrease this percentage not in excess of 19.99% by providing at least 61 days’ prior notice to us.
March 2024 Private Placement with Institutional Investors
On March 4, 2024, we entered into an investment agreement with certain accredited institutional investors pursuant to which we agreed to issue and sell, in a private placement (March 2024 Private Placement), 9,200,998 shares of our Common Stock, for a purchase price of $9.50 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 gross proceeds to us from the March 2024 Private Placement were approximately $87.4 million, before deducting fees and other estimated transaction expenses.
January 2024 Public Offering
On January 17, 2024, we entered into an underwriting agreement (Underwriting Agreement) with Oppenheimer & Co. Inc., as representative of the underwriters named therein (Underwriters), in connection with our underwritten public offering (Public Offering) of 13,207,521 shares (Public Shares) of our Common Stock and in lieu of Public Shares to certain investors, pre-funded warrants (Jan. 2024 Pre-funded Warrants) to purchase 3,008,694 shares of Common Stock. The price to the public for the Public Shares was $3.70 per Public Share, and the price to the public for the Jan. 2024 Pre-funded Warrants was $3.69 per Jan. 2024 Pre-funded Warrant, which represents the per share price for the Public Shares less the $0.01 per share exercise price for each such Jan. 2024 Pre-funded Warrant. Under the terms of the Underwriting Agreement, we granted the Underwriters an option, exercisable for 30 days, to purchase up to an additional 2,432,432 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.
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The gross proceeds to us from the Public Offering were approximately $69.0 million, before underwriting discounts and commissions and estimated expenses of the Public Offering.
The Public Offering was made pursuant to our shelf registration statement on Form S-3 (File No. 333-275638), declared effective by the SEC on December 14, 2023, a base prospectus dated December 14, 2023, and the related prospectus supplement dated January 17, 2024.
The Jan. 2024 Pre-funded Warrants were 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 Jan. 2024 Pre-funded Warrant 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 our stockholders. The Jan. 2024 Pre-funded Warrants did not have an expiration date and were exercisable in cash or by means of a cashless exercise. A holder of Jan. 2024 Pre-funded Warrants could not exercise such Jan. 2024 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 Jan. 2024 Pre-funded Warrants. A holder of Jan. 2024 Pre-funded Warrants could increase or decrease this percentage not in excess of 19.99% by providing at least 61 days’ prior notice to us. The holder of the Jan. 2024 Pre-funded Warrants exercised all of such warrants during the fourth quarter of 2024 by means of the cashless exercise provision and within the other constraints noted above.
2023 ATM Agreement
On April 11, 2024, we sold shares of our Common Stock pursuant to that certain At Market Issuance Sales Agreement, dated as of November 17, 2023, by and among us, Oppenheimer & Co. Inc., B. Riley Securities, Inc. and JonesTrading Institutional Services LLC (2023 ATM Agreement). The sales resulted in gross proceeds to us of approximately $49.5 million. Effective as of August 12, 2024, we terminated the 2023 ATM Agreement. For additional information regarding the 2023 ATM Agreement, see our Form S-3 filed on November 17, 2023, our Form S-3/A filed on December 7, 2023, and Note 3, Investments and Agreements, in this Form 10-K.
Brachytherapy Divestiture
On April 12, 2024 (GT Medical Closing Date), we completed the sale of substantially all of the assets (GT Medical Closing) of Isoray Medical, Inc. (Isoray), our wholly owned subsidiary, to GT Medical Technologies, Inc. (GT Medical). As previously disclosed, on December 7, 2023, we entered into an Asset Purchase Agreement (the GT Medical APA) with Isoray and GT Medical. Pursuant to the GT Medical APA, Isoray sold to GT Medical, and GT Medical purchased 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 including equipment, certain contracts and leases, inventory and intellectual property. Subject to limited exceptions set forth in the GT Medical APA, GT Medical did not assume the liabilities of Isoray.
Pursuant to the terms of, and subject to the conditions specified in, the GT Medical APA, at the GT Medical Closing, (i) GT Medical issued to Isoray 279,516 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 Date and (ii) Isoray has the right to receive, and GT Medical is obligated to pay, certain cash royalty payments during each of the first four years beginning upon the GT Medical Closing Date (each such year, a Measurement Period), as summarized below:
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with respect to GT Medical’s net sales of Cesium-131 brachytherapy seeds for cases that do not utilize GT Medical’s GammaTile Therapy: (a) if such net sales for a Measurement Period are $10.0 million or less, 3.0% of such net sales; (b) if such net sales for a Measurement Period are greater than $10.0 million and less than $15.0 million, 4.0% of such net sales; and (c) if such net sales for a Measurement Period are $15.0 million or more, 5.0% of such net sales; and
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with respect to GT Medical’s net sales of GT Medical’s GammaTile Therapy utilizing Cesium-131 brachytherapy seeds: 0.5% of such net sales for a Measurement Period.
As a result of the transaction, we have effectively exited the brachytherapy segment and are focused exclusively on our radiopharmaceutical development segment, our only operating segment and reporting segment. The sale of the brachytherapy segment represents a strategic shift that had a major effect on our operations. We accounted for the transaction as discontinued operations on the date the divestiture was announced. Prior to the consummation of the sale, we were neither actively marketing the brachytherapy business for sale nor had any intentions to abandon it.
Collaborations
License Agreement with the University of Iowa
On June 5, 2018, we entered into a license agreement, as amended in August 2018, November 2019, January 2020, and June 2020, with the University of Iowa Research Foundation (UIRF) for certain patent rights relating to the composition and use of peptide radiopharmaceutical drugs for the treatment of cancer alone or in combination with approved therapies (collectively, the Patent Rights).
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We hold 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)).
The UIRF License is a royalty-bearing license obligating us to pay a percentage of proceeds received from sales of Licensed Products and/or Licensed Process(es) at a rate that we believe is within market parameters for a newly organized preclinical development stage company. We also agreed to share a percentage of our proceeds that we derive from other agreements, like sublicense agreements, relating to Licensed Products and/or Licensed Process(es) that we may enter into in amounts that we also believe is within market parameters for a newly organized preclinical development stage company. In addition to our obligation to pay royalties, we also agreed to pay UIRF a success fee on the execution of a liquidity event (or an initial public offering of our equity) in lieu of milestone payments. We paid the success fee to UIRF in 2023 following the completion of the merger between us and Viewpoint. We are 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. We have 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 we fail to pay any sum that is due and payable to UIRF within 90 days after receiving written notice of our default from UIRF, then UIRF has the option of terminating the UIRF License. UIRF may also terminate the UIRF License in the event we, 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.
The UIRF License also obligates us to meet certain performance and financial milestones. If we fail 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
In December 2023, we 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 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, unless terminated earlier pursuant to the terms of the agreement.
License Agreement with Stony Brook University
In January 2024, we entered into an exclusive in-licensing of Stony Brook University’s CB7-Adma pre-targeting platform which covers global intellectual property rights. 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.
Facilities
Our corporate headquarters are located at 2401 Elliott Avenue, Suite 320, Seattle, WA 98121. In addition, we lease laboratory and office space in Coralville, IA and Somerset, NJ. In December 2022, we completed the purchase of a 20,000 square-foot building in Coralville, IA that has office and laboratory space which is currently used for office and warehouse space.
Our facilities in Coralville, IA include a radiopharmaceutical manufacturing laboratory (750 square feet) for finished product, clinical use radiopharmaceutical production. Additionally, we have built a second production suite that is also approximately 750 square feet, which we anticipate will be operational by mid 2025. The wet labs have bench, hood and radiochemistry equipment and a separate cell-culture room for discovery lab pipeline development.
In July 2024, August 2024 and October 2024, we purchased buildings located in the Houston, TX, Chicago, IL, and Los Angeles, CA, metropolitan areas, respectively, which we intend to use for the manufacture of our program candidates upon completion of modifications and installation of equipment. The square footage of these buildings range between 27,375 square feet and 41,588 square feet.
In March 2024 and August 2024, we acquired the lease of a Lantheus radiopharmaceutical manufacturing facility and assumed a lease from Progenics for office space, respectively, both of which are located in Somerset, NJ.
In April 2024, we completed the divestiture of the brachytherapy division which included the leased production facility located at the Applied Process Engineering Laboratory in Richland, WA. The facility lease transferred to GT Medical at that time.
We believe that our current facilities and CMO relationships are adequate to meet our existing needs.
Suppliers
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We currently obtain our supply of Thorium-228 (228Th) (the precursor to 212Pb) from a single supplier, the U.S. Department of Energy. The amount of 228Th available to us under our agreement with the DoE was sufficient to support our clinical trials in 2024. We expect this supply agreement to be able to support our clinical trials in 2025. We currently utilize one vendor for the manufacture of resin chromatography columns that are used in our 212Pb generators, and we rely on a single vendor to assemble and load isotopes into the generators that are used to extract 212Pb for use in the doses for our clinical trials.
We have identified additional suppliers both domestically and internationally for 228Th who have represented that they are able to meet our quality requirements and purity standards although we do yet have any of these suppliers validated with our supply chain.
Other Agreements
For information related to in-licensing and patent licensing agreements, see the section entitled “Intellectual Property.”
Financial Information About Segments
We previously presented our results in two segments: Drug Operations and Brachytherapy. Due to the sale of our brachytherapy segment to GT Medical in the second quarter of 2024 and the classification of the assets and operations of the brachytherapy segment as discontinued operations in our consolidated financial statements, we have now determined that we operate in only one segment as we report operating results on an aggregate basis to our chief operating decision maker.
Financial Information About Geographic Areas
All of our long-lived assets are located in the United States.
Government Regulation
Our 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, we 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 preclinical 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 preclinical 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.
In addition to the FFDCA, our operations and properties are subject to a variety of other federal and state laws and regulations, including laws and regulations relating to occupational safety and environmental laws, including laws with respect to any air emissions, wastewater discharges, waste disposal and the management of hazardous substances.
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:
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Completion of extensive non-clinical laboratory tests and animal studies in accordance with the FDA’s Good Laboratory Practices (GLP) regulations, applicable requirements for the humane use of laboratory animals, such as the Animal Welfare Act or other applicable regulations;
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Filing an IND with the FDA for human clinical testing, which must become effective before human clinical trials may begin;
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Approval by an independent IRB or ethics committee overseeing each clinical site before each trial may be initiated at that site;
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Designing and conducting adequate and well-controlled human clinical trials in accordance with Good Clinical Practices (GCP) requirements, and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the drug for each proposed indication;
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Submission to the FDA of an application for marketing approval that includes substantial evidence of safety and effectiveness from results of clinical trials, as well as the results of preclinical testing, detailed information about the chemistry, manufacturing and controls, and proposed labeling and packaging for the product candidate;
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Consideration by an FDA Advisory Committee, if applicable;
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Satisfactory completion of potential FDA audits of the preclinical study and clinical trial sites that generated the data in support of the marketing application;
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Determination by the FDA within 60 days of its receipt of a marketing application to accept and file the application for review;
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Satisfactory completion of an FDA pre-approval inspection of the nonclinical, clinical and/or manufacturing sites or facilities at which the active pharmaceutical ingredient, and finished drug product are produced and tested to assess compliance with CGMP;
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Payment of applicable user fees;
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FDA review and approval of the marketing application, including prescribing information, labeling and packaging of the drug program, agreement on post-marketing commitments, if applicable, prior to any commercial marketing or sale of the drug in the United States; and
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Implementation of a Risk Evaluation & Mitigation Strategies (REMS) program, if applicable, and conduct of any required Phase 4 studies, and compliance with post-approval requirements, including ongoing monitoring and reporting of adverse events related to the product.
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 patients 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 the FDA is able to validate the data from the study through an onsite inspection if deemed necessary.
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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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