Perspective Therapeutics Inc

Previous wording

We utilized our TAT platform to discover, design and develop our initial programs, VMT-α-NET and VMT01, which are currently in ongoing Phase 1 clinical trials, and we plan to continue to leverage our platform to assess the potential of and develop multiple additional pipeline programs. Using our proprietary platform technology, VMT-α-NET and VMT01 are engineered to target cancer-specific receptors on tumor cells.

Current wording

We utilized our TAT platform to discover, design and develop our initial programs, VMT-α-NET and VMT01, which are currently in ongoing Phase 1/2a clinical trials, and we plan to continue to leverage our platform to assess the potential of and develop multiple additional pipeline programs. Using our proprietary platform technology, VMT-α-NET and VMT01 are engineered to target cancer-specific receptors on tumor cells.

Previous wording

[212 Pb]VMT-α-NET is a TAT in development for patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2)-expressing tumors who have not previously received peptide-targeted radiopharmaceutical therapy, such as Lutathera. We have initiated dosing in Cohorts 1 and 2 of our Phase 1/2a study of [212 Pb]VMT-α-NET in patients with unresectable or metastatic SSTR2-expressing neuroendocrine tumors (NETs). In April 2024, we announced that this program was selected by the U.S. Food and Drug Administration (FDA) to participate in the Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) Program. FDA’s CDRP Program was initiated in 2022 to facilitate alignment of CMC development of novel products under investigational new drug (IND) applications with expedited clinical development timeframes based upon the anticipated clinical benefits of earlier patient access. During the quarter ended June 30, 2024, the observation period was completed for dose limiting toxicity (DLT) in seven patients enrolled in Cohort 2. Subsequently, the safety monitoring committee (SMC) determined that the safety data observations during the DLT period supported proceeding with dose escalation to Cohort 3, as well as expanding the number of patients for inclusion in Cohort 2 by 40 for a total of up to 47. The protocol amendment to expand the number of patients dosed at 5 mCi has been allowed to proceed, and patient enrollment is open. Data informing the SMC’s recommendation and FDA consultation is expected to be submitted to an upcoming scientific forum in the second half of 2024. Based on FDA interactions prior to the initiation of patient dosing in this study, the decision to open a Cohort 3 would follow after consultation and alignment with the agency, which is expected prior to year end.

Current wording

[212 Pb]VMT-α-NET is a TAT in development for patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2)-expressing tumors who have not previously received peptide-targeted radiopharmaceutical therapy, such as Lutathera. We have initiated dosing in Cohorts 1 and 2 of our Phase 1/2a study of [212 Pb]VMT-α-NET in patients with unresectable or metastatic SSTR2-expressing neuroendocrine tumors (NETs). In April 2024, we announced that this program was selected by the U.S. Food and Drug Administration (FDA) to participate in the Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) Program. The FDA’s CDRP Program was initiated in 2022 to facilitate alignment of CMC development of novel products under investigational new drug (IND) applications with expedited clinical development timeframes based upon the anticipated clinical benefits of earlier patient access. The observation period was completed for dose limiting toxicity (DLT) in seven patients enrolled in Cohort 2 during the second quarter of 2024. Subsequently, the safety monitoring committee (SMC) determined that the safety data observations during the DLT period supported proceeding with dose escalation to Cohort 3. A protocol amendment to expand the number of patients dosed at 5 mCi (up to 40 patients) has been submitted to sites and patient enrollment is open. During the third quarter, data informing the SMC’s recommendations were submitted to and accepted for presentation at the 2024 North American Tumor Society (NANETS) Multidisciplinary NET Medical Symposium taking place November 21-23, 2024 in Chicago. We plan to host a conference call at the start of the conference and will provide details prior to the call. Based on FDA interactions prior to the initiation of patient dosing in this study, the decision to open a Cohort 3 will follow after consultation and alignment with the agency.

Previous wording

On June 10, 2024, we announced six updates featuring our alpha-particle radiopharmaceuticals at the Society of Nuclear Medicine and Molecular Imaging 2024 Annual Meeting. 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 [203 Pb]-VMT-α-NET in neuroendocrine tumors. Investigators analyzed 48 lesions across nine patients, and the results showed that tumor uptake of [203 Pb]-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 [203 Pb] VMT-α-NET at four hours post-injection has the best overall diagnostic performance, followed closely by imaging at one hour.

Current wording

On June 10, 2024, we announced multiple updates featuring our alpha-particle radiopharmaceuticals at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2024 Annual Meeting. 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 [203 Pb]VMT-α-NET in neuroendocrine tumors. Investigators analyzed 48 lesions across nine patients, and the results showed that tumor uptake of [203 Pb]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 [203 Pb]VMT-α-NET at four hours post-injection has the best overall diagnostic performance, followed closely by imaging at one hour.

Previous wording

Additionally, another investigator reported on 212 Pb-VMT-α-NET planning based on 203 Pb-VMT-α-NET predictive dosimetry in an investigator-sponsored trial. The investigators applied patient-specific dosimetry in a Phase 0 imaging trial (NCT05111509) of [203 Pb]VMT-a-NET and in the first cohort of a Phase I absorbed-dose escalation study (NCT06148636) of [212 Pb]VMT-α-NET. Ten patients with β-PRRT-relapsed or refractory gastroenteropancreatic NETs received [203 Pb]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 ten patients received amino acid infusions while seven patients did not receive amino acids.

Current wording

Also at SNMMI, an investigator reported on [212 Pb]VMT-α-NET planning based on [203 Pb]VMT-α-NET predictive dosimetry in an investigator-sponsored trial. The investigators applied patient-specific dosimetry in a Phase 0 imaging trial (NCT05111509) of [203 Pb]VMT-a-NET and in the first cohort of a Phase 1 absorbed-dose escalation study (NCT06148636) of [212 Pb]VMT-α-NET. Ten patients with β-peptide receptor radionuclide therapy (PRRT)-relapsed or refractory gastroenteropancreatic (GEP)-NETs received [203 Pb]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 ten patients received amino acid infusions while seven patients did not receive amino acids.

Previous wording

The lead investigator reported on an exploratory first-in-human use of [212 Pb]VMT-α-NET in adult patients with histologically confirmed metastatic NETs and medullary thyroid carcinomas in an investigator-led research study in India. The investigator reported updated safety and anti-tumor activity of [212 Pb]VMT-α-NET administered at 2.5 MBq/kg every eight weeks in 13 patients as of the data cut-off date of May 31, 2024. All patients received prior treatments, eight of whom received prior peptide receptor radionuclide therapy (PRRT) treatment. Six patients remained eligible for further treatments as of the data cut-off date.

Current wording

Additionally at SNMMI, the lead investigator reported on an exploratory first-in-human use of [212 Pb]VMT-α-NET in adult patients with histologically confirmed metastatic NETs and medullary thyroid carcinomas in an investigator-led research study in India. The investigator reported updated safety and anti-tumor activity of [212 Pb]VMT-α-NET administered at 67 µCi/kg (2.5 MBq/kg) every eight weeks in 13 patients as of the data cut-off date of May 31, 2024. All patients received prior treatments, eight of whom received prior PRRT treatment. Six patients remained eligible for further treatments as of the data cut-off date.

Previous wording

The investigator concluded that the toxicity profile suggests 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 thirteen 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.

Current wording

The investigator concluded that the toxicity profile suggests 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.

Previous wording

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

Current wording

In March 2024, we entered into a clinical trial collaboration with Bristol Myers Squibb to evaluate the safety and tolerability of [212 Pb]VMT01 in combination with Bristol Myers Squibb’s checkpoint inhibitor nivolumab in patients with histologically confirmed melanoma and positive MC1R imaging scans. A protocol amendment was submitted in July 2024 to explore the combination of nivolumab with [212 Pb]VMT01 in patients with histologically confirmed melanoma and positive MC1R imaging scans in our ongoing Phase 1/2a clinical study of [212 Pb]VMT01.

Previous wording

In March 2024, we disclosed a novel pre-IND stage asset (PSV359) that targets fibroblast activation protein-α, which is associated with a variety of solid tumors. We are currently working on an IND which we expect to file in late 2024. If the study may proceed, we expect that the U.S. Phase 1 study would commence in 2025.

Current wording

In March 2024, we disclosed a novel pre-IND stage asset (PSV359) that targets fibroblast activation protein-α, which is associated with a variety of solid tumors. We are currently working on an IND for PSV359 which we expect to file in late 2024. If the study may proceed, we expect that the U.S. Phase 1 study would commence in 2025.

Previous wording

Researchers also presented a novel cyclic peptide targeting human fibroblast activation protein (FAP), which was discovered by us via phage display methods. FAP 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 Pb-specific chelator via a molecular linker to form a novel construct, PSV-359. The purpose of this study was to evaluate the in vitro and in vivo performance of [203/212 Pb]PSV-359 in preclinical xenograft models. Overall, strong anti-tumor clinical activity of [212 Pb]PSV-359 was found in both FAP on cancer cells and FAP in stromal tissues xenograft models.

Current wording

On June 10, 2024, at the Society of Nuclear Medicine and Molecular Imaging 2024 Annual Meeting, researchers presented a novel fibroblast activation protein (FAP), 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. The peptide was conjugated to a Pb-specific chelator via a molecular linker to form a novel construct, PSV359. The purpose of this study was to evaluate thein vitro andin vivo performance of [203/212 Pb]PSV359 in preclinical xenograft models. Overall, strong anti-tumor clinical activity of [212 Pb]PSV359 was found in both FAP on cancer cells and FAP in stromal tissues xenograft models.

Previous wording

Pre-targeting technology enabling the use of antibodies to direct radiolabeled ligands to tumor sites. Antibodies can bind with high specificity to a wider variety of cancer-specific proteins preferentially expressed on the surface of tumor cells. However, the amount of time required for an adequate amount of antibodies to bind to the cancer-specific proteins may not align with the properties of the desired isotope. By attaching an additional chemical entity to an antibody that would bind to a radioligand, the resultant modified antibodies may be administered separately from and in advance of the radioligand as appropriate. Preclinical optimization of this platform is underway, and initial targeting antibodies have been identified for further investigation.

Current wording

Pre-targeting technology is designed to enable the use of antibodies to direct radiolabeled ligands to tumor sites. Antibodies can bind with high specificity to a wider variety of cancer-specific proteins preferentially expressed on the surface of tumor cells. However, the amount of time required for an adequate amount of antibodies to bind to the cancer-specific proteins may not align with the properties of the desired isotope. By attaching an additional chemical entity to an antibody that would bind to a radioligand, the resultant modified antibodies may be administered separately from and in advance of the radioligand as appropriate. Preclinical optimization of this platform is underway, and initial targeting antibodies have been identified for further investigation.

Previous wording

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

Current wording

Also in January 2024, we entered into an exclusive in-licensing of Stony Brook University’s Cuburbit[7]uril-admantane (CB7-Adma) pre-targeting platform which covers the global intellectual property rights to such platform. 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 remarkable specificity, delivering radiation dose selectively to the tumor sites. Central to this innovation is CB7-Adma (host-guest) complex formation, driving the interaction between the antibody and radioligand. The chosen host-guest pair, CB7-Adma, demonstrates promising in vivo stability, modularity and low immunogenicity. The platform’s potential was validated through in vivo profiling of ligands, employing a CB7-modified CEA targeting antibody. The agreement with Stony Brook University will expire on the later of the expiration date of the last to expire licensed patents or 20 years from the date of the first sale of a product utilizing the intellectual property.

Previous wording

continue to build our manufacturing capabilities through facility acquisitions;

Current wording

continue to build our manufacturing capabilities;

Previous wording

As of June 30, 2024, we had cash, cash equivalents and short-term investments of $292.9 million. We believe our cash, cash equivalents and short-term investments will be sufficient to fund our current planned operations for at least the next 12 months from the date the consolidated financial statements in this report were issued and into mid-2026. Monthly operating expenses are budgeted to increase for research and development and general and administrative expenses in 2024 as management works to implement its strategy to advance our two clinical assets, VMT01 and VMT-α-NET, in their clinical trials and to progress our preclinical assets towards clinical trials. Management anticipates a significant increase in expenses, particularly in research and development, as it undertakes these activities in 2024.

Current wording

As of September 30, 2024, we had cash, cash equivalents and short-term investments of $267.8 million. We believe our cash, cash equivalents and short-term investments will be sufficient to fund our current planned operations for at least the next 12 months from the date the consolidated financial statements in this report were issued and into mid-2026. Monthly operating expenses are budgeted to increase for research and development and general and administrative expenses as management works to implement its strategy to advance our clinical assets in their clinical trials and to progress our preclinical assets towards clinical trials. Management anticipates a significant increase in expenses, particularly in research and development, as we undertake these activities.

Previous wording

On July 15, 2024 and August 2, 2024, we purchased a building located in Houston, Texas, for $4.7 million and a building in Chicago, Illinois, for $5.0 million, respectively, which we intend to use for the manufacture of our program candidates upon completion of modifications and installation of equipment.

Current wording

On July 15, 2024, August 2, 2024 and October 31, 2024, we purchased a building located in the Houston, Texas, metropolitan area for $4.7 million, a building in the Chicago, Illinois, metropolitan area for $5.0 million, and a building in the Los Angeles, California, 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.

Previous wording

In March 2024, we acquired the assets and associated lease of Lantheus’ radiopharmaceutical manufacturing facility in Somerset, New Jersey. We believe we will be able to convert the facility, which has three production suites, to manufacture finished radiopharmaceutical product. As a Current Good Manufacturing Practice (CGMP) compliant facility, we intend to utilize the facility to manufacture clinical supply of high quality 203 Pb-labeled tumor-specific peptides to visualize and diagnose tumors, and 212 Pb-labeled radiopharmaceuticals to treat target tumors with TAT. Moreover, with its three CGMP suites at the facility, we expect to have the capacity to meet future clinical trial and commercial demands at major cancer treatment centers throughout the Northeastern U.S. We intend to continue to expand our manufacturing and supply network during 2024 as we anticipate increasing our clinical trial activities.

Current wording

In March 2024, we acquired the assets and associated lease of Lantheus’ radiopharmaceutical manufacturing facility in Somerset, New Jersey. We believe we will be able to convert the facility, which has three production suites, to manufacture finished radiopharmaceutical product. As a Current Good Manufacturing Practice (CGMP) compliant facility, we intend to utilize the facility to manufacture clinical supply of high quality 203 Pb-labeled tumor-specific peptides to visualize and diagnose tumors, and 212 Pb-labeled radiopharmaceuticals to treat target tumors with TAT. As of October 2024, this facility is operational to supply investigational products to support VMT-α-NET clinical studies, in addition to the Coralville, Iowa facility which has been producing our investigational products since 2023. Moreover, with three CGMP suites at the facility, we expect to have the capacity to meet future clinical trial and commercial demands at major cancer treatment centers throughout the Northeastern U.S. We intend to continue to expand our manufacturing and supply network in the future as we anticipate increasing our clinical trial activities.

Previous wording

We continue to seek other facilities as we look to expand our research and development capabilities.

Current wording

We continue to evaluate the suitability of additional facilities as we look to expand our research and development capabilities.

Previous wording

On May 31, 2024, we held our 2024 Annual Meeting of Stockholders (Annual Meeting). At the Annual Meeting, our stockholders approved our Third Amended and Restated 2020 Equity Incentive Plan (the Amended and Restated Plan) which, among other things, (a) increased the aggregate number of shares of Common Stock authorized for issuance under the Amended and Restated Plan by 4,870,092 for a total of 12,500,000 shares of Common Stock, and (b) adjusted the “evergreen” provision included therein, such that the number of shares of Common Stock available for the grant of awards under the Amended and Restated Plan will automatically increase on January 1 of each year in an amount equal to 5% of the number of shares of Common Stock issued and outstanding on December 31 of the immediately preceding year (subject to adjustment in the event of stock splits and other similar events); provided, however, that our Board of Directors may act prior to January 1 of a given year to provide that there will be no increase in the share limit for such year or provide that the increase for such year will be a lesser number of shares of Common Stock.

Current wording

On May 31, 2024, we held our 2024 Annual Meeting of Stockholders (Annual Meeting). At the Annual Meeting, our stockholders approved our Third Amended and Restated 2020 Equity Incentive Plan (the Amended and Restated Plan) which, among other things, (a) increased the aggregate number of shares of Common Stock authorized for issuance under the Amended and Restated Plan by 4,870,092 for a total of 12,500,000 shares of Common Stock, and (b) adjusted the “evergreen” provision included therein, such that the number of shares of Common Stock available for the grant of awards under the Amended and Restated Plan will automatically increase on January 1 of each year in an amount equal to 5% of the number of shares of Common Stock issued and outstanding on December 31 of the immediately preceding year (subject to adjustment in the event of stock splits and other similar events); provided, however, that our Board of Directors may act prior to January 1 of a given year to provide that there will be no increase in the share limit for such year or provide that the increase for such year will be a lesser number of shares of Common Stock. On August 14, 2024, we filed a Form S-8 to register 4,870,092 additional shares of Common Stock authorized for issuance under the Amended and Restated Plan as approved by stockholders at the Annual Meeting.

Previous wording

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 million or less, 3.0% of such net sales; (b) if such net sales for a Measurement Period are greater than $10 million and less than $15 million, 4.0% of such net sales; and (c) if such net sales for a Measurement Period are $15 million or more, 5.0% of such net sales; and

Current wording

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

Previous wording

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 million, before underwriting discounts and commissions and expenses associated with the Registered Offering.

Current wording

On May 24, 2024, we entered into an underwriting agreement with BofA Securities, Inc., as representative of the underwriters named therein, in connection with its 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.