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What changed in PMV Pharmaceuticals, Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of PMV Pharmaceuticals, Inc.'s 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+366 added−347 removedSource: 10-K (2025-03-03) vs 10-K (2024-02-29)

Top changes in PMV Pharmaceuticals, Inc.'s 2024 10-K

366 paragraphs added · 347 removed · 288 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

84 edited+19 added−12 removed233 unchanged
Biggest changeIn July 2022, we announced a clinical collaboration agreement with Merck to evaluate the combination of PC14586 and Merck’s anti-PD1 antibody, KEYTRUDA (pembrolizumab), in patients with advanced solid tumors in patients with a p53 Y220C mutation. This study is being conducted as a separate Phase 1b arm of our ongoing Phase 1/2 PYNNACLE trial in patients with advanced solid tumors.
Biggest changeWe also expect to provide interim data on the Phase 2 monotherapy registrational portion of the PYNNACLE trial by mid-2025. In October 2024, we discontinued enrollment in the Phase 1b combination arm of the PYNNACLE trial evaluating rezatapopt in combination with Merck and Co.’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors harboring a TP53 Y220C 2 mutation.
The widespread recognition that cancer is a genetic disease, as much as it is a disease defined by histology or anatomical location, has driven the increased use of genetic sequencing, which is now employed by approximately 75% of oncologists in the United States. As DNA sequencing technology advances, the availability of well-defined genomic sequencing tests increases.
The widespread recognition that cancer is a genetic disease, as much as it is a disease defined by histology or anatomical location, has driven the increased use of genomic sequencing, which is now employed by approximately 75% of oncologists in the United States. As DNA sequencing technology advances, the availability of well-defined genomic sequencing tests increases.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters or untitled letters; • clinical holds on clinical studies; 16 • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; • consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; • mandated modification of promotional materials and labeling and the issuance of corrective information; • the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters or untitled letters; • clinical holds on clinical studies; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; • consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs; 16 • mandated modification of promotional materials and labeling and the issuance of corrective information; • the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or • injunctions or the imposition of civil or criminal penalties.
The process required by the FDA before a drug may be marketed in the United States generally involves the following: • completion of preclinical laboratory tests, animal studies and formulation studies in accordance with FDA’s good laboratory practice requirements and other applicable regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • approval by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before each trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with good clinical practice, or GCP, requirements to establish the safety and efficacy of the proposed drug for its intended use; • submission to the FDA of an NDA after completion of all pivotal trials; • determination by the FDA within 60 days of its receipt of an NDA to accept the filing for substantive review; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and of selected clinical investigation sites to assess compliance with GCP requirements; and • FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the United States.
The process required by the FDA before a drug may be marketed in the United States generally involves the following: • completion of preclinical laboratory tests, animal studies and formulation studies in accordance with FDA’s good laboratory practice requirements and other applicable regulations; • submission to the FDA of an IND, which must become effective before human clinical trials may begin; • approval by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before each trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with good clinical practice, or GCP, requirements to establish the safety and efficacy of the proposed drug for its intended use; • submission to the FDA of an new drug application, or NDA, after completion of all pivotal trials; • determination by the FDA within 60 days of its receipt of an NDA to accept the filing for substantive review; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and of selected clinical investigation sites to assess compliance with GCP requirements; and • FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the United States.
We believe integrating responsible environmental, social, and governance principles into our corporate strategy will drive sustainable value creation for our shareholders, employees, patients, and caregivers over the long term. We have formed an internal ESG Working Group with cross-functional senior leadership that meets periodically, with oversight by the nominating and corporate governance committee of our board of directors.
We believe integrating responsible environmental, social, and governance principles into our corporate strategy will drive sustainable value creation for our shareholders, employees, patients, and caregivers over the long term. We have formed an internal ESG Working Group with cross-functional senior leadership that meets periodically, with oversight by the 23 nominating and corporate governance committee of our board of directors.
We believe we are well positioned to leverage our deep experience in p53 biology, precision oncology platform and foundational knowledge acquired through our lead program to bring these therapies to patients. The critical components of our strategy include: • Advancing our lead product candidate, PC14586 (rezatapopt), as a tumor-agnostic, oral small molecule therapy for cancer patients .
We believe we are well positioned to leverage our deep experience in p53 biology, precision oncology platform and foundational knowledge acquired through our lead program to bring these therapies to patients. The critical components of our strategy include: • Advancing our lead product candidate, rezatapopt, as a tumor-agnostic, oral small molecule therapy for cancer patients .
The Food and Drug Omnibus Reform Act made several changes to the FDA’s authorities and its regulatory framework, including, among other changes, reforms to the accelerated approval pathway, such as requiring the FDA to specify conditions for post-approval study requirements and setting forth procedures for the FDA to withdraw a product on an expedited basis for non-compliance with post-approval requirements.
The Food and Drug Omnibus Reform Act made several changes to the FDA’s authorities and its regulatory framework, including, among other changes, reforms to the accelerated approval pathway, such as requiring the FDA to specify conditions 15 for post-approval study requirements and setting forth procedures for the FDA to withdraw a product on an expedited basis for non-compliance with post-approval requirements.
In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. In Catalyst Pharms., Inc. v.
In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. 17 In Catalyst Pharms., Inc. v.
With the increasing number of approved targeted therapies, we believe that 4 physicians will seek a better understanding of the underlying genetic and protein abnormalities associated with a specific type of cancer in order to determine the optimal course of treatment. Advances in genomic sequencing are leading to transformations in the discovery and development of new targeted oncology drugs.
With the increasing number of approved targeted therapies, we believe that physicians will seek a better understanding of the underlying genetic and protein abnormalities associated with a specific type of cancer in order to determine the optimal course of treatment. Advances in genomic sequencing are leading to transformations in the discovery and development of new targeted oncology drugs.
The availability of an oral small molecule selective for the p53 Y220C mutation may offer a novel precision therapy for this population, which we believe could potentially change the treatment paradigm for such patients. Clinical Development Plan of PC14586 (rezatapopt) We initiated a Phase 1/2 clinical trial, PYNNACLE, for PC14586 in October 2020.
The availability of an oral small molecule selective for the p53 Y220C mutation may offer a novel precision therapy for this population, which we believe could potentially change the treatment paradigm for such patients. Clinical Development Plan of Rezatapopt We initiated a Phase 1/2 clinical trial, PYNNACLE, for rezatapopt in October 2020.
The vast majority of these mutations occur as a result of missense mutations that are found in the DNA binding domain. p53 Y220C mutations are found in approximately 1.0% of all cancers. This particular mutation is expressed in a large variety of solid tumors, including breast, NSCLC, colorectal, pancreatic and ovarian cancers.
The vast majority of these mutations occur as a result of missense mutations that are found in the DNA binding domain. P53 Y220C mutations are found in approximately 1% of all cancers. This particular mutation is expressed in a large variety of solid tumors, including breast, NSCLC, colorectal, pancreatic and ovarian cancers.
The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace.
The FDA also may condition approval on, among other things, changes to proposed 14 labeling or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace.
As a condition of approval, the FDA may require 15 that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials. In addition, the FDA currently requires pre-approval of promotional materials as a condition for accelerated approval, which could adversely impact the timing of the commercial launch of the product.
As a condition of approval, the FDA may require that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials. In addition, the FDA currently requires pre-approval of promotional materials as a condition for accelerated approval, which could adversely impact the timing of the commercial launch of the product.
If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not approvable letter. A not approvable letter will outline the deficiencies in the application and, where practical, will identify what is necessary to make the PMA approvable.
If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not approvable letter. A 22 not approvable letter will outline the deficiencies in the application and, where practical, will identify what is necessary to make the PMA approvable.
If PC14586 (rezatapopt) or our future product candidates do not offer sustainable advantages over competing products, we may otherwise not be able to successfully compete against current and future competitors.
If rezatapopt or our future product candidates do not offer sustainable advantages over competing products, we may otherwise not be able to successfully compete against current and future competitors.
Our lead product candidate, PC14586 (rezatapopt), is an orally available small molecule designed to potently and selectively correct p53 misfolding caused by a specific p53 mutation, Y220C, while sparing wild-type p53. The p53 Y220C mutation is associated with approximately 1.0% of all cancers, including breast, non-small cell lung cancer, or NSCLC, colorectal, pancreatic and ovarian cancers.
Our lead product candidate, rezatapopt, is an orally available small molecule designed to potently and selectively correct p53 misfolding caused by a specific p53 mutation, Y220C, while sparing wild-type p53. The p53 Y220C mutation is associated with approximately 1% of all cancers, including breast, non-small cell lung cancer, or NSCLC, colorectal, pancreatic and ovarian cancers.
We have designed PC14586 to be an orally available, tumor-agnostic therapeutic and, if approved, we believe it could become the first agent to address the p53 Y220C mutation-defined patient population. In October 2020, we initiated a Phase 1/2 clinical trial for PC14586 in multiple solid tumors with the p53 Y220C mutation.
We have designed rezatapopt to be an orally available, tumor-agnostic therapeutic and, if approved, we believe it could become the first agent to address the p53 Y220C mutation-defined patient population. In October 2020, we initiated a Phase 1/2 clinical trial for rezatapopt in multiple solid tumors with the p53 Y220C mutation.
This time period is significantly reduced compared to conventional drug development timelines. Despite this progress, a recent analysis found that only 16% of patients with metastatic cancer have tumors with genetic profiles eligible for treatment with an approved targeted agent, which leaves a large opportunity for precision oncology.
This time period is significantly reduced compared to conventional drug development timelines. Despite this progress, a recent analysis found that only 16% of patients with metastatic cancer have tumors with genomic profiles eligible for treatment with an approved targeted agent, which leaves a large opportunity for precision oncology.
In January 2024, FDA announced its plans to reclassify certain high-risk of in vitro diagnostics s, including companion diagnostics, as Class II devices.
In January 2024, FDA announced its plans to reclassify certain high-risk of in vitro diagnostics, including companion diagnostics, as Class II devices.
PC14586 is designed to restore the wild-type conformation by occupying the pocket created by the tyrosine to cysteine mutation in amino acid position 220. We are pursuing a tumor-agnostic development strategy and initiated a Phase 1/2 clinical trial, PYNNACLE, in October 2020.
Rezatapopt is designed to restore the wild-type conformation by occupying the pocket created by the tyrosine to cysteine mutation in amino acid position 220. We are pursuing a tumor-agnostic development strategy and initiated a Phase 1/2 clinical trial, PYNNACLE, in October 2020.
It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA and our business. Other legislative changes have been proposed and adopted since the ACA was enacted.
It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear how such challenges and the healthcare reform measures of the Trump administration will impact the ACA and our business. Other legislative changes have been proposed and adopted since the ACA was enacted.
Third line therapies can include chemotherapy, antibody drugs and small molecule tumor-targeted therapies, more invasive forms of surgery and new technologies. 5 PC14586 (rezatapopt): A Selective Structural Corrector of p53 Y220C Mutations p53 is the most widely mutated gene in human cancers.
Third line therapies can include chemotherapy, antibody drugs and small molecule tumor-targeted therapies, more invasive forms of surgery and new technologies. Rezatapopt: A Selective Structural Corrector of p53 Y220C Mutations P53 is the most widely mutated gene in human cancers.
We believe that these approvals represent a fundamental shift in the development of targeted therapies and will increasingly lead to cancer being characterized for treatment in a genetic, rather than in a tumor-specific, manner, based on a biological rationale.
We believe that these approvals represent a fundamental shift in the development of targeted therapies and will increasingly lead to cancer being characterized for treatment in a genomic, rather than in a tumor-specific, manner, based on a biological rationale.
We face competition with respect to our current product candidates and will face competition with respect to future product candidates, from segments of the pharmaceutical, biotechnology and other related markets that pursue targeted therapies for patients with genetically-defined cancers.
We face competition with respect to our current product candidates and will face competition with respect to future product candidates, from segments of the pharmaceutical, biotechnology and other related markets that pursue targeted therapies for patients with genomically-defined cancers.
Though PC14586 has demonstrated clear and robust tumor regression as a single agent in preclinical animal models and clinical proof of concept, we believe that the mechanism of correcting the structure of mutant 3 p53 can be complementary to other oncology therapies.
Though rezatapopt has demonstrated clear and robust tumor regression as a single agent in preclinical animal models and clinical proof of concept, we believe that the mechanism of correcting the structure of mutant p53 can be complementary to other oncology therapies.
The majority of adverse events were mild or moderate (Grade 1 or 2) in severity with the most frequent adverse events being nausea, vomiting, aspartate transaminase (AST)/alanine transaminase (ALT) increase, anemia, blood creatinine increase and fatigue.
The majority of adverse events were mild or moderate (Grade 1 or 2) in severity with the most frequent adverse events being nausea, vomiting, aspartate transaminase, or AST,/alanine transaminase, or ALT, increase, anemia, blood creatinine increase and fatigue. Phase 2 and Combination Studies.
For example, Retevmo in RET-altered NSCLC and thyroid cancers (Lilly/Loxo); Ayvakit, in platelet-derived growth factor receptor alpha exon 18 mutated advanced gastrointestinal stromal tumor, or GIST (Blueprint); Rozlytrek, in solid tumors with a neurotrophic tropomyosin receptor kinase, or NTRK, gene fusion (Roche); Vitrakvi, in solid tumors with an NTRK gene fusion (Loxo/Bayer); Zykadia, in anaplastic lymphoma kinase-positive, or ALK+, advanced NSCLC (Novartis); Zelboraf, in advanced melanoma with a BRAF V600E mutation (Roche Genentech); Xalkori, in ALK+ advanced NSCLC (Pfizer); Tagrisso, in epidermal growth factor receptor mutation-positive, or EGFR+, advanced NSCLC (AstraZeneca); Qinlock, in GIST (Deciphera), and Krazati and Lumakras in KRAS G12C mutated NSCLC (Mirati and Amgen) all received approvals within five years of first dosing in humans.
For example, Retevmo in RET-altered NSCLC and thyroid cancers (Lilly/Loxo); Ayvakit, in platelet-derived growth factor receptor alpha exon 18 mutated advanced gastrointestinal stromal tumor, or GIST (Blueprint); Rozlytrek, in solid tumors with a neurotrophic tropomyosin receptor kinase, or NTRK, gene fusion (Roche); Vitrakvi, in solid tumors with an NTRK gene fusion (Loxo/Bayer); Zykadia, in anaplastic lymphoma kinase-positive, or ALK+, advanced NSCLC (Novartis); Zelboraf, in advanced melanoma with a BRAF V600E mutation (Roche Genentech); Xalkori, in ALK+ advanced NSCLC (Pfizer); Tagrisso, in epidermal growth factor receptor mutation-positive, or EGFR+, advanced NSCLC (AstraZeneca); Qinlock, in GIST (Deciphera); Krazati and Lumakras in KRAS G12C mutated NSCLC (Mirati and Amgen); Augtyro in ROS1 positive NSCLC tumors (Turning Point); and Bizengri in NSCLC and pancreatic tumors with a NRG1-positive gene fusion (Merus) all received approvals within five years of first dosing in humans.
For our lead product candidate, PC14586, we are actively working with physicians and leading clinical trial institutions to enroll patients with the p53 Y220C mutation identified via NGS in our Phase 1/2 clinical trial.
For our lead product candidate, rezatapopt, we are actively working with physicians and leading clinical trial institutions to enroll patients with the p53 Y220C mutation identified via NGS in our Phase 2 clinical trial.
Our ESG Work Group oversees our sustainability efforts, and we have documented our initiatives in our inaugural 2022 ESG Highlights Report, which is available on our website at ir.pmvpharma.com. The content provided in our 2022 ESG Highlights Report or accessible through our website is not incorporated by reference as part of this Annual Report on Form 10-K.
Our ESG Working Group oversees our sustainability efforts, and we have documented our initiatives in our 2024 ESG Highlights Report, which is available on our website at ir.pmvpharma.com. The content provided in our 2024 ESG Highlights Report or accessible through our website is not incorporated by reference as part of this Annual Report on Form 10-K.
Best response of stable disease (SD) or confirmed partial response was observed in 14 of the 16 patients (88%). 6 PC14586 was observed to be generally well-tolerated (across 67 patients treated with PC14586 monotherapy as of September 5, 2023).
Best response of SD or confirmed partial response was observed in 14 of the 16 patients (88%). 6 Rezatapopt was observed to be generally well-tolerated (across 67 patients treated with rezatapopt monotherapy as of September 5, 2023).
In addition, we were granted FDA Fast Track designation of PC14586 for the treatment of patients with locally advanced or metastatic solid tumors with a p53 Y220C mutation in October 2020. We dosed our first patient in this clinical trial in the fourth quarter of 2020.
In addition, we were granted FDA Fast Track designation of rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors with a p53 Y220C mutation in October 2020. We dosed our first patient in this clinical trial in the fourth quarter of 2020. Phase 1 Completion.
We are also aware of selective small molecule inhibitors that are designed to target wild-type p53 containing tumors through the p53-MDM2 interaction, which are in various stages of clinical development being tested by Aileron Therapeutics, Ascentage Pharma, Boehringer Ingelheim, Daiichi Sankyo (out-licensed worldwide rights to Rain Therapeutics), Kartos Therapeutics, Kymera Therapeutics, Otsuka Pharmaceutical, Novartis and Roche, including testing MDM2 inhibitors in combination with a variety of other anti-cancer agents.
We are also aware of selective small molecule inhibitors that are designed to target wild-type p53 containing tumors through the p53-MDM2 interaction, which are in various stages of clinical development being tested by Aileron Therapeutics, Ascentage Pharma, Boehringer Ingelheim, Kartos Therapeutics, Kymera Therapeutics, Otsuka Pharmaceuticals, Novartis and Roche, including testing MDM2 inhibitors in combination with a variety of other anti-cancer agents.
If we obtain early and encouraging clinical results, we may seek breakthrough therapy designation from the FDA, which, if granted, is intended to expedite clinical development and regulatory review. We intend to maximize the benefit of our product candidates by pursuing a tumor-agnostic approach. • Identifying and exploring combination therapy approaches for our product candidates .
Based on our encouraging PYNNACLE clinical results, we plan to seek breakthrough therapy designation from the FDA for rezatapopt, which, if granted, is intended to expedite clinical development and regulatory review. We intend to maximize the benefit of our product candidates by pursuing a tumor-agnostic approach. • Identifying and exploring combination therapy approaches for our product candidates .
For example, there are now multiple tumor-agnostic product approvals that are based on a genetic mutation that defines the disease, as opposed to the tumor type. These include the aforementioned Vitrakvi and Rozlytrek approvals as well as KEYTRUDA and Jemperli, respectively, approval in metastatic microsatellite instability-high, or MSI-high, or deficient mismatch repair, or dMMR, solid tumors.
For example, there are now multiple tumor-agnostic product approvals that are based on a genomic mutation that defines the disease, as opposed to the tumor type. These include the aforementioned Vitrakvi, Rozlytrek and Augtyro approvals in NTRK gene fusion-positive solid tumors as well as KEYTRUDA and Jemperli, respectively, approval in metastatic microsatellite instability-high or deficient mismatch repair solid tumors.
We also evaluated patients at the recommended Phase 2 dose of 2000 mg QD. Among the 16 patients treated at the recommended Phase 2 dose level, confirmed partial responses were observed per investigator assessment (RECIST v1.1) in 6 patients (38%) across multiple tumor types, including those noted above.
Among the 16 patients treated at the recommended Phase 2 dose level, confirmed partial responses were observed per investigator assessment (RECIST v1.1) in 6 patients (38%) across multiple tumor types, including those noted above.
Corporate Information We were incorporated in Delaware in March 2013 under the name “PJ Pharmaceuticals, Inc.” In July 2013, we changed our name to “PMV Pharmaceuticals, Inc.” Our principal executive offices are located at 1 Research Way, Princeton, New Jersey 08540. Our telephone number is (609) 642-6670. Our website address is www.pmvpharma.com.
Corporate Information We were incorporated in Delaware in March 2013 under the name “PJ Pharmaceuticals, Inc.” In July 2013, we changed our name to “PMV Pharmaceuticals, Inc.” Our principal executive offices are located at 400 Alexander Park Drive, Suite 301, Princeton, New Jersey 08540. Our telephone number is (609) 642-6670. Our website address is www.pmvpharma.com.
KEYTRUDA is also approved in tumor mutational burden-high-(TMB-H) solid tumors. In addition, the combination of Taflinar and Mekinist was approved for BRAF V600E mutation positive unresectable or metastatic solid tumors (with the exception of colorectal cancer).
KEYTRUDA is also approved in tumor mutational burden-high-(TMB-H) solid tumors. In addition, the combination of Taflinar and Mekinist was approved for BRAF V600E mutation positive unresectable or metastatic solid tumors (with the exception of colorectal cancer). In addition, Retevmo was approved for RET gene fusion-positive solid tumors and Enhertu was approved for HER2-Positive (IHC 3+) unresectable or metastatic solid tumors.
We are aware of molecules in development that also are being explored for p53 upregulation/activation in various stages of preclinical or clinical development being tested by Jacobio Pharmaceuticals, among others.
We are aware of molecules in development that also are being explored for p53 upregulation/activation in various stages of preclinical or clinical development being tested by Jacobio Pharmaceuticals, Frontier Medicines, Nutshell Therapeutics, Scorpion Therapeutics and AstraZeneca, among others.
In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. 13 While the IND is active and before approval, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.
While the IND is active and before approval, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans and any clinically important 13 increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.
The FDA also may inspect foreign facilities that export products to the United States. Employees and Human Capital Resources As of February 29, 2024, we had 63 full-time employees, including 24 employees with Ph.D., M.D. or Pharm.D. degrees. Of these full-time employees, 50 employees are engaged in research and development activities.
The FDA also may inspect foreign facilities that export products to the United States. Employees and Human Capital Resources As of March 3, 2025 , we had 47 full-time employees, including 14 employees with Ph.D., M.D. or Pharm.D. degrees. Of these full-time employees, 36 employees are engaged in research and development activities.
The six issued US patents are expected to expire between 2037 and 2041, without taking into account any possible patent term adjustment or extensions.
The nine issued U.S. patents are expected to expire between 2037 and 2043, without taking into account any possible patent term adjustment or extensions.
We expect to initially seek approval of our product candidates in most instances, including with PC14586 (rezatapopt), at least as a second line therapy or for patients with no satisfactory alternative treatments or where the cancer has progressed following other treatment.
(3) In IND-Enabling Studies, we conduct preclinical studies, in accordance with GLP required for an IND submission to the FDA. We expect to initially seek approval of our product candidates in most instances, including with rezatapopt, at least as a second line therapy or for patients with no satisfactory alternative treatments or where the cancer has progressed following other treatment.
A recent study found that 75% of oncologists in the United States employ genetic sequencing. We believe p53 mutations are particularly well-suited for the evolving precision oncology paradigm, as a single mutation can cause p53 malfunction, and p53 is one of the genes commonly sequenced in NGS panels.
We believe p53 mutations are particularly well-suited for the evolving precision oncology paradigm, as a single mutation can cause p53 malfunction, and p53 is one of the genes commonly sequenced in NGS panels.
In October 2023, we provided an update on the Phase 1 portion of the Phase 1/2 trial at the 2023 American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC) International Conference on Molecular Targets and Cancer Therapeutics Annual Meeting.
In October 2023, we presented our updated Phase 1 clinical data for rezatapopt at the 2023 American Association for Cancer Research, or AACR, the National Cancer Institute, or NCI, and the European Organisation for Research and Treatment of Cancer, or EORTC, International Conference on Molecular Targets and Cancer Therapeutics Annual Meeting.
In October 2023, we presented our updated Phase 1 clinical data at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Meeting and we continue to enroll patients in this trial. The pivotal Phase 2 monotherapy portion of our PYNNACLE trial is planned to be initiated in the first quarter of 2024.
In October 2023, we presented our updated Phase 1 clinical data for rezatapopt at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Meeting. We dosed our first patient in the pivotal Phase 2 monotherapy portion of the PYNNACLE study in the first quarter of 2024.
These changes include aggregate reductions to Medicare payments to providers of 2% per fiscal year, effective April 1, 2013, which will remain in effect through 2032, unless additional Congressional action is taken. 20 Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted legislation designed, among other things, to bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for pharmaceutical products.
Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted legislation designed, among other things, to bring more transparency to product pricing, 20 review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for pharmaceutical products.
We initiated a Phase 1/2 clinical trial for PC14586 in October 2020. In addition, we were granted FDA Fast Track designation of PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation in October 2020. We dosed our first patient in this clinical trial in the fourth quarter of 2020.
In October 2020, we were granted FDA Fast Track designation of rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation.
In the efficacious dose range, confirmed partial responses were observed per investigator assessment (RECIST v1.1) in 13 patients (34%) across multiple different tumor types including breast, endometrial, ovarian and small cell lung. Best response of stable disease (SD) or confirmed partial response was observed in 33 of the 38 patients (87%) in the efficacious dose range.
In the efficacious dose range, confirmed partial responses were observed per investigator assessment (RECIST v1.1) in 13 patients (34%) across multiple different tumor types including breast, endometrial, ovarian, small cell lung and prostate cancer. After the data cutoff date, a confirmed partial response was also observed in a head and neck cancer patient.
Diagnostic tests are currently used by physicians in their practice to identify patients with p53 mutations. Given the high prevalence of p53 mutations in cancers, we believe that an effective way to address p53-driven cancers is by targeting individual p53 mutations using a precision oncology approach and significantly expanding the scope of patients who can benefit from targeted therapies.
Given the high prevalence of p53 mutations in cancers, we believe that an effective way to address p53-driven cancers is by targeting individual p53 mutations using a precision oncology approach and significantly expanding the scope of patients who can benefit from targeted therapies. 4 Our Product Candidate and Development Programs We are leveraging our precision oncology platform to develop a pipeline of oral small molecule product candidates.
Our approach has yielded a highly selective product candidate, which we believe can maximize the potential therapeutic potency and minimize risk to normal functioning cells.
Rezatapopt is designed to bind to the mutation site and structurally correct the misfolded p53 protein, while sparing wild-type p53. Our approach has yielded a highly selective product candidate, which we believe can maximize the potential therapeutic potency and minimize risk to normal functioning cells.
Using our extensive in-house expertise, deep understanding of chemistry and decades of experience researching the p53 protein, we believe that we will be able to leverage and apply foundational knowledge from the advancement of PC14586 to the discovery and development of additional product candidates.
Using our extensive in-house expertise, deep understanding of chemistry and decades of experience researching the p53 protein, we believe that we will be able to leverage and apply foundational knowledge from the advancement of rezatapopt to the discovery and development of additional product candidates. 3 Background on Targeted Therapies Cancer is a genetic disease that results from changes in a person’s DNA that causes cells to grow and divide uncontrollably.
In notable cases, the clinical outcomes have been dramatic enough to support expedited regulatory approval of these therapies.
Targeted therapies have the potential to transform treatment of some cancers by providing robust clinical benefit to patients. In notable cases, the clinical outcomes have been dramatic enough to support expedited regulatory approval of these therapies.
Targeted therapies have the potential to transform treatment of some cancers by providing robust clinical benefit to patients. In many cases, clinical responses can be dramatic enough to support expedited regulatory approval of these therapies. Further, recent advancements in next-generation-sequencing, or genomic NGS, have accelerated the development of targeted therapies.
In many cases, clinical responses can be dramatic enough to support expedited regulatory approval of these therapies. Further, recent advancements in next-generation-sequencing, or NGS, have accelerated the development of targeted therapies. A recent study found that 75% of oncologists in the United States employ genomic sequencing.
We are conducting our clinical trials in this genetically-defined patient population and leverage learnings from recently approved tumor-agnostic drugs to inform the clinical and regulatory pathways for PC14586.
We are conducting our clinical trials in this genomically-defined patient population and leverage learnings from recently approved tumor-agnostic drugs to inform the clinical and regulatory pathways for rezatapopt. In October 2023, we presented our Phase 1 clinical data for rezatapopt and observed partial responses across multiple tumor types.
As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the Quality System Regulation, or QSR, which imposes elaborate testing, control, documentation and other quality assurance requirements. 22 PMA approval is not guaranteed, and the FDA may ultimately respond to a PMA submission with a not approvable determination based on deficiencies in the application and require additional clinical trial or other data that may be expensive and time-consuming to generate and that can substantially delay approval.
PMA approval is not guaranteed, and the FDA may ultimately respond to a PMA submission with a not approvable determination based on deficiencies in the application and require additional clinical trial or other data that may be expensive and time-consuming to generate and that can substantially delay approval.
Wild-type p53 in a normal cell is at low to undetectable levels, but an external insult such as UV radiation or exposure to a carcinogen results in activation and upregulation of the protein.
Our lead product candidate, rezatapopt, is designed to be an orally available small molecule that structurally corrects a p53 protein containing the Y220C mutation and restores wild-type p53 function. 5 Wild-type p53 in a normal cell is at low to undetectable levels, but an external insult such as UV radiation or exposure to a carcinogen results in activation and upregulation of the protein.
In preclinical studies, PC14586 has shown selective on-target activity ( i.e. , primarily functions in cells with the p53 Y220C mutation) and exhibited robust anti-tumor activity evidenced by potent tumor growth inhibition, or TGI, and strong tumor regression as a single agent. Further, preclinical studies have demonstrated significant synergistic effects in combination with anti-PD-1 therapy.
In preclinical studies, rezatapopt has shown selective on-target activity ( i.e. , primarily functions in cells with the p53 Y220C mutation) and exhibited robust anti-tumor activity evidenced by potent tumor growth inhibition, or TGI, and strong tumor regression as a single agent. We initiated a Phase 1/2 clinical trial, PYNNACLE, in October 2020 for our lead product candidate, rezatapopt.
In addition, companion diagnostic tests that are used with applicable pharmaceutical products require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical products.
In addition, companion diagnostic tests that are used with applicable pharmaceutical products require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical products. Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical products, will apply to companion diagnostics. Moreover, third-party payors are increasingly reducing coverage and reimbursement for pharmaceutical products and related services.
Recent advances in genomic sequencing and a better understanding of the genomic alterations that drive tumor development and growth have facilitated precise, gene and protein-specific drug development, known as targeted therapies. Targeted therapies have the potential to transform treatment of some cancers by providing robust clinical benefit to patients.
MDACC dosed its first patient for this Phase 1b study in the first quarter of 2025. A better understanding of mutations that drive cancers have facilitated the development of precise, gene- and protein-specific drugs known as targeted therapies. Targeted therapies have the potential to transform treatment of some cancers by providing robust clinical benefit to patients.
As of January 31, 2024, we owned six issued US patents and seven granted foreign patents relating to methods of use and composition of matter of PMV compounds, including PC14586, at least 15 pending US patent applications, and at least 30 pending foreign patent applications, each of which relates to methods of use and composition of matter of PMV compounds.
As of February 21, 2025, we owned nine issued U.S. patents and nine granted foreign patents relating to methods of use and composition of matter of PMV compounds, including rezatapopt, at least 10 pending U.S. patent applications, and at least 40 pending foreign patent applications, each of which relates to methods of use and composition of matter of PMV compounds.
These programs have been developed using our precision oncology platform and expertise. We are able to utilize the same general principles and similar drug discovery methods developed from our PC14586 (p53 Y220C) program to facilitate the development of additional new product candidates. We study the structural and functional properties of the target.
We are able to utilize the same general principles and similar drug discovery methods developed from our rezatapopt, p53 Y220C, program to facilitate the development of additional new product candidates. We study the structural and functional properties of the target. We use assays, screens, preclinical model systems and biomarkers to assess and optimize selective small molecules.
Among the other benefits of ODD are tax credits for certain research and a waiver of the NDA application user fee. 17 A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received ODD.
A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received ODD.
Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical products, will apply to companion diagnostics. 19 Moreover, third-party payors are increasingly reducing coverage and reimbursement for pharmaceutical products and related services. The U.S. government and state legislatures have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products.
The U.S. government and state legislatures have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for 19 substitution of generic products. Third-party payors are increasingly challenging the prices charged, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical products, in addition to questioning their safety and efficacy.
If a Complete Response Letter is issued, the sponsor must resubmit the NDA to address all of the deficiencies identified in the letter, or withdraw the application.
If a Complete Response Letter is issued, the sponsor must resubmit the NDA to address all of the deficiencies identified in the letter, or withdraw the application. Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval.
The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel though the granting of stock-based and cash-based compensation awards, to increase stockholder value and our success by motivating such individuals to perform to the best of their abilities and achieve our objectives. 23 Environmental, Social and Governance (ESG) Initiatives As a clinical-stage precision oncology company, we are rooted in our mission to fundamentally disrupt the course of cancer for patients with p53 gene mutations and other p53-related cancers.
The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel though the granting of stock-based and cash-based compensation awards, to increase stockholder value and our success by motivating such individuals to perform to the best of their abilities and achieve our objectives.
Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval. 14 If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed.
If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the NDA with a REMS to ensure the benefits of the product outweigh its risks.
Our lead product candidate, PC14586 (rezatapopt), is designed to be an orally available small molecule that structurally corrects the mutant p53 protein with the Y220C mutation. The p53 Y220C mutation results from tyrosine being substituted by a cysteine at amino acid position 220 and is associated with approximately 1.0% of all cancers, including breast, NSCLC, colorectal, pancreatic and ovarian cancers.
The p53 Y220C mutation results from tyrosine being substituted by a cysteine at amino acid position 220 and is associated with approximately 1% of all cancers, including breast, NSCLC, colorectal, pancreatic and ovarian cancers. There are currently no products approved by the FDA that selectively target the p53 Y220C mutation.
Food and Drug Administration, or FDA, Fast Track designation of PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation. In July 2023, we met with the FDA at an End of Phase 1 meeting where alignment was obtained on our pivotal Phase 2 study design.
Food and Drug Administration, or FDA, Fast Track designation of rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation.
Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.
Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition. Among the other benefits of ODD are tax credits for certain research and a waiver of the NDA application user fee.
Our Product Candidate and Development Programs We are leveraging our precision oncology platform to develop a pipeline of oral small molecule product candidates. We own worldwide commercial rights to all of our programs. An overview of our development pipeline is shown in the table below. (1) In Discovery, we screen compounds against biological assays to identify lead compounds.
We own worldwide commercial rights to all of our programs. An overview of our development pipeline is shown in the table below. (1) In Discovery, we screen compounds against biological assays to identify lead compounds. (2) In Lead Optimization, we modify the lead compound to improve potency, selectivity, pharmacokinetic and toxicity parameters and physical chemical properties important for clinical development.
PC14586 and Pipeline We are leveraging our precision oncology platform to develop a pipeline of orally available, potent and highly selective small molecule product candidates that target p53 mutations or other p53-related cancers. 1 An overview of our development pipeline is shown in the table below. (1) In Discovery, we screen compounds against biological assays to identify lead compounds.
We believe that our precision oncology platform offers a substantial opportunity to expand the number of patients who will benefit from targeted therapies. 1 Rezatapopt and Pipeline We are leveraging our precision oncology platform to develop a pipeline of orally available, potent and highly selective small molecule product candidates that target p53 mutations or other p53-related cancers.
In October 2023, we presented updated Phase 1 data, as of a September 5, 2023 data cutoff date, at the 2023 American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC) International Conference on Molecular Targets and Cancer Therapeutics. PC14586 was generally well tolerated.
In October 2023, we presented our updated Phase 1 clinical data for rezatapopt at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Meeting.
Third-party payors are increasingly challenging the prices charged, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical products, in addition to questioning their safety and efficacy. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product.
Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product.
Alterations in some genes can lead to the expression of mutant proteins with impaired or abnormal functions that can cause cancer. Cancer has historically been both diagnosed and treated based on a tumor’s organ site, such as the breast, lung, ovary, brain, pancreas, skin, bone or blood.
Cancer has historically been both diagnosed and treated based on a tumor’s organ site, such as the breast, lung, ovary, brain, pancreas, skin, bone or blood. Recent advances in genomic sequencing and a better understanding of the genomic alterations that drive tumor development and growth have facilitated precise, gene and protein-specific drug development, known as targeted therapies.
(2) In Lead Optimization, we modify the lead compound to improve potency, selectivity, pharmacokinetic and toxicity parameters and physical chemical properties important for clinical development. (3) In IND-Enabling Studies, we conduct preclinical studies, in accordance with GLP required for an IND submission to the FDA.
An overview of our development pipeline is shown in the table below. (1) In Discovery, we screen compounds against biological assays to identify lead compounds. (2) In Lead Optimization, we modify the lead compound to improve potency, selectivity, pharmacokinetic and toxicity parameters and physical chemical properties important for clinical development.
In addition, orphan drug exclusivity, as described above, may offer a seven-year period of marketing exclusivity, except in certain circumstances. 18 Other Healthcare Laws Pharmaceutical manufacturers are subject to additional healthcare fraud and abuse laws, regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business.
Further, changes in the leadership of the FDA and other federal agencies under the Trump administration may lead to new policies, changes in the regulations, or disruptions to the operations of federal agencies, any of which may impact our clinical development plans. 18 Other Healthcare Laws Pharmaceutical manufacturers are subject to additional healthcare fraud and abuse laws, regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business.
Alignment with the FDA was obtained on the recommended Phase 2 dose as well as key elements of the Phase 2 registrational portion of the PYNNACLE trial. The Phase 2 portion of the study will be initiated based on this alignment with the FDA.
In July 2023, we met with the FDA at an End of Phase 1 meeting where alignment was obtained on the recommended Phase 2 dose and key elements of the single arm, Phase 2 registrational portion of the PYNNACLE study.
Our lead product candidate, PC14586 (rezatapopt), is designed to be an orally available small molecule that structurally corrects a p53 protein containing the Y220C mutation and restores wild-type p53 function.
(3) In IND-Enabling Studies, we conduct preclinical studies, in accordance with Good Laboratory Practice, or GLP, required for an IND submission to the FDA. Our lead product candidate, rezatapopt, is designed to be an orally available small molecule that structurally corrects the mutant p53 protein with the Y220C mutation.
Background on Targeted Therapies Cancer is a genetic disease that results from changes in a person’s DNA that causes cells to grow and divide uncontrollably. Genes are the distinct segments in a cell’s DNA that can encode proteins with structural or functional roles in the body.
Genes are the distinct segments in a cell’s DNA that can encode proteins with structural or functional roles in the body. Alterations in some genes can lead to the expression of mutant proteins with impaired or abnormal functions that can cause cancer.
Among the 16 patients treated at the recommended Phase 2 dose, confirmed partial responses were observed per investigator assessment (RECIST v1.1) in 6 patients (38%) across multiple tumor types, including those noted above. Our Strategy Our vision is to become a leading precision oncology company by designing, developing and commercializing novel precision medicines for every patient with a p53-driven tumor.
MDACC dosed its first patient for this Phase 1b study in the first quarter of 2025. Our Strategy Our vision is to become a leading precision oncology company by designing, developing and commercializing novel precision medicines for every patient with a p53-driven tumor.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeAccordingly, our future results could be harmed directly or indirectly by a variety of factors, including: • differing regulatory requirements in foreign countries, changes in existing regulatory requirements, or implementation of new regulatory requirements or policies that impact our clinical development and business operations in foreign countries; • foreign regulatory authorities may disagree with the design, implementation or results of our clinical trials or our interpretation of data from preclinical studies or clinical trials; • approval policies or regulations of foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval; • impact of a global pandemic or other public health emergencies on our ability to produce our product candidates and conduct clinical trials in foreign countries; • sociopolitical instability in particular foreign economies and markets; • unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements; • legislation or other measures that restrict business, trade, or use of government fundings for any product or service rendered by certain companies based in China due to national security concerns or geopolitical issues, and our reliance on such Chinese companies, including CROs, CMOs, suppliers, and other vendors or contractors based in China; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign taxes, including withholding of payroll taxes; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and obligations incident to doing business in another country; • difficulties staffing and managing foreign operations; • workforce uncertainty in countries where labor unrest is more common than in the United States; • potential liability under the Foreign Corrupt Practices Act of 1977 or comparable foreign regulations; • challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States; • trade protection measures, import or export licensing requirements or other restrictive actions by U.S. or non-U.S. governments; production or supply shortages resulting directly or indirectly from any events affecting raw material supply or manufacturing capabilities abroad, including, but not limited to, impacts due to the ongoing Ukraine-Russia war or the ongoing conflict between Israel and Hamas, addition of certain suppliers or companies to the Unverified List under the Export Administration Regulations, implementation of other export controls, restrictions or sanctions that can impact the supply chain, our business, or business operations of our suppliers, contractors or partners; • business interruptions resulting directly or indirectly from geo-political actions, including the ongoing Ukraine-Russia war, other regional or geo-political conflicts, including the conflict between Israel and Hamas, and terrorism; and supply and other disruptions resulting from the impact of public health epidemics on our strategic partners, third-party manufacturers, suppliers and other third parties upon which we rely. 37 These and other risks associated with international operations may materially adversely affect our business, financial condition, and results of operations.
Biggest changeThis new or proposed legislation, or similar legislation in the future, could adversely impact our current or future third-party arrangements with certain companies, including those in China or Chinese-owned U.S. companies, which could delay or impact clinical trials and consequently delay or obstruct successful commercialization of our drug candidates; • regulations or other potentially new measures that, for national security or geopolitical reasons, affect the transfer of certain types of data abroad, including to China; for example, the Department of Justice recently issued a final rule which takes effect in April 2025 that places limitations, and in some cases prohibitions, on certain transfers of sensitive personal data to business partners located in China and other designated countries, or with other specified links to China and other designated countries; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign taxes, including withholding of payroll taxes; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and obligations incident to doing business in another country; • difficulties staffing and managing foreign operations; • workforce uncertainty in countries where labor unrest is more common than in the United States; • potential liability under the Foreign Corrupt Practices Act of 1977 or comparable foreign regulations; • challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States; • trade protection measures, import or export licensing requirements or other restrictive actions by U.S. or non-U.S. governments; production or supply shortages resulting directly or indirectly from any events affecting raw material supply or manufacturing capabilities abroad, including, but not limited to, impacts due to the ongoing Ukraine-Russia war or the conflict in the Middle East, addition of certain suppliers or companies to the Unverified List under the Export Administration Regulations, implementation of other export controls, restrictions or sanctions that can impact the supply chain, our business, or business operations of our suppliers, contractors or partners; • business interruptions resulting directly or indirectly from geo-political actions, conflicts and terrorism; and supply and other disruptions resulting from the impact of public health epidemics on our strategic partners, third-party manufacturers, suppliers and other third parties upon which we rely.
We have little experience as a company in the development of diagnostics. As such, we expect to rely on future partners for the design, development and manufacture of appropriate diagnostics to pair with our current or future product candidates.
We have little experience as a company in the development of diagnostics. As such, we expect to rely on partners for the design, development and manufacture of appropriate diagnostics to pair with our current or future product candidates.
We may experience disruptions that could severely impact our business and clinical trials due to global pandemics, public health concerns or other public emergencies, including: • delays or difficulties in enrolling and retaining patients in our clinical trials; • delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff; • diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials; • interruption of key clinical trial activities, such as clinical trial site data monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others or interruption of clinical trial subject visits and study procedures (such as endoscopies that are deemed non-essential), which may impact the integrity of subject data and clinical study endpoints; 34 • interruption or delays in the operations of the FDA or other regulatory authorities, which may impact review and approval timelines; • interruption of, or delays in receiving, supplies of our product candidates from our contract manufacturing organizations due to staffing shortages, production slowdowns or stoppages and disruptions in delivery systems; • interruptions in preclinical studies due to restricted or limited operations at our laboratory facility; • limitations on employee resources that would otherwise be focused on the conduct of our preclinical studies and clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people; • interruption or delays to our sourced discovery and clinical activities; and • changes in clinical site procedures and requirements as well as regulatory requirements for conducting clinical trials during the pandemic.
We may experience disruptions that could severely impact our business and clinical trials due to global pandemics, public health concerns or other public emergencies, including: • delays or difficulties in enrolling and retaining patients in our clinical trials; • delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff; • diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials; • interruption of key clinical trial activities, such as clinical trial site data monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others or interruption of 34 clinical trial subject visits and study procedures (such as endoscopies that are deemed non-essential), which may impact the integrity of subject data and clinical study endpoints; • interruption or delays in the operations of the FDA or other regulatory authorities, which may impact review and approval timelines; • interruption of, or delays in receiving, supplies of our product candidates from our contract manufacturing organizations due to staffing shortages, production slowdowns or stoppages and disruptions in delivery systems; • interruptions in preclinical studies due to restricted or limited operations at our laboratory facility; • limitations on employee resources that would otherwise be focused on the conduct of our preclinical studies and clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people; • interruption or delays to our sourced discovery and clinical activities; and • changes in clinical site procedures and requirements as well as regulatory requirements for conducting clinical trials during the pandemic.
Patient enrollment for our current or any future clinical trials may be affected by other factors, including: • size and nature of the patient population; • severity of the disease under investigation; • availability and efficacy of approved drugs for the disease under investigation; • patient eligibility criteria for the trial in question as defined in the protocol; • perceived risks and benefits of the product candidate under study; 35 • clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved or future product candidates being investigated for the indications we are investigating; • clinicians’ willingness to screen their patients for biomarkers to indicate which patients may be eligible for enrollment in our clinical trials; • delays in or temporary suspension of the enrollment of patients in our clinical trials due to a global pandemic or other public health emergencies; • ability to obtain and maintain patient consents; • patient referral practices of physicians; • the ability to monitor patients adequately during and after treatment; • proximity and availability of clinical trial sites for prospective patients; and • the risk that patients enrolled in clinical trials will drop out of the trials before completion, including as a result of other health conditions, or, because they may be late-stage cancer patients, will not survive the full terms of the clinical trials.
Patient enrollment for our current or any future clinical trials may be affected by other factors, including: • size and nature of the patient population; • severity of the disease under investigation; • availability and efficacy of approved drugs for the disease under investigation; • patient eligibility criteria for the trial in question as defined in the protocol; • perceived risks and benefits of the product candidate under study; • clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved or future product candidates being investigated for the indications we are investigating; • clinicians’ willingness to screen their patients for biomarkers to indicate which patients may be eligible for enrollment in our clinical trials; 35 • delays in or temporary suspension of the enrollment of patients in our clinical trials due to a global pandemic or other public health emergencies; • ability to obtain and maintain patient consents; • patient referral practices of physicians; • the ability to monitor patients adequately during and after treatment; • proximity and availability of clinical trial sites for prospective patients; and • the risk that patients enrolled in clinical trials will drop out of the trials before completion, including as a result of other health conditions, or, because they may be late-stage cancer patients, will not survive the full terms of the clinical trials.
Various factors will influence whether our product candidates are accepted in the market, including: • the clinical indications for which our product candidates are approved; • physicians, hospitals, cancer treatment centers and patients considering our product candidates as a safe and effective treatment; • the potential and perceived advantages of our product candidates over alternative treatments; • our ability to demonstrate the advantages of our product candidates over other cancer medicines; • the prevalence and severity of any side effects; 41 • the prevalence and severity of any side effects for other precision medicines and public perception of other precision medicines; • product labeling or product insert requirements of the FDA or other regulatory authorities; • limitations or warnings contained in the labeling approved by the FDA; • the timing of market introduction of our product candidates as well as competitive products; • the cost of treatment in relation to alternative treatments; • the availability of adequate coverage, reimbursement and pricing by third-party payors and government authorities; • the willingness of patients to pay out-of-pocket in the absence of coverage by third-party payors and government authorities; • relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies; and • the effectiveness of our sales and marketing efforts.
Various factors will influence whether our product candidates are accepted in the market, including: • the clinical indications for which our product candidates are approved; • physicians, hospitals, cancer treatment centers and patients considering our product candidates as a safe and effective treatment; • the potential and perceived advantages of our product candidates over alternative treatments; • our ability to demonstrate the advantages of our product candidates over other cancer medicines; • the prevalence and severity of any side effects; • the prevalence and severity of any side effects for other precision medicines and public perception of other precision medicines; • product labeling or product insert requirements of the FDA or other regulatory authorities; 41 • limitations or warnings contained in the labeling approved by the FDA; • the timing of market introduction of our product candidates as well as competitive products; • the cost of treatment in relation to alternative treatments; • the availability of adequate coverage, reimbursement and pricing by third-party payors and government authorities; • the willingness of patients to pay out-of-pocket in the absence of coverage by third-party payors and government authorities; • relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies; and • the effectiveness of our sales and marketing efforts.
Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for our product candidates or products that we may develop; • injury to our reputation; • withdrawal of clinical trial participants • initiation of investigations by regulators; • costs to defend the related litigation; • diversion of management’s time and our resources; • substantial monetary awards to trial participants or patients; • product recalls, withdrawals or labeling, marketing or promotional restrictions; 44 • loss of revenue; • exhaustion of any available insurance and our capital resources; • the inability to commercialize any product candidate; and • a decline in our share price.
Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for our product candidates or products that we may develop; • injury to our reputation; • withdrawal of clinical trial participants; • initiation of investigations by regulators; • costs to defend the related litigation; • diversion of management’s time and our resources; • substantial monetary awards to trial participants or patients; • product recalls, withdrawals or labeling, marketing or promotional restrictions; • loss of revenue; • exhaustion of any available insurance and our capital resources; 44 • the inability to commercialize any product candidate; and • a decline in our share price.
In addition to the factors discussed in this “Risk Factors” section and elsewhere in this Annual Report on Form 10-K, these factors include: • the results of our ongoing, planned or any future preclinical studies, clinical trials or clinical development programs; • the commencement, enrollment, or results of clinical trials of our product candidates or any future clinical trials we may conduct, or changes in the development status of our product candidates; • adverse results or delays in preclinical studies and clinical trials; • our decision to initiate a clinical trial, not to initiate a clinical trial, or to terminate an existing clinical trial, including due to the suspension of a clinical trial by the FDA or other regulatory authorities; • any delay in our regulatory filings or any adverse regulatory decisions, including failure to receive regulatory approval of our product candidates; • changes in laws or regulations applicable to our products, including but not limited to clinical trial requirements for approvals; • adverse developments concerning our manufacturers or our manufacturing plans; • our inability to obtain adequate product supply for any licensed product or inability to do so at acceptable prices; • our inability to establish collaborations if needed; • our failure to commercialize our product candidates; • additions or departures of key scientific or management personnel; • unanticipated serious safety concerns related to the use of our product candidates; • introduction of new products or services offered by us or our competitors; • announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors; • our ability to effectively manage our growth; • the size and growth of our initial cancer target markets; • our ability to successfully treat additional types of cancers or at different stages; • actual or anticipated variations in quarterly operating results; • our cash position; • our failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • publication of research reports about us or our industry, or immunotherapy in particular, or positive or negative recommendations or withdrawal of research coverage by securities analysts; • changes in the market valuations of similar companies; • overall performance of the equity markets; • sales of our common stock by us or our stockholders in the future; 81 • trading volume of our common stock; • changes in accounting practices; • ineffectiveness of our internal controls; • disputes or other developments relating to intellectual property or proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; • significant lawsuits, including intellectual property or stockholder litigation; • the impact of any natural disasters or public health emergencies; • general economic, political, industry and market conditions, including the rising rate of inflation, the Ukraine-Russia war and the ongoing conflict between Israel and Hamas; and • other events or factors, many of which are beyond our control.
In addition to the factors discussed in this “Risk Factors” section and elsewhere in this Annual Report on Form 10-K, these factors include: • the results of our ongoing, planned or any future preclinical studies, clinical trials or clinical development programs; • the commencement, enrollment, or results of clinical trials of our product candidates or any future clinical trials we may conduct, or changes in the development status of our product candidates; • adverse results or delays in preclinical studies and clinical trials; • our decision to initiate a clinical trial, not to initiate a clinical trial, or to terminate an existing clinical trial, including due to the suspension of a clinical trial by the FDA or other regulatory authorities; • any delay in our regulatory filings or any adverse regulatory decisions, including failure to receive regulatory approval of our product candidates; • changes in laws or regulations applicable to our products, including but not limited to clinical trial requirements for approvals; • adverse developments concerning our manufacturers or our manufacturing plans; • our inability to obtain adequate product supply for any licensed product or inability to do so at acceptable prices; • our inability to establish collaborations if needed; • our failure to commercialize our product candidates; • additions or departures of key scientific or management personnel; • unanticipated serious safety concerns related to the use of our product candidates; • introduction of new products or services offered by us or our competitors; • announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors; • our ability to effectively manage our growth; • the size and growth of our initial cancer target markets; • our ability to successfully treat additional types of cancers or at different stages; • actual or anticipated variations in quarterly operating results; • our cash position; • our failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • publication of research reports about us or our industry, or immunotherapy in particular, or positive or negative recommendations or withdrawal of research coverage by securities analysts; • changes in the market valuations of similar companies; • overall performance of the equity markets; • sales of our common stock by us or our stockholders in the future; 82 • trading volume of our common stock; • changes in accounting practices; • ineffectiveness of our internal controls; • disputes or other developments relating to intellectual property or proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; • significant lawsuits, including intellectual property or stockholder litigation; • the impact of any natural disasters or public health emergencies; • general economic, political, industry and market conditions, including the rising rate of inflation, the Ukraine-Russia war and the conflict between Israel and Hamas; and • other events or factors, many of which are beyond our control.
Our ability to generate revenue depends on a number of factors, including, but not limited to: • successful enrollment and timely completion of our clinical trials for our lead product candidate, PC14586, and timely initiation and completion of our preclinical studies for our future product candidates, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors; • establishing and maintaining relationships with contract research organizations, or CROs, and clinical sites for the clinical development of PC14586 and our future product candidates; • our ability to complete IND-enabling studies and successfully submit and receive authorization to proceed under INDs or comparable applications; • whether we are required by the FDA or other comparable foreign regulatory authorities to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates; • our ability to demonstrate to the satisfaction of the FDA and comparable foreign regulatory authorities the safety, efficacy, consistent manufacturing quality and acceptable risk-benefit profile of our small molecule product candidates or any future product candidates, and such regulatory authorities’ acceptance of our tumor-agnostic development strategy; • the prevalence, duration and severity of potential side effects or other safety issues experienced with our product candidates or future product candidates, if any; • the timely receipt of necessary marketing approvals from the FDA and comparable foreign regulatory authorities; • the willingness of physicians, operators of clinics and patients to utilize or adopt any of our product candidates or future product candidates over alternative or more conventional therapies, such as chemotherapy, to treat solid tumors; • the actual and perceived availability, cost, risk profile and side effects and efficacy of our product candidates, if approved, relative to existing and future alternative cancer therapies and competitive product candidates and technologies; • our ability and the ability of third parties with whom we contract to manufacture adequate clinical and commercial supplies of our product candidates or any future product candidates, remain in good standing with regulatory authorities and develop, validate and maintain commercially viable manufacturing processes that are compliant with cGMP requirements; 28 • our ability to successfully develop a commercial strategy and thereafter commercialize our product candidates or any future product candidates in the United States and internationally, if approved for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others; • patient demand for our product candidates and any future product candidates, if approved; • our ability to establish and enforce intellectual property rights in and to our product candidates or any future product candidates; • obtaining coverage and adequate reimbursement by third-party payors for our product candidates; • addressing any competing therapies and technological and market developments; and • attracting, hiring and retaining qualified personnel.
Our ability to generate revenue depends on a number of factors, including, but not limited to: • successful enrollment and timely completion of our clinical trials for our lead product candidate, rezatapopt, and timely initiation and completion of our preclinical studies for our future product candidates, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors; • establishing and maintaining relationships with contract research organizations, or CROs, and clinical sites for the clinical development of rezatapopt and our future product candidates; • our ability to complete IND-enabling studies and successfully submit and receive authorization to proceed under INDs or comparable applications; • whether we are required by the FDA or other comparable foreign regulatory authorities to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates; • our ability to demonstrate to the satisfaction of the FDA and comparable foreign regulatory authorities the safety, efficacy, consistent manufacturing quality and acceptable risk-benefit profile of our small molecule product candidates or any future product candidates, and such regulatory authorities’ acceptance of our tumor-agnostic development strategy; • the prevalence, duration and severity of potential side effects or other safety issues experienced with our product candidates or future product candidates, if any; • the timely receipt of necessary marketing approvals from the FDA and comparable foreign regulatory authorities; • the willingness of physicians, operators of clinics and patients to utilize or adopt any of our product candidates or future product candidates over alternative or more conventional therapies, such as chemotherapy, to treat solid tumors; • the actual and perceived availability, cost, risk profile and side effects and efficacy of our product candidates, if approved, relative to existing and future alternative cancer therapies and competitive product candidates and technologies; • our ability and the ability of third parties with whom we contract to manufacture adequate clinical and commercial supplies of our product candidates or any future product candidates, remain in good standing with regulatory authorities and develop, validate and maintain commercially viable manufacturing processes that are compliant with cGMP requirements; • our ability to successfully develop a commercial strategy and thereafter commercialize our product candidates or any future product candidates in the United States and internationally, if approved for marketing, reimbursement, sale and distribution in such countries and territories, whether alone or in collaboration with others; 28 • patient demand for our product candidates and any future product candidates, if approved; • our ability to establish and enforce intellectual property rights in and to our product candidates or any future product candidates; • obtaining coverage and adequate reimbursement by third-party payors for our product candidates; • addressing any competing therapies and technological and market developments; and • attracting, hiring and retaining qualified personnel.
These provisions, among other things: • establish a classified board of directors so that not all members of our board are elected at one time; • permit only the board of directors to establish the number of directors and fill vacancies on the board; • provide that directors may only be removed “for cause” and only with the approval of two-thirds of our stockholders; • authorize the issuance of “blank check” preferred stock that our board could use to implement a stockholder rights plan (also known as a “poison pill”); • eliminate the ability of our stockholders to call special meetings of stockholders; • prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders; • prohibit cumulative voting; • authorize our board of directors to amend the bylaws; • establish advance notice requirements for nominations for election to our board or for proposing matters that can be acted upon by stockholders at annual stockholder meetings; and • require a super-majority vote of stockholders to amend some provisions described above.
These provisions, among other things: • establish a classified board of directors so that not all members of our board are elected at one time; • permit only the board of directors to establish the number of directors and fill vacancies on the board; • provide that directors may only be removed “for cause” and only with the approval of two-thirds of our stockholders; • authorize the issuance of “blank check” preferred stock that our board could use to implement a stockholder rights plan (also known as a “poison pill”); • eliminate the ability of our stockholders to call special meetings of stockholders; • prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders; • prohibit cumulative voting; • authorize our board of directors to amend the bylaws; • establish advance notice requirements for nominations for election to our board or for proposing matters that can be acted upon by stockholders at annual stockholder meetings; and 84 • require a super-majority vote of stockholders to amend some provisions described above.
Any potential acquisition or strategic partnership may entail numerous risks, including: • increased operating expenses and cash requirements; • the assumption of additional indebtedness or contingent liabilities; • the issuance of our equity securities; • assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; • the diversion of our management’s attention from our existing programs and initiatives in pursuing such a strategic merger or acquisition; 69 • retention of key employees, the loss of key personnel and uncertainties in our ability to maintain key business relationships; • risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and marketing approvals; and • our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs.
Any potential acquisition or strategic partnership may entail numerous risks, including: • increased operating expenses and cash requirements; • the assumption of additional indebtedness or contingent liabilities; • the issuance of our equity securities; • assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; • the diversion of our management’s attention from our existing programs and initiatives in pursuing such a strategic merger or acquisition; • retention of key employees, the loss of key personnel and uncertainties in our ability to maintain key business relationships; • risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and marketing approvals; and • our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs.
Our product candidates could be delayed in receiving, or fail to receive, regulatory approval for many reasons, including the following: • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials, including our Phase 1/2 clinical trial design for PC14586, or require us to modify the design of our clinical trials, including additional procedures and contingency measures in response to the COVID-19 pandemic or as required by clinical sites, IRBs, FDA or other regulatory authorities; • the FDA or comparable foreign regulatory authorities may disagree with our tumor-agnostic development strategy; • the population studied in the clinical trial may not be sufficiently broad or representative to assure efficacy and safety in the full population for which we seek approval; • we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a drug candidate is safe and effective for its proposed indication, or a related companion diagnostic is suitable to identify appropriate patient populations; • the FDA or other comparable regulatory authorities may fail to approve companion diagnostic tests that may be required for our product candidates; 46 • the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval; • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks, or that a product candidate has an acceptable benefit-risk ratio for its proposed indication; • the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the United States or elsewhere; • the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes, test procedures, specifications or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; • our third-party contractors may fail to comply with regulatory requirements or otherwise fail or be unable to adequately perform their obligations to allow for the conduct of our planned or future clinical studies; and • the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Our product candidates could be delayed in receiving, or fail to receive, regulatory approval for many reasons, including the following: • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials, including our Phase 1/2 clinical trial design for rezatapopt, or require us to modify the design of our clinical trials, including additional procedures and contingency measures in response to the COVID-19 pandemic or as required by clinical sites, IRBs, FDA or other regulatory authorities; • the FDA or comparable foreign regulatory authorities may disagree with our tumor-agnostic development strategy; • the population studied in the clinical trial may not be sufficiently broad or representative to assure efficacy and safety in the full population for which we seek approval; • we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a drug candidate is safe and effective for its proposed indication, or a related companion diagnostic is suitable to identify appropriate patient populations; • the FDA or other comparable regulatory authorities may fail to approve companion diagnostic tests that may be required for our product candidates; • the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval; 46 • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks, or that a product candidate has an acceptable benefit-risk ratio for its proposed indication; • the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the United States or elsewhere; • the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes, test procedures, specifications or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; • our third-party contractors may fail to comply with regulatory requirements or otherwise fail or be unable to adequately perform their obligations to allow for the conduct of our planned or future clinical studies; and • the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
In August 2022, Congress passed the Inflation Reduction Act of 2022, which includes prescription drug provisions that have significant implications for the pharmaceutical industry and Medicare beneficiaries, 54 including allowing the federal government to negotiate a maximum fair price for certain high-priced single source Medicare drugs, imposing penalties and excise tax for manufacturers that fail to comply with the drug price negotiation requirements, requiring inflation rebates for all Medicare Part B and Part D drugs, with limited exceptions, if their drug prices increase faster than inflation, and redesigning Medicare Part D to reduce out-of-pocket prescription drug costs for beneficiaries, among other changes.
In August 2022, Congress passed the Inflation Reduction Act of 2022, which includes prescription drug provisions that have significant implications for the pharmaceutical industry and Medicare beneficiaries, including allowing the federal government to negotiate a maximum fair price for certain high-priced single source Medicare drugs, imposing penalties and excise tax for manufacturers that fail to comply with the drug price negotiation requirements, requiring inflation rebates for all Medicare Part B and Part D drugs, with limited exceptions, if their drug prices increase faster than inflation, and redesigning Medicare Part D to reduce out-of-pocket prescription drug costs for beneficiaries, among other changes.
Clinical trials can be delayed or terminated for a variety of reasons, including delays or failures related to: • the availability of financial resources to commence and complete clinical trials; • the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of our clinical trials; • the FDA or comparable foreign regulatory authorities disagreeing with our tumor-agnostic development strategy; • delays in obtaining regulatory approval or authorization to commence a clinical trial, including delays or issues relating to any future companion diagnostics which we may develop; 50 • reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • obtaining IRB or ethics committee approval at each clinical trial site; • recruiting an adequate number of suitable patients to participate in a clinical trial; • the number of patients required for clinical trials of our product candidates may be larger than we anticipate; • the cost of clinical trials of our product candidates may be greater than we anticipate, for example, if we experience delays or challenges in identifying patients with the mutations required for our clinical trials, we may have to reimburse sites for genetic sequencing costs in order to encourage sequencing of additional patients; • having subjects complete a clinical trial or return for post-treatment follow-up; • clinical trial sites deviating from clinical trial protocol or dropping out of a clinical trial; • having third-party contractors fail to complete their obligations in a timely manner or failing to comply with applicable regulatory requirements; • addressing subject safety concerns that arise during the course of a clinical trial; • adding a sufficient number of clinical trial sites; or • obtaining sufficient product supply of product candidate for use in preclinical studies or clinical trials from third-party suppliers.
Clinical trials can be delayed or terminated for a variety of reasons, including delays or failures related to: • the availability of financial resources to commence and complete clinical trials; • the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of our clinical trials; • the FDA or comparable foreign regulatory authorities disagreeing with our tumor-agnostic development strategy; • delays in obtaining regulatory approval or authorization to commence a clinical trial, including delays or issues relating to any future companion diagnostics which we may develop; 50 • reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • obtaining IRB or ethics committee approval at each clinical trial site; • recruiting an adequate number of suitable patients to participate in a clinical trial; • the number of patients required for clinical trials of our product candidates may be larger than we anticipate; • the cost of clinical trials of our product candidates may be greater than we anticipate, for example, if we experience delays or challenges in identifying patients with the mutations required for our clinical trials, we may have to reimburse sites for genomic sequencing costs in order to encourage sequencing of additional patients; • having subjects complete a clinical trial or return for post-treatment follow-up; • clinical trial sites deviating from clinical trial protocol or dropping out of a clinical trial; • having third-party contractors fail to complete their obligations in a timely manner or failing to comply with applicable regulatory requirements; • addressing subject safety concerns that arise during the course of a clinical trial; • adding a sufficient number of clinical trial sites; or • obtaining sufficient product supply of product candidate for use in preclinical studies or clinical trials from third-party suppliers.
We may be exposed to, or threatened with, future litigation by third parties having patent or other intellectual property rights alleging that our product candidates and/or proprietary technologies infringe their intellectual property rights. 78 If a third party claims that we infringe its intellectual property rights, we may face a number of issues, including, but not limited to: infringement and other intellectual property claims which, regardless of merit, may be expensive and time-consuming to litigate and may divert our management’s attention from our core business; substantial damages for infringement, which we may have to pay if a court decides that the product candidate or technology at issue infringes on or violates the third party’s rights, and, if the court finds that the infringement was willful, we could be ordered to pay treble damages and the patent owner’s attorneys’ fees; a court prohibiting us from developing, manufacturing, marketing or selling our product candidates, or from using our proprietary technologies, unless the third party licenses its product rights to us; however, the third party is not required to grant the license; if a license is available from a third party, we may have to pay substantial royalties, upfront fees and other amounts, and/or grant cross-licenses to intellectual property rights for our products; and redesigning our product candidates or processes so they do not infringe; redesign may not be possible or may require substantial monetary expenditures and time.
We may be exposed to, or threatened with, future litigation by third parties having patent or other intellectual property rights alleging that our product candidates and/or proprietary technologies infringe their intellectual property rights. 79 If a third party claims that we infringe its intellectual property rights, we may face a number of issues, including, but not limited to: infringement and other intellectual property claims which, regardless of merit, may be expensive and time-consuming to litigate and may divert our management’s attention from our core business; substantial damages for infringement, which we may have to pay if a court decides that the product candidate or technology at issue infringes on or violates the third party’s rights, and, if the court finds that the infringement was willful, we could be ordered to pay treble damages and the patent owner’s attorneys’ fees; a court prohibiting us from developing, manufacturing, marketing or selling our product candidates, or from using our proprietary technologies, unless the third party licenses its product rights to us; however, the third party is not required to grant the license; if a license is available from a third party, we may have to pay substantial royalties, upfront fees and other amounts, and/or grant cross-licenses to intellectual property rights for our products; and redesigning our product candidates or processes so they do not infringe; redesign may not be possible or may require substantial monetary expenditures and time.
Because specific genetic mutations will be used to identify the appropriate patients for our programs and our current or future product candidates, we believe that our success may depend, in part, on our ability to use existing diagnostic tests and genetic sequencing, or to develop novel companion diagnostics in collaboration with partners. 33 Such companion diagnostics would be used during our clinical trials as well as in connection with the commercialization of our product candidates.
Because specific genetic mutations will be used to identify the appropriate patients for our programs and our current or future product candidates, we believe that our success may depend, in part, on our ability to use existing diagnostic tests and genomic sequencing, or to develop novel companion diagnostics in collaboration with partners. 33 Such companion diagnostics would be used during our clinical trials as well as in connection with the commercialization of our product candidates.
In addition, we have not yet conducted market research to determine how treating physicians would expect to prescribe a product that is approved for multiple tumor types if there are different lines of approved therapies for each such tumor type. 36 Our business may become subject to economic, political, regulatory, and other risks associated with international operations directly or indirectly.
In addition, we have not yet conducted market research to determine how treating physicians would expect to prescribe a product that is approved for multiple tumor types if there are different lines of approved therapies for each such tumor type. Our business may become subject to economic, political, regulatory, and other risks associated with international operations directly or indirectly.
Key product features that would affect our ability to effectively compete with other therapeutics include the efficacy, safety and convenience of our products. Our long-term prospects depend in part upon discovering, developing and commercializing additional product candidates, which may fail in development or suffer delays that adversely affect their commercial viability.
Key product features that would affect our ability to effectively compete with other therapeutics include the efficacy, safety and convenience of our products. 38 Our long-term prospects depend in part upon discovering, developing and commercializing additional product candidates, which may fail in development or suffer delays that adversely affect their commercial viability.
The FDA may also require a risk evaluation and mitigation strategy, or REMS, in order to approve our product candidates, which could entail requirements for a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.
The FDA may also require a risk evaluation and mitigation strategy, or REMS, in order to approve our product candidates, which could entail 52 requirements for a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.
Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. The availability of coverage and extent of reimbursement by governmental and private payors is essential for most patients to be able to afford treatments such as gene therapy products.
Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. The availability of coverage and extent of reimbursement by 42 governmental and private payors is essential for most patients to be able to afford treatments such as gene therapy products.
If we are not able to effectively expand our organization by hiring new employees and/or engaging additional third-party service providers, we may not be able to successfully implement the tasks necessary to further develop and commercialize PC14586 and future product candidates and, accordingly, may not achieve our research, development and commercialization goals. 61 Our internal computer systems, or those of any of our CROs, manufacturers, other contractors or consultants or potential future collaborators, may fail or suffer security or data privacy breaches or other unauthorized or improper access to, use of, or destruction of our proprietary or confidential data, employee data, or personal data, which could result in additional costs, loss of revenue, significant liabilities, harm to our brand and material disruption of our operations.
If we are not able to effectively expand our organization by hiring new employees and/or engaging additional third-party service providers, we may not be able to successfully implement the tasks necessary to further develop and commercialize rezatapopt and future product candidates and, accordingly, may not achieve our research, development and commercialization goals. 61 Our internal computer systems, or those of any of our CROs, manufacturers, other contractors or consultants or potential future collaborators, may fail or suffer security or data privacy breaches or other unauthorized or improper access to, use of, or destruction of our proprietary or confidential data, employee data, or personal data, which could result in additional costs, loss of revenue, significant liabilities, harm to our brand and material disruption of our operations.
Our inability to promptly obtain coverage and profitable reimbursement rates from third-party payors for any approved products that we develop could have a material adverse effect on our business, financial condition and results of operations, our ability to raise capital needed to commercialize products and our overall financial condition.
Our inability to promptly obtain coverage and profitable reimbursement rates from third-party payors for any approved products that we develop 43 could have a material adverse effect on our business, financial condition and results of operations, our ability to raise capital needed to commercialize products and our overall financial condition.
We announced preliminary results for our Phase 1/2 clinical trial of our lead product candidate, PC14586 (rezatapopt), in June 2022, and announced updated Phase 1 results in October 2023. We are continuing to transition from a company with a research focus to a company capable of supporting clinical development and commercial activities.
We announced preliminary results for our Phase 1/2 clinical trial of our lead product candidate, rezatapopt, in June 2022, and announced updated Phase 1 results in October 2023. We are continuing to transition from a company with a research focus to a company capable of supporting clinical development and commercial activities.
The occurrence of any event or penalty described above may inhibit our ability to commercialize our product candidates, if approved, and generate revenue. 53 Healthcare legislative measures aimed at reducing healthcare costs may have a material adverse effect on our business and results of operations.
The occurrence of any event or penalty described above may inhibit our ability to commercialize our product candidates, if approved, and generate revenue. Healthcare legislative measures aimed at reducing healthcare costs may have a material adverse effect on our business and results of operations.
Changes in regulations, statutes or the interpretation of existing regulations could impact our business in the future by requiring, for example: (i) changes to our manufacturing arrangements; (ii) additions or modifications to product labeling; (iii) the recall or discontinuation of our products; or (iv) additional record-keeping requirements.
Changes in regulations, statutes or the interpretation of existing 53 regulations could impact our business in the future by requiring, for example: (i) changes to our manufacturing arrangements; (ii) additions or modifications to product labeling; (iii) the recall or discontinuation of our products; or (iv) additional record-keeping requirements.
If we or our future partners are unable to successfully develop, validate and obtain approval for such companion diagnostics, or experience significant delays in doing so, we may not realize the full commercial potential of our future product candidates.
If we or our collaboration partners are unable to successfully develop, validate and obtain approval for such companion diagnostics, or experience significant delays in doing so, we may not realize the full commercial potential of our future product candidates.
Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage 42 and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.
Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.
Like Fast Track designation, breakthrough therapy designation is within the discretion of the FDA. Accordingly, even if we believe a product candidate we develop meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation.
Like Fast Track designation, breakthrough therapy designation is within the discretion of the FDA. Accordingly, even if we believe a product 48 candidate we develop meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation.
We are also required to disclose changes made in our internal controls and procedures on a quarterly basis. 85 The requirements of these rules and regulations are difficult, time-consuming and costly, and place significant strain on our personnel, systems and resources.
We are also required to disclose changes made in our internal controls and procedures on a quarterly basis. The requirements of these rules and regulations are difficult, time-consuming and costly, and place significant strain on our personnel, systems and resources.
Further, if this occurs, our competitors may take advantage of our investment in development and trials by referencing our clinical and preclinical data and launch their product earlier than might otherwise be expected, and our competitive position, business, financial condition, results of operations and prospects could be materially adversely affected. 76 Also, there are detailed rules and requirements regarding the patents that may be submitted to the FDA for listing in the Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book.
Further, if this occurs, our competitors may take advantage of our investment in development and trials by referencing our clinical and preclinical data and launch their product earlier than might otherwise be expected, and our competitive position, business, financial condition, results of operations and prospects could be materially adversely affected. 77 Also, there are detailed rules and requirements regarding the patents that may be submitted to the FDA for listing in the Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book.
We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase substantially if and as we: • continue our research and development efforts and submit investigational new drug, or IND, applications for our product candidates; • conduct preclinical studies and clinical trials; • fail to demonstrate adequate efficacy or an acceptable safety profile in our clinical trials; • seek marketing approvals for any product candidates that successfully complete clinical trials; • experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results, safety issues or other regulatory challenges; • establish a sales, marketing and distribution infrastructure and scale-up manufacturing capabilities, whether alone or with third parties, to commercialize any product candidates for which we may obtain regulatory approval, if any; • obtain, expand, maintain, enforce and protect our intellectual property portfolio; • hire additional clinical, regulatory and scientific personnel; and • operate as a public company.
We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase substantially if and as we: • continue our research and development efforts and submit IND applications for our product candidates; • conduct preclinical studies and clinical trials; • fail to demonstrate adequate efficacy or an acceptable safety profile in our clinical trials; • seek marketing approvals for any product candidates that successfully complete clinical trials; • experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results, safety issues or other regulatory challenges; • establish a sales, marketing and distribution infrastructure and scale-up manufacturing capabilities, whether alone or with third parties, to commercialize any product candidates for which we may obtain regulatory approval, if any; • obtain, expand, maintain, enforce and protect our intellectual property portfolio; • hire additional clinical, regulatory and scientific personnel; and • operate as a public company.
The applicable exclusivity period is 10 years in Europe. The European exclusivity period can be reduced to six years if a drug no longer meets the criteria for ODD or if the drug is sufficiently profitable so that market exclusivity is no longer justified.
The applicable exclusivity period is 10 years in Europe. The European 47 exclusivity period can be reduced to six years if a drug no longer meets the criteria for ODD or if the drug is sufficiently profitable so that market exclusivity is no longer justified.
Future growth would impose significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining and motivating additional employees; • managing our internal development efforts effectively, including the clinical, FDA and other comparable foreign regulatory agencies’ review process for PC14586 and any future product candidates, while complying with any contractual obligations to contractors and other third parties we may have; and • improving our operational, financial and management controls, reporting systems and procedures.
Future growth would impose significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining and motivating additional employees; • managing our internal development efforts effectively, including the clinical, FDA and other comparable foreign regulatory agencies’ review process for rezatapopt and any future product candidates, while complying with any contractual obligations to contractors and other third parties we may have; and • improving our operational, financial and management controls, reporting systems and procedures.
For example, FDA has issued various COVID-19 related guidance documents for trial sponsors and manufacturers during the COVID-19 national and public health emergencies, and may do so in response to other public health concerns in the future.
For example, the FDA issued various COVID-19 related guidance documents for trial sponsors and manufacturers during the COVID-19 national and public health emergencies, and may do so in response to other public health concerns in the future.
This will require us to be cognizant of the time from invention to filing of a patent application. 70 In addition to the protection afforded by patents, we seek to rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable, processes for which patents are difficult to enforce and any other elements of our drug discovery and development processes that involve proprietary know-how, information or technology that is not covered by patents.
This will require us to be cognizant of the time from invention to filing of a patent application. 71 In addition to the protection afforded by patents, we seek to rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable, processes for which patents are difficult to enforce and any other elements of our drug discovery and development processes that involve proprietary know-how, information or technology that is not covered by patents.
If it is later determined that our activities or product candidates infringe this intellectual property we may be liable for damages, enhanced damages or subjected to an injunction, any of which could have a material adverse effect on our business. 72 The patent position of pharmaceutical and biotechnology companies generally is highly uncertain and involves complex legal and factual questions for which many legal principles remain unresolved.
If it is later determined that our activities or product candidates infringe this intellectual property we may be liable for damages, enhanced damages or subjected to an injunction, any of which could have a material adverse effect on our business. 73 The patent position of pharmaceutical and biotechnology companies generally is highly uncertain and involves complex legal and factual questions for which many legal principles remain unresolved.
In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.
In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also 51 ultimately lead to the denial of regulatory approval of our product candidates.
In addition, if we are unable to effectively manage our outsourced activities or if the quality or accuracy of the services provided by third-party service providers is compromised for any reason, our clinical trials may be extended, delayed or terminated, and we may not be able to obtain marketing approval of PC14586 and any future product candidates or otherwise advance our business.
In addition, if we are unable to effectively manage our outsourced activities or if the quality or accuracy of the services provided by third-party service providers is compromised for any reason, our clinical trials may be extended, delayed or terminated, and we may not be able to obtain marketing approval of rezatapopt and any future product candidates or otherwise advance our business.
The expiration of these patents could also have a similar material adverse effect on our business, results of operations, financial condition and prospects. 73 Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.
The expiration of these patents could also have a similar material adverse effect on our business, results of operations, financial condition and prospects. 74 Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.
In such an event, our competitors might be able to enter the market, which would have a material adverse effect on our business. 74 Any issued patents we may own covering our product candidates could be narrowed or found invalid or unenforceable if challenged in court or before administrative bodies in the United States or abroad, including the USPTO.
In such an event, our competitors might be able to enter the market, which would have a material adverse effect on our business. 75 Any issued patents we may own covering our product candidates could be narrowed or found invalid or unenforceable if challenged in court or before administrative bodies in the United States or abroad, including the USPTO.
Uncertainties resulting from the initiation and continuation of patent litigation or other intellectual property related proceedings could adversely affect our ability to compete in the marketplace. 79 If we fail to comply with our obligations in the agreements under which we license intellectual property rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose license rights that are important to our business.
Uncertainties resulting from the initiation and continuation of patent litigation or other intellectual property related proceedings could adversely affect our ability to compete in the marketplace. 80 If we fail to comply with our obligations in the agreements under which we license intellectual property rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose license rights that are important to our business.
If one or more of these analysts cease coverage of us or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline. 82 Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
If one or more of these analysts cease coverage of us or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline. 83 Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
Risks Related to Product Development Our discovery and product development is focused on the development of precision medicines for patients with genetically defined cancers, which is a rapidly evolving area of science, and the approach we are taking to discover and develop drugs targeting p53 is novel, may never lead to marketable products and may not ultimately represent a significant market.
Risks Related to Product Development Our discovery and product development is focused on the development of precision medicines for patients with genomically defined cancers, which is a rapidly evolving area of science, and the approach we are taking to discover and develop drugs targeting p53 is novel, may never lead to marketable products and may not ultimately represent a significant market.
All of our other product candidates are still in preclinical development and have never been tested in human subjects. Our ability to generate product revenue, which we do not expect will occur for many years, if ever, will depend heavily on the successful clinical development and eventual commercialization of PC14586 and one or more of our future product candidates.
All of our other product candidates are still in preclinical development and have never been tested in human subjects. Our ability to generate product revenue, which we do not expect will occur for many years, if ever, will depend heavily on the successful clinical development and eventual commercialization of rezatapopt and one or more of our future product candidates.
For example, we may in the future enter into license agreements that are not assignable or transferable, or that require the licensor’s express consent in order for an assignment or transfer to take place. 80 Risks Related to Ownership of Our Common Stock The price of our stock may be volatile, and you could lose all or part of your investment.
For example, we may in the future enter into license agreements that are not assignable or transferable, or that require the licensor’s express consent in order for an assignment or transfer to take place. 81 Risks Related to Ownership of Our Common Stock The price of our stock may be volatile, and you could lose all or part of your investment.
Such a loss of patent protection would have a material adverse impact on our business. 75 Even if resolved in our favor, litigation or other legal proceedings relating to our intellectual property rights may cause us to incur significant expenses, and could distract our technical and management personnel from their normal responsibilities.
Such a loss of patent protection would have a material adverse impact on our business. 76 Even if resolved in our favor, litigation or other legal proceedings relating to our intellectual property rights may cause us to incur significant expenses, and could distract our technical and management personnel from their normal responsibilities.
Further, even if our Phase 1/2 trial for PC14586 is successful, the FDA may not agree that such study can serve as a pivotal study, which would require us to conduct additional clinical trials prior to approval. We are substantially dependent on our lead product candidate, PC14586.
Further, even if our Phase 1/2 trial for rezatapopt is successful, the FDA may not agree that such study can serve as a pivotal study, which would require us to conduct additional clinical trials prior to approval. We are substantially dependent on our lead product candidate, rezatapopt.
Our projections of both the number of people who have the p53 hotspot mutations we are targeting, who may have their tumors genetically sequenced, as well as the subset of people with these mutations in a position to receive a particular line of therapy and who have the potential to benefit from treatment with our product candidates, are based on our assumptions and estimates.
Our projections of both the number of people who have the p53 hotspot mutations we are targeting, who may have their tumors genomically sequenced, as well as the subset of people with these mutations in a position to receive a particular line of therapy and who have the potential to benefit from treatment with our product candidates, are based on our assumptions and estimates.
At this time, we have not conducted any studies to determine the annual limitations, that resulted from such an ownership change.
At this time, we have not conducted any studies to determine the annual limitations, if any, that resulted from such an ownership change.
It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA and our business. In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted.
It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear how such challenges and the healthcare reform measures of the Trump administration will impact the ACA and our business. In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted.
If the competitor files a patent application on such an advance before we do, then we may no longer be able to protect the technology, we may require a license from the competitor, and if the license is not available on commercially-viable terms, then we may not be able to launch our product. 71 In the future we may in-license intellectual property from licensors.
If the competitor files a patent application on such an advance before we do, then we may no longer be able to protect the technology, we may require a license from the competitor, and if the license is not available on commercially-viable terms, then we may not be able to launch our product. 72 In the future we may in-license intellectual property from licensors.
Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects. 77 If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.
Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects. 78 If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.
For example, it is expected that some of the patients enrolled in our PC14586 clinical trials will die or experience major clinical events either during the course of our clinical trials or after participating in such trials. Results of our trials could reveal a high and unacceptable severity and prevalence of these or other side effects.
For example, it is expected that some of the patients enrolled in our rezatapopt clinical trials will die or experience major clinical events either during the course of our clinical trials or after participating in such trials. Results of our trials could reveal a high and unacceptable severity and prevalence of these or other side effects.
If a product is intended for the treatment of a serious or life-threatening condition and preclinical or clinical data demonstrate the potential to address an unmet medical need for this condition, the product sponsor may apply for Fast Track designation. In October 2020, we received Fast Track designation for PC14586 from the FDA.
If a product is intended for the treatment of a serious or life-threatening condition and preclinical or clinical data demonstrate the potential to address an unmet medical need for this condition, the product sponsor may apply for Fast Track designation. In October 2020, we received Fast Track designation for rezatapopt from the FDA.
Our future operating results are dependent on our ability to successfully discover, develop, obtain regulatory approval for and commercialize product candidates beyond our lead product candidate, PC14586, and those we currently have in preclinical development. A product candidate can unexpectedly fail at any stage of preclinical and clinical development.
Our future operating results are dependent on our ability to successfully discover, develop, obtain regulatory approval for and commercialize product candidates beyond our lead product candidate, rezatapopt, and those we currently have in preclinical development. A product candidate can unexpectedly fail at any stage of preclinical and clinical development.
If we are unable to advance PC14586 or any of our future product candidates through clinical development, obtain regulatory approval and ultimately commercialize PC14586 or any of our future product candidates, or experience significant delays in doing so, our business, financial condition and results of operations will be materially adversely affected.
If we are unable to advance rezatapopt or any of our future product candidates through clinical development, obtain regulatory approval and ultimately commercialize rezatapopt or any of our future product candidates, or experience significant delays in doing so, our business, financial condition and results of operations will be materially adversely affected.
Such a stock price decline could occur even when we have met any previously publicly stated guidance we may provide. 87
Such a stock price decline could occur even when we have met any previously publicly stated guidance we may provide.
Patient enrollment is a significant factor in the timing of clinical trials. Our ability to enroll eligible patients may be limited or may result in slower enrollment than we anticipate. For example, our enrollment for clinical trials of PC14586 will require patients to have the specific p53 Y220C mutation.
Patient enrollment is a significant factor in the timing of clinical trials. Our ability to enroll eligible patients may be limited or may result in slower enrollment than we anticipate. For example, our enrollment for clinical trials of rezatapopt will require patients to have the specific p53 Y220C mutation.
Our lead product candidate, PC14586, is in clinical development and all of our other product candidates are in discovery or preclinical development and their risk of failure is high. It is impossible to predict when or if any of our product candidates will prove effective and safe in humans or will receive regulatory approval.
Our lead product candidate, rezatapopt, is in clinical development and all of our other product candidates are in discovery or preclinical development and their risk of failure is high. It is impossible to predict when or if any of our product candidates will prove effective and safe in humans or will receive regulatory approval.
Before obtaining regulatory approvals for the commercial sale of our product candidates, including our lead product candidate PC14586, we must demonstrate through lengthy, complex and expensive preclinical studies and clinical trials that our product candidates are both safe and effective for each targeted indication.
Before obtaining regulatory approvals for the commercial sale of our product candidates, including our lead product candidate rezatapopt, we must demonstrate through lengthy, complex and expensive preclinical studies and clinical trials that our product candidates are both safe and effective for each targeted indication.
Our operations have consumed substantial amounts of cash since inception, and we expect our expenses to increase in connection with our ongoing activities, particularly as we conduct clinical trials of, and seek marketing approval for, PC14586, and advance our future product candidates.
Our operations have consumed substantial amounts of cash since inception, and we expect our expenses to increase in connection with our ongoing activities, particularly as we conduct clinical trials of, and seek marketing approval for, rezatapopt, and advance our future product candidates.
If our Phase 1/2 trial for PC14586 does not support a tumor-agnostic indication, but we observe clinical benefit in certain tumor or cancer types, we may decide to pursue a tumor- or cancer-specific indication which may require additional clinical trials.
If our Phase 1/2 trial for rezatapopt does not support a tumor-agnostic indication, but we observe clinical benefit in certain tumor or cancer types, we may decide to pursue a tumor- or cancer-specific indication which may require additional clinical trials.
We allocate the majority of our efforts and financial resources to the development of our lead product candidate, PC14586. Our future success is dependent on our ability to timely and successfully complete clinical trials, obtain marketing approval for and successfully commercialize PC14586.
We allocate the majority of our efforts and financial resources to the development of our lead product candidate, rezatapopt. Our future success is dependent on our ability to timely and successfully complete clinical trials, obtain marketing approval for and successfully commercialize rezatapopt.
Additionally, our PC14586 Phase 1/2 clinical trial is, and other clinical trials we conduct in the future may be, open-label in study design and conducted at a limited number of clinical sites on a limited number of patients.
Additionally, our rezatapopt Phase 1/2 clinical trial is, and other clinical trials we conduct in the future may be, open-label in study design and conducted at a limited number of clinical sites on a limited number of patients.
We face competition with respect to our current product candidates and will face competition with respect to future product candidates, from segments of the pharmaceutical, biotechnology and other related markets that pursue targeted therapies for patients with genetically-defined cancers.
We face competition with respect to our current product candidates and will face competition with respect to future product candidates, from segments of the pharmaceutical, biotechnology and other related markets that pursue targeted therapies for patients with genomically-defined cancers.
These candidates include PC14586 and others, their respective components, formulations, methods used to manufacture them and methods of treatment. Our commercial success will also depend on successfully defending these patents against third-party challenges.
These candidates include rezatapopt and others, their respective components, formulations, methods used to manufacture them and methods of treatment. Our commercial success will also depend on successfully defending these patents against third-party challenges.
The discovery and development of precision medicines for patients with genetically defined cancers is an emerging field, and the scientific discoveries that form the basis for our efforts to discover and develop product candidates are relatively new. The scientific evidence to support the feasibility of developing product candidates 30 based on these discoveries is both preliminary and limited.
The discovery and development of precision medicines for patients with genomically defined cancers is an emerging field, and the scientific discoveries that form the basis for our efforts to discover and develop product candidates are relatively new. The scientific evidence to support the feasibility of developing product candidates based on these discoveries is both preliminary and limited.
These current or future laws and regulations may impair our research, development or commercialization efforts. Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions. 59 We are subject to certain U.S. and foreign anti-corruption, anti-money laundering, export control, sanctions and other trade laws and regulations.
These current or future laws and regulations may impair our research, development 59 or commercialization efforts. Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions. We are subject to certain U.S. and foreign anti-corruption, anti-money laundering, export control, sanctions, foreign investment, data transfer and other trade laws and regulations.
For instance, we do not know whether PC14586 will perform in its clinical trials as PC14586 has performed in preclinical studies, nor can we predict how our future product candidates will perform in future preclinical studies or clinical trials.
For instance, we do not know whether rezatapopt will perform in its clinical trials as rezatapopt has performed in preclinical studies, nor can we predict how our future product candidates will perform in future preclinical studies or clinical trials.
Furthermore, our operating results may fluctuate due to a variety of other factors, many of which are outside of our control and may be difficult to predict, including the following: • the timing and cost of, and level of investment in, research and development activities relating to our current product candidates and any future product candidates and research-stage programs, which will change from time to time; • our ability to enroll patients in clinical trials and the timing of enrollment; • the cost of manufacturing our current product candidates and any future product candidates, which may vary depending on FDA or other comparable foreign regulatory authority guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers; • expenditures that we will or may incur to acquire or develop additional product candidates and technologies or other assets; • the timing and outcomes of clinical trials for our future product candidates, or competing product candidates; • the need to conduct unanticipated clinical trials or trials that are larger or more complex than anticipated; • competition from existing and potential future products that compete with our product candidates and any of our future product candidates, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners; • any delays in regulatory review or approval of our product candidates; • the level of demand for our future product candidates, if approved, which may fluctuate significantly and be difficult to predict; • the risk/benefit profile, cost and reimbursement policies with respect to our product candidates, if approved, and existing and potential future products that compete with our product candidates; • our ability to commercialize our product candidates, if approved, inside and outside of the United States, either independently or working with third parties; • our ability to establish and maintain future collaborations, licensing or other arrangements; • our ability to adequately support future growth; • potential unforeseen business disruptions that increase our costs or expenses; • future accounting pronouncements or changes in our accounting policies; and • the changing and volatile global economic and political environment.
Furthermore, our operating results may fluctuate due to a variety of other factors, many of which are outside of our control and may be difficult to predict, including the following: • the timing and cost of, and level of investment in, research and development activities relating to our current product candidates and any future product candidates and research-stage programs, which will change from time to time; • our ability to enroll patients in clinical trials and the timing of enrollment; • the cost of manufacturing our current product candidates and any future product candidates, which may vary depending on FDA or other comparable foreign regulatory authority guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers; • expenditures that we will or may incur to acquire or develop additional product candidates and technologies or other assets; • the timing and outcomes of clinical trials for our future product candidates, or competing product candidates; • the need to conduct unanticipated clinical trials or trials that are larger or more complex than anticipated; • competition from existing and potential future products that compete with our product candidates and any of our future product candidates, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners; • any delays in regulatory review or approval of our product candidates; • the level of demand for our future product candidates, if approved, which may fluctuate significantly and be difficult to predict; • the risk/benefit profile, cost and reimbursement policies with respect to our product candidates, if approved, and existing and potential future products that compete with our product candidates; • our ability to commercialize our product candidates, if approved, inside and outside of the United States, either independently or working with third parties; • our ability to establish and maintain future collaborations, licensing or other arrangements; • our ability to adequately support future growth; • potential unforeseen business disruptions that increase our costs or expenses; • future accounting pronouncements or changes in our accounting policies; and • the changing and volatile global economic and political environment. 87 The cumulative effect of these factors could result in large fluctuations and unpredictability in our quarterly and annual operating results.
If PC14586 or our future product candidates do not offer sustainable advantages over competing products, we may otherwise not be able to successfully compete against current and future competitors.
If rezatapopt or our future product candidates do not offer sustainable advantages over competing products, we may otherwise not be able to successfully compete against current and future competitors.
Our anticipated reliance on a limited number of third-party manufacturers exposes us to a number of risks, including the following: • we may be unable to identify manufacturers on acceptable terms or at all because the number of potential manufacturers is limited and the FDA must inspect any manufacturers for cGMP compliance as part of our marketing application; • a new manufacturer would have to be educated in, or develop substantially equivalent processes for, the production of our product candidates; • our third-party manufacturers might be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any; • contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; • our future contract manufacturers may not perform as agreed, may not devote sufficient resources to our product candidates or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store and distribute our products, if any; • manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards and we have no control over third-party manufacturers’ compliance with these regulations and standards; • we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; • our third-party manufacturers could breach or terminate their agreements with us; • raw materials and components used in the manufacturing process, particularly those for which we have no other source or supplier, may not be available or may not be suitable or acceptable for use due to material or component defects; • our contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; and • our contract manufacturers may have unacceptable or inconsistent product quality success rates and yields, and we have no direct control over our contract manufacturers’ ability to maintain adequate quality control, quality assurance and qualified personnel. 66 Our business could be materially adversely affected by business disruptions to our third-party providers that could materially adversely affect our potential future revenue and financial condition and increase our costs and expenses.
Our anticipated reliance on a limited number of third-party manufacturers exposes us to a number of risks, including the following: • we may be unable to identify manufacturers on acceptable terms or at all because the number of potential manufacturers is limited and the FDA must inspect any manufacturers for cGMP compliance as part of our marketing application; • a new manufacturer would have to be educated in, or develop substantially equivalent processes for, the production of our product candidates; • our third-party manufacturers might be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any; • contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; • our future contract manufacturers may not perform as agreed, may not devote sufficient resources to our product candidates or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store and distribute our products, if any; • manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards and we have no control over third-party manufacturers’ compliance with these regulations and standards; • we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; • our third-party manufacturers could breach or terminate their agreements with us; 66 • raw materials and components used in the manufacturing process, particularly those for which we have no other source or supplier, may not be available or may not be suitable or acceptable for use due to material or component defects; • our contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; and • our contract manufacturers may have unacceptable or inconsistent product quality success rates and yields, and we have no direct control over our contract manufacturers’ ability to maintain adequate quality control, quality assurance and qualified personnel.
In addition, because our approach targets genetically defined cancer patients and not specific tumors based on tumor or cancer types, we are initially pursuing a tumor-agnostic development strategy ( i.e. , pursuing approval for a potential indication based on a specific genetic mutation rather than a specific type of tissue).
In addition, because our approach targets genomically defined cancer patients and not specific tumors based on tumor or cancer types, we are pursuing a tumor-agnostic development strategy (i.e., pursuing approval for a potential indication based on a specific genetic mutation rather than a specific type of tissue).
Patients treated with PC14586 or any of our future product candidates may also be undergoing surgical, radiation and chemotherapy treatments, which can cause side effects or adverse events that are unrelated to our product candidate but may still impact the success of our clinical trials.
Patients treated with rezatapopt or any of our future product 39 candidates may also be undergoing surgical, radiation and chemotherapy treatments, which can cause side effects or adverse events that are unrelated to our product candidate but may still impact the success of our clinical trials.
We may experience delays in obtaining the FDA’s authorization to initiate clinical trials, completing ongoing clinical trials of PC14586 and preclinical studies of our other product candidates and initiating our planned preclinical studies and clinical trials.
We may experience delays in obtaining the FDA’s authorization to initiate clinical trials, completing ongoing clinical trials of rezatapopt and preclinical studies of our other product candidates and initiating our planned preclinical studies and clinical trials.
Therefore, we do not know if our approach of treating patients with genetically defined cancers will be successful, and if our approach is unsuccessful, our business will be materially adversely affected.
Therefore, we do not know if our approach of treating patients with genomically defined cancers will be successful, and if our approach is unsuccessful, our business will be materially adversely affected.
In addition, our ability to raise additional capital may be adversely impacted by potential worsening global economic conditions, inflation expectations, rising interest rates and the disruptions to and volatility in the credit and financial markets in the United States and worldwide resulting from a global pandemic or other public health emergencies, geopolitical tensions (such as the Ukraine-Russia war, the ongoing conflict between Israel and Hamas and trade restrictions between the U.S. and China) among other global conditions affecting financial markets.
In addition, our ability to raise additional capital may be adversely impacted by potential worsening global economic conditions, inflation expectations, rising interest rates and the disruptions to and volatility in the credit and financial markets in the United States and worldwide resulting from a global pandemic or other public health emergencies, geopolitical tensions (such as the Ukraine-Russia war, the conflict in the Middle East and trade restrictions between the U.S. and China) among other global conditions affecting financial markets.
Patients may not be able to tolerate PC14586 or any of our future product candidates in combination with other therapies or dosing of PC14586 or any of our future product candidates in combination with other therapies may have unexpected consequences.
Patients may not be able to tolerate rezatapopt or any of our future product candidates in combination with other therapies or dosing of rezatapopt or any of our future product candidates in combination with other therapies may have unexpected consequences.
Our future financial performance and our ability to successfully develop and, if approved, commercialize PC14586 and future product candidates will depend, in part, on our ability to effectively manage any future growth.
Our future financial performance and our ability to successfully develop and, if approved, commercialize rezatapopt and future product candidates will depend, in part, on our ability to effectively manage any future growth.
Additionally, we rely on our founders and other scientific and clinical advisors and consultants to assist us in formulating our research, development and clinical strategies. These advisors and consultants are not our employees and may have commitments to, or consulting or advisory contracts with, other entities that may limit their availability to us.
Additionally, we rely on our founders, members of our board of directors, and other scientific and clinical advisors and consultants to assist us in formulating our research, development and clinical strategies. These advisors and consultants are not our employees and may have commitments to, or consulting or advisory contracts with, other entities that may limit their availability to us.
We are also aware of selective small molecule inhibitors that are designed to target wild-type p53 containing tumors through the p53-murine double minute 2, or MDM2, interaction, which are in various stages of clinical development being tested by Aileron Therapeutics, Ascentage Pharma, Boehringer Ingelheim, Daiichi Sankyo (out-licensed worldwide rights to Rain Therapeutics), Kartos Therapeutics, Kymera Therapeutics, Otsuka Pharmaceutical, Novartis and Roche, including testing MDM2 inhibitors in combination with a variety of other anti-cancer agents.
We are also aware of selective small molecule inhibitors that are designed to target wild-type p53 containing tumors through the p53-murine double minute 2, or MDM2, interaction, which are in various stages of clinical development being tested by Aileron Therapeutics, Ascentage Pharma, Boehringer Ingelheim, Kartos Therapeutics, Kymera Therapeutics, Otsuka Pharmaceutical, Novartis and Roche, including testing MDM2 inhibitors in combination with a variety of other anti-cancer agents.

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Item 2. Properties

Properties — owned and leased real estate

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Biggest changeItem 2. Pro perties. Our corporate headquarters is located at 1 Research Way, Princeton, New Jersey 08540, where we lease a facility containing 50,581 square feet of office and laboratory space. The lease term extends through 2032, and has a five-year extension option.
Biggest changeItem 2. Pro perties. Our corporate headquarters is located at 400 Alexander Park Drive, Suite 301, Princeton, New Jersey 08540, where we sublease 14,201 square feet of office space. This lease term extends through 2027. We also sublease 3,205 square feet of laboratory space located at 311 Pennington Rocky Hill Road, Hopewell, New Jersey 08534.
We believe that our current facility is suitable and adequate for our current and near term conduct of our business operations and that suitable additional or substitute space at commercially reasonable terms will be available as needed to accommodate any future expansion of our operations.
This lease term extends through 2029, and has a three-year extension option. We believe that our current facilities are suitable and adequate for our current and near term conduct of our business operations and that suitable additional or substitute space at commercially reasonable terms will be available as needed to accommodate any future expansion of our operations.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. Legal Proceedings. From time to time, we may become involved in legal proceedings arising in the ordinary course of our business. As of February 29, 2024, we were not a party to any legal matters or claims that, in the opinion of management, are likely to have a material effect on our business.
Biggest changeItem 3. Legal Proceedings. From time to time, we may become involved in legal proceedings arising in the ordinary course of our business. As of March 3, 2025, we were not a party to any legal matters or claims that, in the opinion of management, are likely to have a material effect on our business.
Regardless of outcome, litigation, or other legal proceedings can have an adverse impact on us because of legal fees and settlement costs, diversion of management resources, and other factors. Item 4. Reserved. 89 PART II
Regardless of outcome, litigation, or other legal proceedings can have an adverse impact on us because of legal fees and settlement costs, diversion of management resources, and other factors. Item 4. Re served. 89 PART II

Item 4. Mine Safety Disclosures

Mine Safety Disclosures — required of mining issuers

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Biggest changeItem 4. Reserved 89 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 90 Item 6. Reserved 91 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 92
Biggest changeItem 4. Reserved 89 PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 90 Item 6. Reserved 90 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 91

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeGoldman Sachs & Co. LLC, BofA Securities, Cowen, and Evercore IS acted as joint book-running managers for the offering. There has been no material change in the planned use of proceeds from the IPO from that described in the prospectus filed with the SEC pursuant to Rule 424(b)(4) under the Securities Act on September 24, 2020.
Biggest changeThere has been no material change in the planned use of proceeds from our initial public offering as described our final prospectus filed with the SEC pursuant to Rule 424(b)(4) under the Securities Act on September 24, 2020. Purchases of Equity Securities by the Issuer and Affiliated Purchases None.
Holders As of February 29, 2024, there were approximately 7 holders of record of our common stock. We believe actual number of stockholders is greater than this number of record holders. The approximate number of holders includes holders who are beneficial owners, but whose shares are held in street name by brokers and other nominees.
Holders As of March 3, 2025 , there were approximately 7 holders of record of our common stock. We believe the actual number of stockholders is greater than this number of record holders. The approximate number of holders includes holders who are beneficial owners, but whose shares are held in street name by brokers and other nominees.
Recent Sales of Unregistered Securities There were no unregistered sales of our equity securities during the fiscal year ended December 31, 2023. Use of Proceeds On September 24, 2020, our registration statement on Form S-1 (File No. 333-248627) relating to our IPO of common stock was declared effective by the SEC.
Recent Sales of Unregistered Securities There were no unregistered sales of our equity securities during the fiscal year ended December 31, 2024. Use of Proceeds Our initial public offering of our common stock was effected pursuant to a registration statement on Form S-1 (File No. 333-248627), which was declared effective by the SEC on September 24, 2020.
Removed
The IPO closed on September 25, 2020 at which time we issued 13,529,750 shares of common stock (including the exercise in full by the underwriters of their option to purchase an additional 1,764,750 shares of common stock) at a public offering price of $18.00 per share.
Removed
We received net proceeds from the IPO of approximately $223.2 million, after deducting the underwriting discounts and commissions of approximately $17.0 million and estimated offering related expenses of approximately $3.3 million. None of the expenses associated with the IPO were paid to directors, officers, persons owning 10% or more of any class of equity securities, or to our affiliates.
Removed
We have a shelf registration statement on Form S-3 (File No. 333-260012), which was declared effective by the SEC on April 28, 2022, pursuant to which we may offer and sell, from time to time, up to $200 million of common stock, preferred stock, various series of debt securities and warrants to purchase any of such securities in one or more registered offerings, and up to $150 million of common stock pursuant to our at-the-market equity offering program, dated October 4, 2021, or the ATM Program.
Removed
During the year ended December 31, 2023, we sold 5,149,446 shares of common stock under the ATM Program at a weighted average price of $6.97 per share for $35.1 million in proceeds, net of fees. As of December 31, 2023, we have approximately $113.8 million remaining in gross proceeds available for future issuances of common stock under the ATM Program.
Removed
There has been no material change in the planned use of proceeds as described in the shelf registration statement. None of the expenses associated with the follow-on offering were paid to directors, officers, persons owning 10% or more of any class of equity securities, or to our affiliates. 90 Purchases of Equity Securities by the Issuer and Affiliated Purchases None.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeResults of Operations Comparison of the Years Ended December 31, 2023 and 2022 The following table summarizes our results of operations (in thousands): Year Ended December 31, Statement of operations data: 2023 2022 Change Operating expenses: Research and development $ 55,885 $ 51,988 $ 3,897 General and administrative 24,247 25,052 (805 ) Total operating expenses 80,132 77,040 3,092 Loss from operations (80,132 ) (77,040 ) (3,092 ) Other income (expense): Interest income, net 11,171 3,627 7,544 Other income (expense), net 3 87 (84 ) Total other income (expense) 11,174 3,714 7,460 Loss before (benefit) provision for income taxes (68,958 ) (73,326 ) 4,368 (Benefit) provision for income taxes 2 (9 ) 11 Net loss $ (68,960 ) $ (73,317 ) $ 4,357 Research and Development Expenses The following table summarizes our research and development expenses incurred during the periods indicated (in thousands): Year Ended December 31, Statement of operations data: 2023 2022 Change Research $ 5,307 $ 6,712 $ (1,405 ) Development 31,740 32,470 (730 ) Personnel related 13,320 9,340 3,980 Stock-based compensation 5,518 3,466 2,052 Total $ 55,885 $ 51,988 $ 3,897 94 Research and development expenses were $55.9 million for the year ended December 31, 2023, compared to $52.0 million for the year ended December 31, 2022.
Biggest changeInterest Income, Net Interest income, net primarily consists of interest income from our interest-bearing cash, cash equivalents, and marketable securities and interest costs related to accretion and amortization of discounts and premiums on marketable securities. 93 Results of Operations Comparison of the Years Ended December 31, 2024 and 2023 The following table summarizes our results of operations (in thousands): Year Ended December 31, Statement of operations data: 2024 2023 Change Operating expenses: Research and development $ 58,527 $ 55,885 $ 2,642 General and administrative 26,921 24,247 2,674 Total operating expenses 85,448 80,132 5,316 Loss from operations (85,448 ) (80,132 ) (5,316 ) Other income (expense): Interest income, net 10,655 11,171 (516 ) Other income (expense), net (16 ) 3 (19 ) Total other income (expense) 10,639 11,174 (535 ) Loss before provision (benefit) for income taxes (74,809 ) (68,958 ) (5,851 ) Provision (benefit) for income taxes (16,100 ) 2 (16,102 ) Net loss $ (58,709 ) $ (68,960 ) $ 10,251 Research and Development Expenses The following table summarizes our research and development expenses incurred during the periods indicated (in thousands): Year Ended December 31, Statement of operations data: 2024 2023 Change Research $ 5,914 $ 5,307 $ 607 Development 35,295 31,740 3,555 Personnel related 13,662 13,320 342 Stock-based compensation 3,656 5,518 (1,862 ) Total $ 58,527 $ 55,885 $ 2,642 Research and development expenses were $58.5 million for the year ended December 31, 2024, compared to $55.9 million for the year ended December 31, 2023.
If our development efforts for our product candidates are successful and result in regulatory approval, or license agreements with third parties, we may generate revenue in the future from product sales. However, there can be no assurance as to when we will generate such revenue, if at all.
If our development efforts for our product candidates are successful and result in regulatory approval, or result in license agreements with third parties, we may generate revenue in the future from product sales or license agreements. However, there can be no assurance as to when we will generate such revenue, if at all.
We may never succeed in achieving regulatory approval for any of our product candidates. As a result of the uncertainties discussed above, we are unable to determine the duration and completion costs of our research and development projects. 93 General and Administrative Expenses General and administrative expenses include personnel costs, expenses for outside professional services and other allocated expenses.
We may never succeed in achieving regulatory approval for any of our product candidates. As a result of the uncertainties discussed above, we are unable to determine the duration and completion costs of our research and development projects. General and Administrative Expenses General and administrative expenses include personnel costs, expenses for outside professional services and other allocated expenses.
We do not currently have any product candidates approved for sale, and we continue to incur significant research and development and general administrative expenses related to our operations. We initiated a Phase 1/2 clinical trial, PYNNACLE, in October 2020 for our lead product candidate, PC14586 (rezatapopt).
We do not currently have any product candidates approved for sale, and we continue to incur significant research and development and general administrative expenses related to our operations. We initiated a Phase 1/2 clinical trial, PYNNACLE, in October 2020 for our lead product candidate, rezatapopt.
Investing Activities Our investing activities used $50.5 million of cash during the year ended December 31, 2023, which consisted primarily of purchases of marketable securities of $220.5 million, along with purchase of property and equipment of $1.0 million, partially offset by maturities of marketable securities of $171.0 million.
Our investing activities used $50.5 million of cash during the year ended December 31, 2023, which consisted primarily of purchases of marketable securities of $220.5 million, along with purchase of property and equipment of $1.0 million, offset by maturities of marketable securities of $171.0 million.
We expect to continue to incur significant losses for the foreseeable future. 92 Our ability to generate product revenue will depend on the successful development, regulatory approval, and eventual commercialization of one or more of our product candidates.
We expect to continue to incur significant losses for the foreseeable future. Our ability to generate product revenue will depend on the successful development, regulatory approval, and eventual commercialization of one or more of our product candidates.
To date, there have not been any material adjustments to our prior estimates of accrued research and development expenses. Recent Accounting Pronouncements For a description of recent accounting pronouncements, see Note 2 of the notes to our audited consolidated financial statements for the year ended December 31, 2023 included elsewhere in this Annual Report on Form 10-K. Item 7A.
To date, there have not been any material adjustments to our prior estimates of accrued research and development expenses. 99 Recent Accounting Pronouncements For a description of recent accounting pronouncements, see Note 2 of the notes to our audited consolidated financial statements for the year ended December 31, 2024 included elsewhere in this Annual Report on Form 10-K. Item 7A.
The following summary should be read in conjunction with Note 2 of the notes to our audited consolidated financial statements for the year ended December 31, 2023 included elsewhere in this Annual Report on Form 10-K. 98 Research and Development Costs, Accrued Research and Development Costs and Related Prepaid Expenses Research and development costs are expensed as incurred.
The following summary should be read in conjunction with Note 2 of the notes to our audited consolidated financial statements for the year ended December 31, 2024 included elsewhere in this Annual Report on Form 10-K. Research and Development Costs, Accrued Research and Development Costs and Related Prepaid Expenses Research and development costs are expensed as incurred.
The timing and amount of our operating expenditures will depend largely on: • the timing and progress of preclinical and clinical development activities; • the number and scope of preclinical and clinical programs we decide to pursue; • the timing and amount of milestone payments we may receive under any future collaboration agreements; • our ability to maintain future licenses and research and development programs and to establish new collaboration and/or in-licensing arrangements; • the costs involved in prosecuting and enforcing patent and other intellectual property claims; • the cost and timing of regulatory approvals; • the costs involved in implementing our announced reduction in force and related reorganization; and • our efforts to manage our office and laboratory headquarters, enhance operational systems and hire additional personnel to support development of our product candidates and satisfy our obligations as a public company.
The timing and amount of our operating expenditures will depend largely on: • the timing and progress of preclinical and clinical development activities; • the number and scope of preclinical and clinical programs we decide to pursue; • the timing and amount of milestone payments we may receive under any future collaboration agreements; • our ability to maintain future licenses and research and development programs and to establish new collaboration and/or in-licensing arrangements; • the costs involved in prosecuting and enforcing patent and other intellectual property claims; • the cost and timing of regulatory approvals; and • our efforts to manage our office and laboratory headquarters, enhance operational systems and hire additional personnel to support development of our product candidates and satisfy our obligations as a public company.
Interest Income, Net Interest income, net primarily consists of interest income from our interest-bearing cash, cash equivalents and marketable securities and interest costs related to amortization of premiums and discounts on marketable securities. Interest income, net was $11.2 million for the year ended December 31, 2023, compared to $3.7 million for the year ended December 31, 2022.
Interest Income, Net Interest income, net primarily consists of interest income from our interest-bearing cash, cash equivalents, and marketable securities and interest costs related to amortization of premiums and discounts on marketable securities. Interest income, net was $10.7 million for the year ended December 31, 2024, compared to $11.2 million for the year ended December 31, 2023.
We have incurred additional expenses as a public company, including expenses related to compliance with the rules and regulations of the SEC, and those of any national securities exchange on which our securities are traded, additional insurance expenses, investor relations activities and other administrative and professional services.
We have incurred expenses related to compliance with the rules and regulations of the SEC, and those of any national securities exchange on which our securities are traded, additional insurance expenses, investor relations activities and other administrative and professional services.
We have not yet commercialized any of our product candidates and we do not expect to generate revenue from sales of any product candidates for several years, if at all. As of December 31, 2023, we had cash, cash equivalents, and marketable securities of $228.6 million and an accumulated deficit of $310.0 million.
We have not yet commercialized any of our product candidates and we do not expect to generate revenue from sales of any product candidates for several years, if at all. As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $183.3 million and an accumulated deficit of $368.7 million.
We have incurred an accumulated deficit of $310.0 million through December 31, 2023. We expect to incur substantial additional losses in the future as we expand our research and development activities. 96 Our cash operating expenditures were $55.7 million in 2023 and $63.8 million in 2022.
We have incurred an accumulated deficit of $368.7 million through December 31, 2024. We expect to incur substantial additional losses in the future as we expand our research and development activities. Our cash operating expenditures were $51.3 million in 2024 and $55.7 million in 2023.
In particular, with respect to internal costs, several of our departments support multiple product candidate research and development programs, and therefore the costs cannot be allocated to a particular product candidate or development program. Substantially all of our research and development costs are associated with our lead product candidate, PC14586 (rezatapopt).
In particular, with respect to internal costs, several of our departments support multiple product candidate research and development programs, and therefore the costs cannot be allocated to a particular product candidate or development program. Substantially all of our research and development costs are associated with our lead product candidate, rezatapopt. We initiated a Phase 1/2 clinical trial in October 2020.
Our net losses were $69.0 million, $73.3 million, and $57.8 million for the years ended December 31, 2023, 2022, and 2021, respectively. As of December 31, 2023, we had an accumulated deficit of $310.0 million.
Our net losses were $58.7 million, $69.0 million, and $73.3 million for the years ended December 31, 2024, 2023, and 2022, respectively. As of December 31, 2024, we had an accumulated deficit of $368.7 million.
In July 2023, we concluded our End of Phase 1 meeting with the FDA with alignment on the recommended Phase 2 dose and key elements of the single arm, Phase 2 registrational portion of the PYNNACLE study.
In July 2023, we met with the FDA at an End of Phase 1 meeting where alignment was obtained on the recommended Phase 2 dose and key elements of the single arm, Phase 2 registrational portion of the PYNNACLE study.
These contracts generally provide for termination on notice, and therefore are cancelable contracts and not included in the table of contractual obligations and commitments. In January 2021, we signed a lease for 50,581 square feet of office and laboratory space at 1 Research Way in Princeton, New Jersey. That lease term extends through 2032, has a five-year extension option.
These contracts generally provide for termination on notice, and therefore are cancelable contracts and not included in the table of contractual obligations and commitments. In January 2021, we signed a lease for 50,581 square feet of office and laboratory space at One Research Way in Princeton, New Jersey, or the One Research Way Lease.
General and Administrative Expenses General and administrative expenses were $24.2 million for the year ended December 31, 2023, compared to $25.1 million for the year ended December 31, 2022.
General and Administrative Expenses General and administrative expenses were $26.9 million for the year ended December 31, 2024, compared to $24.2 million for the year ended December 31, 2023.
Financing Activities Our financing activities provided $35.6 million of cash during the year ended December 31, 2023. This consisted of $35.1 million of common stock issued under our ATM Program, net of issuance costs, and $0.5 million of proceeds from the exercise of stock options and issuance of common stock under the 2020 ESPP.
Financing Activities Our financing activities provided $0.3 million of cash during the year ended December 31, 2024 which consisted of $0.3 million of proceeds from the exercise of stock options and issuance of common stock under the 2020 ESPP. Our financing activities provided $35.6 million of cash during the year ended December 31, 2023.
We have increased our headcount significantly to support our operations as a public company. We also expect to increase our general and administrative expenses as we advance our product candidates through preclinical research and development, manufacturing, clinical development, and commercialization.
We also expect to increase our general and administrative expenses as we advance our product candidates through preclinical research and development, manufacturing, clinical development, and commercialization.
We dosed our first patient in this clinical trial in the fourth quarter of 2020. In October 2023, we presented our updated Phase 1 clinical data for PC14586 at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Meeting.
In October 2023, we presented our updated Phase 1 clinical data for rezatapopt at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Annual Meeting. We dosed our first patient in the pivotal Phase 2 monotherapy portion of the PYNNACLE study in the first quarter of 2024.
The increase of $3.9 million was primarily due to the following: • $6.0 million increase in expenses for personnel related costs and stock-based compensation, primarily driven by increased headcount; offset by • $2.1 million decrease in research and development expenses largely driven by decreased contractual research organization costs.
The increase of $2.6 million was primarily due to the following: • $4.1 million increase in research and development expenses largely driven by increased contractual research organization costs; offset by • $1.5 million decrease in expenses for personnel related costs and stock-based compensation, primarily as a result of the restructuring that occurred in January 2024.
If we are not able to secure adequate additional funding, we may be forced to make reductions in spending, extend payment terms with suppliers, liquidate assets where possible, and/or suspend or curtail planned programs. Any of these actions could materially and adversely affect our business, financial condition, results of operations and prospects.
If we are not able to secure adequate additional funding, we may be forced to make reductions in spending, extend payment terms with suppliers, liquidate assets where possible, and/or suspend or curtail planned programs.
Cash Flows The following table summarizes our cash flows for the period indicated (in thousands): Year Ended December 31, 2023 2022 2021 Cash used in operating activities $ (55,657 ) $ (63,760 ) $ (46,571 ) Cash used in investing activities (50,545 ) (1,368 ) (143,584 ) Cash provided by financing activities 35,577 958 2,022 Impact of exchange rates on cash, cash equivalents, and restricted cash 34 — — Net (decrease) increase in cash, cash equivalents, and restricted cash $ (70,591 ) $ (64,170 ) $ (188,133 ) 97 Operating Activities Net cash used in operating activities for the year ended December 31, 2023, was $55.7 million, which consisted primarily of net loss of $69.0 million decreased by non-cash charges of $7.9 million and a net change of $5.4 million in our net operating assets and liabilities.
Any of these actions could materially and adversely affect our business, financial condition, results of operations and prospects. 97 Cash Flows The following table summarizes our cash flows for the period indicated (in thousands): Year Ended December 31, 2024 2023 2022 Cash used in operating activities $ (51,282 ) $ (55,657 ) $ (63,760 ) Cash used in investing activities 53,352 (50,545 ) (1,368 ) Cash provided by financing activities 313 35,577 958 Impact of exchange rates on cash, cash equivalents, and restricted cash (35 ) 34 — Net (decrease) increase in cash, cash equivalents, and restricted cash $ 2,348 $ (70,591 ) $ (64,170 ) Operating Activities Net cash used in operating activities for the year ended December 31, 2024, was $51.3 million, which consisted primarily of net loss of $58.7 million decreased by non-cash charges of $9.0 million and decreased by a net change of $1.6 million in our net operating assets and liabilities.
These website addresses are intended to be inactive, textual references only. None of the materials on, or accessible through, these websites are part of this report or are incorporated by reference herein.
None of the materials on, or accessible through, these websites are part of this report or are incorporated by reference herein.
Our investing activities used $1.4 million of cash during the year ended December 31, 2022, which consisted primarily of purchases of marketable securities of $229.2 million, along with purchase of property and equipment of $8.0 million, partially offset by maturities of marketable securities of $235.8 million.
Investing Activities Our investing activities provided $53.4 million of cash during the year ended December 31, 2024, which consisted primarily of maturities of marketable securities of $202 million, offset by purchases of marketable securities of $148.3 million, along with purchase of property and equipment of $0.7 million.
Net cash used in operating activities for the year ended December 31, 2022, was $63.8 million, which consisted primarily of net loss of $73.3 million decreased by non-cash charges of $10.1 million and a net change of $0.6 million in our net operating assets.
Net cash used in operating activities for the year ended December 31, 2023, was $55.7 million, which consisted primarily of net loss of $69.0 million decreased by non-cash charges of $7.9 million and a net change of $5.4 million in our net operating assets and liabilities.
A discussion of our financial performance for the year ended December 31, 2023 as compared to the year ended December 31, 2022 appears below under the captions “Results of Operations” and “Liquidity and Capital Resources.” A discussion of our financial performance for the year ended December 31, 2022 compared to the year ended December 31, 2021 can be found in our Annual Report filed on Form 10-K, in the “Part II, Item 7, Management’s Discussion and Analysis of Financial Condition and Results of Operations”, under the same captions, filed with the SEC on March 1, 2023, which is available free of charge on the SEC’s website at www.sec.gov and our Investor Relations website at ir.pmvpharma.com/financial-information/sec-filings .
A discussion of our financial performance for the year ended December 31, 2024 as compared to the year ended December 31, 2023 appears below under the captions “Results of Operations” and “Liquidity and Capital Resources.” A discussion of our financial performance for the year ended December 31, 2023 compared to the year ended December 31, 2022 can be found in our Annual Report filed on Form 10-K, in the “Part II, Item 7.
Liquidity and Capital Resources Our financial condition is summarized as follows (in thousands): As of December 31, 2023 2022 Change Financial assets: Cash and cash equivalents $ 37,706 $ 108,297 $ (70,591 ) Marketable securities – current 165,351 132,757 32,594 Marketable securities – noncurrent 25,505 2,495 23,010 Total financial assets $ 228,562 $ 243,549 $ (14,987 ) Working capital: Current assets $ 207,409 $ 247,006 $ (39,597 ) Current liabilities 14,029 10,832 3,197 Total working capital $ 193,380 $ 236,174 $ (42,794 ) 95 Sources of Liquidity Since our inception, we have not generated any revenue from any product sales or any other sources and have incurred significant operating losses and negative cash flows from our operations.
Liquidity and Capital Resources Our financial condition is summarized as follows (in thousands): As of December 31, 2024 2023 Change Financial assets: Cash and cash equivalents $ 40,876 $ 37,706 $ 3,170 Marketable securities – current 128,578 165,351 (36,773 ) Marketable securities – noncurrent 13,843 25,505 (11,662 ) Total financial assets $ 183,297 $ 228,562 $ (45,265 ) Working capital: Current assets $ 175,658 $ 207,409 $ (31,751 ) Current liabilities 14,370 14,029 341 Total working capital $ 161,288 $ 193,380 $ (32,092 ) 95 Sources of Liquidity Since our inception, we have not generated any revenue from any product sales or any other sources and have incurred significant operating losses and negative cash flows from our operations.
Critical Accounting Policies and Estimates The preparation of our consolidated financial statements in conformity with accounting principles generally accepted in the United States requires us to make estimates and judgments that affect the amounts reported in those consolidated financial statements and accompanying notes.
This consisted of $35.1 million of common stock issued under our ATM Program, net of issuance costs, and $0.5 million of proceeds from the exercise of stock options and issuance of common stock under the 2020 ESPP. 98 Critical Accounting Policies and Estimates The preparation of our consolidated financial statements in conformity with accounting principles generally accepted in the United States requires us to make estimates and judgments that affect the amounts reported in those consolidated financial statements and accompanying notes.
We expect our research and development expenses to increase substantially in absolute dollars in the future as we advance our product candidates into and through clinical trials and pursue regulatory approval of our product candidates. The process of conducting the necessary clinical research to obtain regulatory approval is costly and time-consuming.
MDACC dosed its first patient for this Phase 1b study in the first quarter of 2025. We expect our research and development expenses to increase substantially in absolute dollars in the future as we advance our product candidates into and through clinical trials and pursue regulatory approval of our product candidates.
We initiated a Phase 1/2 clinical trial, PYNNACLE, in October 2020 for our lead product candidate, PC14586. In October 2020, we were granted FDA Fast Track Designation of PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation.
Our strategy is to seek approval under an accelerated pathway, and we believe our PYNNACLE clinical trial has the potential to serve as a pivotal study. In October 2020, we were granted FDA Fast Track designation of rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation.
We have a shelf registration statement on Form S-3 on file with the SEC, which registers the offering, issuance, and sale of up to $200 million of various equity and debt securities and up to $150 million of common stock pursuant to our ATM Program.
On November 20, 2024 we filed a shelf registration statement on Form S-3 (File No. 333-283349) with the SEC and a prospectus supplement, which registered the offering, issuance and sale of up to $200,000,000 of various equity and debt securities and up to $113.8 million of common stock pursuant to an at-the-market equity offering program with Jefferies LLC, dated October 4, 2021, or the ATM Program.
Based on our research and development plans, we expect that our cash balances as of December 31, 2023 will be sufficient to fund our operations at least into the second half of 2026. We have based this estimate on assumptions that may prove to be wrong, however, and we could use our capital resources sooner than we expect.
We have based this estimate on assumptions that may prove to be wrong, however, and we could use our capital resources sooner than we expect.
The increase of $7.5 million in 2023 is driven by increased interest rates from cash investments in marketable securities and U.S. treasuries.
The decrease of $0.5 million in 2024 was primarily due to decreased interest rates from cash investments in marketable securities and U.S. treasuries.
In October 2020, we were granted FDA Fast Track Designation of PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation. We dosed our first patient in this clinical trial in the fourth quarter of 2020.
In October 2020, we were granted FDA Fast Track designation of rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation. In October 2023, we presented our updated Phase 1 clinical data for rezatapopt at the 2023 AACR-NCI-EORTC International Conference 92 on Molecular Targets and Cancer Therapeutics Meeting.
We expect the reduction in workforce to be substantially completed by June 30, 2024, and fully completed by the end of the third quarter of 2024. As announced, we are taking these steps in order to streamline operations, reduce costs and preserve capital as we advance our lead candidate, PC14586, into late-stage development.
We undertook these steps in order to streamline operations, reduce costs and 96 preserve capital as we advance our lead candidate, rezatapopt, into late-stage development.
The decrease of $0.9 million was primarily due to the following: • $1.0 million decrease in director and officer insurance fees and a $0.8 million decrease in facility related costs due to the expiration of three leases; offset by • $0.3 million increase in personnel costs driven by an increase in stock compensation and a $0.6 million increase in general and administrative consulting costs.
The increase of $2.7 million was primarily due to the following: 94 • $5.3 million increase in facility related costs due to the termination of our prior lease for our headquarters at One Research Way in Princeton, New Jersey, and $0.4 million increase in general and administrative consulting costs; offset by • $2.5 million decrease in expenses for personnel related costs and stock-based compensation driven by the restructuring that occurred in January 2024, and $0.5 million decrease in director and officer insurance fees.
The change in our net operating assets and liabilities was primarily due to an increase in prepaid expenses and other assets, an decrease in accrued expenses, and a decrease in outstanding payables.
The non-cash charges primarily consisted of stock-based compensation of $8.9 million, depreciation of $1.1 million, and accretion of discounts on marketable securities of $5.4 million. The change in our net operating assets and liabilities was primarily due to an increase in operating lease liabilities and other assets and an increase in accrued expenses.
During the year ended December 31, 2023, we sold 5,149,446 shares of common stock under the ATM Program at a weighted average price of $6.97 per share for $35.1 million in proceeds, net of fees. As of December 31, 2023, we have approximately $113.8 million remaining in gross proceeds available for future issuances of common stock under the ATM Program.
The SEC declared the registration statement effective on November 27, 2024. During the year ending December 31, 2024, we did not sell any shares of our common stock pursuant to the ATM Program. As of December 31, 2024, we had approximately $113.8 million remaining in gross proceeds available for future issuances of common stock under the ATM Program.
Plan of Operation and Future Funding Requirements We use our capital resources primarily to fund operating expenses, mainly research and development expenditures. On January 18, 2024, we announced a restructuring plan involving the reduction of our workforce by approximately 30% of our employees.
On January 18, 2024, we announced a restructuring plan involving the reduction of our workforce by approximately 30% of our employees and incurred costs of $0.6 million in connection therewith during the fiscal year ending on December 31, 2024.
Payments under this lease will total $19.9 million through May 2032. Amounts related to future lease payments under the 1 Research Way lease as of December 31, 2023, totaled $15.5 million, with $1.6 million to be paid within the next 12 months.
The 400 Alexander Sublease term extends until February 2027, and the 311 Pennington Sublease term extends until December 2029 and has a three-year extension option. Amounts related to future lease payments for 311 Pennington Sublease as of December 31, 2024, totaled $0.7 million with $0.1 million to be paid within the next 12 months.
Removed
In October 2023, we presented our updated Phase 1 clinical data for PC14586 at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Meeting. The pivotal Phase 2 monotherapy portion of our PYNNACLE trial is planned to be initiated in 1Q of 2024.
Added
Management’s Discussion and Analysis of Financial Condition and Results of Operations”, under the same captions, filed with the SEC on February 29, 2024, which is available free of charge on the SEC’s website at www.sec.gov and our Investor Relations website at ir.pmvpharma.com/financial-information/sec-filings . These website addresses are intended to be inactive, textual references only.
Removed
In addition, in December 2022, we opened a separate Phase 1b arm within the existing Phase 1/2 PYNNACLE trial combining PC14586 with KEYTRUDA® (pembrolizumab) in collaboration with Merck and Co.
Added
We are continuing to dose patients in the pivotal Phase 2 monotherapy portion of our PYNNACLE trial, and have activated over 90% of sites globally across the U.S., U.K., Europe and Asia-Pacific. We also expect to provide interim data on the Phase 2 monotherapy registrational portion of the PYNNACLE trial by mid-2025.
Removed
Furthermore, we have incurred and will continue to incur additional costs associated with operating as a public company that we did not experience as a private company.
Added
In October 2024, we discontinued enrollment in the Phase 1b combination arm of the PYNNACLE trial evaluating rezatapopt in combination with Merck and Co.’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors harboring a TP53 Y220C mutation.
Removed
In addition, in December 2022, we opened a separate Phase 1b arm within the existing Phase 1/2 clinical trial combining PC14586 with KEYTRUDA® (pembrolizumab) in collaboration with Merck and Co.
Added
Additionally, we announced that we are collaborating with the MDACC and MSK to support an investigator-initiated Phase 1b study, which is designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of rezatapopt monotherapy in combination with azacitidine in R/R AML and MDS patients harboring a TP53 Y220C mutation.
Removed
Interest Income, Net Interest income, net primarily consists of interest income from our interest-bearing cash, cash equivalents and marketable securities and interest costs related to accretion of premiums and amortization of discounts on marketable securities.
Added
MDACC dosed its first patient for this Phase 1b study in the first quarter of 2025. 91 In January 2024, we announced a restructuring plan involving the reduction of our workforce by approximately 30%.
Removed
We have financed our operations primarily through issuances of our convertible preferred and common stock. In July 2020, we sold an aggregate of 5,321,864 shares of our Series D convertible preferred stock to accredited investors, generating gross proceeds of $70.0 million.
Added
This workforce reduction resulted in non-recurring charges of $0.6 million in fiscal year ended December 31, 2024, consisting primarily of employee severance and benefit costs associated with the restructuring. We undertook these steps in order to streamline operations, reduce costs and preserve capital as we advance into late-stage development of rezatapopt.
Removed
In September 2020, we completed an IPO of 13,529,750 shares of our common stock, which includes the exercise in full by the underwriters of their option to purchase 1,764,750 additional shares of common stock, at a public offering price of $18.00 per share for aggregate gross proceeds of $243.5 million.
Added
We recorded these charges in research and development expenses in the accompanying consolidated statements of operations and comprehensive loss based on responsibilities of the impacted employees.
Removed
We received $223.2 million in net proceeds after deducting underwriting discounts and commissions and other offering expenses payable by us.
Added
We are continuing to dose patients and have activated over 90% of sites globally across the U.S., U.K., Europe and Asia-Pacific, in the registrational, tumor-agnostic PYNNACLE Phase 2 trial of rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation and KRAS wild-type.
Removed
The non-cash charges primarily consisted of stock-based compensation of $10.2 million, depreciation of $0.3 million, and non-cash lease expense of $0.3 million, partially offset by changes in premiums on marketable securities of $0.6 million.
Added
We also expect to provide interim data on the Phase 2 monotherapy registrational portion of the PYNNACLE trial by mid-2025. In October 2024, we discontinued enrollment in the Phase 1b combination arm of the PYNNACLE trial evaluating rezatapopt in combination with Merck and Co.’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors harboring a TP53 Y220C mutation.
Removed
Our financing activities provided $1.0 million of cash during the year ended December 31, 2022, which consisted primarily of common stock issued under the employee stock purchase plan and proceeds from the exercise of stock options.
Added
Additionally, we announced that we are collaborating with the MDACC and MSK to support an investigator-initiated Phase 1b study, which is designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of rezatapopt monotherapy in combination with azacitidine in R/R AML and MDS patients harboring a TP53 Y220C mutation.
Added
The process of conducting the necessary clinical research to obtain regulatory approval is costly and time-consuming.
Added
Refer to Note 12 of the notes to our audited consolidated financial statements for the year ended December 31, 2024 included elsewhere in this Annual Report on Form 10-K for details on the restructuring.
Added
We have financed our operations primarily through issuance and sales of our equity securities.
Added
On August 5, 2024, we entered into a Lease Termination Agreement, or the Termination Agreement, with BMR-One Research Way LLC, a Delaware limited liability company, or the Landlord, to terminate the One Research Way Lease.
Added
We and the Landlord agreed to terminate the One Research Way Lease effective as of September 30, 2024, contingent on the sale of the property by the Landlord to a prospective new buyer, or the Contingency.
Added
Pursuant to the Termination Agreement, and subject to the Contingency, we agreed to surrender our then-current headquarters at One Research Way and pay a total termination fee of approximately $1.42 million. The Contingency was satisfied in October 2024 and we paid the termination fee to the Landlord in October 2024.
Added
No further amounts or payments related to the One Research Way Lease are owed.
Added
The foregoing descriptions of the Termination Agreement is not complete and is qualified in its entirety by reference to the full text of the Termination Agreement, a copy of which was filed as Exhibit 10.1 to our Form 8-K filed with the SEC on August 8, 2024.
Added
In September 2024, we signed two subleases, one for 14,201 square feet of office space at 400 Alexander Park Drive, Suite 301, in Princeton, New Jersey, to be used as our new headquarters, or the 400 Alexander Sublease, and the other for 3,205 square feet of office and laboratory space at 311 Pennington Rocky Hill in Hopewell, New Jersey, to be used for our new laboratory space, or the 311 Pennington Sublease.
Added
Amounts related to future lease payments for 400 Alexander Sublease as of December 31, 2024, totaled $0.7 million with $0.3 million to be paid within the next 12 months. Plan of Operation and Future Funding Requirements We use our capital resources primarily to fund operating expenses, mainly research and development expenditures.
Added
Based on our research and development plans, we expect that our cash, cash equivalents, and marketable securities balances as of December 31, 2024 will be sufficient to fund our planned operations at least through the end of 2026.

Other PMVP 10-K year-over-year comparisons