New England Journal of Medicine Publishes First-in-Human Rezatapopt Data Showing Selective Reactivation of Mutant p53 in Advanced Solid Tumors

PRINCETON, N.J., Feb. 26, 2026 (GLOBE NEWSWIRE) -- PMV Pharmaceuticals, Inc. (("PMV Pharma" or the "Company", NASDAQ:PMVP), a precision oncology company pioneering the discovery and development of small molecule therapies targeting p53, today announced that results from the Phase 1, first-in-human portion of the ongoing Phase 1/2 PYNNACLE study evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation were published in the New England Journal of Medicine (NEJM). The publication provides a summary of the Phase 1 safety and efficacy results across 77 patients.

The study published in NEJM entitled, "Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C-Mutated Tumors," highlighted the antitumor activity of rezatapopt in heavily pretreated patients across multiple solid tumor-types establishing proof-of-concept for p53 reactivation. All responding patients had a TP53 Y220C mutation and were KRAS wild-type. The manuscript can be accessed here.

In the Phase 1 portion of the PYNNACLE clinical trial, 77 heavily pretreated patients with advanced solid tumors harboring a TP53 Y220C mutation received oral rezatapopt across dose-escalation cohorts to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D), characterize safety, pharmacokinetics, and biomarker effects. Rezatapopt was generally well tolerated; dose-limiting toxicities were infrequent, supporting selection of the RP2D. Objective responses were observed across multiple tumor types. Clinical activity and biomarker data were consistent with selective binding to the Y220C pocket and restoration of wild-type p53 tumor suppressor function.

"Publication of the rezatapopt Phase 1 results in the New England Journal of Medicine underscores the emerging clinical impact of reactivating p53 in patients whose cancers are driven by a TP53 Y220C mutation," said Deepika Jalota, Pharm.D., Chief Development Officer of PMV Pharma. "These peer-reviewed findings further validate our scientific approach, support our registrational Phase 2 strategy and our plan to submit a New Drug Application in platinum-resistant/refractory ovarian cancer in the first quarter of 2027. We remain focused on advancing rezatapopt as a potential first-in-class therapy for ovarian cancer patients harboring a TP53 Y220C mutation, an area of high unmet medical need."

In October 2025, the Company presented updated interim clinical results from the Phase 2 pivotal portion of the PYNNACLE study, highlighting confirmed responses in patients whose tumors were TP53 Y220C mutated and KRAS wild-type across eight tumor types, including ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder cancers, and ampullary carcinoma. As of the September 4, 2025 data cutoff date, the overall response rate (ORR) across all cohorts was 34% (35/103 patients), with an ORR of 46% (22/48 patients) in ovarian cancer per investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including confirmed and unconfirmed responses. Across all cohorts, the median time to response was 1.3 months, and the median duration of response was 7.6 months. In the ovarian cancer cohort, the median time to response was 1.3 months and the median duration of response was 8.0 months.

About Rezatapopt

Rezatapopt (PC14586) is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the pocket in the p53 Y220C mutant protein, restoring the wild-type tumor-suppressor function. The U.S. Food and Drug Administration granted Fast Track designation to rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors with a p53 Y220C mutation.

About the PYNNACLE Clinical Trial

The ongoing Phase 1/2 PYNNACLE clinical trial is evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation. The primary objective of the Phase 1 portion of the clinical trial was to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) of rezatapopt when administered orally to patients. Safety, tolerability, pharmacokinetics and effects on biomarkers were also assessed. The Phase 2 portion is a registrational, single arm, expansion basket clinical trial comprising five cohorts (ovarian, lung, breast, and endometrial cancers, and other solid tumors) with the primary objective of evaluating the efficacy of rezatapopt at the RP2D in patients with TP53 Y220C and KRAS wild-type advanced solid tumors. For more information about the Phase 1/2 PYNNACLE clinical trial, refer to www.clinicaltrials.gov (NCT trial identifier NCT04585750).

About PMV Pharma

PMV Pharma is a precision oncology company pioneering the discovery and development of small molecule therapies targeting p53. TP53 mutations are found in approximately half of all cancers. The Company's co-founder, Dr. Arnold Levine, established the field of p53 biology when he discovered the p53 protein in 1979. Bringing together leaders in the field to utilize more than four decades of p53 biology, PMV Pharma combines unique biological understanding with a pharmaceutical development focus. PMV Pharma is headquartered in Princeton, New Jersey. For more information, please visit www.pmvpharma.com.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the Company's clinical development activities, future plans, projected timelines or expectations for rezatapopt, including targeted timelines for the Company's New Drug Application submission and initial U.S. Food and Drug Administration (FDA) approval for platinum-resistant /refractory ovarian cancer, ongoing safety and response rate of participants in the PYNNACLE study, as well as the adequacy of the data from clinical trials to support proof-of-concept and/or the Company's pursuit of regulatory approval, and expectations regarding timing and success of the Phase 2 portion of the current clinical trial for rezatapopt. Any forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the Company's preclinical studies and clinical trials may not be successful; the FDA may not agree with the Company's interpretation of the data from clinical trials of its product candidates; the Company may decide, or the FDA may require the Company, to conduct additional clinical trials or to modify its ongoing clinical trials, which could result in enrollment or other delays to the Company's anticipated timelines; the Company may experience delays in the commencement, enrollment, completion, or analysis of clinical testing for its product candidates, or significant issues regarding the adequacy of the Company's clinical trial designs or the execution of its clinical trials may arise, which could result in increased costs and delays, or limit the Company's ability to pursue or obtain regulatory approval; the commencement, enrollment, and completion of clinical trials and the reporting of data; a global pandemic, other public health emergencies or geopolitical tensions or conflicts may disrupt the Company's business and that of the third parties on which the Company is dependent on, including delaying or otherwise disrupting the Company's clinical trials and preclinical studies, manufacturing and supply chain, or impairing employee productivity; the Company's product candidates may not receive regulatory approval or be successfully commercialized; unexpected adverse side effects or inadequate therapeutic efficacy of the Company's product candidates could delay or prevent regulatory approval or commercialization; the Company may not be able to obtain additional financing on terms acceptable or at all; as well as those risks and uncertainties set forth in the section entitled "Risk Factors" in the Company's Annual Report on Form 10-K, filed with the Securities and Exchange Commission (the "SEC") on March 3, 2025, the Company's Quarterly Report on Form 10-Q for the three months ended March 31, 2025, filed with the SEC on May 9, 2025, and the Company's Quarterly Report on Form 10-Q for the three months ended June 30, 2025, filed with the SEC on August 7, 2025, and its other filings filed with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

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