PMV Pharmaceuticals Q3 2024 Financial Results

PMV Pharmaceuticals, Inc., a leader in precision oncology, has recently provided an update on their progress in the ongoing Phase 2 portion of the PYNNACLE clinical trial. This trial focuses on evaluating rezatapopt, a small molecule therapy, as a monotherapy in patients with TP53 Y220C and KRAS wild-type advanced solid tumors. The company announced that more than 75% of trial sites have been activated across the United States, Europe, and Asia-Pacific, with an interim analysis anticipated by mid-2025.

Dr. David Mack, President and CEO of PMV Pharma, expressed optimism about the current progress. The Phase 2 monotherapy portion of the PYNNACLE trial is designed as a multicenter, single-arm, registrational trial, assessing 2000 mg of rezatapopt once daily. The primary evaluation criterion is the overall response rate as reviewed by a blinded independent central panel. This segment aims to enroll 114 patients across five cohorts at approximately 60 sites.

Additionally, PMV Pharmaceuticals has teamed up with the MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center to initiate a Phase 1b study. This investigation will assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of rezatapopt alone and in combination with azacitidine in patients with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) harboring a TP53 Y220C mutation. Enrollment is anticipated to commence in the first quarter of 2025.

In September 2024, PMV Pharmaceuticals presented data on the food effect of rezatapopt at the American College of Clinical Pharmacology Annual Conference. The findings indicated that patients who took rezatapopt with food had a significant increase in drug exposure levels, as measured by AUC0-24 and Cmax, by 42% and 40%, respectively. The variability in exposure was also reduced. These results confirmed that the 2000 mg once-daily dose, when taken with food, was well-tolerated and associated with fewer gastrointestinal adverse events compared to higher doses in a fasted state. Consequently, the 2000 mg dose taken with food was recommended for the ongoing Phase 2 study.

The Phase 1b PYNNACLE trial also explored a combination of rezatapopt with Merck’s KEYTRUDA® (pembrolizumab). However, due to dose-limiting toxicities and limited clinical benefit at the established maximum tolerated dose of 500 mg of rezatapopt daily with 200 mg of pembrolizumab every three weeks, PMV Pharma decided to discontinue this combination arm.

Financially, PMV Pharmaceuticals ended the third quarter with $197.9 million in cash, cash equivalents, and marketable securities, compared to $238.1 million the previous year. The net cash used in operations for the first nine months of 2024 was $34.6 million, a decrease from the $43.6 million used in the same period in 2023. The net loss for the third quarter was $19.2 million, up from $16.6 million in the third quarter of 2023, primarily due to increased research and development expenses.

Research and development expenses rose to $16.9 million in the third quarter of 2024, from $13.6 million in the same period the previous year, reflecting ongoing efforts to advance their lead product candidate. General and administrative expenses decreased to $4.9 million, down from $6.0 million, mainly due to reduced facility and operational costs.

Rezatapopt, also known as PC14586, is a pioneering small molecule designed to reactivate the p53 protein by binding to its Y220C mutant form, restoring its tumor-suppressing function. The U.S. FDA granted Fast Track designation to rezatapopt for treating patients with locally advanced or metastatic solid tumors with a TP53 Y220C mutation.

The PYNNACLE clinical trial's Phase 1/2 stages are aimed at determining the maximum tolerated dose and recommended Phase 2 dose of rezatapopt, assessing its safety, tolerability, pharmacokinetics, and effects on biomarkers. In Phase 1, a 38% overall response rate was achieved in the 16 evaluable patients at the recommended Phase 2 dose. The ongoing Phase 2 trial is an expansion basket trial including patients with various advanced solid tumors, such as ovarian, lung, breast, and endometrial cancers, along with other solid tumors.

PMV Pharma, headquartered in Princeton, New Jersey, continues its mission to develop innovative, tumor-agnostic therapies targeting the p53 protein, a critical factor in approximately half of all cancers.