PMV sidelines 2 programs as lead tumor suppressor candidate picks up pace in clinic

PMV Pharmaceuticals has pressed pause on two preclinical tumor candidates to funnel all resources into getting its lead precision oncology med through the clinic.

The “primary focus” of PMV is now the clinical development of PC14586, which is currently in a phase 1/2 trial in patients with advanced solid tumors with a p53 Y220C mutation, the company announced in its latest earnings report. The biotech has also enrolled the first patient in an arm of the study giving patients PC14586 in combination with Merck & Co.’s checkpoint inhibitor Keytruda.

The push for PC14586 comes at the expense of two of PMV’s earlier assets that, like PC14586, are small molecule, tumor-agnostic therapies targeting p53 mutations. One of these, which is in the lead optimization stage of development, is a wild-type p53-induced phosphatase (WIP1) inhibitor. The other, which is still in the discovery stage, targets the mutation R273H.

By putting the two projects on hold, PMV expects its cash runway to stretch out into the first half of 2025. The biotech ended 2022 with $243.5 million in cash, equivalents and securities, around $70 million less than it started the year with. R&D expenses rose to $52 million last year, which the company attributed to increased headcount and clinical expenses tied to pushing PC14586 into the clinic.

“The initial PC14586 data have demonstrated clinical proof of concept for PC14586 as a monotherapy to selectively reactivate p53 across multiple tumor types,” CEO David Mack, Ph.D., explained in the release. “In alignment with FDA draft guidance on Project Optimus, we continue to enroll additional patients in the PYNNACLE study and intend to provide a comprehensive clinical and regulatory update, including our recommended phase 2 dose, in the second half of 2023.” 

The wild-type, or normal, p53 protein is part of the body’s natural defense against cancer. However, mutations in p53 are known to drive the formation of several kinds of cancer. PMV’s approach is designed to restore misfolded p53 proteins to their normal function, which it believes could lead to the killing of cancer cells without harming normal tissues.

The company has been working on multiple tumor-agnostic treatments that are designed to target mutations across tumor types, rather than zero in on tumors in specific tissues.