PMV Pharma Presents Late-Breaking Preclinical Data on Lead Product Candidate PC14586 at the American Association for Cancer Research Annual Meeting 2021
- PC14586 selectively stabilizes the p53 Y220C mutant and restores p53 activity
- Robust in vivo tumor regression observed with once daily oral dosing
- Pharmacodynamic biomarkers of p53 activation developed for clinical trials
- PC14586 is being tested in a Phase 1/2 clinical trial in patients with advanced solid tumors that have a p53 Y220C mutation
CRANBURY, N.J., April 10, 2021 (GLOBE NEWSWIRE) -- PMV Pharmaceuticals, Inc. (Nasdaq: PMVP), a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53 mutants, today presented preclinical data on PC14586, the Company’s first-in-class, tumor-agnostic, small molecule p53 reactivator at the American Association for Cancer Research Annual Meeting 2021.
"The preclinical data provide compelling evidence that PC14586 selectively reactivates the p53 Y220C mutant protein, both in vitro and in vivo,” said David Mack, Ph.D., President and Chief Executive Officer of PMV. “PC14586 stabilization of the p53 Y220C mutant in the wild-type conformation reactivates p53 activity, which leads to robust tumor regression in mouse xenograft models and has the potential to offer a novel treatment for patients with Y220C genetically defined cancers.”
Key Presentation Highlights:
Oral presentation titled, “PC14586: The First Orally Bioavailable Small Molecule Reactivator of Y220C Mutant p53 in Clinical Development” presented by Melissa L. Dumble, Ph.D., Vice President Preclinical Development and Translational Science of PMV.
- PC14586 non-covalently binds to and stabilizes the p53 Y220C mutant in the wild-type conformation
- PC14586 selectively reactivates p53-mediated transcription in cells harboring the p53 Y220C mutation, with no observed activity in wild-type cells or those with other p53 mutations
- PC14586 inhibits proliferation across cell lines harboring the p53 Y220C mutation, with no effects on p53 knock-out or wild-type cells
- Once daily oral administration of PC14586 results in robust tumor regression in a NUGC3 human gastric cancer xenograft mouse model
- Pharmacodynamic biomarkers of p53 activity (e.g. target gene expression, p21, MDM2 and MIC-1 protein expression) have been developed and modeled for clinical implementation
- Enrollment is ongoing in a Phase 1/2 clinical trial of PC14586 in patients with advanced solid tumors with a p53 Y220C mutation. For information on the Phase 1/2 trial, please visit www.clinicaltrials.gov (NCT study identifier NCT04585750)