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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)
p53 plays a pivotal role in preventing abnormal cells from becoming a tumor by inducing programmed cell death. Mutant p53 takes on oncogenic properties that endow cancer cells with a growth advantage and resistance to anti-cancer therapy. The p53 Y220C mutation is associated with many cancers, including but not limited to breast, non-small cell lung cancer, colorectal, pancreatic, and ovarian cancers.
PC14586 is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the crevice present in the p53 Y220C mutant protein, hence, restoring the wild-type, or normal, p53 protein structure and tumor suppressing function. PC14586 is being developed for the treatment of patients with locally advanced or metastatic solid tumors that have the p53 Y220C mutation.
About PMV Pharma
PMV Pharma is a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53 mutants. p53 mutations are found in approximately half of all cancers. The field of p53 biology was established by our co-founder Dr. Arnold Levine when he discovered the p53 protein in 1979. Bringing together leaders in the field to utilize over four decades of p53 biology, PMV Pharma combines unique biological understanding with pharmaceutical development focus. PMV Pharma is headquartered in Cranbury, New Jersey. For more information, please visit www.pmvpharma.com.
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 future plans or expectations for PC14586, including expectations regarding the success of its current clinical trial for PC14586; and the future plans or expectations for the Company’s discovery platform. Any forward-looking statements in this statement 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. These risks and uncertainties include, among others, the factors 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, 2021, 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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