PMV Pharma is preparing to file for approval of its oral p53 protein reactivator drug rezatopopt in the first quarter of 2027, after reporting positive results in a phase 2 trial in ovarian cancer.
Targeting the “Undruggable”
The schedule means Princeton, New Jersey-based PMV has a chance of bringing the first drug targeting p53 – a tumour suppressor protein long considered an “undruggable” target – through regulatory approval and onto the market.
p53 acts as a nuclear transcription factor, rather than having a traditional enzymatic pocket for small molecules to bind, making it challenging to design molecules that could affect its function. Rezatopopt binds and stabilises the TP53 Y220C mutation – found in around 3% of ovarian cancers and 1% of all solid tumours – which causes a structural change in the p53 protein, and is designed to revert it to its original, unmutated state.
PMV is targeting a 2027 launch for the drug in platinum-resistant/refractory ovarian cancer (PROC), and thinks there are around 1,900 patients eligible for the drug in the US and larger European markets, with a global market potential of up to $1 billion, assuming it can command a list price of $65,000 to $80,000 per month.
Competitive Setting
Its closest rival in the category, Aprea Therapeutics, took eprenetapopt into phase 3 testing, but discontinued the programme after disappointing results in TP53-mutant myelodysplastic syndromes (MDS).
After a recent meeting with the FDA, PMV believes data from its ongoing PYNNACLE clinical trial of rezatopopt could be sufficient to win accelerated approval from the US regulator as a second-line treatment for a specific form of PROC.
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Interim results from the study in 76 patients with solid tumours harbouring a specific mutation in the gene coding for p53, known as TP53 Y220C, showed that a once-daily 200 mg dose of the p53 reactivator achieved a response in 35 of them, giving an overall response rate of 46%. There were four confirmed complete responses, 29 confirmed partial responses, and two unconfirmed partial responses, according to PMV, with a median time to response of 1.3 months and a median duration of response of 10 months among confirmed cases.
Expanding into endometrial and breast cancer could add another 400 and 2,300 patients, respectively, to that tally.
Nasdaq-listed PMV’s filing and commercialisation plans for rezatopopt will be supported by a just-completed $50 million public financing, providing lifeline funding for a company that ended the second quarter with $79 million in cash. That was enough for around a year at the rate it was going through reserves in the first half of 2026.
For patients currently facing limited options for PROC, this timeline offers a concrete path toward a new treatment class, though the reliance on accelerated approval pathways means the efficacy of rezatopopt will face intense scrutiny before it reaches patients. White House reaches deals with more pharmas in similar areas, highlighting the regulatory interest in this class. The scientific challenge of restoring p53 function remains significant, but the potential to stabilize a protein that has lost its regulatory power represents a unique mechanism of action in oncology.
PMV will now focus on finalising the filing package.
