Rezatopopt sees a path forward after all

PMV Pharmaceuticals appears to have moved a step closer to turning p53 into a druggable target, with its lead asset, rezatopopt, meeting a minimum level of activity the company wanted to see in the pivotal stage of its Pynnacle study.

The highlight of the data, revealed pre-market on Wednesday, is a 43% response rate among 44 evaluable ovarian cancer patients, clearing a 30% ORR bar that PMV had set in this, rezatopopt's first targeted cancer setting. However, the need to enrol an additional 20 to 25 ovarian cancer patients has pushed US filing into 2027, just when PMV's current cash is expected to run out.

This might not be a problem if the company can use the positive data update to raise more money, of course. PMV had earlier expected to file rezatopopt in 2026, and reported $148m of cash in mid-2025, a sum it says is expected to last "through" the first quarter of 2027.

Importantly, PMV reiterated its view that accelerated approval was still on the cards for rezatopopt, meaning that a US green light could come later in 2027, to be confirmed subsequently with additional single-arm data from Pynnacle. PMV claims that controlled data aren't required for full approval.

High-dose risks allayed?

As for efficacy, the ovarian cancer cohort, comprising 44 KRAS wild-type patients with the p53 Y220C mutation, has yielded 19 responses, one of these being classes as complete.

These all relate to a 2g daily dose that PMV took forward, having seen promise at 1.15-1.5g in Pynnacle's phase 1 part. One major risk was that 2g could show significant adverse events, given that 1.5g had already yielded two dose-limiting toxicities, but this doesn't appear to have materialised.

PMV said administration of rezatopopt with food had decreased the incidence of gastrointestinal adverse events. Liver enzyme elevations are still notable, however: among all 109 patients there was one grade 4 and six grade 3 ALT elevations, but PMV said most cases were manageable and transient.

The group's stock closed up 14% on Tuesday after PMV said it would unveil the pivotal Pynnacle data the following day, but on Wednesday morning it fell back 10%, presumably on fears of imminent dilution.

PMV says it will take until the first quarter of 2026 to enrol the additional 20-25 ovarian cancer patients, delaying analysis of the full dataset until the fourth quarter of next year, and thus pushing filing into 2027.

Potential

Ovarian cancer represents a relatively small setting, and for rezatopopt to fulfil its potential it needs to be approved in other cancer types, eventually perhaps even shooting for a tumour-agnostic label defined only by KRAS and p53 mutation status.

On an investor call PMV confirmed endometrial and breast cancers as the next possible monotherapy settings, while lung, pancreatic and haematological cancers could be pursued in combinations. Among all 97 evaluable patients in Pynnacle's pivotal part there were ORRs of 18% in breast cancer (11 patients treated), 60% in endometrial (five), 22% in lung (18) and 21% in other solid tumours (19).

These included five unconfirmed partial responses, but PMV said all of these had been confirmed subsequently.

Such data lend support to rezatapopt becoming the first molecule able to target mutated p53 and restore its wild-type activity to maintain DNA stability and prevent tumour formation. But now PMV needs cash, either from investors or – a dream scenario – from a significant biopharma partner.