Analysts are extremely encouraged by Phase 2 trial results for Relay Therapeutics’ PI3KA inhibitor in treating vascular malformations (VM), prompting the biotech to eye a potential path to accelerated approval.
Relay’s investigational PI3KA inhibitor has elicited a 60% response rate in patients with vascular malformations, toppling Novartis’ 11% overall response rate seen in a failed Phase 2 study of Vijoice. The biotech’s execs are now looking to the FDA’s accelerated approval pathway for the oral PI3KA inhibitor, called zovegalisib, pending additional data and feedback from regulators.
The early-stage data include adults and children older than 12 years with vascular anomalies—an umbrella term for rare disorders marked by abnormal development of blood vessels, lymphatic vessels and nearby tissues. As of April 15, 32 patients were enrolled in the Phase 2 ReInspire trial, of which 22 patients had PIK3Ca-related overgrowth spectrum (PROS)—disorders caused by mutations in the PI3Ka gene.
Of 20 evaluable patients, 12—or 60%—achieved a volumetric response at 12 weeks, according to data set for presentation Wednesday at the International Society for the Study of Vascular Anomalies World Congress 2026. The overall response rate (ORR) doubles Leerink Partners’ “prior bar for success” of 20%–25% ORR and is higher than the 11% ORR seen at week 16 for Novartis’ oral PI3K inhibitor Vijoice in a failed PROS study.
After Relay’s data cutoff of April 15, one additional patient had an unconfirmed response, resulting in a 65% (13/20) ORR, according to the Cambridge, Massachusetts–based biotech.
The data show “the full potential of what a mutant selective inhibitor can do in these vascular anomaly patients,” Relay CEO Sanjiv Patel said on a Tuesday conference call. “[We] believe this leaves very little room for improvement of our volumetric response rate for anyone that will come behind us.”
At 12 weeks, interim investigator-measured impressions of change showed 89% of patients experiencing clinical improvement, while patient reports for the same metric were 79%. Pain scores, as measured by investigators, demonstrated clinical improvement for 71% of symptoms.
“Given these superlative results, we think it is possible RLAY shares could exceed our anticipated >10% move as some investors may adopt VM as the main value driver,” Leerink said.
Since market open, the biotech’s stock has risen 9% to $13.29 per share.
The trial is testing doses of 100 mg, 300 mg and 400 mg twice daily. “We believe there is no further efficacy left on the table,” Patel said about the 300-mg dosing regimen. “As you go above that, you’re just seeing greater tolerability challenges, and so we don’t think there’s any room for us to go higher than 300.”
The rates of treatment-related adverse events (TRAEs) among 22 patients were “proportional to dose level,” with no dose discontinuations, according to Relay. Two patients (9%) experienced a grade 3 or higher TRAE.
Zovegalisib wasn’t tied to rashes or stomatitis of any grade, and no cases of grade 3 or higher hyperglycemia or diarrhea were reported, though the biotech did not disclose all the data for adverse events.
Overall, zovegalisib’s tolerability profile was generally “as expected and consistent with mutant-selective PI3Kα inhibition,” according to Relay. The rates of key adverse events such as hyperglycemia, stomatitis and rash were lower than or similar to Vijoice, according to Leerink.
Based on the newest findings, Relay is opening multiple expansion cohorts at 400 mg once a day and 300 mg twice daily in patients 12 years and older, with a dose-finding trial for patients aged six to 11 years ongoing. Zovegalisib is also in later-stage testing for multiple metastatic breast cancers.
