CAMBRIDGE, Mass., May 19, 2026
Relay Therapeutics announced promising initial Phase 2 clinical data for zovegalisib, its investigational mutant-selective PI3Kα inhibitor, demonstrating encouraging efficacy, symptomatic improvement, and a favorable tolerability profile in patients with PIK3CA-driven vascular anomalies. The findings, presented at the International Society for the Study of Vascular Anomalies (ISSVA) World Congress 2026 in Philadelphia, position zovegalisib as a potential differentiated long-term treatment option for patients with rare vascular disorders driven by PIK3CA mutations, including PIK3CA-related overgrowth spectrum (PROS), lymphatic malformations (LM), and venous malformations (VeM). The early-stage clinical data strengthen Relay Therapeutics’ precision medicine strategy by demonstrating that selective inhibition of mutant PI3Kα may provide clinically meaningful benefit while reducing the toxicities commonly associated with broader PI3K inhibition approaches.
Zovegalisib Demonstrates Strong Early Clinical Responses
The data were generated from the ongoing Phase 2 ReInspire trial, evaluating zovegalisib in adults, adolescents, and pediatric patients with vascular anomalies driven by PIK3CA mutations. Interim findings from the adult and adolescent cohort showed that 60% of evaluable patients achieved a volumetric response at the first MRI assessment after 12 weeks of treatment, while 95% experienced measurable lesion reduction. Importantly, all responding patients remained on therapy at the time of data cutoff, supporting the potential durability of treatment benefit. After the cutoff date, an additional patient converted to a response, increasing the overall response rate to 65% across dose groups.
Clinical benefit extended beyond imaging outcomes. Investigator- and patient-reported assessments demonstrated substantial symptomatic improvement, with 89% of patients achieving investigator-reported improvement and 79% reporting personal clinical improvement at week 12. Pain symptoms also improved in the majority of patients evaluated. Responses were observed across multiple vascular anomaly subtypes and among patients previously treated with therapies such as sirolimus or alpelisib, highlighting zovegalisib’s potential utility in difficult-to-treat populations. Relay Therapeutics noted that several patients who reached 24-week evaluations demonstrated deeper lesion shrinkage over time, suggesting continued therapeutic benefit with ongoing dosing.
Mutant-Selective PI3Kα Inhibition May Improve Long-Term Safety
A major focus of the ReInspire study is identifying a treatment regimen suitable for chronic long-term use, as vascular anomalies are lifelong conditions often requiring sustained therapy. Zovegalisib is designed as the first allosteric, pan-mutant, isoform-selective PI3Kα inhibitor, aiming to selectively inhibit mutant PI3Kα while sparing wild-type PI3Kα activity that contributes to treatment-limiting toxicities seen with earlier PI3K inhibitors.
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The interim safety profile supports this differentiated strategy. Among patients treated at the lower 100mg BID and 300mg BID dose levels, no treatment discontinuations due to adverse events were reported, while only 9% experienced Grade 3 or higher treatment-related adverse events. Common toxicities associated with non-selective PI3K inhibition, including severe hyperglycemia, rash, stomatitis, and severe diarrhea, were notably limited or absent. Median dose intensity exceeded 99%, suggesting patients were able to maintain consistent therapy without substantial dose interruptions. Relay Therapeutics stated that the higher 400mg BID dose demonstrated less favorable tolerability and has been deprioritized for future development.
According to Relay Therapeutics President of Research and Development Dr. Don Bergstrom, the combination of lesion reduction, symptomatic improvement, and manageable long-term tolerability supports the potential for zovegalisib to significantly improve the current treatment landscape for patients with rare vascular anomalies, many of whom have limited therapeutic options and experience chronic pain, swelling, impaired mobility, and progressive tissue overgrowth.
Expansion Cohorts and Precision Medicine Strategy Advance
Relay Therapeutics has already initiated Part 2 expansion cohorts of the ReInspire trial using 400mg once daily and 300mg BID dosing regimens in adults and adolescents, while pediatric dose-finding studies continue for younger patient populations. The company is also developing a fit-for-purpose patient-reported outcomes tool tailored specifically to vascular anomaly patients in order to better capture quality-of-life improvements and long-term symptom control.
Beyond vascular anomalies, zovegalisib remains a central component of Relay Therapeutics’ broader oncology pipeline. The investigational therapy is simultaneously advancing through the Phase 3 ReDiscover-2 trial in PI3Kα-mutated HR+/HER2- metastatic breast cancer, where mutant-selective PI3Kα inhibition may also improve efficacy while minimizing toxicity. The company plans additional frontline breast cancer development activities beginning in 2027, pending regulatory discussions.
The early ReInspire data underscore growing industry interest in applying precision medicine approaches beyond oncology into rare genetic and vascular diseases. If longer-term studies continue to confirm durable efficacy with improved tolerability, zovegalisib could emerge as one of the first targeted therapies specifically optimized for chronic treatment of PIK3CA-driven vascular anomalies.
Source: Relay Therapeutics press release
