On March 16, 2026 Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage, small molecule precision medicine company developing potentially life-changing therapies for patients living with cancer and genetic disease, reported data from the Phase 1/2 ReDiscover trial of zovegalisib (RLY-2608) + fulvestrant at the recommended Phase 3 dose of 400mg twice daily (BID) taken with food (fed) in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. The data are being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Targeted Anticancer Therapies (TAT) Congress 2026 in Paris, France.

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"As supported by the data presented, the 400mg BID fed regimen maintains robust efficacy with a safety profile consistent with mutant-selective PI3Kα inhibition," said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. "These results further support our decision to advance this regimen into the ongoing Phase 3 ReDiscover-2 trial and reinforce our confidence in selectively targeting PI3Kα mutations as a potentially differentiated approach for CDK4/6-experienced patients."

Phase 1/2 ReDiscover Trial – Zovegalisib 400mg Fed Cohort Data Consistent with 600mg Fasted Data

Zovegalisib is currently being evaluated in ReDiscover, an ongoing first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of zovegalisib in combination with fulvestrant and in combination with fulvestrant and CDK inhibitors in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer.

As of the January 13, 2026 data cut-off date, 60 patients had received the 400mg BID fed regimen. The efficacy population consisted of 57 patients who did not have a PTEN or AKT co-mutation, consistent with the planned pivotal population. All patients had previously received a CDK4/6 inhibitor and at least one prior endocrine therapy in the advanced setting.

Pharmacokinetics of Both Doses are Similar

Pharmacokinetic analyses demonstrate that the 400mg BID fed regimen achieves exposures comparable to the previously evaluated 600mg BID fasted dose, with mean concentrations approaching IC90 in majority of patients and nearly all patients maintaining exposure above the IC80 throughout the dosing interval.

Efficacy Consistent with 600mg BID Fasted

As of the January 13, 2026 data cut-off date, among the 57 efficacy-evaluable patients at the 400mg BID fed dose, which is the recommended Phase 3 dose (RP3D):

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Median follow-up was 12.0 months
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Median progression-free survival (PFS) was 11.1 months (95% CI: 7.3–13.0)
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Median PFS was 11.2 months in patients with kinase mutations (n=33) and 11.0 months in patients with non-kinase mutations (n=24)
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Among 35 patients with measurable disease, confirmed objective response rate (ORR) was 43% (15/35) and in second line only patients the ORR was 52% (11/21)

Maintained Favorable and Differentiated Tolerability Profile

Zovegalisib + fulvestrant at the 400mg BID fed dose was generally well tolerated in the 60 treated patients as of the January 13, 2026 data cut-off. The overall tolerability profile consisted primarily of low-grade, manageable and reversible treatment-related adverse events (TRAEs).

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Safety profile consistent with previously disclosed 600mg BID fasted data
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Majority of hyperglycemia events were Grade 1; no Grade 4-5 hyperglycemia observed
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In the limited cases of Grade 2/3 hyperglycemia, the vast majority occurred in patients that were pre-diabetic at baseline
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Only four patients discontinued due to TRAEs

The data presentation from the ESMO (Free ESMO Whitepaper) TAT Congress 2026 is available on the Relay Therapeutics website in the "Publications/Presentations" section through the following link: View Source

ReDiscover-2 – Ongoing Phase 3 Trial

The Phase 3 ReDiscover-2 trial (NCT06982521) is evaluating zovegalisib 400mg BID administered in combination with fulvestrant versus capivasertib + fulvestrant in patients with PI3Kα-mutated, HR+/HER2- advanced breast cancer who have progressed on prior CDK4/6 inhibitor therapy. The study initiated in mid-2025 and is enrolling globally.

Zovegalisib + fulvestrant has received FDA Breakthrough Therapy designation for the Phase 3 ReDiscover-2 trial population.

About Zovegalisib

Zovegalisib is the lead program in Relay Therapeutics’ efforts to discover and develop mutant selective inhibitors of PI3Kα, the most frequently mutated kinase in all cancers and all vascular anomalies. Zovegalisib has the potential, if approved, to address a significant portion of the approximately 140,000 patients with HR+/HER2- breast cancer with a PI3Kα mutation and the estimated 170,000 patients with vascular anomalies driven by a PI3Kα mutation per year in the United States, one of the largest patient populations for a precision medicine.

Traditionally, the development of PI3Kα inhibitors has focused on the active, or orthosteric, site. The therapeutic index of orthosteric inhibitors is limited by the lack of clinically meaningful selectivity for mutant versus wild-type (WT) PI3Kα and off-isoform activity. Toxicity related to inhibition of WT PI3Kα and other PI3K isoforms results in sub-optimal inhibition of mutant PI3Kα with reductions in dose intensity and frequent discontinuation. The Dynamo platform enabled the discovery of zovegalisib, the first known allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor, designed to overcome these limitations. Relay Therapeutics solved the full-length cryo-EM structure of PI3Kα, performed computational long time-scale molecular dynamic simulations to elucidate conformational differences between WT and mutant PI3Kα, and leveraged these insights to support the design of zovegalisib. Zovegalisib is currently being evaluated in multiple metastatic breast cancer studies and a first-in-human study designed to treat patients with PIK3CA (PI3Kα) mutation driven vascular anomalies. For more information on zovegalisib, please visit here.

(Press release, Relay Therapeutics, MAR 16, 2026, View Source [SID1234663574])