On February 3, 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 that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to zovegalisib (RLY-2608) in combination with fulvestrant for the treatment of adults with PIK3CA mutant, hormone receptor positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locally advanced or metastatic breast cancer following recurrence or progression on or after treatment with a CDK4/6 inhibitor.

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"Approximately 40% of patients with HR+/HER2- advanced breast cancer harbor PIK3CA mutations, and most experience disease recurrence or progression following treatment with CDK4/6 inhibitors, leaving limited therapeutic options," said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. "This Breakthrough Therapy designation underscores the FDA’s recognition of the potential of zovegalisib in combination with fulvestrant to meaningfully improve outcomes for these patients, reinforcing the impact of the encouraging clinical evidence we have demonstrated to date. We look forward to continuing to collaborate closely with the FDA as we work to advance this program as efficiently as possible for patients."

The FDA’s BTD is designed to accelerate the development and review of therapies for serious conditions when early clinical evidence suggests the potential for substantial improvement over available treatments. BTD provides eligibility for all Fast Track designation features, along with enhanced FDA guidance on development and increased engagement with senior FDA leadership.

BTD for zovegalisib was supported by clinical data generated to date from the Phase 1/2 ReDiscover trial, 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. Specifically, the application included data across all PIK3CA mutations (kinase and non-kinase) for two doses with comparable exposures: 600mg BID fasted (N=52) and 400mg BID fed (N=57), the dose being used in the ongoing Phase 3 trial, ReDiscover-2.

Safety and efficacy from the 600mg BID fasted data referenced above were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting, with an additional efficacy subgroup analysis presented at the 2025 San Antonio Breast Cancer Symposium (SABCS).

Data for the 400mg BID fed (the Phase 3 dose) will be presented for the first time at ESMO (Free ESMO Whitepaper) Targeted Anticancer Congress 2026 on Monday, March 16.

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 per year in the United States and the estimated 170,000 patients with vascular anomalies driven by a PI3Kα mutation per year in the United States.

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.

About PIK3CA-mutated, HR+/HER2- Advanced Breast Cancer

Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is the most common subtype of breast cancer. Approximately 40% of patients with HR+/HER2- breast cancer harbor activating mutations in the PIK3CA gene, which drive tumor growth and are associated with poorer outcomes compared to patients without these mutations. Despite CDK4/6 inhibitors plus endocrine therapy being the standard of care in advanced disease, many patients with PIK3CA-mutated tumors have poorer outcomes and there are no approved regimens incorporating a pan-mutant selective PI3Kα inhibitor.

(Press release, Relay Therapeutics, FEB 3, 2026, View Source [SID1234662431])