Relay Therapeutics Reports Strong Phase 1/2 Data for Zovegalisib + Fulvestrant at ESMO TAT 2026, Advancing to Phase 3

Key Highlights for Investors

• Positive efficacy data: Median progression-free survival (PFS) of 11.1 months reported for zovegalisib plus fulvestrant at the recommended Phase 3 dose in heavily pre-treated patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer.
• Consistent efficacy across mutation types: Median PFS was 11.2 months for patients with kinase domain mutations and 11.0 months for those with non-kinase mutations, indicating broad activity.
• Favorable safety profile: Safety and tolerability at 400mg BID (fed) were consistent with previous higher-dose data (600mg BID fasted), with most adverse events being low-grade and manageable. No Grade 4-5 hyperglycemia events observed.
• Regulatory momentum: Zovegalisib has received FDA Breakthrough Therapy designation for the current Phase 3 trial population, a potentially significant catalyst for accelerated development and market entry.
• Advance to Phase 3: The ongoing Phase 3 ReDiscover-2 trial is comparing zovegalisib + fulvestrant to capivasertib + fulvestrant in PI3Kα-mutated, HR+/HER2- advanced breast cancer post-CDK4/6 inhibitor therapy.
• Market opportunity: Zovegalisib targets a large patient population, with approximately 140,000 HR+/HER2- breast cancer patients and 170,000 vascular anomalies patients with a PI3Kα mutation annually in the US alone.
• First-in-class mechanism: Zovegalisib is the first known allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor, designed to overcome limitations of prior PI3K inhibitors.

In-Depth Report

Relay Therapeutics, Inc. (Nasdaq: RLAY) has announced highly encouraging data from its ongoing Phase 1/2 ReDiscover trial of zovegalisib (RLY-2608) in combination with fulvestrant, presented at the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) Congress 2026 in Paris.

Phase 1/2 ReDiscover Trial Results

• The newly reported data focus on the 400mg twice daily (BID) dose taken with food, selected as the recommended Phase 3 dose (RP3D).
• As of January 13, 2026, 60 patients had been treated with this regimen, with 57 included in the efficacy analysis (excluding those with PTEN or AKT co-mutations).
• All patients had prior treatment with a CDK4/6 inhibitor and at least one prior endocrine therapy in the advanced/metastatic setting.
• Efficacy:
  • Median follow-up: 12.0 months
  • Median PFS: 11.1 months (95% CI: 7.3–13.0)
  • Median PFS by mutation type: 11.2 months (kinase domain, n=33), 11.0 months (non-kinase, n=24)
  • Objective response rate (ORR): 43% (15/35) among patients with measurable disease; 52% ORR (11/21) in second-line only patients
• Pharmacokinetics: 400mg BID (fed) achieves exposures comparable to 600mg BID (fasted), with most patients maintaining therapeutic exposure throughout the dosing interval.
• Safety and tolerability:
  • Adverse events were primarily low-grade and reversible.
  • Hyperglycemia events were mostly Grade 1; no Grade 4 or 5 events recorded.
  • Grade 3 hyperglycemia was rare and mostly occurred in pre-diabetic patients.
  • Only four patients discontinued due to treatment-related adverse events (TRAEs).

Regulatory & Clinical Program Updates

• Phase 3 ReDiscover-2 trial: This pivotal study (NCT06982521) began in mid-2025 and is enrolling globally. It is evaluating zovegalisib + fulvestrant versus capivasertib + fulvestrant in patients with PI3Kα-mutated, HR+/HER2- advanced breast cancer who have progressed following prior CDK4/6 inhibitor therapy.
• FDA Breakthrough Therapy designation: This designation for zovegalisib plus fulvestrant in the Phase 3 patient population could expedite development, review, and potential market approval.

Market Opportunity and Drug Differentiation

• Zovegalisib’s potential: Targets two large US populations—HR+/HER2- breast cancer (~140,000 patients/year) and PI3Kα-driven vascular anomalies (~170,000 patients/year).
• First-in-class mechanism: Unlike previous PI3K inhibitors that target the orthosteric (active) site, zovegalisib is an allosteric, pan-mutant, isoform-selective inhibitor designed using Relay’s Dynamo® platform. This approach aims to achieve better mutant selectivity and reduce toxicities, potentially allowing higher dosing and improved efficacy.
• Pipeline breadth: Beyond zovegalisib, Relay is developing programs targeting NRAS-driven solid tumors and Fabry disease, reflecting a broader precision medicine strategy.

Implications for Shareholders

• The robust median PFS and ORR data, coupled with a favorable safety profile, de-risk zovegalisib’s ongoing Phase 3 program and support its differentiation from other PI3K inhibitors, which have struggled with toxicity.
• The FDA Breakthrough Therapy designation is a major regulatory milestone that can accelerate the drug’s path to market, potentially increasing the company’s valuation.
• Zovegalisib directly addresses significant unmet needs in a large and clearly defined patient population, supporting a large commercial opportunity.
• The positive data and regulatory progress are likely to be viewed favorably by investors and may be price-sensitive, potentially impacting RLAY’s share price.

About Relay Therapeutics

Relay Therapeutics is a clinical-stage, small molecule precision medicine company focused on cancer and genetic diseases. Its Dynamo® platform integrates computational and experimental methods to drug previously intractable protein targets. Zovegalisib is the company’s lead asset and the first pan-mutant selective PI3Kα inhibitor in clinical development, currently in Phase 3 for HR+/HER2- metastatic breast cancer and in early studies for vascular anomalies.

Disclaimer

This article contains forward-looking statements based on current information available to Relay Therapeutics as of the date of the press release. Actual results may differ materially due to risks and uncertainties, including clinical development risks, regulatory decisions, commercialization challenges, and other factors described in company filings with the U.S. Securities and Exchange Commission. This article is for informational purposes only and does not constitute investment advice.

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