Relay Therapeutics Announces Efficacy Subset Analysis of Zovegalisib (RLY-2608) + Fulvestrant in Breast Cancer Patients Pre-Treated with SERD or with ESR1 Mutations at SABCS 2025

Rhea-AI Summary

Relay Therapeutics (Nasdaq: RLAY) reported subset efficacy from its ReDiscover program for zovegalisib (RLY-2608) + fulvestrant presented at SABCS 2025. In a 52-patient efficacy cohort (600mg BID fasted, no PTEN/AKT co-mutation; data cut-off Oct 15, 2025; median follow-up 20.2 months), median PFS was 10.3 months overall and 11.4 months in 2L patients. Among 31 patients with measurable disease, ORR was 39% (47% in 2L). Prior SERD patients showed PFS 11.4 months (ORR 44%); ESR1-mutant patients showed PFS 8.8 months (ORR 60%). Safety remained mostly low-grade and manageable.

Positive

• Median PFS 10.3 months in overall 52-patient efficacy cohort
• Median PFS 11.4 months in second-line (2L) patients
• Objective response rate 39% in 31 measurable-disease patients
• ESR1-mutant subgroup ORR 60% (6/10 patients)

Negative

• Efficacy population limited to 52 patients (600mg BID fasted cohort)
• ESR1-mutant subgroup median PFS only 8.8 months
• Interim data; Phase 3 ReDiscover-2 remains ongoing (not yet confirmatory)

Key Figures

Median PFS (all) 10.3 months Zovegalisib + fulvestrant efficacy population, 600mg BID, no PTEN/AKT co-mutation

Median PFS (2L) 11.4 months Second-line zovegalisib + fulvestrant cohort

Patients enrolled 118 patients Zovegalisib + fulvestrant arm, ReDiscover trial as of Oct 15, 2025

ORR (measurable disease) 39% 31 patients with measurable disease at 600mg BID

ORR (2L patients) 47% Second-line zovegalisib + fulvestrant subgroup

ORR (ESR1-mut+) 60% (6/10) Patients with detectable ESR1 mutation at baseline

Median PFS (prior SERD) 11.4 months Patients with prior SERD exposure

Median follow-up 20.2 months Efficacy population at 600mg BID, no PTEN/AKT co-mutation

Market Reality Check

$7.79 Last Close

Volume Volume 1,308,943 is 0.65x the 20-day average of 2,000,165, indicating subdued activity pre-announcement. low

Technical Price $7.79 is trading above the 200-day MA of $4.25, reflecting a pre-existing uptrend.

Peers on Argus 1 Down

RLAY was up 2.64% while close peers were mixed: NRIX -2.85%, AVBP -0.69%, TNGX -0.76%, versus IMTX +1.52% and VIR +1.22%. Momentum scanner only flagged RZLT at -5.0%, reinforcing a stock-specific move.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 06	Q3 2025 earnings	Positive	-0.3%	Reported Q3 results, strong cash of $596.4M, R&D spend down YoY.
Nov 03	Investor conferences	Neutral	-2.8%	Announced participation in two November healthcare investor fireside chats.
Oct 30	Earnings date notice	Neutral	-2.7%	Scheduled Q3 2025 earnings release and highlighted corporate focus.
Aug 28	Investor conferences	Neutral	-2.7%	Outlined September 2025 conference appearances and webcast availability.
Aug 07	Q2 2025 earnings	Positive	-7.7%	Reported Q2 results and promising RLY‑2608 breast cancer PFS and ORR data.

Pattern Detected

Recent news, including earnings and conference updates, has often been followed by modest to notable price declines, suggesting a pattern of weak or negative reactions even to operational progress.

Recent Company History

Over the last six months, Relay Therapeutics has mainly reported earnings and investor conference participation. Earnings updates on Aug 7 and Nov 6 2025 highlighted substantial cash (up to $656.8M) and advancing RLY‑2608 programs, including the Phase 3 ReDiscover‑2 breast cancer trial. Conference announcements in August and November kept investors informed of outreach efforts. Despite generally constructive fundamentals, shares tended to trade down after these releases, so today’s efficacy-focused update follows a history of cautious market reactions.

Market Pulse Summary

The stock is up +9.1% following this news. A strong positive reaction aligns with the robust efficacy signals reported, such as median PFS of 10.3 to 11.4 months and ORR up to 60% in ESR1‑mutated patients. Historically, RLAY news often saw negative price follow‑through even on constructive updates, so any large upside move would have contrasted with that pattern. Investors would likely weigh these data against prior sell‑the‑news behavior and existing insider net selling when judging sustainability.

Key Terms

progression free survival medical

"showing 10.3-month median PFS in all patients and 11.4-month median PFS"

Progression free survival is the length of time during and after a treatment when a disease, such as cancer, does not get worse or spread. It is an important measure because longer periods of stability can indicate that a treatment is effectively controlling the condition. For investors, it provides insight into the potential durability and success of a therapy or medication.

objective response rate medical

"Among the total of 31 patients with measurable disease, objective response rate (ORR) was 39%"

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

HR+/HER2- medical

"PI3Kα-mutated, HR+/HER2- metastatic breast cancer, regardless of prior fulvestrant"

A cancer subtype where tumor cells have hormone receptors for estrogen and/or progesterone (HR+) but lack excess HER2 protein (HER2−). Think of receptors as locks: HR+ tumors have locks that can be targeted by hormone-blocking drugs, while HER2− means a different lock is absent, so HER2-targeted medicines won’t work. For investors this classification matters because it determines which therapies are appropriate, how large the patient market is, and which clinical trials and regulatory paths are relevant.

CDK4/6 inhibitor medical

"at least one prior endocrine therapy and at least one prior CDK4/6 inhibitor."

A CDK4/6 inhibitor is a type of cancer drug that blocks two proteins (CDK4 and CDK6) that tell cells to divide, effectively slowing or stopping the growth of tumors. Think of it as cutting power to a photocopier that keeps making cancer cells; that control can shrink tumors or delay progression. For investors, these drugs matter because clinical trial results, regulatory approvals, patent life, safety issues and competition directly affect sales potential and company value.

pharmacokinetics medical

"designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics"

Pharmacokinetics is the study of how a substance, such as a drug or chemical, moves through and is processed by the body over time. It tracks how it is absorbed, distributed, broken down, and eventually eliminated. For investors, understanding pharmacokinetics helps gauge the effectiveness, safety, and potential risks of new medications or treatments, which can influence a company’s success and valuation in the healthcare industry.

pharmacodynamics medical

"designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics"

Pharmacodynamics is how a drug actually affects the body — the strength, type and duration of its effects and the relationship between dose and response. Think of it like how turning a thermostat changes room temperature: it shows what the drug does and how much is needed to get the desired effect. Investors care because these properties drive clinical success, dosing convenience, safety profile and competitive advantage, all of which influence commercial potential and regulatory approval.

metastatic medical

"PI3Kα-mutated, HR+/HER2- metastatic breast cancer, regardless of prior fulvestrant"

Metastatic describes cancer that has spread from its original spot to other organs or tissues, like weeds moving from one garden bed into several others. For investors, metastatic disease matters because it often requires more complex, long-term treatments, larger clinical trials, and can drive demand for specialized drugs and diagnostics—factors that affect a drug’s development costs, regulatory risk, market size, and potential revenue.

AI-generated analysis. Not financial advice.

Efficacy data remain consistent with previous disclosures, showing 10.3-month median PFS in all patients and 11.4-month median PFS in 2L patients

Subset analyses show broad activity in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer, regardless of prior fulvestrant or other SERD exposure, or ESR1 mutation status

Phase 3 ReDiscover-2 trial in CDK4/6-experienced breast cancer ongoing

CAMBRIDGE, Mass., Dec. 12, 2025 (GLOBE NEWSWIRE) -- 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, today announced a subset analysis of interim clinical data for zovegalisib (RLY-2608), the first known investigational allosteric, pan-mutant and isoform-selective inhibitor of PI3Kα. These data are being presented today at the 2025 San Antonio Breast Cancer Symposium (SABCS).

“Data presented today demonstrate the robust activity of zovegalisib + fulvestrant across subgroups of patients whose baseline characteristics are known to affect outcomes, such as prior fulvestrant or SERD and ESR1 mutation status,” said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. “The broad range of activity highlights the importance of selectively targeting the driver of disease, mutant PI3Kα, and gives us confidence that the data observed to date should translate to our ongoing Phase 3 trial, ReDiscover-2.”

ReDiscover – Zovegalisib First-in-Human Study

Zovegalisib is currently being evaluated in ReDiscover, an ongoing first-in-human study, which was 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.

As of the data cut-off date of October 15, 2025, 118 patients had enrolled into the zovegalisib + fulvestrant arm of the ReDiscover study. Across all doses, all patients had received a significant level of prior therapy in the advanced setting, including at least one prior endocrine therapy and at least one prior CDK4/6 inhibitor. Among the 64 patients who received 600mg twice daily (BID) fasted, 44% of patients (n=28) had received two or more prior lines of therapy, 52% of patients (n=33) had received prior SERD (includes fulvestrant or oral SERD), and 29% of patients (n=18) had detectable ESR1 mutations at baseline.

Efficacy Consistent Across Subset Populations

The data cut-off date was October 15, 2025 for this analysis. The total efficacy population consisted of 52 zovegalisib + fulvestrant patients who received 600mg BID fasted and did not have a PTEN or AKT co-mutation. Median follow-up was 20.2 months.

The median progression free survival (PFS) was 10.3 months for all patients. Among the total of 31 patients with measurable disease, objective response rate (ORR) was 39%. For second line (2L) patients, median PFS was 11.4 months and ORR was 47%.

Efficacy was generally consistent across other subsets of patients. For patients who received prior SERD, median PFS was 11.4 months and ORR was 44% (7/16), and for patients who had a detectable ESR1 mutation at baseline, median PFS was 8.8 months and ORR was 60% (6/10).

The overall tolerability profile remained consistent with mutant-selective PI3Kα inhibition, with treatment-related adverse events that were mostly low-grade, manageable and reversible.

Anticipated Zovegalisib Next Steps

• Breast Cancer
  • Continued enrollment of Phase 3 ReDiscover-2 trial of zovegalisib + fulvestrant in PI3Kα-mutated, CDK4/6 pre-treated, HR+/HER2- advanced breast cancer
  • Continued dose escalation in Phase 1/2 ReDiscover trial, advancing triplet cohorts that will inform which regimen could be used in a future frontline metastatic trial
• Vascular Malformations
  • Continued enrollment of ongoing Phase 1/2 ReInspire clinical trial in vascular malformations
    
    

The data presentation from SABCS is available on the Relay Therapeutics website in the “Publications/Presentations” section through the following link: https://relaytx.com/publications/.

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 malformations. Zovegalisib has the potential, if approved, to address nearly 500,000 patients 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 malformations. For more information on zovegalisib, please visit here.

About Relay Therapeutics

Relay Therapeutics (Nasdaq: RLAY) is a clinical-stage, small molecule precision medicine company developing potentially life-changing therapies for patients living with cancer and genetic disease. Relay's Dynamo^® platform integrates an array of leading-edge computational and experimental approaches designed to drug protein targets that have previously been intractable or inadequately addressed. The company’s lead clinical asset, zovegalisib, is the first pan-mutant selective PI3Kα inhibitor to enter clinical development and is currently in a Phase 3 clinical trial (ReDiscover-2) in HR+/HER2- metastatic breast cancer. Zovegalisib is also being investigated in a group of genetic disease indications called PI3Kα-driven vascular malformations. Relay's pipeline also includes late-stage research programs for NRAS-driven solid tumors and Fabry disease. For more information, please visit www.relaytx.com or follow us on LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Relay Therapeutics’ strategy, business plans and focus; the progress and timing of the clinical development of the programs across Relay Therapeutics’ portfolio; the expected therapeutic benefits and potential efficacy and tolerability of zovegalisib , both as a monotherapy and in combination with other agents, and its other programs; the clinical data for zovegalisib; the interactions with regulatory authorities and any related approvals; and the potential market opportunity for zovegalisib. The words “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability and conflicts, or public health epidemics or outbreaks of an infectious disease on countries or regions in which Relay Therapeutics has operations or does business, as well as on the timing and anticipated results of its clinical trials, strategy, future operations and profitability; the delay or pause of any current or planned clinical trials or the development of Relay Therapeutics’ drug candidates; the risk that the preliminary or interim results of its preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials of its product candidates and that interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures; Relay Therapeutics’ ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of its planned interactions with regulatory authorities; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Relay Therapeutics’ most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Relay Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Relay Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.

Contact:
Pete Rahmer
prahmer@relaytx.com

Media:
Dan Budwick
1AB
973-271-6085
dan@1abmedia.com

FAQ

What were the median PFS results for RLAY zovegalisib + fulvestrant reported on Dec 12, 2025?

The reported median PFS was 10.3 months overall and 11.4 months in second-line patients (data cut-off Oct 15, 2025).

How many patients were in the zovegalisib efficacy cohort for RLAY at SABCS 2025?

The efficacy population consisted of 52 patients who received 600mg BID fasted without PTEN/AKT co-mutations.

What objective response rates did Relay report for RLAY zovegalisib in the SABCS 2025 subset analysis?

Overall ORR was 39% among 31 measurable patients, and 47% in second-line patients; ESR1-mutant ORR was 60% (6/10).

Does the SABCS 2025 data for RLAY change the Phase 3 program for zovegalisib?

Relay said the subset data support confidence in the ongoing Phase 3 ReDiscover-2 trial, which remains active and enrolling.

What safety profile did Relay report for zovegalisib (RLAY) at SABCS 2025?

Safety was described as consistent with mutant-selective PI3Kα inhibition, with treatment-related adverse events that were mostly low-grade, manageable, and reversible.

Where can investors find the RLAY SABCS 2025 presentation and data?

The data presentation is available in the company's Publications/Presentations section at the Relay Therapeutics website.