Relay Therapeutics Reports Positive Interim Data for RLY-2608 Showing Clinically Meaningful Progression-Free Survival

Relay Therapeutics, Inc. recently announced encouraging interim results for their investigational drug RLY-2608, an allosteric, pan-mutant, and isoform-selective inhibitor of PI3Kα. The data from their ongoing ReDiscover study indicate that patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer, who had undergone extensive prior treatment, demonstrated a median progression-free survival (PFS) of 9.2 months when treated with RLY-2608 in combination with fulvestrant.

The study included 118 patients, with 64 receiving the recommended Phase 2 dose (RP2D) of 600mg BID. Among these, 52 patients without PTEN or AKT co-mutations were evaluated for efficacy. The results were promising, with an overall response rate (ORR) of 33% across all patients and 53% in those with kinase mutations at RP2D. This data suggests that RLY-2608 has the potential to provide significant benefits to patients who have not responded to existing treatments, with fewer adverse effects.

Dr. Don Bergstrom, President of R&D at Relay Therapeutics, expressed optimism about the findings, noting that the selective targeting of mutant PI3Kα could offer unprecedented benefits to patients. The company is preparing to share these results with regulatory authorities and is planning a pivotal study to commence in 2025.

The ReDiscover study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of RLY-2608 both as a monotherapy and in combination with fulvestrant, as well as in triplet combinations with ribociclib or atirmociclib. The interim data cutoff as of August 12, 2024, showed that RLY-2608 in combination with fulvestrant was well tolerated, with mostly low-grade, manageable, and reversible treatment-related adverse events (TRAEs). Only two patients discontinued treatment due to adverse events at RP2D, and only one patient experienced Grade 3 hyperglycemia.

In terms of future developments, Relay Therapeutics plans to initiate two front-line triplet regimens – one with ribociclib and another with atirmociclib – moving into dose expansion in the first half of 2025. The triplet combination with atirmociclib is also on track to start by the end of the year.

Relay Therapeutics remains focused on advancing its portfolio and maintaining financial stability. The company reported approximately $688 million in cash, cash equivalents, and investments as of the end of the second quarter of 2024. This funding is expected to support their operating plan into the second half of 2026, assuming all current programs remain fully owned and pursued.

RLY-2608 represents a significant advancement in the treatment of cancers with PI3Kα mutations, which are present in about 14% of patients with solid tumors. Traditional PI3Kα inhibitors have been limited by their lack of selectivity and associated toxicities. RLY-2608, designed using Relay Therapeutics' Dynamo® platform, aims to overcome these limitations by selectively inhibiting mutant PI3Kα without affecting the wild-type or other PI3K isoforms. This has the potential to reduce toxic side effects and improve patient outcomes.

Relay Therapeutics, a clinical-stage precision medicine company, is dedicated to transforming the drug discovery process through the integration of computational and experimental technologies. Their focus is on developing small molecule therapeutics for targeted oncology and genetic disease indications, pushing the boundaries of what is possible in drug discovery.