Relay Therapeutics and Pfizer to Collaborate on Clinical Trial for Atirmociclib and RLY-2608

On June 5, 2024, Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company, announced a collaboration with Pfizer Inc. (NYSE: PFE) for a clinical trial. This trial will evaluate the combination of Pfizer’s investigational selective-CDK4 inhibitor, atirmociclib, with Relay’s RLY-2608 and fulvestrant in patients with PI3Kα-mutated, HR+, HER2- metastatic breast cancerHRHER2.

Dr. Don Bergstrom, President of R&D at Relay Therapeutics, expressed enthusiasm about this collaboration, noting that combining atirmociclib and RLY-2608 could potentially avoid the off-target toxicities commonly associated with non-selective agents that target CDK6 and wild-type PI3Kα. This is significant as the breast cancer treatment landscape is rapidly evolving, and RLY-2608's promising safety profile positions it well for next-generation therapies.

Under the agreement, Pfizer will supply atirmociclib for the study, which Relay will conduct. The combination trial of RLY-2608, atirmociclib, and fulvestrant is expected to commence by the end of 2024.

RLY-2608 is a lead program in Relay Therapeutics' pipeline, aiming to develop mutant-selective inhibitors of PI3Kα, a kinase frequently mutated in various cancers. Oncogenic mutations of PI3Kα are present in approximately 14% of patients with solid tumors. If approved, RLY-2608 could potentially treat over 250,000 patients annually in the U.S., representing a significant patient population for precision oncology medicine.

Historically, the development of PI3Kα inhibitors has targeted the active, or orthosteric, site of the kinase. However, orthosteric inhibitors often lack the selectivity needed to differentiate between mutant and wild-type PI3Kα, leading to off-isoform activity and toxicity. This toxicity often results in sub-optimal inhibition of mutant PI3Kα, decreased dose intensity, and frequent treatment discontinuation.

The Dynamo™ platform from Relay Therapeutics was instrumental in the discovery of RLY-2608, the first known allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor. This platform enables the design of inhibitors that overcome the limitations of orthosteric inhibitors. Relay Therapeutics achieved this by solving the full-length cryo-EM structure of PI3Kα, performing computational long time-scale molecular dynamic simulations to understand conformational differences between wild-type and mutant PI3Kα, and using these insights to design RLY-2608.

Currently, RLY-2608 is being evaluated in a first-in-human trial for patients with advanced solid tumors harboring a PIK3CA (PI3Kα) mutation.

Relay Therapeutics, a clinical-stage precision medicine company, aims to revolutionize the drug discovery process by integrating cutting-edge computational and experimental technologies. The company is pioneering a new approach to drug discovery, focusing on protein targets that have been challenging or inadequately addressed in the past. Their Dynamo™ platform combines various advanced techniques to enhance the discovery of small molecule therapies, particularly in targeted oncology and genetic diseases.

Relay Therapeutics' mission is to push the boundaries of what is possible in drug discovery, with the ultimate goal of delivering life-changing therapies to patients.