Our Science

Our Dynamo^® platform and approach are creating new possibilities in drug discovery

Relay Therapeutics® is advancing a pipeline of promising therapeutic candidates designed to solve problems that were previously intractable or inadequately addressed with traditional drug discovery.

Program

Discovery

IND Enabling

Phase 1

Phase 2

Phase 3

Zovegalisib
(RLY-2608)

PI3Kα^PAN
Breast Cancer

Zovegalisib (RLY-2608) is designed to be the first allosteric, pan-mutant (including Kinase mutations like H1047X and non-Kinase mutations like E542X and E545X) and isoform-selective PI3Kα inhibitor.

PI3Kα is the central regulator of a signaling pathway that has been linked to a diverse group of cellular functions related to cancer including cell growth, proliferation and survival. Data collected as a part of large sequencing efforts identifies PI3Kα as the most frequently mutated kinase in cancer.

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 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. Zovegalisib (RLY-2608) is designed to overcome these limitations.

We 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 (RLY-2608).

The first-in-human ReDiscover trial for zovegalisib (RLY-2608) evaluates the safety and efficacy of zve in combination with fulvestrant and a CDK inhibitor in patients with HR+, HER2-, PI3Kα-mutated advanced breast cancer.

In mid-2025, we initiated the Phase 3 ReDiscover-2 trial, which evaluates the safety and efficacy of zovegalisib (RLY-2608) plus fulvestrant in PI3Kα-mutated, HR+/HER2- advanced breast cancer patients previously treated with a CDK4/6 inhibitor in either the adjuvant or metastatic setting.

Phase 3 ReDiscover-2 Clinical Trial

Zovegalisib
(RLY-2608)

PI3Kα^PAN
Vascular Anomalies

Vascular anomalies are a series of rare syndromes that occur due to atypical development of lymphatic and/or blood vessels, which enlarge or form tangles, pockets or shunting vessels that cause abnormal blood flow. They can occur in different parts of the body, vary in severity and may cause symptoms such as pain, swelling, skin discoloration, limb asymmetry and functional limits. The anomalies typically grow over time, and, depending on what vessel(s) are involved, can become life-threatening.

The primary vessel(s) involved determine the sub-type of anomaly, which can include venous malformations, cerebral cavernous malformations, lymphatic malformations and PIK3CA-related overgrowth spectrum (PROS). PI3Kα is the most common driver mutation among these sub-types, causing an estimated 55 percent of these vascular anomalies. In the U.S., an estimated 170,000 people have one of these sub-types driven by a PI3Kα mutation.

We believe the selectivity of zovegalisib (RLY-2608) for mutant PI3Kα provides the opportunity for greater target coverage, leading to the potential for improved efficacy and better chronic tolerability.

Zovegalisib (RLY-2608) is currently being evaluated in adults and children with PROS and vascular anomalies driven by PIK3CA mutation in a global Phase 1/2 clinical trial.

Clinical Trial