Our focus on protein motion is creating new possibilities in drug discovery
RLY-1971 is designed to be an oral, small molecule, potent and selective inhibitor of the protein tyrosine phosphatase SHP2 that binds and stabilizes SHP2 in its inactive conformation.
SHP2 promotes cancer cell survival and growth through the RAS pathway by transducing signals downstream from receptor tyrosine kinases (RTKs). As a critical signaling node and regulator, SHP2 drives cancer cell proliferation and plays a key role in the way cancer cells develop resistance to targeted therapies.
We believe that inhibition of SHP2 could be effective as a monotherapy in cancers with specific alterations and could block a common path that cancer cells exploit to avoid killing by other antitumor agents, thus overcoming or delaying the onset of resistance to those therapies.
We are currently evaluating the safety and tolerability of RLY-1971 in a Phase 1 dose escalation study in patients with advanced or metastatic solid tumors.
RLY-4008 is designed to be an oral, small molecule, selective inhibitor of FGFR2, a receptor tyrosine kinase that is frequently altered in certain cancers.
FGFR2 is one of four members of the FGFR family, a set of closely related proteins with highly similar protein sequences and properties. Non-selective, pan-FGFR inhibitors produced by other companies have demonstrated clinical proof-of-concept in patients with intrahepatic cholangiocarcinoma bearing FGFR2 gene fusions. However, these existing FGFR therapies are constrained by a dose-limiting side effects caused by inhibition of FGFR1.
Our drug candidate, RLY-4008, has demonstrated potent FGFR2-dependent killing in cancer cell lines while showing minimal inhibition of other targets, including other members of the FGFR family. We have demonstrated in in vivo animal models that RLY-4008 does not induce FGFR1-mediated toxicities. RLY-4008 also retains activity against the most common FGFR2 resistance mutations reported in the medical literature.
Our clinical development plan for RLY-4008 seeks to leverage the unique potential for enhanced tolerability and broad FGFR2 mutational coverage to rapidly generate proof-of-concept in molecularly defined patient subsets.
We are currently evaluating the safety and tolerability of RLY-4008 in a first-in-human dose escalation study in patients who have FGFR2 alterations in advanced solid tumors.
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.
Current inhibitors of PI3Kα target the catalytic site of PI3Kα and are very challenging for many patients to tolerate given a vast array of toxicities caused by inhibition of wild-type PI3Kα and inhibition of other PI3K isoforms.
Our approach to the challenge of mutant selectivity led us to solve the first full-length protein structure of PI3Kα, which provided us with unprecedented insights into the mechanism of activation of PI3Kα and the impact of mutations on its function. We are now developing a franchise of programs that selectively target the cancer-associated mutant variants of PI3Kα that spare the wild-type protein.
While our initial focus has been on enhancing small molecule therapeutic discovery in precision oncology, protein conformational dynamics are implicated in a wide variety of therapeutic areas. We are continuing to leverage the power of our Dynamo platform to further diversify our pipeline and have begun drug discovery programs focused on genetically validated targets in monogenic diseases.
Our current discovery programs are focused in targeted oncology and genetic disease.
We also continue to evaluate potential additional therapeutic areas beyond precision oncology and genetic disease that we could enter in the future.
At Relay Therapeutics, we know that patients need new medicines now. This is the driving force behind everything we do.