On July 27, 2022 Relay Therapeutics, Inc. (Nasdaq: RLAY) a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies, reported the anticipated registrational path for RLY-4008 and three new programs within a growing HR+/HER2- breast cancer franchise at a virtual analyst and investor event from 8:00 a.m. to 9:00 a.m. ET (Press release, Relay Therapeutics, JUN 27, 2022, View Source [SID1234616263]).

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"2022 has proven to be an extremely productive year so far for Relay Therapeutics and we’re looking forward to sharing updates across our portfolio today," said Sanjiv Patel, M.D., Relay Therapeutics’ president and chief executive officer. "We are excited to be announcing the anticipated registrational path for RLY-4008 and the maturation of the data to support that pathway. In addition, building on the foundation of our PI3Kα franchise, we will outline a broad commitment to developing comprehensive treatment options for breast cancer patients. We believe our platform and approach have the potential to address some of the hardest-to-treat diseases and are excited to do just that in the coming years."

RLY-4008 Regulatory and Clinical Data Update

Relay Therapeutics conducted an end-of-phase 1 meeting with the FDA to discuss next steps for the clinical development of RLY-4008. Based on discussions with the FDA, the Company has decided to move forward with a single arm trial design for FGFRi-naïve FGFR2-fusion CCA at 70 mg once daily to potentially support accelerated approval. The Company also intends to add additional supportive CCA cohorts to an NDA submission, including frontline, FGFRi-experienced and FGFR2 mutation and amplification patients that could potentially facilitate a line and alteration agnostic label if the submission is approved.

The interim data shared with the FDA included a data cut-off of April 19, 2022, from the dose escalation portion of the ongoing study. The interim data included a safety database of 115 patients, with 58 patients treated with the once daily (QD) dosing schedule, and 13 of these patients were FGFRi-naïve FGFR2-fusion CCA patients treated with the once daily schedule ranging from 20 mg up to 70 mg. Also, in addition to the 17 patients previously disclosed at a twice daily (BID) schedule, an additional 40 patients were evaluated with an intermittent dosing schedule, both of which have been deprioritized.

The safety analysis as of the April 19, 2022 cut-off date was consistent with the analysis from the initial October 2021 data disclosure. Most treatment emergent adverse events were expected FGFR2 on target, low-grade, monitorable, manageable, and largely reversible. There were no observed Grade 4 or 5 adverse events. Notable off-target toxicities of hyperphosphatemia and diarrhea continued to be clinically insignificant.

The efficacy analysis from this interim data on the once daily dosing schedule presented to the FDA demonstrated confirmed partial responses in eight out of thirteen (62%) FGFRi-naïve FGFR2-fusion CCA patients across the 20 mg to 70 mg QD cohorts. There were four patients treated at the registrational trial dose of 70 mg QD as of the April 19, 2022 cut-off date, all of which had confirmed partial responses.

An update from the FGFRi-naïve FGFR2-fusion CCA patients treated at 70 mg QD across dose escalation and expansion is expected to be presented at a medical meeting in the second half of 2022. The entirety of the dose escalation data is expected to be presented at a medical meeting or published by the end of the first half of 2023. Lastly, initial data from the non-CCA expansion cohorts is expected to be presented in 2023.

Breast Cancer Portfolio and New Targets

Relay Therapeutics today disclosed three new programs from a growing breast cancer franchise including a selective CDK2 inhibitor, a rationally designed ERα degrader, and a chemically distinct pan-mutant selective PI3Kα inhibitor (RLY-5836).

CDK2 is a common cause of resistance to the over 50,000 patients a year in the U.S. on CDK4/6 inhibitors and potentially an important PI3Kα combination partner. Relay Therapeutics progressed from first compound synthesized to an advanced CDK2 lead compound with robust selectivity over other CDK family members in less than a year. This program is expected to enter the clinic in Q4 2023 or Q1 2024.
Leveraging the Dynamo platform, Relay Therapeutics has been able to move from the traditional empirical design of bi-functional degraders to rationally designed molecules. The company expects to nominate an ERα degrader development candidate in 2023.
As a demonstration of Relay Therapeutics’ commitment to PI3Kα mutant inhibition, the Company has designed a selective and chemically distinct pan-mutant PI3Kα inhibitor, RLY-5836. RLY-5836 is expected to be ready to enter the clinic in 2023.
Conference Call Information

Relay Therapeutics will host a live webcast and conference call today beginning at 8:00 am E.T. The virtual analyst and investor event will be webcast live and may be accessed through Relay Therapeutics’ website under Events in the News & Events section through the following link: View Source An archived replay of the webcast will be available following the event.

About RLY-4008

RLY-4008 is a potent, selective and oral small molecule 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. Preclinically, RLY-4008 demonstrated FGFR2-dependent killing in cancer cell lines and induced regression in in vivo models, while minimal inhibition of other targets was observed, including other members of the FGFR family. In addition, RLY-4008 demonstrated strong activity against known clinical on-target resistance mutations in cellular and in vivo preclinical models. RLY-4008 is currently being evaluated in a clinical trial in patients with advanced or metastatic FGFR2-altered solid tumors with a single arm, potentially registration-enabling cohort for pan-FGFR ("FGFRi") treatment-naïve FGFR2-fusion CCA. To learn more about the clinical trial of RLY-4008, please visit here.