Relay Therapeutics

Isomorphic Labs, the AI-first drug discovery company, has appointed Dr. Ben Wolf as Chief Medical Officer to lead translation of AI-driven discoveries into clinical medicines.

Relay Therapeutics presented updated interim data for RLY-2608 plus fulvestrant showing consistent median progression-free survival of 11.0 months in second-line patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer.

Relay Therapeutics plans to initiate ReDiscover-2, a Phase 3 trial evaluating RLY-2608 plus fulvestrant in PI3Kα-mutated, HR+/HER2- advanced breast cancer patients, with enrollment target of 540 patients.

• Korean pharmaceutical company HLB anticipates FDA approval for Rivoceranib in liver cancer by March 20, with plans to expand its use to adenoid cystic carcinoma through NCCN guidelines. • HLB subsidiary Elevar Therapeutics aims to submit a new drug application for RLY-4008 in bile duct cancer by end of 2024, following successful patient recruitment in clinical trials. • The company is pursuing development of RLY-4008 as a tumor-agnostic drug, following the successful model of Merck's Keytruda, targeting multiple solid tumor types.

• Updated clinical data on RLY-2608 plus fulvestrant will be presented at the San Antonio Breast Cancer Symposium, showcasing its efficacy in advanced breast cancer. • RLY-2608 targets PI3Kα mutations, which are present in approximately 14% of solid tumors, potentially addressing a large patient population. • The allosteric mechanism of RLY-2608 aims to improve selectivity for mutant PI3Kα over wild-type, reducing toxicity and improving treatment outcomes.

• RLY-2608, an oral, mutant-selective PI3Kα inhibitor developed by Relay Therapeutics, is currently undergoing Phase I clinical trials. • The drug is being evaluated both as a single agent and in combination with fulvestrant for the treatment of HR+/HER2- breast cancer. • RLY-2608 aims to overcome toxicities associated with wild-type PI3Kα inhibition, a limitation of existing PI3Kα modulators like alpelisib and inavolisib. • This innovative molecule targets specific PI3Kα mutations, potentially reducing side effects such as hyperglycemia and rash observed with less selective inhibitors.

• Relay Therapeutics and Elevar Therapeutics have entered an exclusive global licensing agreement for lirafugratinib, targeting FGFR2-driven cholangiocarcinoma and other solid tumors. • Elevar gains worldwide development and commercialization rights, while Relay could receive up to $500 million in milestone payments and royalties. • Lirafugratinib has breakthrough therapy and orphan drug designations from the FDA, with a recommended NDA filing for FGFR2-driven CCA. • The agreement allows Relay to focus on its PI3Kα programs while Elevar expands its oncology pipeline with a potential best-in-class FGFR2 inhibitor.

• The FDA approved Roche's Itovebi (inavolisib) in combination with Ibrance and Faslodex for HR+, HER2- advanced or metastatic breast cancer with PIK3CA mutation. • The approval was based on the Phase 3 INAVO120 trial, which showed a 57% reduction in disease progression or death compared to Ibrance and Faslodex alone. • Relay Therapeutics' stock is influenced by this approval, with analysts maintaining positive ratings due to the inclusion of Relay's drug candidate in the Roche therapy. • The combination therapy demonstrated a significantly higher objective response rate (58.4%) compared to the control group (25%) in the INAVO120 trial.

• Relay Therapeutics is laying off approximately 10% of its workforce, affecting about 30 employees, as part of a streamlining effort to enhance research efficiency. • The restructuring aims to save the company around $50 million annually, following a reported net loss of $92.2 million in the second quarter of 2024. • Despite the layoffs, Relay Therapeutics is advancing clinical trials, including a collaboration with Pfizer and positive Phase I/II data for RLY-2608 in breast cancer. • The company plans to engage with regulators to design a pivotal trial for RLY-2608, aiming to start it next year.

• Relay Therapeutics' RLY-2608, combined with fulvestrant, demonstrated a median progression-free survival of 9.2 months in pre-treated patients. • The ReDiscover trial data supports advancing RLY-2608 into a pivotal Phase 2 study in 2025 for metastatic breast cancer. • RLY-2608 exhibited a favorable tolerability profile, with few patients discontinuing treatment due to adverse events. • Relay Therapeutics plans to present updated data on lirafugratinib at the AACR-NCI-EORTC conference in October 2024.