Relay Therapeutics (RLAY) JMP Hematology and Oncology Summit summary

Industry trends and positioning

• Breast cancer treatment is shifting toward next-generation all-oral combination therapies, with a focus on targeted agents for PIK3CA-mutated patients.

• Oral SERDs and selective CDK4/6 inhibitors are gaining traction, aiming for improved efficacy and reduced toxicity.

• Recent inavolisib triplet approval provides proof of mechanism but highlights the need for more selective agents due to toxicity and patient exclusion.

• The field is moving away from infused agents toward oral regimens, raising the bar for new entrants.

Clinical development and data highlights

• RLY-2608 is a mutant-selective PI3Kα inhibitor with improved safety and efficacy, showing a 9.2-month median PFS in second-line HR+/HER2- breast cancer, outperforming current standards.

• Only 25% of patients experienced grade 3 treatment-related AEs, with minimal hyperglycemia risk, supporting broader patient eligibility.

• Subpopulation analysis shows consistent efficacy across ESR1 mutations and prior SERD treatment, with exclusion of PTEN and AKT co-mutations for phase III.

• The clean safety profile allows for combinability with other agents, including oral SERDs and next-gen CDK4/6 inhibitors.

Combination strategies and future plans

• Phase III pivotal trial for RLY-2608 in second-line breast cancer is planned for 2025, with fulvestrant as the initial SERD, and future phase II studies to explore oral SERDs.

• Triplet combinations with selective CDK4 inhibitors, such as atirmociclib, are in development, aiming to reduce toxicity and improve outcomes.

• Triplet safety studies focus on demonstrating combinability without synergistic toxicity, with key AEs being hyperglycemia, rash, diarrhea, stomatitis, and neutropenia.

• Differentiation from competitors includes broader metabolic eligibility, preference for ribociclib over palbociclib, and unique collaborations in the CDK4 space.