Relay Therapeutics (RLAY) Guggenheim Securities Inaugural Healthcare Innovation Conference summary

Key clinical data and development plans

• RLY-2608 demonstrated a 33% response rate and median PFS of 9.2 months in heavily pretreated, HR+/HER2- metastatic breast cancer patients, with only one case of grade 3 hyperglycemia among 64 patients, indicating superior tolerability and efficacy compared to existing PI3K inhibitors.

• Plans are underway for a randomized phase III trial in second-line breast cancer, comparing RLY-2608 to capivasertib, with expectations of favorable outcomes due to better tolerability and efficacy, especially in less heavily pretreated patients.

• Stringent inclusion criteria for competing PI3K inhibitors like inavolisib exclude up to 50% of U.S. patients due to metabolic risks, while RLY-2608’s safety profile could broaden patient eligibility.

• Upcoming data presentations at SABCS will focus on previously disclosed results, with no new sub-analyses planned due to limited patient numbers.

Expansion into new indications and combinations

• Triplet dose exploration with ribociclib is ongoing, leveraging RLY-2608’s favorable tolerability to overcome past combination challenges seen with other PI3K inhibitors.

• A clinical trial supply agreement with Pfizer will enable triplet studies with atirmociclib, aiming to initiate dosing by year-end and align with evolving standards in CDK4/6 inhibitor use.

• Initial triplet studies are in patients previously treated with CDK4/6 inhibitors, focusing first on safety and dose finding before assessing efficacy.

• Phase III go decisions in first-line settings depend on evolving treatment landscapes and patient exposure to CDK4/6 inhibitors in adjuvant and metastatic settings.

Competitive positioning and pipeline updates

• RLY-2608 is positioned as the first mutant-selective PI3K inhibitor with a clear safety and efficacy advantage, aiming for first-mover status as competitors face hurdles with non-selectivity and administration routes.

• In vascular malformations, 25–40% of 170,000 U.S. patients could be eligible for systemic therapy, with RLY-2608 trials starting in Q1 next year and initial focus on PROS and lymphatic malformations.

• The FGFR2 inhibitor RLY-4008 has shown robust activity in cholangiocarcinoma and other FGFR2-driven tumors, with plans for NDA filing and potential global out-licensing.

• Fabry disease program targets both amenable and non-amenable mutations with a non-inhibitory chaperone, aiming for broader efficacy than Galafold and potential combination with ERT.

• NRAS selective inhibitor addresses a 28,000-patient U.S. market in solid tumors, offering a precision medicine approach with improved tolerability.