Relay Therapeutics (RLAY) Study result summary

Study background and objectives

• Zovegalisib, a pan-mutant selective PI3Kα inhibitor, is being developed for hormone receptor-positive, HER2-negative metastatic breast cancer, targeting large commercial opportunities in both second-line and frontline settings.

• The frontline regimen combines zovegalisib with atirmociclib (a selective CDK4 inhibitor) and fulvestrant or aromatase inhibitor, aiming for improved efficacy and tolerability over current standards.

• The goal is to offer a better treatment option for the 40% of frontline patients with PI3Kα mutations, with a phase III trial planned for early 2027.

• A supply agreement with Pfizer ensures access to atirmociclib for the experimental arm and palbociclib for the control arm in the upcoming phase III trial.

Commercial opportunity overview

• Zovegalisib targets major US markets: 2L breast cancer ($2-3B), 1L breast cancer ($7-8B), and vascular anomalies ($6-8B).

• Estimated 35,000 1L breast cancer patients in G7 markets have PIK3CA mutations.

Study design and patient population

• Dose escalation and ongoing studies enrolled heavily pretreated, median third-line patients, many with prior CDK4/6 inhibitor, endocrine therapy, chemotherapy, and PI3K pathway inhibitor exposure.

• 69 patients enrolled; 62 at or below potential Phase 3 dose; 34 evaluable for response.

• Nearly half of patients were pre-diabetic, over 60% had visceral disease, and over 40% had co-occurring ESR1 mutations.

• Median follow-up was 7.4 months; 77% remain on study as of data cut-off.