Erasca achieves key milestones for naporafenib, ERAS-801

Erasca announced program updates for pan-RAF inhibitor naporafenib and central nervous system-penetrant EGFR inhibitor ERAS-801, as well as a strategic program prioritization that extends its projected cash runway from H2 2025 to H1 2026. Recent Program Updates: Naporafenib Plus Trametinib for Patients with NRAS mutant Melanoma in Pivotal SEACRAFT-2 Trial. End of Phase 2 meetings with U.S. Food and Drug Administration and European health authorities confirm SEACRAFT-2 Phase 3 trial design and provide clarity on registrational pathway: Enrollment of patients with high unmet medical need who progressed on, or are intolerant to, standard of care immune checkpoint inhibitor therapy; Comparator arm is physicians’ choice of cytotoxic chemotherapy or trametinib; Dual primary endpoint evaluation of progression free survival and overall survival, with PFS acceptable for potential initial approval; The Phase 3 trial consists of two stages: a randomized, controlled, dose optimization stage, for which we expect to have a data readout in 2025, and a randomized, controlled stage to support regulatory approval; Phase 3 SEACRAFT-2 trial initiation remains on track for H1 2024. ERAS-801 for Patients with Recurrent GBM in Phase 1 THUNDERBBOLT-1 Trial: MTD identified as 240 mg once a day and MTD-1 identified as 160 mg QD for ERAS-801; ERAS-801 was safe and tolerable at the MTD and MTD-1 dose levels; ERAS-801 exhibited well behaved pharmacokinetic characteristics; Expansion cohorts actively enrolling to collect additional safety, tolerability, and preliminary efficacy data to support dose optimization and selection; Phase 1 dose escalation data to be presented at a scientific meeting in H1 2024; expansion cohort data are anticipated in H2 2024. Prioritized Clinical Programs and Key Upcoming Milestones: Naporafenib – Pan-RAF Inhibitor: Dosing of the first patient in pivotal Phase 3 SEACRAFT-2 trial in patients with NRASm melanoma expected H1 2024; Initial signal-seeking Phase 1b efficacy data in relevant tumor types from patients with RAS Q61X solid tumors in ongoing SEACRAFT-1 trial expected between Q2-Q4 2024. ERAS-801 – CNS-penetrant EGFR Inhibitor: Phase 1 monotherapy dose escalation and expansion data in rGBM expected in 2024. ERAS-007 – ERK1/2 Inhibitor: Initial dose expansion data from Phase 1b/2 HERKULES-3 trial further evaluating encouraging early efficacy data with ERAS-007 in combination with EC in EC-naive patients with BRAF mutant CRC expected between H2 2023 and H1 2024. Deprioritized Opportunities: Select trials or programs were deprioritized, despite their potential differentiation, to focus the company’s resources on the most promising programs, which is expected to extend the company’s cash runway from H2 2025 to H1 2026: FLAGSHP-1 – Phase 1b combination trial of ERAS-601 SHP2 inhibitor with cetuximab was deprioritized. Though ERAS-601 achieved confirmed responses as a monotherapy and in combination with cetuximab, preliminary data do not justify further development of this combination in FLAGSHP-1 indications; ERAS-5 – Preclinical ULK inhibitor; ERAS-10 – Preclinical protein degrader