Erasca (ERAS) R&D Update summary

RAS-targeting franchise progress

• ERAS-0015 and ERAS-4001 exhibit best-in-class potential, with ERAS-0015 showing 8-20x higher CypA binding affinity and 5-10x greater in vivo potency than RMC-6236.

• Both compounds have demonstrated favorable ADME, PK, and toxicology profiles, supporting planned IND filings in H1 2025 for ERAS-0015 and Q1 2025 for ERAS-4001.

• ERAS-0015 shows preferential tumor distribution, longer residence time, and consistent anti-tumor activity across multiple models.

• ERAS-4001 potently inhibits KRAS in both GTP- and GDP-bound states, achieving tumor stasis and regression in sensitive KRAS G12D and G12V models.

• Good Laboratory Practice toxicology studies are progressing as planned: ERAS-0015 completed, ERAS-4001 near completion.

Naporafenib clinical update (SEACRAFT-1 and SEACRAFT-2)

• SEACRAFT-1 trial showed a 40% response rate in NRAS-mutant melanoma, with durable responses and improved tolerability, supporting SEACRAFT-2's focus on this indication.

• 70% of patients in SEACRAFT-1 remained on treatment at data cutoff, including all responders.

• Mandatory primary rash prophylaxis reduced grade ≥3 dermatologic toxicities from ~30% to ~12% and drug discontinuations from ~20% to <10%.

• Median relative dose intensity for naporafenib and trametinib improved to nearly 99% and 100%, respectively, in SEACRAFT-1.

• SEACRAFT-2 pivotal trial for NRAS-mutant melanoma is ongoing, with stage I data expected in 2025.

Regulatory and strategic focus

• Regulatory alignment with US and European agencies paves the way for potential tissue-specific approval in melanoma; Fast Track Designation received from FDA for NRASm melanoma.

• Naporafenib development is now focused on NRAS-mutant melanoma, with increased probability of success based on recent data.

• Enrollment in SEACRAFT-1 has stopped at 82 patients, as data do not support a tissue-agnostic label.