Erasca (ERAS) Guggenheim Securities Inaugural Healthcare Innovation Conference summary

Pipeline focus and strategy

• Nearly all efforts are concentrated on the RAS-targeting franchise, with lead molecules ERAS-15 (pan-RAS molecular glue) and ERAS-4001 (pan-KRAS switch-II pocket binder) both advancing toward IND filings in H1 and Q1 2025, respectively.

• Naporafenib remains the most advanced pan-RAS inhibitor, with recent data showing a 40% response rate in NRAS mutant melanoma, outperforming historical benchmarks.

• The SEACRAFT-2 phase III trial for naporafenib is ongoing, currently in the dose optimization stage, with pivotal randomized stage to follow after dose selection in 2025.

• Dose selection for SEACRAFT-2 will be based on efficacy and tolerability, with the 201 dose showing strong promise due to improved safety and high relative dose intensity.

• The commercial opportunity for NRAS melanoma is estimated at several hundred million dollars in peak revenue, targeting a patient population of a few thousand in the US and Europe.

Clinical data and differentiation

• Naporafenib plus trametinib demonstrated a median PFS of about five months and OS of 13–14 months, doubling historical controls in post-IO NRAS melanoma.

• Mandatory rash prophylaxis in SEACRAFT-1 and 2 reduced rash rates from mid-30% to 10–11% and lowered discontinuations due to adverse events.

• ERAS-15 shows 8–20x higher CypA binding affinity and 8–10x higher in vivo potency compared to a leading competitor, with superior tumor tissue biodistribution.

• ERAS-4001 exhibits single-digit nanomolar potency against key KRAS variants in both GTP and GDP states, with strong in vivo tumor regression and selectivity for KRAS over H and NRAS.

• Both ERAS-15 and ERAS-4001 are positioned to address significant unmet needs in major tumor types, with plans for broad development across pancreatic, lung, and colorectal cancers.

Forward-looking statements and development plans

• IND filings for ERAS-15 and ERAS-4001 are on track for H1 and Q1 2025, respectively, with preclinical and CMC activities progressing as planned.

• Phase I studies for both molecules will use dose escalation and expansion in relevant cohorts, with potential for better tolerability in KRAS-selective approaches.

• Future development will allow each molecule to find its optimal fit across the spectrum of RAS-driven tumor types and mutations.

• Pipeline expansion is under consideration, but the bar for new assets remains high, with current focus on execution of existing programs.

• The company has received significant inbound interest following recent licensing deals, but remains selective in evaluating new opportunities.