Erasca (ERAS) Morgan Stanley 22nd Annual Global Healthcare Conference summary

Pipeline overview and strategic focus

• Pipeline prioritizes ERAS-0015 (pan-RAS molecular glue), ERAS-4001 (pan-KRAS inhibitor), and naporafenib (pan-RAF inhibitor in phase III for NRAS-mutant melanoma).

• ERAS-0015 and ERAS-4001 are preclinical, targeting IND filings in H1 and Q1 2025, respectively.

• Naporafenib is being studied in SEACRAFT-2 (phase III, NRAS-mutant melanoma) and SEACRAFT-1 (phase I-B, RAS Q61X solid tumors).

• Focus remains on the RAS/MAPK pathway, using both single agent and combination approaches.

• Portfolio prioritization is data-driven, with deprioritization of ERK and SHP2 inhibitors due to insufficient clinical activity.

ERAS-0015 and ERAS-4001 development and differentiation

• ERAS-0015 shows fourfold higher CYPA binding and tenfold higher potency in preclinical models compared to RMC-6236.

• Demonstrates longer tumor tissue residence time and favorable PK characteristics, suggesting potential best-in-class status.

• IND filing for ERAS-0015 remains on track for H1 2025, with GLP tox and CMC as key milestones.

• ERAS-4001 is KRAS-selective, sparing H and NRAS, potentially offering a wider therapeutic window and better tolerability.

• Combination of ERAS-0015 and ERAS-4001 is being considered to address resistance and isoform switching in RAS-driven tumors.

Competitive landscape and clinical benchmarks

• Pan-RAS molecular glue space is limited to three main molecules, with ERAS-0015 differentiated by preclinical attributes.

• Pan-KRAS space is crowded, but no clinical data have been disclosed yet; first data expected in 2025.

• Revolution Medicines' recent data in pancreatic cancer serve as a benchmark, showing higher PFS and OS, and supporting optimism for the class.

• Future non-small cell lung cancer data from competitors will provide further benchmarks for ERAS-0015.