Company: ERAS
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0000950170-25-042682
Chunk: 35

Company: Erasca, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 35
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 suggests potentially lower concern for cardiovascular risk.

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Initial clinical development strategy for ERAS-0015

We are planning an initial clinical trial for ERAS-0015 which we refer to as AURORAS-1. The AURORAS-1 trial is expected to assess ERAS-0015 as a monotherapy and in combination with approved and unapproved therapies for the treatment of patients with RASm solid tumors. We plan to file an IND for the AURORAS-1 trial in mid-Q2 2025, with an anticipated Phase 1 monotherapy data readout in 2026.

ERAS-4001: our pan-KRAS small molecule inhibitor

Biophysical characterization and preclinical potency of ERAS-4001

ERAS-4001 is a pan-KRAS small molecule inhibitor that demonstrated high affinity and long target residence time in vitro against multiple KRAS G12X mutations as well as KRAS wildtype, and selectivity for KRAS wildtype over HRAS wildtype and NRAS wildtype.

ERAS-4001 potently and selectively inhibited multiple cell lines that represent KRAS G12X, G13D, and wildtype with single digit nanomolar potency. Demonstrating selective inhibition of KRAS, ERAS-4001 showed no activity in two KRAS independent cell lines, which are shown at the bottom.

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In biochemical assays, ERAS-4001 potently inhibited KRAS in both the GTP- and GDP-bound states with single digit nanomolar IC50s. ERAS-4001’s potent disruption of binding between KRAS G12D and the RAS-binding domain peptide is intended to model ERAS-4001’s potential to block KRAS from signaling downstream via the RAS/MAPK pathway. ERAS-4001 showed the potential to inhibit KRAS mutants where KRAS spends more time in the activated GTP-bound state, such as G12D and G12V mutations.

Preclinical activity of ERAS-4001

ERAS-4001 showed encouraging in vivo activity in multiple CDX models. ERAS-4001 achieved tumor stasis and regression in three sensitive KRAS G12D models and one sensitive KRAS G12V model. In addition, ERAS-4001 showed promising activity in the pan-KRAS inhibitor insensitive model, the KRAS G12V mutant CDX NCI-H727.

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ERAS-4001 has also demonstrated antitumor activity