Company: ERAS
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0000950170-25-042682
Chunk: 36

Company: Erasca, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 36
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 in combination with an anti-PD-1 in a KPC KRAS G12D CDX model where tumor regression was maintained even after treatment was stopped on Day 38. Furthermore, no tumors formed in the rechallenge study, suggesting the combination of ERAS-4001 and anti-PD-1 can stimulate immunologic antitumor memory in the rechallenged mouse.

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Pharmacokinetics and ADME of ERAS-4001

ERAS-4001 showed encouraging PK results, including oral bioavailability in mouse, rat, and dog.

ERAS-4001 demonstrated favorable ADME results in vitro. The GLP cardiovascular telemetry study in dogs showed no QTc prolongation.

Initial clinical development strategy for ERAS-4001

We are planning an initial clinical trial for ERAS-4001, which we refer to as BOREALIS-1. The BOREALIS-1 trial is expected to assess ERAS-4001 as a monotherapy and in combination with approved and unapproved therapies for the treatment of patients with KRASm solid tumors. We plan to file an IND for the BOREALIS-1 trial in the second quarter of 2025, with an anticipated Phase 1 monotherapy data readout in 2026.

ERAS-12: our EGFR D2/D3 biparatopic antibody program

Inhibition of activated EGFR signaling mediated by overexpression of EGFR has shown promise in treating various tumors, including CRC and head and neck squamous cell carcinoma. In tumors where overexpression of wildtype EGFR is thought to be a primary driver of EGFR signaling, an antibody-based approach is an effective way to target the receptor, and approved antibodies have demonstrated good tolerability as well as activity by inhibiting EGFR activation and mediating antibody-dependent cellular cytotoxicity, a process by which the antibody alerts the immune system to attack 

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the bound tumor cell. However, all approved anti-EGFR antibodies target D3 only, which is the main site for ligand binding, and no approved antibodies target D2, which is responsible for dimerization of EGFR upon ligand binding. Binding of D2 prevents both EGFR homodimerization as well as heterodimerization. Overexpression of EGFR activates EGFR signaling by facilitating both homo- and heterodimerization. Consequently, an antibody that targets D2, the receptor domain responsible for dimerization upon ligand binding, would be predicted to be particularly