Company: ERAS
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0000950170-25-042682
Chunk: 32

Company: Erasca, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 32
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 to file the IND in the second quarter of 2025. Phase 1 monotherapy data readouts are expected for each of the ERAS-0015 AURORAS-1 and ERAS-4001 BOREALIS-1 clinical studies in 2026.

Both molecules exceed our target product profile across three key attributes: potency, favorable ADME/PK properties including oral bioavailability, and strong IP position. Improved potency and oral bioavailability may enable dosing at a lower dose, particularly for ERAS-0015, which could translate into linear PK across biologically relevant doses, better GI tolerability profile given the lower drug load in the GI tract, and an improved therapeutic window. 

We are pursuing a clinical development strategy that we believe could enable us to address RAS mutant tumor types where there is the highest unmet medical need, including CRC, PDAC, and NSCLC. We plan to move swiftly into strategic combinations while, in parallel, characterizing the monotherapy activity and combination potential of each program. We also plan on capitalizing on our unique portfolio which has complementary proposed mechanisms of action and target profiles to develop these novel combinations. 

ERAS-0015: our pan-RAS molecular glue

Biophysical characterization of ERAS-0015

ERAS-0015 is a pan-RAS molecular glue that we believe has the potential to treat patients with RAS mutant solid tumors. The molecule forms a tripartite complex with Cyclophilin A (CypA) and the active form of RAS to inhibit RAS-dependent signaling. In surface plasmon residence (SPR) and isothermal titration calorimetry (ITC) binding assays, ERAS-0015 has demonstrated 8-21-fold higher binding affinity to cyclophilin A relative to RMC-6236 (the leading pan-RAS molecular glue in development), which we believe may enable more potent inhibition.

We performed a tumor PK distribution assessment in TGI studies of ERAS-0015 versus RMC-6236 in PK-59 and PSN-1 CDX models. PK concentrations of paired tumor and blood samples were measured at 4 and 24 hours after the last dose of the TGI studies.

In the PK-59 CDX study, the dose normalized ERAS-0015 (across 3 ERAS-0015 dose levels: 0.1, 0.3, and 1 milligrams per kilograms (mpk)) tumor PK exposures