Company: IMRX
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0001790340-25-000042
Chunk: 31

Company: Immuneering Corp
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 31
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 in on-target drug-related toxicities that limit clinical durability and potential drug-drug combinations. Furthermore, sustained irreversible covalent inhibition of these pathways may lead to treatment resistance, as highlighted in a study in the New England Journal of Medicine (N Engl J Med 2021; 384:2382-2393). The study focused on patients treated with adagrasib, an irreversible covalent inhibitor of KRASG12C, and reported that 45% of patients (17 patients out of 38) in the study receiving adagrasib monotherapy developed resistance. Of these patients, many resistance mechanisms were observed involving non-G12C variations in KRAS, variations in NRAS or BRAF, or other resistance mechanisms related to the MAPK pathway. A second study published in Nature (November 10, 2021) evaluated 43 patients treated with sotorasib, an irreversible covalent inhibitor of KRASG12C, and reported 27 patients with multiple treatment-emergent resistance alterations. Of these, 70% (19 out of 27) patients reported resistance mechanisms involving RAS/RAF mutations (Nature 2021; 599:679-683). A third study in the New England Journal of Medicine (N Engl J Med 2023; 389:710-721) also described acquired alterations that may confer resistance to divarasib (another irreversible covalent inhibitor of KRASG12C) including many alterations in KRAS, BRAF, NRAS, and other elements of the MAPK pathway.

Developing novel therapeutics to effectively, broadly and safely target this pathway may provide clinical benefit in large patient populations with significant unmet needs. In addition, although this pathway represents one of the most active areas in cancer drug discovery and development, targeted therapeutics that more effectively and safely normalize, but not chronically ablate, ERK signaling may uncouple drug activity and tolerability, while optimizing both. Our pipeline is designed to disrupt molecular pathways in a pulsatile way that undermines tumor addiction while limiting drug-related toxicity of normal healthy cells that are less reliant on a sustained high level of signaling along these pathways.

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IMM-1-104 Design and Preclinical Overview

Background of MEK Inhibitors

Activating mutations of RAS and/or RAF in the MAPK pathway are observed in approximately 30% of all cancer patients, and inappropriate activation of this pathway is observed in up to 50% of all tumors and represents one of