Company: IMRX
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0001790340-25-000042
Chunk: 40

Company: Immuneering Corp
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 40
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 inhibitors) for the treatment of certain solid tumors, which are often poorly immunologically accessible.

In October 2023, we presented preclinical data at the AACR-NCI-EORTC Conference in which IMM-6-415 in combination with encorafenib demonstrated better tumor growth inhibition and improved durability when compared head-to-head with binimetinib plus encorafenib in animal models of RAF mutant melanoma and colorectal cancer, and IMM-6-415 as a single agent demonstrated high sensitivity in a wide range of MAPK-driven tumor types, including models of RAS or RAF mutant disease.

Preclinical Studies: Resistance to CRAF-bypass

We evaluated IMM-6-415 head-to-head against two FDA-approved MEK inhibitors to assess their control of pMEK, pERK and CRAF-bypass in a NRAS, HRAS, NF1 and BRAF mutant melanoma tumor models. We exposed the tumor cells with 100 nM of each drug for 2 hours and evaluated MEK and ERK activation levels. We observed that IMM-6-415 reduced overall activity of the MAPK pathway at ERK and pathway reactivation at MEK through a decrease in MEK and ERK activation, resulting in CRAF-bypass resistance. In contrast, we observed that both FDA-approved MEK inhibitors displayed an increase in activated MEK, resulting in CRAF-bypass in RAS and NF1 mutant tumors (as depicted below).

Head-to-Head Comparison of IMM-6-415 against Two FDA-Approved MEK Inhibitors Using a Panel of Nine Melanoma Tumor Models: Observed Activity in RAS and RAF Mutant Tumors and Prevented Downstream Activation of ERK (↓ pERK) and Inhibited Activation of MEK (↓ pMEK)

Key Mutations & 3D-TGA Response[Melanoma Tumor Models]

Tumor cell lines were acquired from ATCC, ECACC and DSMZ. 3D-Tumor Growth Assay (3D-TGA) sensitivity (green fill) defined as IC50 < 10uM in 72-hour ECM-based assay with %EdU readout, and IC50 ≥10uM considered resistant. Cell-based 2D in vitro molecular assays were performed to assess cellular levels of phosphorylated and total ERK and MEK across 9 melanoma models (100 nM drug for 2-hours followed by quantitative Western blot analysis for pERK, total ER