Immuneering (IMRX) Jefferies 2024 Global Healthcare Conference summary

Program overview and scientific rationale

• IMM-1-104 aims for broad activity across RAS mutations by targeting the MAP kinase pathway at the MEK level, using a novel Deep Cyclic Inhibition approach to improve tolerability and efficacy.

• Deep Cyclic Inhibition delivers high drug concentration pulses with rapid clearance, minimizing toxicity by allowing healthy cells to recover, unlike first-generation MEK inhibitors.

• Malignant cells are more dependent on sustained MAP kinase signaling than healthy cells, enabling selective tumor targeting.

Phase 1 clinical data and safety profile

• Phase 1 enrolled heavily pretreated, late-line cancer patients, mostly with pancreatic cancer, to assess safety and tolerability.

• Top-line safety data showed a highly differentiated profile, with minimal grade 3 or 2 adverse events and favorable tolerability compared to existing MAP kinase pathway drugs.

• Favorable tolerability opens opportunities for combination therapies and broader patient eligibility.

Pharmacodynamics, efficacy, and resistance mechanisms

• IMM-1-104 achieved unprecedented suppression of MAP kinase signaling, maintaining >90% inhibition of phosphorylated ERK for several hours at key doses.

• Circulating tumor DNA analysis showed no acquired RAS mutations as resistance, indicating pan-RAS activity; resistance arose only via non-MAP kinase pathways.

• Tumor shrinkage was observed in about half of patients, with individual lesion regressions up to 35.7% and best RECIST SLD of 18.9% over 5 months.