Immuneering Corporation announced positive initial pharmacokinetic (PK), pharmacodynamic (PD) and safety data from the Phase 1 trial of IMM-1-104 which are being shared in a poster presentation titled “Humanized 3D tumor models that are mutationally aligned with AACR GENIE patients predict IMM-1-104 activity in RAS-addicted tumors” at the American Association for Cancer Research (AACR) annual meeting. The Phase 1/2a clinical trial is an open-label study designed to evaluate the safety, tolerability, PK and preliminary efficacy of IMM-1-104 in patients with advanced RAS mutant solid tumors. The Phase 1 portion of the study, which is being conducted at five clinical sites in the United States, is evaluating IMM-1-104 following a Bayesian mTPI-2 escalation design, which includes a dose escalation phase and dose evaluation phase to establish an optimized RP2D candidate.

Following selection of the RP2D candidate, the Company expects to conduct a Phase 2a dose expansion phase to assess the safety and efficacy of IMM-1-104 at the RP2D in RAS mutated pancreatic, melanoma, lung and colorectal cancers. Highlights of the initial IMM-1-104 Phase 1 PK, PD and safety data presented at AACR include (as of data cut-off date of April 10, 2023, including patients with pancreatic and colon cancer): · Significant PK Cmax levels (plasma concentration of therapy in a specific area of the body) observed with IMM-1-104 of over 2,000 ng/mL (or approximately 1 uM drug free-fraction at 160 mg once daily oral dose) · Greater than 90% PD inhibition of phosphorylated extracellular signal-regulated kinase (pERK) with IMM-1-104 compared to pretreatment baseline for patients at the third dose level (160 mg once daily oral) · A median plasma half-life (t1/2) of 1.94 hours observed with IMM-1-104 across the first three dose levels evaluable (40 mg, 80 mg and 160 mg once daily oral), in patients with pancreatic and colorectal cancer with different RAS mutations, including KRAS-G12D, the most common mutation present in pancreatic cancer · IMM-1-104 was well tolerated with no DLTs or SAEs observed and no drug-related adverse events beyond Grade 1 observed Based on the encouraging initial data presented today, Immuneering has updated guidance for the anticipated timing of announcing a RP2D for IMM-1-104 for its Phase 1/2a study. Management now expects to announce the RP2D in early 2024, versus prior guidance of mid-2024.

In addition, IMM-1-104 was evaluated in humanized 3D preclinical tumor models displaying diverse mitogen-activated protein kinase (MAPK) pathway activation events. The MAPK pathway consists of a series of protein kinases such as RAS, RAF, MEK and ERK that are involved in many important cellular processes including cell proliferation, differentiation and survival. The antitumor activity of IMM-1-104 was evaluated in 132 tumor models spanning 12 distinct tumor types in a proprietary humanized 3D tumor growth assay (3D-TGA) conducted in Immuneering's labs in San Diego.

Based on drug-response sensitivity and resistance profiles, a biomarker signature for IMM-1-104 was developed to project potential therapeutic response in more than 100,000 cancer patients found in the AACR Project GENIE® database. Mutational landscapes of patients within GENIE helped identify preclinical models that represent patient profiles likely to be encountered in the clinic. These results were utilized in prioritizing indications for the planned Phase 2a clinical trial.

IMM-1-104 aims to achieve universal-RAS activity that selectively impacts cancer cells to a greater extent than healthy cells, through deep cyclic inhibition of the MAPK pathway with once-daily dosing. IMM-1-104 is currently being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations (NCT05585320).