Elicio Therapeutics Updates ELI-002 Phase 1 Data at SITC 2024 Annual Meeting

Elicio Therapeutics, Inc., a biotechnology firm focusing on innovative cancer immunotherapies, has shared promising preliminary data from the AMPLIFY-7P Phase 1 clinical trial of ELI-002 during the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC). ELI-002 is an Amphiphile (AMP) cancer vaccine designed to target KRAS-mutant tumors. The study evaluates ELI-002 in patients with solid tumors driven by KRAS mutations, following standard locoregional treatment, who are at risk of disease recurrence. The Phase 2 of the AMPLIFY-7P trial, involving pancreatic cancer patients, continues with completion of enrollment anticipated by the end of 2024.

The immunogenicity of ELI-002 was assessed through a longitudinal ex vivo analysis of peripheral T cells from 12 evaluable patients. These patients received either 1.4 mg or the recommended Phase 2 dose (RP2D) of 4.9 mg, with data cut off on September 11, 2024. Key observations include the following: mKRAS-specific T cell responses were observed in all evaluable patients, with the median response in the 4.9 mg group being 12 times higher compared to the 1.4 mg group. The T cell specificities covered all seven KRAS mutants targeted by ELI-002, with the strongest responses against KRAS variants G12R, G12D, and G12V. Furthermore, the mKRAS-specific T cells were found to be fully functional, secreting both granzyme B and perforin. There was a correlation between the magnitude of T cell response and duration of disease-free survival (DFS), with the highest three quartiles of T cell responders not yet reaching median DFS, while the lowest quartile showed a median DFS of 3.1 months.

The durability of the T cell responses against mKRAS antigens was notable, extending up to 1.5 years. Additionally, antigen spreading was detected in all RP2D-treated patients, with T cell responses observed against 67.5% of tested neoantigens identified from patient-specific mutanomes. This suggests that ELI-002 may induce tumor immunosurveillance beyond mKRAS antigens. As of May 23, 2024, the safety data indicated that ELI-002 remains safe and well-tolerated, with no dose-limiting toxicities or cytokine release syndrome observed.

Dr. Christopher Haqq, Elicio’s Executive Vice President, Head of Research and Development, and Chief Medical Officer, expressed optimism about the expansion of T cells targeting mutant KRAS antigens and the observed correlation between T cell response and DFS in the Phase 1 study. He highlighted the significance of induced T cell reactivity against personalized neoantigens, which could enhance the breadth and durability of tumor immunosurveillance. These preliminary findings are consistent with previous results from the AMPLIFY-201 study, published earlier in Nature Medicine. Further clinical data updates from AMPLIFY-201 are expected in December.

Elicio Therapeutics aims to advance its lead program, ELI-002, an off-the-shelf vaccine candidate targeting common KRAS mutations, which are responsible for approximately 25% of all solid tumors. ELI-002 is being studied in an ongoing, randomized clinical trial in patients with mKRAS-positive pancreatic cancer who have completed standard therapy but remain at high risk of relapse. Elicio’s pipeline also includes additional off-the-shelf therapeutic cancer vaccines, such as ELI-007 and ELI-008, targeting BRAF-driven cancers and p53 hotspot mutations, respectively.

The AMP platform developed by Elicio delivers investigational immunotherapeutics directly to the lymph nodes, the central hub of the immune system. This targeted delivery is expected to efficiently educate, activate, and amplify critical immune cells, potentially resulting in potent adaptive immunity required to treat various diseases. Preclinical models have demonstrated lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function, and durability. Elicio believes that their AMP lymph node-targeted approach will yield superior clinical benefits compared to immunotherapies that do not engage the lymph nodes based on preclinical studies.

The AMP platform, originally developed at the Massachusetts Institute of Technology, holds significant potential in the cancer space. It aims to advance multiple development initiatives through internal activities, in-licensing arrangements, or development collaborations and partnerships. The platform’s capability to deliver immunotherapeutics directly to the lymph nodes by latching onto the protein albumin at the local injection site, as it travels to lymphatic tissue, has been observed in preclinical models, driving potent immune responses.