Elicio Therapeutics Advances ELI-002, a Multivalent KRAS Mutation-Targeting Cancer Vaccine, into Clinical Development

Elicio Therapeutics, an emerging immuno-oncology company, recently presented significant preclinical data for its cancer vaccine targeting seven KRAS mutant variants (mKRAS). The results demonstrated that the cancer vaccine targeting mKRAS antigens can induce potent cytolysis. Elicio’s “AMP KRAS Vaccine” program, ELI-002, is expected to enter initial clinical studies in patients with pancreatic cancer in the first quarter of 2020.

Mutations in the KRAS gene are closely associated with the development, progression, and recurrence of human malignancies. Genetic and biochemical studies have demonstrated that KRAS-dependent signaling plays a critical role in regulating the growth, proliferation, invasion, and metastasis of various cancer cells. However, due to the lack of druggable pockets on the KRAS protein structure for small-molecule binding, researchers have made limited progress in developing targeted therapies against it in recent years, leading to its widespread classification as an “undruggable” target. It was not until this year that the first clinical trial results for small-molecule inhibitors targeting the KRAS G12C mutant were reported. Nevertheless, the KRAS G12C mutation represents only a small fraction of all KRAS gene mutations.

Elicio Therapeutics’ Amphiphipe Platform enables precise and efficient delivery of vaccines directly to the lymph nodes. By incorporating albumin-binding moieties onto peptide chains, this platform facilitates the targeted delivery of cancer vaccines to the lymph nodes, thereby enhancing their recognition by antigen-presenting cells (APCs) within these structures. The APCs present the vaccine antigens to T cells in the lymph nodes, triggering T cell activation and proliferation. This process endows the T cells with potent anti-tumor activity and programs them to establish long-lasting immunological memory, helping to prevent disease recurrence.

ELI-002 is the company’s “AMP KRAS vaccine,” which comprises seven mutant KRAS (mKRAS) peptides. The immune response elicited by this vaccine generates a robust immunity against mutant KRAS proteins. Furthermore, this vaccine not only activates CD8-positive T cells but also stimulates responses in CD4-positive T cells. Upon restimulation with mKRAS-specific peptides in vitro, it induces high levels of Th1 helper cytokines. In vivo, T cells generated through the vaccine-induced immune response exhibit potent cytolytic activity against target cells expressing mKRAS. This vaccine can cover 99% of tumors harboring KRAS gene mutations.

“Previous vaccine approaches using synthetic peptides failed to effectively target key immune cells residing in lymph nodes, eliciting only weak or undetectable immune responses in patients,” said Dr. Peter DeMuth, Vice President of Research at Elicio Therapeutics. “The Amphiphile technology delivers peptide antigens carrying potent adjuvants directly to the lymph nodes, significantly amplifying the resulting immune response and generating highly effective mKRAS-specific T cells that kill mKRAS-expressing tumor cells in vivo, enabling us to simultaneously elicit immune responses against seven common mutants found in KRAS-driven cancers.”

References:

[1] Elicio Therapeutics Presents In Vivo Data for a Universal Amphiphile Vaccine Targeting KRAS-Driven Cancers，Retrieved August 9, 2019, from https://www.businesswire.com/news/home/20190807005528/en/

[2] Elicio official website Retrieved August 9, 2019, from https://elicio.com/amphiphile-technology/amphiphile-vaccines/

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