On August 7, 2019 Elicio Therapeutics, a next generation immuno-oncology company, reported that significant preclinical data from a novel lymph-node targeted vaccine targeting the seven KRAS mutations that drive 99% of all KRAS-driven cancers, estimated to be 25% of all human solid tumors (Press release, Elicio Therapeutics, AUG 7, 2019, View Source [SID1234538290]). Elicio’s "AMP KRAS vaccine" ELI-002 will enter initial patient studies in pancreatic cancer patients in Q1-2020.
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These studies, described in "Amphiphile-modifications target mKRAS-antigen and adjuvant to lymph nodes and enable polyfunctional mKRAS-specific immune responses with potent cytolytic activity," co-authored by Peter DeMuth, PhD., Elicio Vice President of Research, will be presented at the Immuno-Oncology Summit in Boston on August 8th, 2019.
"Previous vaccine approaches utilizing synthetic peptides have not effectively targeted the critical immune cells residing in the lymph nodes and have elicited only weak or undetectable immune responses in patients," said Dr. DeMuth. "The Amphiphile technology allows us to simultaneously generate immune response to the seven mutations commonly present in KRAS driven cancers by targeting peptides with a powerful adjuvant directly to the lymph nodes, significantly amplifying the resulting immune responses, and producing highly functional mKRAS-specific T cells capable of killing mKRAS-presenting cells in vivo."
Elicio has demonstrated in multiple tumor models that improving the targeting of immunogens and cell-therapy activators to lymph nodes, where resident immune cells potently orchestrate immunity, can substantially amplify their ability to induce effective tumor-killing immune responses. ELI-002 is an "AMP KRAS vaccine" containing seven Amphiphile mKRAS peptides and a proprietary Amphiphile adjuvant, administered subcutaneously.
The "AMP KRAS vaccine" administration and resulting immune response yields robust activation against all common mutations in the KRAS protein compared to low or undetectable responses generated by soluble or benchmark treatments which fail to effectively reach the lymph nodes. Further, this response is composed of CD4+ as well as CD8+ T-cells resulting in the production of high levels of Th1-associated cytokines upon re-stimulation with mKRAS-specific peptides in vitro. In vivo, robust cytolytic function towards mKRAS-presenting targets can be measured in the T-cells generated through the AMP vaccination regimen.
"To date, ‘drugging’ mKRAS directly has only been achieved in early clinical studies for the G12C allele, using covalent inhibitors. While validating mKRAS as a target in lung cancer, most human tumors have different mutations, or G12C is not a driver mutation. The concern is that chasing mutations is difficult and keeping up with the genomic instability of cancer may lead to resistance. The AMP vaccine approach covers 99% of all mKRAS tumors and G12X or G13X mutations need only be expressed, and not necessarily as driver mutations," said Julian Adams PhD, Elicio’s Chairman.
Elicio is developing ELI-002 to treat and prevent disease recurrence for hundreds of thousands of patients with mKRAS-driven cancers, including pancreatic, colorectal and lung cancer. KRAS mutations are present in 90% of pancreatic cancers, 40% of colorectal cancers, and 30% of non-small cell lung cancers. ELI-002has completed preclinical validation, IND-enabling GLP toxicology studies, GMP manufacturing, and a pre-IND meeting with the FDA and intends to enter initial patient studies in the first half of 2020. These trials will be multi-site, randomized, controlled studies.
About the Amphiphile Platform
The Elicio Amphiphile platform enables precise targeting and delivery of immunogens and cell-therapy activators directly to the lymphatic system, the "brain center" of the immune response, to significantly amplify and enhance the body’s own system of defenses, defeat solid and hematologic cancers, and prevent their recurrence. Once in the lymph nodes, Amphiphile immunotherapies are taken up by antigen presenting cells (APC’s) to orchestrate signaling to natural or engineered immune cells in order to maximize therapeutic immune responses to disease. This strategy has been used to improve the activity of immunostimulatory agents, antigens, adjuvants, and cell-therapies that generate little to no response when used in the conventional forms. By precisely targeting these immunotherapies to the lymph nodes, Amphiphiles can unlock their full potential to generate and amplify anti-tumor immune responses. This substantially enhanced anti-tumor functionality and long-term protective memory may someday unlock the full potential of the immune response to eliminate cancer.