Announcement • Jun 02
Elicio Therapeutics, Inc. Publishes Preclinical Data On AMP-DNA Adjuvant Technology In Science Advances
Elicio Therapeutics, Inc. announced the publication of a peer-reviewed manuscript in Science Advances, published by the American Association for the Advancement of Science, describing a series of novel AMP-DNA adjuvant candidates built from the lymph node-targeting Amphiphile (AMP) platform technology. The manuscript, titled “Lymph node targeted DNA engages TBK1/IFN-I driven innate immunity to induce potent T cell responses and durable memory in mice and NHPs,” highlights the ability of these preclinical novel AMP-DNA adjuvants to drive robust, durable immune responses through targeted delivery to lymph nodes and activation of innate immune pathways. This work further builds on the development of the TLR-9-specific AMP-CpG (ELI-004), providing an expanded portfolio of potent lymph node-targeted AMP immunomodulators. The findings further expand the scientific foundation of Elicio’s AMP platform, which is designed to enhance immune responses by directing therapeutics to the lymph nodes—where immune responses are initiated and coordinated—while minimizing systemic toxicity. Preclinically, AMP-DNA outperformed current clinical and commercial benchmark adjuvants in head-to-head comparisons, inducing substantially more robust cellular immunity. AMP-DNA elicited high frequencies of antigen-specific, polyfunctional CD8+ and CD4+ T cell responses across tissues. Durable immune memory was observed for at least nine months, with rapid and robust recall responses upon antigen re-exposure. Findings were replicated in non-human primates, demonstrating strong cellular and humoral immune responses in a translationally relevant model. AMP-DNA targets lymph nodes to create a localized, highly immunostimulatory environment. Immune activation is driven through TBK1/IFN-I signaling pathways, supporting a differentiated mechanism compared to AMP-CpG which activates TLR-9. Preclinical results demonstrated that AMP-DNA adjuvants significantly enhanced both cellular and humoral immune responses compared to unmodified DNA and clinically relevant adjuvant benchmarks. The technology enabled efficient lymph node delivery and induction of a pro-inflammatory cytokine environment critical for adaptive immunity. In non-human primates, AMP-DNA induced strong T cell responses and high titers of neutralizing antibodies, supporting its potential translational relevance for human applications. Elicio’s lead product candidate, ELI-002, is a structurally novel investigational AMP cancer immunotherapy that targets cancers that are driven by mutations in the KRAS-gene—a prevalent driver of many human cancers. ELI-002 is comprised of two powerful components that are built with Elicio’s AMP technology consisting of AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified CpG oligodeoxynucleotide adjuvant that is available as an off-the-shelf subcutaneous administration. ELI-002 2P (2-peptide formulation) has been studied in the Phase 1 (AMPLIFY-201) trial in patients with high relapse risk mKRAS-driven solid tumors, following surgery and chemotherapy (NCT04853017). ELI-002 7P (7-peptide formulation) is currently being studied in a Phase 1/2 (AMPLIFY-7P) trial in patients with mKRAS-driven pancreatic cancer (NCT05726864). The ELI-002 7P formulation is designed to provide immune response coverage against seven of the most common KRAS mutations present in 25% of all solid tumors, thereby increasing the potential patient population for ELI-002. ELI-004 is a structurally novel, investigational AMP-modified immune-stimulatory CpG oligonucleotide. CpG oligonucleotide sequences are potent stimulators of TLR-9 which induce activation of innate immune cells, and production of supportive inflammatory effector molecules critical for enhancing innate and adaptive immunity. AMP-modification of CpG oligonucleotides promotes several mechanisms which may enhance tumor-directed immune responses: as an adjuvant administered with an antigen to the peripheral tissue, association with tissue albumin promotes delivery from the injection site to the lymph nodes where targeted uptake can enhance action on key immune cells which promote anti-tumor activity; following local injection into a solid tumor, AMP-mediated retention of CpG sequences concentrates immune activation within the target tumor, likely restricting systemic dissemination to irrelevant or toxicity-inducing sites throughout the body. Elicio’s proprietary AMP platform delivers investigational immunotherapeutics directly to the “brain center” of the immune system – the lymph nodes. Elicio believes this site-specific delivery of disease-specific antigens, adjuvants and other immunomodulators may efficiently educate, activate and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, Elicio observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability. Elicio’s AMP platform, originally developed at the Massachusetts Institute of Technology, has broad potential in the cancer space to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships. The AMP platform has been shown to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the local injection site, as it travels to lymphatic tissue.
