Elicio Therapeutics, Inc. announced the publication of promising preclinical data in Cancer Immunology Research, a journal of the American Association for Cancer Research (?AACR?). These preclinical data demonstrate that Elicio?s proprietary ?AMP? lymph node-targeting immunotherapy platform, carrying cognate peptide and adjuvant cargos, boosted T cell receptor-modified T cell therapies (?TCR-T cells?) enhancing anti-tumor function and eradicating solid tumors.

Previous Elicio studies have demonstrated that AMP immunotherapy promoted specific trafficking and retention of payloads into lymph nodes, yielding enhanced T cell numbers, persistence and functional quality. Preliminary Phase 1 data from the ongoing study of Elicio?s lead asset, ELI-002, an mKRAS-specific AMP vaccine, demonstrated significant T cell responses including both CD4+ and CD8+ when administered as an adjuvant monotherapy in patients with pancreatic and colorectal cancers. The strength of the T cell response induced by ELI-002 was further correlated to significant improvements in tumor biomarker response, and reduced risk of progression and death indicating an association between the ELI-002 mechanism of action and clinical outcome.

Key Study Findings: AMP immunotherapy in combination with TCR-T cell therapy led to complete eradication and durable responses against established murine solid tumors refractory to TCR-T cell monotherapy. AMP immunotherapy led to enhanced lymph node delivery and correlated with pro-inflammatory lymph node transcriptional reprogramming and increased antigen-presenting cell maturation, resulting in TCR-T cell expansion and functional enhancement. Enhanced anti-tumor efficacy was correlated with simultaneous in vivo invigoration of adoptively transferred TCR-T cells and in situ expansion of the endogenous anti-tumor T cell repertoire.

AMP immunotherapy enhanced the infiltration and function of TCR-T cells in the tumor microenvironment and led to epitope spreading against diverse tumor targets. Long-term protection against tumor recurrence in AMP-treated mice was associated with antigen spreading to additional tumor-associated antigens not targeted by the treatment. In vitro evaluation of AMP peptides with matched human TCR-T cells targeting NY-ESO-1, mutant KRAS and HPV16 E7 illustrated the clinical potential of AMP to enhance human TCR-T cell proliferation, activation and anti-tumor activity.

ELI-002 is a structurally novel investigational AMP therapeutic immunotherapy targeting mutant KRAS-driven cancers. KRAS mutations are among the most prevalent human cancers. The seven KRAS driver mutations targeted by the ELI-002 7P formulation are present in 25% of all solid tumors.

In particular, 93% of pancreatic ductal adenocarcinoma and 52% of colorectal cancers, those most prevalent in the AMPLIFY-201 study, are positive for KRAS mutations. In addition, 27% of non-small cell lung cancers are positive for KRAS mutations. ELI-002 is comprised of AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified immune-stimulatory oligonucleotide CpG adjuvant available as an off-the-shelf subcutaneous administration.

The AMP mKRAS peptides and AMP CpG are targeted to the lymph node where they can potentially enhance the action of key immune cells. ELI-002 2P is currently being studied in a Phase 1 trial (AMPLIFY-201) in patients with high relapse risk mKRAS-driven solid tumors, following surgery and chemotherapy (NCT04853017). ELI-002 7P, is currently being studied in AMPLIFY-7P, a Phase 2 trial in patients with high relapse risk mKRAS-driven solid tumors (NCT05726864).

The ELI-002 7P formulation is designed to provide immune response coverage against seven of the most common KRAS mutations, thereby increasing the potential patient population for ELI-002 and potentially reducing the chance of bypass resistance mechanisms.