Elicio Therapeutics, Inc. announced promising preliminary relapse-free survival (RFS) data from the ongoing Phase 1 (AMPLIFY-201) study of its lead asset, ELI-002. This study evaluated ELI-002 2P, a 2-peptide formulation designed to treat cancers driven by G12D and G12R mutations in KRAS, as a monotherapy in patients with mutant KRAS-driven solid tumors. The data will be presented September 29th from 4:40pm - 6:40pm ET at the AACR Special Conference on Pancreatic Cancer in Boston, Massachusetts, taking place from September 27-30, 2023.

Presentation Summary: Title: T cell responses and clinical outcomes in pancreatic and colorectal cancer patients with Minimal Residual Disease in AMPLIFY-201, a phase 1 trial of a first-in-class amphiphile lymph node targeted mutant KRAS vaccine. Session: Poster Session C; Presenter: Eileen O?Reilly, M.D., Winthrop Rockefeller Endowed Chair of Medical Oncology; Co-Director, Medical Initiatives, David M. Rubenstein Center for Pancreatic Cancer Research; Section Head, Hepatopancreaticobilary & Neuroendocrine Cancers, Memorial Sloan Kettering Cancer Center (MSK). Study Design: AMPLIFY-201 is a multicenter Phase 1 trial assessing the safety, immunogenicity and antitumor activity of ELI-002 in patients with mutant KRAS-driven tumors who are at high risk for relapse due to detection of MRD following standard surgery and chemotherapy.

The analysis involved patients with resected PDAC (n=20) or CRC (n=5) tumors harboring KRAS G12D or G12R who had MRD defined as elevated ctDNA and/or serum tumor biomarker (CA19-9/CEA). Patients received up to six priming doses and four booster doses separated by a 3-month rest period of subcutaneous ELI-002 2P vaccine monotherapy comprised of Amph-peptides (700 mcg each G12D/G12R), admixed with Amph-CpG-7909 at 0.1, 0.5, 2.5, 5.0 and 10.0 mg per cohort dose level. Primary endpoints included safety and the recommended Phase 2 dose (RP2D) of Amph-CPG-7909, and the secondary endpoint included biomarker reduction/clearance.

Exploratory endpoints included RFS using immune Response Evaluation Criteria in Solid Tumors (iRECIST) and immunogenicity assessed by direct ex vivo Fluorospot and intracellular cytokine staining of peripheral blood mononuclear cells. Preliminary Study Findings: Direct ex vivo polyfunctional mKRAS-specific T cell responses to ELI-002 2P were observed in 20/23 (87%; 50% induced both CD4+ and CD8+ T cells, median 13-fold and mean 56-fold increase from baseline), with T cell response in 9/9 (100%) patients treated at the highest two dose levels including the 10 mg RP2D. The median RFS in evaluable pts (n=22) was 16.3 months, and the median OS has not been reached.

Tumor biomarker response was observed in 17/22 (77%), with clearance in 6/22 (27%). Clinical efficacy correlated with T cell response: Median tumor biomarker reduction/clearance was -86.9% vs -1.0% in above vs below median T cell responders, respectively (p < 0.0017). At 7.6 months median follow-up, the median RFS was not reached compared to 3.9 months in above versus below median T cell responders (HR 0.14; 95% CI 0.03-0.61; p = 0.013).

The association of RFS with T cell response was not confounded by other baseline prognostic variables (including tumor stage, recovery from prior cytotoxic therapy as assessed by absolute neutrophil count or immune system subsets such as %CD4+ or %CD8+ of CD3+ lymphocytes). No safety concerns were identified, and there were no dose limiting toxicities and no = Grade 3 treatment related adverse events. 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. 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 1/2 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.