Slide 1: T cell responses and clinical outcomes in AMPLIFY-201 with ELI-002 mKRAS vaccine
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 Zev A. Wainberg1, Shubham Pant2, Colin D. Weekes3, Muhammad Furqan4, Pashtoon M. Ka
Slide 2: AMPLIFY-201: Background
AMPLIFY-201: Background Mutant KRAS Drives 25% of Solid Human Cancers (Pancreas >90%, Colon ~50%) Mutant KRAS Neoantigens are Promising Immunotherapy Targets: • HLA C*08:02 restricted G12D KRAS T cells -> PR in pancreatic1 and colorectal cancers • Adoptive therapy is limited to selected HLAs / mutat
Slide 3: ELI-002 2P Vaccine Components
ELI-002 2P Vaccine Components O Amphiphile mKRAS Long Peptide O 12 Antigens O ELI-002 2P O 1 Amph-mKRAS G12D 2 Amph-mKRAS G12R Albumin Binding Lipid PEG Linker G12D or G12R Peptide O Amphiphile TLR-9 Agonistic DNA NH Adjuvant O NH Amph-CpG-7909 Albumin Binding Lipid CpG-7909 DNA PRESENTED BY:
Slide 4: ELI-002 2P Mechanism: Targeting Lymph Nodes to Increase Immune Response
ELI-002 2P Mechanism: Targeting Lymph Nodes to Increase Immune Response Tissue Injection Site Lymph Node Amphiphiles Endogenous Albumin Albumin-bound Amphiphiles Albumin-bound Amphiphiles Antigen Presenting Cell T Cell 1 Subcutaneous 2 Albumin 3 Lymph node 4 Delivery to injection binding targeting i
Slide 5: AMPLIFY-201 Study Design
AMPLIFY-201 Study Design Endpoint Description Primary Safety, tolerability and RP2D Tumor Biomarker Reduction and Prior Therapy Screening Period Amph-Peptides 2P 1.4 mg + 0.1, 0.5, 2.5, 5 or 10 mg Amph-CpG-7909 Clearance mKRAS+ Secondary ctDNA and/or serum tumor Locoregional G12R+ or Prime No Dosing
Slide 6: AMPLIFY-201 Baseline Characteristics
6 AMPLIFY-201 Baseline Characteristics Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Overall • High relapse risk population: (0.1 mg) (0.5 mg) (2.5 mg) (5.0 mg) (10.0 mg) n=3 n=6 n=5 n=5 n=6 n=25 • ctDNA+ pancreatic cancer exhibits 5-month Age (years) Median 50.0 54.5 67.0 67.0 59.0 61.0 median relap
Slide 7: AMPLIFY-201 Safety
7 AMPLIFY-201 Safety Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Overall • No Grade ≥3 related adverse events (AEs), no (0.1 mg) (0.5 mg) (2.5 mg) (5.0 mg) (10.0 mg) n=3 n=6 n=5 n=5 n=6 n=25 cytokine release syndrome, no DLTs Adverse Event Term a Patients with Any Related 1 (33.3) 3 (50.0) 2 (40.0)
Slide 8: AMPLIFY-201 Waterfall Plot: Biomarker Reduction/Clearance
AMPLIFY-201 Waterfall Plot: Biomarker Reduction/Clearance 100 Cohort 1: 0.1 mg Best Overall Biomarker Response 75 Cohort 2: 0.5 mg Cohort 3: 2.5 mg 50 (% of Baseline) Cohort 4: 5 mg 25 Cohort 5: 10 mg 280 90 38 22 0 -100 -100 -100 -100 -100 -100 -28 -30 -41 -44 -47 -74 0 -2 -2 -9 -11 -25 -18 -50 -75
Slide 9: AMPLIFY-201: mKRAS-specific T cell Induction
AMPLIFY-201: mKRAS-specific T cell Induction 87% Direct Ex Vivo T Cell Response, Including CD4 and CD8, Polyfunctionality, Memory Phenotype Direct Ex Vivo T Cell Response mKRAS-specific Cytokine+ T Cells 450 ELI-002-induced mKRAS T Cell Responses 13 Patients with: 50 CD4 + CD8 T cells Fold change fr
Slide 10: Direct Ex-vivo Assessment Indicates Robust Polyclonal T Cell Responses
Direct ex-vivo Assessment Indicates Robust Polyclonal T Cell 10 Responses, Patient 11 Amph-Peptides 2P 1.4 mg + 0.1, 0.5, 2.5, 5 or 10 mg Amph-CpG-7909 PBMCs Week S/B 0 1 2 3 4 5 6 7 8 9 17 20 21 22 23 24 25 Dose G12D / R Responses G12V / C / A / S / G13D Responses 1200 600 IFN and/or GrB SFC / 1x1
Slide 11: CD3+ T cell infiltration of pancreatic tumor, 0.1 mg dose level
11 CD3+ T cell infiltration of pancreatic tumor, 0.1 mg dose level 002-001-102-003 (PDAC, Stage IVC) • Preliminary clinical evidence that ELI-002 induced T cells penetrate tumors • ctDNA doubling time progressively lengthening after initial flare: N T Collection Timepoint ctDNA Tumor Growth Rate Int
Slide 12: CD3+ T cell Infiltration and MRD Clearance, 2.5 mg Dose Level
CD3+ T cell Infiltration and MRD Clearance, Pancreatic Tumor, 2.5 mg Dose 12 Level ctDNA clearance observed with 72 T cells/hpf observed at time of progression, patient received intermediate 2.5 mg dose level: Collection ctDNA Tumor Growth Rate Interval Doubling Time Timepoint date Results vs Baseli
Slide 13: T Cell Fold Change Predicts Tumor Biomarker Response
T Cell Fold Change Predicts Tumor Biomarker Response All Patients with T cell Responses Over Median (13x) Showed Tumor Biomarker Response Strength of T cell response to ELI-002 is Strongly Correlated to Best Overall Biomarker Response Tumor Biomarker Response Clearance Reduction • 100% of the above
Slide 14: Median Relapse-Free Survival of Above Median T Cell Responders Prolonged
Median Relapse-Free Survival of Above Median T Cell Responders was Significantly Prolonged 86% Reduction in the Risk of Progression or Death in Above Median T cell Responders ≥ Median T Cell Response (n = 12) Strength of T Cell Response to ELI-002 is Strongly Correlated < Median T Cell Response (n =
Slide 15: Swimmer's Plot and ELI-002 2P-Induced Dual Positive CD4/8 T Cells
Swimmer’s Plot and ELI-002 2P-Induced Dual Positive CD4/8 T Cells Above Median T Cell Response, Dual CD4 + CD8 Associated with Clinical Outcome Biomarker Non-responder Subsequent Therapy ctDNA T Cells Cohort Biomarker Reduction iCPD CA19-9 / CEA ≥ Median Biomarker Clearance RFS Censor Date D G12D <
Slide 16: No Effect of Tumor Stage on Median Relapse-Free Survival
No Effect of Tumor Stage on Median Relapse-Free Survival Analysis Lymphocyte Recovery after Chemotherapy/Radiation to Normal Levels Required for ELI-002 response Tumor Stage Absolute Neutrophil at Screening Absolute Lymphocytes at Screening Stage III and IV (n = 14) ≥ Median (n = 11) Quartiles Respo
Slide 17: Take Home Messages
Take Home Messages Monotherapy with Lymph node-Targeted Therapeutic mKRAS-specific Cancer Vaccine ELI-002: Well-tolerated with No Dose-Limiting Toxicity • No Grade 3/4 TEAEs, no CRS, no DLTs; 11/25 (44%) had Grade 1 or 2 AEs Robust mKRAS-Specific T cell Responses • Large Direct Ex Vivo T cell respon