Promune (agatolimod) / Pfizer - LARVOL DELTA

Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. (PubMed, Nat Med) - P1 | "Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). ELI-002 2P was safe and induced considerable T cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors. ClinicalTrials.gov identifier: NCT04853017 ."

IO biomarker • Journal • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • KRAS

Durable immunogenicity of ELI-002 2P in AMPLIFY-201: Lymph node targeted mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer (AACR 2024) - P1, P1/2 | "ELI-002 2P consists of 2 Amph-modified mKRAS peptide antigens, Amph-G12D and Amph-G12R (Amph-Peptides 2P), and an Amph-modified immune-stimulatory oligonucleotide adjuvant (Amph-CpG-7909). ELI-002 is an off-the-shelf vaccine targeting common KRAS tumor mutations demonstrating several key advantages: lymph node-targeted vaccine design, high immunogenicity, with balanced CD4+ and CD8+ T cell responses, HLA-agnostic activity, and targeting of vaccine antigens critical for tumor survival. A randomized Phase 2 clinical trial (NCT05726864) investigating a 7-peptide formulation (G12D, R, V, A, C, S, G13D) is underway."

First-in-human • IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Solid Tumor • CD4 • CD8 • GZMB • IFNG • IL2 • KRAS • TNFA

AMPLIFY-201, a first-in-human safety and efficacy trial of adjuvant ELI-002 2P immunotherapy for patients with high-relapse risk with KRAS G12D- or G12R-mutated pancreatic and colorectal cancer. (ASCO 2023) - P1, P1/2 | "In a 3+3 dose escalation, n=22 received a subcutaneous course of 6 prime and 4 booster injections of fixed dose Amph-peptides (1.4 mg), admixed with escalating Amph-CpG-7909 (Table). ELI-002 2P, evaluated in a novel MRD+ trial, was safe with ctDNA and serum tumor biomarker reduction and clearance and notable immune responses. The RP2D is the start dose for a phase 1/randomized phase 2 study evaluating a new seven peptide formulation for G12 D, R, V, S, A, C, and G13D mutated solid tumors (NCT05726864). Clinical trial information: NCT04853017."

Clinical • IO biomarker • P1 data • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Oncology • Pain • Pancreatic Cancer • Solid Tumor • CA 19-9 • CD4 • CD8 • KRAS • NRAS • RAS

Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results. (PubMed, Nat Med) - P1 | "We present the final results of the phase 1 AMPLIFY-201 trial, in which patients who completed standard locoregional treatment, with minimal residual mKRAS disease (n = 25, 20 pancreatic cancer and 5 colorectal cancer), received monotherapy vaccination with lymph node-targeting ELI-002 2P, including mutant KRAS (mKRAS) amphiphile-peptide antigens (G12D, G12R) and amphiphile-adjuvant CpG-7909. Therefore, lymph node-targeting amphiphile vaccination induces persistent T cell responses targeting oncogenic driver KRAS mutations, alongside personalized, tumor antigen-specific T cells, which may correlate to clinical outcomes in pancreatic and colorectal cancer. ClinicalTrials.gov registration: NCT04853017 ."

IO biomarker • Journal • P1 data • Colorectal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • KRAS

Intradermal IMO-2125 versus placebo as adjuvant treatment in patients with stage II pT3-4/cN0 melanoma: Interim efficacy and safety results of the randomized phase II INTRIM study (ESMO 2022) - P2 | "CPG7909, a Toll-like receptor-9 (TLR9) agonist, injected at the primary tumour excision site in patients with clinical stage I/II melanoma, was found to boost loco-regional and systemic anti-melanoma immunity. Conclusions Single-dose IMO-2125 has a reasonable safety profile and significantly reduces tumour positive SLN rates in pT3-T4 melanoma patients. Provided that SLN status accurately reflects future RFS, IMO-2125 has the potential to improve outcomes of early-stage melanoma patients."

Clinical • Late-breaking abstract • P2 data • Melanoma • Oncology • Solid Tumor

A Safety and Immunogenicity Trial of Boost-2867 Vaccine, Via Intranasal and Intramuscular Routes (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Sex-based considerations in the choice for a TLR9 or TLR7/8 agonist to arm the sentinel lymph node in early-stage melanoma. (PubMed, Oncoimmunology) - "Correlation analyses suggested that IFNα, TNF, and IL-6 were key for CPG7909-induced LNR-cDC activation, whereas R848's effect appeared more cytokine-independent. We conclude that combining locally delivered CPG7909 and R848 in early-stage melanoma will ensure full-range DC subset activation and robust pro-inflammatory T-cell responses in melanoma SLN, independent of sex."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • CD80 • CD83 • CXCL10 • IFNA1 • IFNG • IL10 • IL12A • IL1B • IL6 • TLR9

ACM-CpG, a polymersome-delivered TLR9 agonist, elicits rapid and broad immune activation in a phase I trial for advanced solid tumors (AACR 2026) - P1 | "Background: ACM-CpG is a novel innate immune activator comprising of TLR9 agonist CpG7909 encapsulated within polymer vesicles ("polymersomes")... ACM-CpG induces rapid, broad-spectrum immune activation, engaging both innate and adaptive compartments and enhancing cytokine and T-cell responses with a favorable safety profile. These early clinical findings support continued development of ACM-CpG as a potent monotherapy and a versatile immunologic amplifier for combination immunotherapy."

IO biomarker • Metastases • P1 data • Oncology • Solid Tumor • CCL8 • CD38 • CD40 • CD69 • CD8 • CD86 • CXCL10 • CXCL11 • IFNG • PD-1

Impact of Epstein-Barr Virus LMP2A on Toll-Like Receptor 9 (TLR9) expression and function (IMMUNOLOGY 2026) - "Additionally, these cells were stimulated with the TLR9 agonist, agatolimod (ODN2006), and the production of IL-6 was assessed by ELISA. The data indicate that LMP2A does not consistently alter TLR9 levels, but does enhance TLR9-induced cytokines, such as IL-6. TLR9 is an important innate sensing mechanism to identify the presence of pathogen's DNA intracellularly. The ability of EBV to modulate signaling through these receptors may provide insight into mechanisms by which latency proteins regulate latency and B cell activation."

IO biomarker • B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • IL6 • TLR9

Immunogenicity, safety, and lot consistency of the anthrax vaccine adsorbed, adjuvanted for post-exposure prophylaxis of anthrax in healthy adults: A phase 3, randomized, double-blind trial. (PubMed, Vaccine) - P3 | "The study met the pre-defined endpoint criteria, demonstrating protective level of immune response and non-inferiority of CYFENDUS to BioThrax vaccination. The CYFENDUS vaccine was well-tolerated in healthy adults."

Clinical • Journal • P3 data

A Safety and Immunogenicity Trial of Boost-2867 Vaccine, Via Intranasal and Intramuscular Routes (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Intravenous administration of CpG7909 lipoplex enhances anti-PD1 immunotherapy by modulating the tumor microenvironment and inducing durable tumor regression. (PubMed, Sci Rep) - "To our knowledge, this study is among the first to evaluate the combination of CpG7909 lipoplexes with anti-PD1 antibodies in the context of cancer immunotherapy. The findings suggest that this approach may convert the TME from an immunologically "cold" to "hot" state, thereby enhancing tumor suppression and potentially improving the response rate to ICIs."

Biomarker • Journal • Lung Cancer • Oncology • Solid Tumor • CD8

AMPLIFY-7P Phase 2: T cell responses induced by ELI-002 7P, a lymph node-targeted amphiphile therapeutic cancer vaccine in patients with KRAS mutated pancreatic ductal adenocarcinoma (SITC 2025) - "ELI-002 7P includes Amph-modified G12D, V, R, C, S, A and G13D mKRAS peptides with an Amph-modified immune-stimulatory oligonucleotide adjuvant (Amph-CpG-7909)...Prior ELI-002 2P Phase 1A results indicated initial safety, tolerability, and robust induction of mKRAS-specific T cell responses associated with improved disease-free survival (DFS) and overall survival (OS).1 2 The randomized Phase 2 trial is proceeding to final DFS analysis.Methods The ongoing randomized multicenter Phase 2 cohort was designed to assess the primary endpoint of DFS and immunogenicity as an exploratory endpoint...Local IRB approvals included: Memorial Sloan Kettering Cancer Center IRB (#22-352 and 22-352A(8)), Advarra (ID#s Pro00065733 and Pro00067455), the University of Iowa IRB (ID# 202212072), Feinstein Institutes for Medical Research, Northwell Health IRB (ID# 22-0814), University of California, Los Angeles Office of the Human Research Protection Program (ID# 22-001911), Mass General..."

Clinical • IO biomarker • Late-breaking abstract • P2 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • CD4 • CD8 • IFNG • IL2 • KRAS • TNFA

Amphiphile (AMP)-Immunomodulator therapy controls growth and eradicates syngeneic solid tumors (SITC 2025) - P1, P1/2 | "Amphiphile (AMP)-CpG-7909 (ELI-004) is an ideal candidate in this context, as it has been designed to enhance tumor tissue retention by anchoring into cell membranes via its lipophilic AMP-tail.1 ELI-004 has been evaluated in multiple phase 1/2 trials (NCT04853017/NCT05726864) as part of an AMP-CpG-7909-adjuvanted peptide immunotherapy targeting mutant KRAS antigens (ELI-002). On day 42, ten days after the therapy phase concluded, tumor growth remained well controlled with 25% of mice achieving complete response and long-term non-progression, and no mice reaching euthanasia criteria. The 5 nmol AMP-CpG-7909 in situ treatment was well tolerated with no adverse safety observations.Conclusions Overall, these results demonstrate the potential for AMP-immunomodulators as promising off-the-shelf agents for in situ immunotherapy that is not patient-restricted or limited to specific tumor mutations and can induce potent cellular immune responses to control tumor growth."

Immunomodulating • IO biomarker • Oncology • Solid Tumor • KRAS

A Safety and Immunogenicity Trial of Boost-2867 Vaccine, Via Intranasal and Intramuscular Routes (clinicaltrials.gov) - P1 | N=140 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P1 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Enhanced immunostimulatory and anti-tumor activity of TLR9 agonist CpG oligodeoxynucleotide encapsulated within ACM polymersomes (CICON 2025) - P1 | "A completed phase 1 clinical trial (ClinicalTrials.gov identifier: NCT05385991) using ACM-CpG7909 as an adjuvant for a SARS-CoV-2 booster vaccine (ACM-001) showed that it was well tolerated and induced good efficacy signals. An investigator-initiated dose-escalation/expansion trial to examine the safety and efficacy of ACM-CpG7909 in patients with advanced/metastatic solid tumors is ongoing at the National Cancer Center Singapore (ClinicalTrials.gov identifier: NCT06587295)."

Infectious Disease • Oncology • Respiratory Diseases • Solid Tumor • CD4 • CD8 • IFNA1 • IFNG • IL10 • IL1R1 • IL6

Intradermal tilsotolimod versus placebo as adjuvant treatment in patients with stage II, pT3-4cN0 melanoma: recurrence-free survival data of the randomized double blinded phase II INTRIM study (EADO-WCM 2025) - "Background CPG7909, a Toll-like receptor-9 (TLR9) agonist, injected intradermally at the primary tumor excision site in patients with clinical stage I/II melanoma, was found to boost loco-regional and systemic anti-melanoma immunity...Upon establishing positive SLN status, i.e. stage III disease, 13% of the tilsotolimod-injected patients and 39% of the placebo patients were treated with adjuvant anti-PD1 (7 vs 20) or dabrafenib/trametinib (0 vs 1)...Tilsotolimod treatment was mainly associated with grade 1 and 2 injection site reactions (54%) and flu-like symptoms (46%). Conclusions Adjuvant single-dose tilsotolimod in patients with pT3-T4 cN0 melanoma has a favorable benefit-risk profile and demonstrates significant improvements over placebo in tumor-positive SLN rate and RFS, with a 69% reduction in the risk of recurrence or death after a median follow-up of 24 months."

Clinical • P2 data • Melanoma • Oncology • Solid Tumor

AMPLIFY-7P phase 1a: lymph node-targeted amphiphile therapeutic cancer vaccine in patients with high relapse risk KRAS mutated pancreatic ductal adenocarcinoma and colorectal cancer (SITC 2024) - P1/2 | "ELI-002 7P consists of Amph-modified G12D, V, R, C, S, A and G13D mKRAS peptides with an Amph-modified immune-stimulatory oligonucleotide adjuvant (Amph-CpG-7909). Ethics Approval The study was approved by the local institutional review board at each study site and conducted under an FDA Investigational New Drug application or 'IND'. Consent All patients provided written informed consent."

Clinical • IO biomarker • Late-breaking abstract • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Solid Tumor • CD4 • CD8 • KRAS

Enhanced immunostimulatory and anti-tumor activity of TLR agonists encapsulated within ACM polymersomes (CRI-ENCI-AACR ICIC 2024) - P1 | "A recently completed phase 1 clinical trial (ClinicalTrials.gov identifier: NCT05385991) of ACM-CpG 7909 as an adjuvant for a SARS-CoV-2 booster vaccine (ACM-001) showed that it was well tolerated and induced good efficacy signals. An investigator-initiated dose-escalation/expansion trial to examine the safety and efficacy of ACM-CpG 7909 in patients with advanced/metastatic solid tumors is being planned at the National Cancer Center Singapore."

Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • CD4 • CD8 • IFNA1 • IFNG • IL10 • IL1R1 • IL6

AMPLIFY-7P, a first-in-human safety and efficacy trial of adjuvant mKRAS-specific lymph node targeted amphiphile ELI-002 7P vaccine in patients with minimal residual disease–positive pancreatic and colorectal cancer. (ASCO 2024) - P1/2 | "Earlier ELI-002 2P showed high rates of T cell and tumor biomarker response (both 21/25, 84%), with median relapse-free survival not reached versus 4.01 months (HR 0.14; p=0.0167) comparing patients (pts) above versus below T cell median (12.75X)...Pts with elevated circulating tumor DNA (ctDNA) and/or serum tumor biomarker (CA19-9/CEA), and KRAS mutation were enrolled and treated with subcutaneous fixed dose Amph-CpG-7909 and 1.4 mg or 4.9 mg of Amph-Peptides 7P (Table)... ELI-002 7P was safe with median RP2D T cell responses exceeding the prior formulation (7P median 109.2; 2P 12.75), and early indications of antitumor activity. The randomized phase II is now open in patients with pancreas cancer."

Clinical • Minimal residual disease • P1 data • Residual disease • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9 • CD4 • CD8 • KRAS

An Open-Label Study of Subcutaneous CpG Oligodeoxynucleotide (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer. (PubMed, Cancer Control) - "CpG ODN and trastuzumab treatment of metastatic HER2 + breast cancer was safe but was not tolerable for all patients. This combination did induce potentially predictive immune profile changes in treated patients with metastatic HER2 + breast cancer, the significance of which needs to be further explored."

Combination therapy • Journal • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-1 • VEGFD

Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: City of Hope Medical Center | Active, not recruiting ➔ Completed

Trial completion • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Adult T-Cell Leukemia-Lymphoma • Bone Marrow Transplantation • Burkitt Lymphoma • Chronic Eosinophilic Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • CNS Lymphoma • Cutaneous T-cell Lymphoma • Cytomegalovirus Infection • Dermatology • Diffuse Large B Cell Lymphoma • Essential Thrombocythemia • Follicular Lymphoma • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Hypereosinophilic Syndrome • Indolent Lymphoma • Infectious Disease • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Monoclonal Gammopathy • Multiple Myeloma • Mycosis Fungoides • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Plasmacytoma • Polycythemia Vera • Prolymphocytic Leukemia • Sezary Syndrome • Small Lymphocytic Lymphoma • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • Thrombocytosis • Transplantation • Waldenstrom Macroglobulinemia • HLA-DRB1

AMPLIFY-7P: Phase 1 and randomized phase 2 study of amphiphile immunotherapy ELI-002 7P as adjuvant treatment for subjects with G12D, G12R, G12V, G12C, G12A, G12S and G13D Kirsten rat sarcoma (KRAS)-mutated pancreatic ductal adenocarcinoma. (ASCO-GI 2024) - P1/2 | "ELI-002 2P is a lymph node targeted immunotherapy comprised of Amphiphile (Amph)-modified G12D, G12R, G12V, G12C, G12A, G12S and G13D mutant KRAS peptides together with an Amph-modified CpG oligonucleotide adjuvant...Subsequent patients will receive up to 10 doses of Amph-peptides 7P 700 mcg each (4.9 mg total), together with Amph-CpG-7909 (10.0 mg) administered over a five-month treatment period...An interim analysis is planned using group sequential design for control of overall alpha 0.10. Clinical trial information: NCT05726864."

IO biomarker • P1 data • P2 data • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9 • KRAS

Efficacy of different AV7909 dose regimens in a nonclinical model of pulmonary anthrax. (PubMed, Hum Vaccin Immunother) - "The vaccine AV7909, consisting of the licensed anthrax drug substance AVA adjuvanted with CpG7909, induces high levels of toxin neutralizing antibodies in healthy adults using fewer doses than AVA. The toxin neutralizing assay (TNA) titer and anti-PA IgG responses were proportional to the protective efficacy, with a 50% TNA neutralizing factor (NF) greater than 0.1 associated with survival in animals receiving two doses of vaccine. The strong protection at relatively low TNA NF titers in this guinea pig model supports the exploration of lower doses in clinical trials to determine if these protective levels of neutralizing antibodies can be achieved in humans; however, protection with a single dose may not be feasible."

Journal

ELI-002 immunotherapy induces broad polyfunctional T cell responses in subjects with high relapse risk KRAS mutated pancreatic ductal adenocarcinoma and colorectal cancer (SITC 2023) - P1, P1/2 | "ELI-002 2P consists of 2 Amph-modified mKRAS peptide antigens, Amph-G12D and Amph-G12R (Amph-Peptides 2P), and a Amph-modified immune-stimulatory oligonucleotide adjuvant (Amph-CpG-7909). This off-the-shelf lymph node-targeted vaccine has many advantages including high immunogenicity yielding balanced CD4+ and CD8+ T cell responses targeting vaccine antigens that are critical for tumor survival. A Phase 1/2 clinical trial investigating a new 7 peptide formulation, ELI-002 7P (G12D, R, V, A, C, S, G13D; NCT NCT05726864), is currently in progress."

Clinical • IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Solid Tumor • CD4 • CD8 • GZMB • IFNG • IL2 • KRAS • TNFA