Imprime PGG (odetiglucan) / HiberCell - LARVOL DELTA

DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated-Acute Kidney Injury. (PubMed, Adv Sci (Weinh)) - "Furthermore, we developed Odetiglucan (Ode), a novel agonist targeting DDX3x delactylase function...In summary, DDX3x, function as a delactylase, regulates PANoptosis by influencing H3K9/18/27la. Thus, enhancing the delactylase activity of DDX3x may represent a potential therapeutic strategy for SA-AKI."

Journal • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock • DDX3X • NINJ1

Phase II trial of pembrolizumab in combination with odetiglucan for patients with metastatic colorectal adenocarcinoma with liver-predominant disease. (ASCO 2026) - P2 | "The study includes pre-treatment and on-treatment research biopsies and longitudinal research blood collection for immune pharmacodynamic profiling to investigate mechanisms of treatment response and resistance. NCT07082439."

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Hepatology • Immunology • Oncology • Pancreatic Cancer • Pneumonia • Solid Tumor • Triple Negative Breast Cancer

IGNITE: Maintenance Combinatorial Myeloid Immunotherapy for Unresectable Pancreatic Cancer (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: University of Pennsylvania | Trial completion date: Aug 2027 ➔ Dec 2028 | Trial primary completion date: Feb 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

IGNITE: Maintenance Combinatorial Myeloid Immunotherapy for Unresectable Pancreatic Cancer (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: University of Pennsylvania | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

IGNITE: Maintenance Combinatorial Myeloid Immunotherapy for Unresectable Pancreatic Cancer (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: University of Pennsylvania

New P2 trial • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Pembrolizumab and Odetiglucan in Liver Predominant Metastatic Colorectal Adenocarcinoma (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: Abramson Cancer Center at Penn Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

Pembrolizumab and Odetiglucan in Liver Predominant Metastatic Colorectal Adenocarcinoma (clinicaltrials.gov) - P2 | N=27 | Not yet recruiting | Sponsor: Abramson Cancer Center at Penn Medicine

New P2 trial • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

Safety/Efficacy Study of Imprime PGG With Cetuximab in Patients With Recurrent/Progressive Colorectal Carcinoma (clinicaltrials.gov) - P1/2 | N=32 | Completed | Sponsor: HiberCell, Inc. | Phase classification: P1b ➔ P1/2 | N=48 ➔ 32

Enrollment change • Phase classification • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017. (PubMed, Transl Lung Cancer Res) - P1/2 | "The combination of imprime and pembrolizumab is tolerable but did not improve the outcome of advanced stage NSCLC patients who previously progressed on anti-programmed death 1 (PD-1)/PD-L1 immunotherapies. Further investigation is needed to understand the effects of therapeutic PAMPs to mount a strong innate immune response against cancer."

IO biomarker • Journal • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase 3 open-label, randomized, multicenter study of Imprime PGG in combination with cetuximab in patients with KRAS wild type metastatic colorectal cancer (ASCO-GI 2015) - Abstract #TPS787; P3, N=795; NCT01309126; "The primary endpoint of the study is OS and primary analysis will occur when ~709 deaths have occurred. Secondary endpoints include PFS, ORR (based on RECIST 1.1), quality of life, safety and pharmacokinetics. Exploratory endpoints include biomarker analyses."

Clinical protocol • Biosimilar • Colorectal Cancer • Oncology

Phase 1b study of maintenance soluble beta-glucan (Odetiglucan) in combination with a CD40 agonistic monoclonal antibody (CDX-1140) in patients with metastatic pancreatic adenocarcinoma that had not progressed on first-line chemotherapy (AACRPanCa 2024) - "The combination of odetiglucan and CDX-1140 was feasible and safe when administered as maintenance therapy in patients with mPDAC whose disease had not progressed on 1L chemotherapy. Treatment produced encouraging activity with changes in immunological correlates associated with disease control. These early results support further investigation combining odetiglucan with a CD40 agonist in mPDAC."

Clinical • Combination therapy • Metastases • P1 data • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Leukopenia • Musculoskeletal Pain • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40 • CD8 • CLEC7A • ITGAM

Phase 1b study of maintenance soluble beta-glucan (Odetiglucan) in combination with a CD40 agonistic monoclonal antibody (CDX-1140) in patients with metastatic pancreatic adenocarcinoma that had not progressed on first-line chemotherapy* (AACRPanCa 2024) - "The combination of odetiglucan and CDX-1140 was feasible and safe when administered as maintenance therapy in patients with mPDAC whose disease had not progressed on 1L chemotherapy. Treatment produced encouraging activity with changes in immunological correlates associated with disease control. These early results support further investigation combining odetiglucan with a CD40 agonist in mPDAC."

Clinical • Combination therapy • Metastases • P1 data • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Leukopenia • Musculoskeletal Pain • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40 • CD8 • CLEC7A • ITGAM

Pembrolizumab + Imprime PGG for Metastatic Non-small Cell Lung Cancer After Progression on First-Line Therapy: Big Ten Cancer Research Consortium BTCRC-LUN15-017 (clinicaltrials.gov) - P1/2 | N=35 | Completed | Sponsor: Lawrence Feldman, MD | Active, not recruiting ➔ Completed

Metastases • Trial completion • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

A Maintenance Therapy Study of Odetiglucan With CDX-1140 in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: HiberCell, Inc. | N=45 ➔ 5 | Trial completion date: Apr 2027 ➔ Mar 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2025 ➔ Mar 2024; sponsor decision

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice. (PubMed, Nat Commun) - "Here, we show that macrophages respond to β-glucan (odetiglucan) treatment by inhibiting liver metastasis...Furthermore, β-glucan drove T cell activation and macrophage re-polarization in liver metastases in mice and humans and sensitized metastatic lesions to anti-PD1 therapy. These findings demonstrate the significance of macrophage function in metastasis and identify Kupffer cells as a potential therapeutic target against pancreatic cancer metastasis to the liver."

Journal • Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Maintenance Therapy Study of Odetiglucan With a CD40 Agonist (CDX-1140) in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: HiberCell, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

A Maintenance Therapy Study of Odetiglucan With a CD40 Agonist (CDX-1140) in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=45 | Recruiting | Sponsor: HiberCell, Inc. | N=30 ➔ 45 | Trial completion date: Mar 2026 ➔ Apr 2027

Enrollment change • Trial completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Phase 2 Study of Imprime PGG and Pembrolizumab in Patients With HR+/HER2- Metastatic Breast Cancer (mBCA) (clinicaltrials.gov) - P2 | N=26 | Completed | Sponsor: HiberCell, Inc. | Active, not recruiting ➔ Completed | N=50 ➔ 26 | Trial completion date: Jan 2027 ➔ Apr 2023 | Trial primary completion date: Jan 2025 ➔ Mar 2023

Enrollment change • IO biomarker • Metastases • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CD86 • ER • HER-2 • PD-L1 • PGR • PIK3CA

A phase 1b, open-label, two-part safety, tolerability, and efficacy study of a soluble beta-glucan (odetiglucan) in combination with a CD40 agonistic monoclonal antibody (CDX-1140) in patients with metastatic pancreatic adenocarcinoma whose disease did not progress during first-line (1L) chemotherapy. (ASCO 2023) - P1a | "5 US sites will participate. Clinical trial information: NCT04834778."

Clinical • Combination therapy • Metastases • P1 data • Gastrointestinal Cancer • Immune Modulation • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

HiberCell Doses First Patient in Phase 1b Study Exploring Novel Combination of Odetiglucan and CD40 Agonistic Monoclonal Antibody (CDX-1140) in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) in the Maintenance Setting (GlobeNewswire) - "HiberCell...announced dosing of the first patient in a Phase 1b clinical trial investigating the effects of odetiglucan, a first-in-class immunomodulatory agent, in combination with the CD40 agonistic monoclonal antibody, CDX-1140, in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in the maintenance setting....The Phase 1b, multi-site, open-label trial is a two-part study evaluating the safety, tolerability, and efficacy of odetiglucan in combination with CDX-1140 in metastatic PDAC patients with prior evidence of objective response or stable disease following a minimum of 16, and maximum of 32 weeks, of chemotherapy....HiberCell will highlight additional information on this study with a poster presentation at the 2023 American Society of Clinical Oncology (ASCO) Meeting."

Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A phase 2, open-label study of imprime PGG (Imprime), a novel beta glucan, with pembrolizumab (Pembro) in chemotherapy-resistant metastatic triple negative breast cancer (TNBC) (SABCS 2017) - P2; "in collaboration with Merck & Co. (ClinicalTrials.gov NCT02981303) For information, contact Richard D. Huhn, MD, Biothera Med Dir at [email protected] or 651-256-4657."

Checkpoint inhibition • Melanoma • Triple Negative Breast Cancer

BTCRC-LUN15-017: Phase-Ib Study of Imprime PGG and Pembrolizumab in Stage IV NSCLC after Progression on Platinum Based Therapy (IASLC-WCLC 2018) - P1/2; "Conclusion Imprime in combination with pembrolizumab is well tolerated in outpatient settings and the role of this combination in treatment of NSCLC warrants further investigation. Phase-II enrollment of this trial is ongoing. "

P1 data • PD(L)-1 Biomarker • Non Small Cell Lung Cancer

Imprime PGG, a soluble yeast beta-glucan PAMP, converts the immunosuppressive myeloid tumor microenvironment into an immunoactive one: translation of preclinical findings to melanoma and triple-negative breast cancer (TNBC) patients (EORTC-NCI-AACR 2018) - P2; "Background: Imprime PGG (Imprime), an IV administered soluble yeast -1,3/1,6 glucan is being clinically developed in combination with tumor-targeting antibodies, anti-angiogenics, and checkpoint inhibitors (CPI). Collectively, these data show consistency between preclinical and clinical observations that demonstrate that Imprime/Pembro remodels the immunosuppressive myeloid tumor microenvironment and triggers the infiltration and activation of immune cells in preclinical and patient tumors."

IO biomarker • PD(L)-1 Biomarker • Tumor microenvironment • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Triple Negative Breast Cancer

Phase 2 Study of Imprime PGG and Pembrolizumab in Patients With HR+/HER2- Metastatic Breast Cancer (mBCA) (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: HiberCell, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Metastases • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CD86 • ER • HER-2 • PD-L1 • PGR • PIK3CA

A P1b Study of Odetiglucan With a CD40 (CDX-1140) (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: HiberCell, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer