IMM40H / ImmuneOnco Biopharma - LARVOL DELTA

The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via Fc-mediated effector functions, and interrupts CD70/CD27 signaling. (PubMed, Front Oncol) - "In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively...A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models...IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling."

IO biomarker • Journal • Burkitt Lymphoma • Head and Neck Cancer • Hematological Malignancies • Kidney Cancer • Lung Cancer • Lymphoma • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD27 • CD70 • SIRPA

Preclinical development of a monoclonal antibody targeting CD70 as cancer immunotherapy (AACR 2023) - "Notably, in a U266 multiple myeloma model, IMM40H, at the dose of 0.3 mg/kg, completely inhibited tumor growth in a way that therapeutic effects appeared significantly earlier than that of cusatuzumab at a higher dose of 1 mg/kg. Therapeutic effects of IMM40H at the dose of 3 mg/kg also appeared earlier than that of bortezomib at the dose of 0.5 mg/kg. Interestingly, combination of IMM40H and IMM01 (a SIRPα-IgG1 Fc fusion protein targeting CD47) generated significant therapeutic synergy in models of A498 kidney cancer and Raji lymphoma...IND of IMM40H has been approved in China and US. This antibody is now in a phase 1 study in patients with advanced malignancies expressing CD70."

IO biomarker • Preclinical • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Malignancies • Kidney Cancer • Lung Cancer • Lymphoma • Mesothelioma • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • CD47 • CD70 • SIRPA

IMM40H Phase I Dose Escalation and Expansion (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

New P1 trial • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • PD-L1