REGN5837 / Regeneron - LARVOL DELTA

A CD38xCD28 Costimulatory Bispecific Antibody Demonstrates Potent Preclinical Combinatorial Activity with a BCMAxCD3 T Cell-Engager (ASH 2024) - "In RRMM, linvoseltamab activates T cells by engaging the T cell receptor (TCR)/CD3 complex in the presence of BCMA-expressing MM tumor cells leading to tumor cell killing...CD28-targeting bsAbs, including REGN5668 (MUC16xCD28) and REGN5837 (CD22xCD28), are an emerging class of therapeutics capable of providing targeted costimulation and enhancing T cell effector function in combination with CD3-targeted bsAbs...Based on these promising preclinical results, a Phase 1 clinical trial is planned to evaluate the safety, tolerability, and preliminary efficacy of the CD38xCD28 bsAb REGN7945 and the BCMAxCD3 bsAb linvoseltamab in patients with RRMM. This innovative approach, leveraging the combinatorial potential of CD38xCD28 costimulation with linvoseltamab's targeted cytolytic activity, represents a novel therapeutic strategy with the potential to improve RRMM treatment outcomes."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • CD28

The impact of bispecific antibody CD22xCD28 on anti-tumor efficacy of odronextamab and T cell activation and function in B cell tumor models (SITC 2025) - P1 | "Maximal T cell activation and cytotoxicity requires engagement of the T cell receptor/CD3 complex ('signal 1') and additional engagement of a costimulatory receptor such as CD28 ('signal 2'). Importantly, primate studies show REGN5837 has limited activity and no toxicity as a monotherapy but enhances T cell activation when dosed in combination with odronextamab.Conclusions These data highlight a potential chemotherapy-free approach for DLBCL treatment in REGN5837 plus odronextamab, and this combination is currently under evaluation in a Phase 1 clinical trial for aggressive relapsed/refractory DLBCL (NCT05685173).Ethics Approval All procedures were carried out in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocols were approved by the Regeneron Pharmaceuticals Institutional Animal Care and Use Committee (IACUC), and all animals were maintained under pathogen-free conditions."

Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22 • CD28

TRIAL IN PROGRESS: ATHENA-1 – A PHASE 1 STUDY TO ASSESS SAFETY AND TOLERABILITY OF REGN5837 IN COMBINATION WITH ODRONEXTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA (EHA 2023) - P1, P2 | "This Phase 1, open-label, first-in-human study will assess the safety and tolerability of REGN5837 in combinationwith odronextamab in patients with R/R aggressive B-NHL."

Clinical • Combination therapy • P1 data • Bone Marrow Transplantation • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD22

ATHENA-1: A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Participants With Aggressive B-cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1 | N=91 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Trial in progress: ATHENA-1 - a phase 1, open-label, first-in-human study to assess safety and tolerability of REGN5837 in combination with odronextamab in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphomas (AACR 2023) - P1 | "Secondary endpoints include pharmacokinetics of odronextamab and REGN5837, anti-drug antibody incidence, objective response rate, complete response rate, duration of response, progression-free survival, and overall survival. Enrolment is planned to open in early 2023."

Clinical • Combination therapy • P1 data • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22

ATHENA-1: Study to Assess the Safety and Tolerability of REGN5837 in Combination With Odronextamab in Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=91 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

Combination therapy • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology