MDX2003 / OPKO Health - LARVOL DELTA

From bispecifics to tetraspecifics: Tackling cancer heterogeneity with optimal T cell activation (ESMO-TAT 2026) - "Background: Since the approval of catumaxomab in 2009, several bispecific antibodies have been developed, including successfully launched T cell engagers for patients with hematological malignancies...We generated two novel tetraspecific T cell engagers, MDX2001 (CD3xCD28xcMETxTrop2) and MDX2003 (CD3xCD28xCD19xCD20), designed to optimize T cell activation/survival by dual signaling through CD3 and CD28 and overcome tumor heterogeneity and resistance by binding to two different tumor antigens... The advent of bispecific antibodies constituted the first step towards activating and connecting T cells with tumor antigens. Technological advances allow the targeting of multiple tumor and T cell antigens with a single stable molecule, tackling tumor heterogeneity/resistance while more physiologically activating T cells."

Bispecific • Heterogeneity • Hematological Malignancies • Oncology • BCL2L1 • CD20 • CD69 • IL2RA

MDX2003, a first-in-class CD19xCD20xCD3xCD28 tetraspecific T cell engager (TCE) with potent activity against B cell malignancies and promise in autoimmunity (ESMO-TAT 2026) - P1/2 | "MDX2003 demonstrates robust preclinical efficacy, balanced T cell activation, and favorable tolerability. Its tetraspecific architecture enables dual B-cell targeting with CD3/CD28 costimulation, differentiating it from current CD19 or CD20 TCEs. This design positions MDX2003 as a strong clinical candidate, particularly for patients with relapsed/refractory B-cell lymphomas, including indolent and aggressive subtypes, who may exhibit CD19 or CD20 loss after prior lines of therapy."

B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma (clinicaltrials.gov) - P1/2 | N=180 | Recruiting | Sponsor: ModeX Therapeutics, An OPKO Health Company | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • Waldenstrom Macroglobulinemia • CD20

MDX2003, a novel tetraspecific T cell engager-expander targeting CD19xCD20xCD3xCD28, demonstrates potent preclinical activity against B cell malignancies (ASH 2025) - "MDX2003 is a differentiated tetraspecific T cell engager-expander demonstrating potent anti-tumorefficacy, favorable safety, and a mechanistic rationale for use in B cell malignancies. Its ability to sustaincytotoxicity, overcome antigen heterogeneity, and minimize cytokine-associated toxicities supportscontinued development in relapsed/refractory B cell malignancies. IND-enabling studies are ongoing,with initial clinical evaluation planned in B-cell lymphoma including patients relapsed after prior CD19-targeted therapy."

Preclinical • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2L1 • CD34 • CD69 • IFNG • IL2RA • IL6

This Study is Designed to Characterize the Safety, Tolerability, and Anti-tumor Activity of MDX2003 in Patients With Different Types of Lymphoma (clinicaltrials.gov) - P1/2 | N=180 | Not yet recruiting | Sponsor: ModeX Therapeutics, An OPKO Health Company

New P1/2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • Waldenstrom Macroglobulinemia

OPKO Health Reports Second Quarter 2025 Business Highlights and Financial Results (GlobeNewswire) - "Highlights from the second quarter of 2025 and recent weeks include the following:...The MDX2001 CMet-Trop2/CD3-CD28 tetraspecific antibody has advanced to the fifth dose level in its Phase 1 clinical trial, with Phase 1b studies in selected solid tumors expected in 2026. MDX2004, a multispecific immune rejuvenator, is expected to enter the clinic later this year. Human clinical trials with the MDX2003 tetraspecific antibody for lymphoma/leukemia are expected to begin in early 2026."

New trial • Trial status • Leukemia • Lymphoma • Solid Tumor