ModeX Therapeutics Inc., a subsidiary of OPKO Health (NASDAQ: OPK), has initiated dosing in a Phase 1/2a clinical trial (NCT07110584) evaluating MDX2004, a first-in-class trispecific antibody-fusion protein designed to treat advanced cancers through immune rejuvenation. The study aims to assess the safety, tolerability, and biologic activity of this novel immunotherapy approach.
Novel Trispecific Design Targets Multiple T Cell Pathways
MDX2004 represents a breakthrough in multispecific antibody design, simultaneously targeting three critical T cell receptors: CD3, CD28, and 4-1BB (CD137). This trispecific approach is engineered to stimulate T cells through multiple signaling pathways, enhancing immune activation beyond traditional single-target therapies.
The therapy's unique mechanism focuses on expanding stem and memory T cell populations, which undergo self-renewal and give rise to mature T cells. According to the company, this approach aims to "recruit and replenish, or 'rejuvenate,' cellular immunity." Notably, MDX2004's recognition of 4-1BB differs from previous antibody therapies by binding as a ligand to the natural receptor rather than through conventional antibody binding.
Addressing Unmet Medical Need in Advanced Cancers
"Patients with advanced solid tumors may have limited options with existing treatments, facing challenging disease control rates and low long-term survival," said Giovanni Abbadessa, M.D., Ph.D., Chief Medical Officer of ModeX. "The MDX2004 multispecific antibody aims to rejuvenate T cells and sustain an expanded immune response in a broad range of tumors."
The therapeutic approach targets a fundamental challenge in cancer immunotherapy: maintaining robust and sustained immune responses. The expansion of both stem and mature memory T cell subsets has been associated with favorable responses to immunotherapy, suggesting potential for improved clinical outcomes.
Broader Applications Beyond Oncology
Beyond cancer treatment, MDX2004 may address immune impairment from multiple sources. Phillip Frost, M.D., Chairman and CEO of OPKO Health, and Gary Nabel, M.D., Ph.D., President and CEO of ModeX, noted that the T cell rejuvenator "has potential to treat diverse cancers and reverse immune impairment caused by chemotherapy, chronic diseases, infection and aging."
This broader therapeutic potential positions MDX2004 to address immune dysfunction in patients with underlying conditions such as diabetes, those recovering from infections, or individuals experiencing age-related immune decline.
MSTAR Platform Technology
The development of MDX2004 leverages ModeX's proprietary MSTAR (ModeX Synergistic Targeting of Antibody Receptors) platform. This technology combines natural protein structures using modular building blocks to create multispecific medicines that can address multiple disease pathways simultaneously. The platform represents a strategic advancement beyond traditional bispecific approaches, targeting the complex, multi-pathway nature of many diseases.
Clinical Development and Scientific Presentations
The Phase 1/2a trial represents a critical milestone for ModeX Therapeutics, which develops innovative multispecific biologics for cancer and infectious diseases. The company's pipeline includes candidates targeting both solid and hematologic tumors, as well as viral threats.
Supporting the clinical advancement, two poster presentations featuring preclinical proof-of-concept data and clinical dose selection analyses will be showcased at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in National Harbor, MD, from November 5-9, 2025.
The clinical trial initiation marks a significant step forward for multispecific antibody therapeutics, potentially establishing new standards for immune-based cancer treatment through simultaneous targeting of multiple T cell activation pathways.
