On October 28, 2025 ModeX Therapeutics Inc., an OPKO Health company (NASDAQ: OPK), reported the initiation and recent dosing of the first patient in a Phase 1/2a clinical trial (NCT07110584) with MDX2004, a first-in-class trispecific antibody-fusion protein for oncology and immune disorders. The study is designed to evaluate the safety, tolerability, and biologic activity of MDX2004 as an immunotherapy for advanced cancers.
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MDX2004 is designed to stimulate T cells through three signaling pathways to enhance immune activation. This proprietary multispecific antibody engages CD3, CD28, and 4-1BB and is expected to activate T lymphocytes, including stem and memory T cells. Because stem T cells undergo self-renewal and give rise to mature T cells, the drug aims to recruit and replenish, or "rejuvenate," cellular immunity. Unlike previous 4-1BB antibody therapies, recognition of 4-1BB by this molecule does not involve antibody binding because it binds as a ligand to the natural receptor.
"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. We look forward to exploring further via this clinical trial."
"We are excited to bring MDX2004 to patients as a first-in-class trispecific antibody with a unique design aiming for a specific mechanism of action. By stimulating and sustaining immune function, this T cell rejuvenator has potential to treat diverse cancers and reverse immune impairment caused by chemotherapy, chronic diseases, infection and aging," said Phillip Frost, M.D., Chairman and CEO of OPKO Health and Gary Nabel, M.D., Ph.D., President and CEO of ModeX and Chief Innovation Officer of OPKO Health.
Preclinical proof-of-concept data as well as clinical dose selection analyses to support the MDX2004 development will be showcased in two poster presentations at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), National Harbor, MD, on November 5-9, 2025.
About MDX2004
MDX2004 is a novel trispecific antibody–fusion protein that targets CD3, CD28, and 4-1BB (CD137) on human T cells. It is designed to promote the expansion of stem and memory T cell populations, thereby rejuvenating immune function and enhancing anti-tumor immunity. This trifunctional approach aims to expand and sustain both stem and mature memory T cell subsets, which have been associated with favorable responses to immunotherapy. It may thus help restore immune function in subjects with underlying immune impairment from aging, chronic diseases such as diabetes, infections or chemotherapies.
Beyond bispecifics: ModeX Synergistic Targeting of Antibody Receptors (MSTAR)
Multispecific antibody therapeutics can help generate medicines of the future by targeting multiple disease pathways simultaneously. Many untreatable or complex conditions arise from multiple root causes; yet most medicines only act on a single target. ModeX overcomes these challenges by combining natural protein structures using a platform known as the ModeX Synergistic Targeting of Antibody Receptors (MSTAR) to create unique multispecific medicines. The platform generates multispecific antibodies from modular building blocks intended to modulate potency and maximize specificity to address multiple disease pathways simultaneously.
(Press release, Opko Health, OCT 28, 2025, View Source [SID1234657072])