EVOLVE104, a First-in-Class CD2 Costimulatory Trispecific T Cell Engager, is First Molecule from EVOLVE Platform to Enter the Clinic
Trial Initiation Marks EvolveImmune’s Transition to Clinical-Stage Company
BRANFORD, Conn., Dec. 16, 2025 (GLOBE NEWSWIRE) -- EvolveImmune Therapeutics, a clinical-stage immuno-oncology company developing a new class of multi-specific T cell engagers with integrated CD2 costimulation, today announced the dosing of the first subject in a first-in-human phase 1 clinical trial of EVOLVE104. The study, EIU-104101 (NCT07217171), is evaluating the safety, efficacy, and pharmacokinetics of EVOLVE104 in patients with advanced urothelial and squamous cell carcinomas.
EVOLVE104 is a next-generation trispecific T cell engager featuring integrated CD2 costimulation and represents the first molecule generated from the company’s EVOLVE platform to enter clinical development. The compound targets a novel set of tumor-associated antigens, ULBP2/5/6, which are highly expressed on bladder cancer and a variety of squamous cell carcinomas. Notably, EVOLVE104 is the first T cell-redirecting therapeutic candidate targeting ULBP2/5/6 to enter clinical development.
“The dosing of the first subject in our EVOLVE104 phase 1 trial represents a significant milestone for EvolveImmune, marking our transition to a clinical-stage biotechnology company,” said Stephen Bloch, M.D., chief executive officer of EvolveImmune. “By providing integrated costimulation through binding of CD3 and CD2, our EVOLVE T cell engagers have consistently outperformed bispecific T cell engagers in preclinical models, suggesting their potential to deliver best-in-class therapeutic activity to cancer patients. We are focused on advancing this innovation through clinical development with the goal of delivering a new class of T cell engager therapies to cancer patients who have few treatment options.”
The newly initiated study will begin with a phase 1a dose escalation portion, to be followed by phase 1b dose expansion, and will enroll up to 160 subjects with locally advanced or metastatic bladder cancer (including urothelial and pure squamous histologies) and squamous cell carcinomas of the lung, esophagus, skin, tongue, and anogenital region which are relapsed from or refractory to standard of care therapies. Additional study information may be found at NCT07217171.
EvolveImmune’s proprietary EVOLVE platform is designed to therapeutically co-opt key mechanisms central to efficient immune synapse formation and T cell effector function. This approach aims to bypass low tumor immunogenicity, conditionally activate adaptive immunity and reduce T cell dysfunction, allowing for amplified and sustained T cell tumor killing capacity, to address unmet medical needs in solid tumors and hematologic malignancies.
About EVOLVE104
EVOLVE104 is a next-generation trispecific T cell engager that binds CD3 and CD2 on T cells and the tumor-associated antigens ULBP2/5/6, which have limited expression in normal human tissues and are found on a number of epithelial-derived malignancies, including urothelial carcinoma and a broad array of squamous cell carcinomas. In preclinical studies, EVOLVE104 has demonstrated compelling single-agent activity and combination activity with anti-PD-1 therapy, the ability to reinvigorate dysfunctional T cells, and a promising safety profile. EVOLVE104 is currently being studied in a first-in-human phase 1 clinical trial in subjects with advanced, relapsed or refractory solid tumors (NCT07217171).
About EvolveImmune Therapeutics
EvolveImmune Therapeutics, Inc. is an immuno-oncology company developing first-in-class, multi-specific T cell engagers derived from its EVOLVE platform, which have been inspired by a generation of discoveries in T cell immunology. EVOLVE molecules leverage the power of integrated CD2 costimulation to overcome the therapeutic challenges of cancer cell resistance to current immunotherapies in a range of solid tumors and hematological cancers. The EVOLVE platform has generated a pipeline of internal and partnered programs, the most advanced of which, EVOLVE104, is in active clinical development.
For more information, please visit: www.evolveimmune.com.
