New York-based Prolium Bioscience has initiated a first-in-human Phase I trial of PRO-203, a subcutaneously administered CD20×CD3 bispecific T-cell engager, in patients with systemic sclerosis (SSc) — a severe autoimmune fibrotic disease for which no approved therapy has demonstrated consistent disease modification. The trial is notable for applying a T-cell engager format, previously explored in oncology, to a refractory autoimmune indication where conventional B-cell depletion with rituximab has shown limited durability.
The Phase I study is structured in two sequential parts. Part 1 is a randomized, double-blind, placebo-controlled single-ascending-dose study enrolling up to 70 healthy adult volunteers across five cohorts, with up to two additional optional cohorts. Part 2 is an open-label dose-escalation study enrolling approximately 24 patients with active, treatment-refractory SSc across three cohorts, with an optional long-term extension (LTE) permitting retreatment. Primary endpoints across both parts focus on safety and tolerability, while secondary endpoints focus on PK/PD measurements and immunogenicity assessed by anti-drug antibody incidence. The trial is currently recruiting at Nucleus Network in Melbourne, Australia, with Nanjing Drum Tower Hospital in China listed as not yet recruiting. Primary completion is anticipated in Q1 2027.
Mechanism and rationale
PRO-203 binds simultaneously to CD20 on B cells and CD3ε on T cells, forming an artificial immunological synapse that redirects cytotoxic T cells to kill CD20-expressing B cells through T-cell-dependent cellular cytotoxicity. This mechanism, according to the company's March 2026 launch announcement, is intended to produce deeper B-cell depletion than conventional anti-CD20 antibodies such as rituximab, which depend on NK cell-mediated antibody-dependent cellular cytotoxicity and complement — effector mechanisms that may be less effective in fibrotic tissue environments.
B cells are implicated in SSc pathogenesis through autoantibody production, cytokine secretion, and direct fibroblast activation. Rituximab has been evaluated in SSc with mixed results in small studies, and is listed as a prior therapy against which Part 2 patients must have demonstrated intolerance or inadequate response. The rationale for a TCE in this context rests on the hypothesis that T-cell-mediated killing may deplete B cells more completely — including in tissue compartments — than ADCC-dependent mechanisms.