Kali Therapeutics has initiated a first-in-human Phase I trial of KT502, a CD19 × CD3 bispecific T-cell engager administered subcutaneously, in adults with moderately to severely active rheumatoid arthritis. The California-based company, incorporated in 2024, appears to have developed KT502 internally using a proprietary protein engineering platform that incorporates a CD3 masking technology intended to reduce cytokine release while preserving B-cell cytotoxicity — a design feature that distinguishes it from earlier, unmasked TCE formats.
The Phase I study (NCT07564154) will enroll approximately 27 participants aged 18 to 75 with established RA of at least six months' duration who are seropositive for rheumatoid factor or anti-citrullinated protein antibodies and have had an inadequate response to prior treatment. The trial is structured in two sequential parts: Part A conducts single ascending dose finding with non-fractionated dosing, while Part B uses a step-up fractionated dosing regimen. Sites are located in Auckland, New Zealand and Bayswater, Victoria, Australia, with enrollment expected to begin in Q3 2026 and primary completion anticipated by December 2027. Primary endpoints focus on safety and tolerability, including the incidence and severity of adverse events graded by NCI CTCAE v5.0 and the incidence of cytokine release syndrome graded by 2019 ASTCT criteria, alongside changes in vital signs and clinical laboratory parameters over 12 weeks. Secondary endpoints cover PK/PD assessments.
KT502 bridges CD19 on B cells and CD3 on T cells, redirecting cytotoxic T cells to eliminate CD19-expressing B cells. In RA, B cells contribute to pathology through autoantibody production — the trial's requirement for RF or ACPA seropositivity directly reflects this mechanistic rationale. According to an ACR meeting abstract, preclinical data showed rapid and deep B-cell depletion with low cytokine release, consistent with the company's stated goal of decoupling potency from the CRS risk that has complicated earlier TCE programs.