Abstract
Background/Purpose: Autoimmune cytopenias (AICs), including immune thrombocytopenia (ITP), warm autoimmune hemolytic anemia (wAIHA), cold agglutinin disease (CAD), and Evans Syndrome (ES), are rare, chronic disorders characterized by destruction of blood cells, mediated by autoreactive antibodies. Existing therapies are often immunosuppressive and associated with short- and long-term morbidities. A meaningful proportion of patients are unable to achieve a complete response with standard of care, and some are refractory to multiple lines of therapy. Among patients who do initially respond, durability of response can be challenging, and relapse is not uncommon.
Long-lived plasma cells are critical drivers of autoantibody production but are not specifically targeted by current therapies. OM336 is an investigational, humanized, bispecific, IgG4-like T cell engager antibody that targets both B cell maturation antigen (BCMA) and CD3, leading to depletion of autoreactive plasma cells as well as memory B cells, with the goal of “resetting” the immune system to achieve sustained remission off therapy. Previously published data from an investigator-initiated study have demonstrated the efficacy of OM336 for the treatment of highly refractory AIHA, with durable benefit after discontinuation of standard of care therapies in the absence of any additional transfusions1. Based on these data, this phase 1b study has been initiated (NCT07083960).
Study Design and Methods: This is an open-label, Phase 1b, multinational, multiple ascending dose study to assess the safety and tolerability of OM336 in adult participants with active AICs (e.g., ITP, wAIHA, CAD or mixed forms, including ES), that are relapsed/refractory to standard therapies. Eligible participants will be enrolled into dose escalation cohorts in a sequential fashion. After the completion of dosing in each cohort, an Internal Monitoring Committee will review the emerging safety data to determine whether participants in the next cohort may be dosed. Participants who achieve clinical response may taper or discontinue their background therapies for AIC, per investigator judgment.
A total of up to 32 participants are to be enrolled: three (3) in each dose escalation cohort, for a total of 12 participants across Cohorts A1-A4, and up to five (5) in each dose expansion cohort, for a total of 20 participants across Cohorts B1-B4.
Objectives: The primary endpoints are safety and tolerability as assessed by the incidence and severity of treatment-emergent adverse events. Secondary endpoints include PK profiles and anti-drug antibody titers. Exploratory endpoints include measures of efficacy (cell counts and other laboratory parameters), patient-reported outcomes, biomarkers (e.g., soluble BCMA levels, markers of inflammation), and glucocorticoid- and other immunosuppressive-sparing effects.
Eligibility: Participants must be 18-75 years of age, with active, relapsed/refractory ITP, wAIHA, CAD, mixed hemolysis, or ES, despite ≥1 prior therapy, with or without other concurrent autoimmune diseases. Key exclusion criteria include prior BCMA-targeting therapy, recent B cell depletion, or uncontrolled infection.
Enrolment: Up to 32 participants are to be enrolled across approximately 12 sites in the United States, the United Kingdom, and Australia.
Conclusion: Patients with relapsed/refractory AICs have unmet medical need requiring additional safe and effective therapy options. This Phase 1b study evaluates a potential treatment for AICs utilizing OM336, a novel T cell engager that targets B cell maturation antigen (BCMA) and CD3. The study is open and actively enrolling patients.
References:
Zhang L, et al. BCMA-Targeted T-Cell Engager for Autoimmune Hemolytic Anemia after CD19 CAR T-Cell Therapy. N Engl J Med. 2025 Jun 12;392(22):2282-2284. doi: 10.1056/NEJMc2502297. PMID: 40499177.
