Background:B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) play key roles in B cell development, survival, and differentiation into antibody-secreting cells (ASC). Given their importance in ASC survival and antibody production, inhibition of BAFF and/or APRIL (particularly in combination), is a promising approach for the treatment of a variety of autoimmune or autoantibody-related diseases including autoimmune cytopenias. Significantly higher levels of both BAFF and APRIL have been observed in the serum of patients with autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) compared to healthy subjects. 1,2 An inhibitor of BAFF, belimumab, has demonstrated encouraging efficacy in the treatment of ITP associated with systemic lupus erythematosus and in combination with rituximab in patients with ITP. [3][4][5] Currently, there are no BAFF and/or APRIL inhibitors approved to treat AIHA or ITP. Povetacicept (ALPN-303) is an engineered dual BAFF/APRIL antagonist with the potential to improve outcomes for patients with autoimmune cytopenias. In a mouse AIHA model, povetacicept treatment suppressed anti-erythrocyte antibodies and increased hematocrit. Povetacicept has been well tolerated in adult healthy volunteers and exhibits dose-dependent pharmacokinetic (PK) and pharmacodynamic (PD) effects corresponding to reductions in circulating ASC and immunoglobulins. We present here the design of a Phase 1b clinical trial of povetacicept in adults with autoimmune cytopenias.