AIS-D04, ALPN-303, Autoimmune Cytopenias

Summary of Key Inclusion Criteria:

1. Indication-specific Criteria

   1. Immune Thrombocytopenia (ITP)

      • Documented primary ITP of at least 12 weeks duration
      • History of failure or relapse to at least 2 treatment regimens for ITP
      • History of exposure to a TPO-RA unless otherwise contraindicated or unavailable
      • Documented history of platelets <30 × 10^9/L

   2. Warm Autoimmune Hemolytic Anemia (wAIHA)

      • Diagnosis of primary wAIHA of at least 12 weeks duration documented with a current or prior positive direct antiglobulin test (DAT) for anti-IgG (±C3d)
      • Documented history of anemia with hemoglobin ≤9 g/dL
      • At least one of the following: (i) haptoglobin <LLN (ii) indirect bilirubin >ULN (iii) lactate dehydrogenase>ULN
      • History of failure or relapse to at least 2 treatment regimens for wAIHA

   3. Cold Agglutinin Disease (CAD)

      • Diagnosis of primary CAD of at least 12 weeks duration with all of the following: (i) chronic hemolysis (ii) polyspecific DAT positive (iii) monospecific DAT strongly positive for C3d (iv) cold agglutinin titer ≥64 at 4°C (v) IgG DAT ≤1+ (vi) no overt malignant disease
      • Documented history of anemia with hemoglobin ≤9 g/dL
      • At least one of the following: (i) haptoglobin <LLN (ii) indirect bilirubin >ULN (iii) lactate dehydrogenase>ULN
      • History of failure or relapse to at least 1 treatment regimen for CAD
2. (All indications) If receiving protocol-specified standard-of-care medications, doses must be stable for protocol-specified durations

Summary of Key Exclusion Criteria:

1. Secondary AIHA, CAD, or ITP

2. Treatment with any of the following within the noted period prior to study entry

   1. rituximab: <12 weeks
   2. IVIg: <4 weeks
   3. sutimlimab, other marketed biologic therapeutics: <8 weeks
   4. plasmapheresis, plasma exchange, or double-filtration plasmapheresis: <8 weeks
   5. transfusions with blood, blood products or other rescue medications: <2 weeks
   6. splenectomy: <12 weeks
   7. other immunomodulatory or investigational agents, except for investigational agents for COVID-19 that have been granted emergency use authorization or approved by the applicable national health authority: <5 half-lives and requires agreement of the Medical Monitor
3. Recent serious or ongoing infection; risk or history of serious infection