Research & Development

AMV564, a novel CD33xCD3 bispecific antibody is currently under investigation in a Phase 1 clinical study in patients with relapsed or refractory acute myeloid leukemia (AML). Amphivena plans to launch a Phase 1 clinical study in patients with myelodysplastic syndrome (MDS) in early 2018. The company is also exploring the utility of AMV564 in solid tumors.

AMV564 is a novel T cell engager, derived from human protein sequences, that binds both CD33 and CD3 to mediate T-cell directed lysis of CD33-positive cancer cells. CD33 is expressed on approximately 90% of AML myeloblasts, including leukemic stem cells, and is also found on committed myeloid progenitor cells, myeloid leukemic blasts, mature monocytes and other leukocytes, but not on normal pluripotent hematopoietic stem cells.

AMV564 is comprised of two VH and VL amino acid chains that form four antigen-binding single chain variable fragments (scFvs). AMV564 is bivalent for each of the CD33 and CD3 antigens providing avidity for each target and twice the molecular weight of monovalent constructs. Differences between AMV564 and competitor molecules may translate to potency and safety advantages in the clinic.

In preclinical studies, this novel CD33/CD3 bispecific antibody demonstrated potent activity against AML patient samples that was independent of CD33 expression level, disease stage and cytogenetic risk.Ā  The antibody eliminated nearly all blasts from bone marrow and spleen in a stringent AML patient-derived xenograft murine model. In addition, Amphivena established a therapeutic window for AMV564 in cynomologus monkeys, with rapid, sustained elimination of CD33-expressing cells during AMV564 dosing and rapid hematopoietic recovery following dosing.




  1. Safety and clinical activity of AMV564, a CD33/CD3 t-cell engager, in patients with relapsed/refractory acute myeloid leukemia (AML): Updated results from the phase 1 first-in-human trial


  1. Phase 1 First-In-Human Trial of AMV564, a Bivalent Bispecific (2:2) CD33/CD3 T-Cell Engager, in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)
  2. The Therapeutic Potential of AMV564, A Novel Bispecific Bivalent (2×2) T-Cell Engager, for the Treatment of CD33-Expressing Hematologic Malignancies
  3. In vitro and in vivo killing of AML using tetravalent bispecific CD33/CD3 TandAbs
  4. Construction and Characterization of Novel CD33/CD3 Tandem Diabodies (TandAbsĀ®) for the Treatment of Acute Myeloid Leukemia (AML)
  5. Development Of A Bispecific Tetravalent CD33/CD3 TandAb For The Treatment of AML

Journal articles:

  1. BioCentury on BioBusiness Dec.10, 2018 issue Cover Story, Product Development section article, “Intermittent move beyond Blincyto” written by Ms. Erin McCallister, BioCentury Senior Editor
  2. Characterization of CD33/CD3 Tetravalent Bispecific Tandem Diabodies (TandAbs) for the Treatment of Acute Myeloid Leukemia


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