Date: 2015-06-01
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Amphivena Therapeutics (USA - CA)
Product: AMV-564
Action
mechanism:
- bispecific antibody. AMV-564 is one of Amphivena’s proprietary first-in-class, tetravalent, bispecific TandAb antibodies. The novel immunotherapy recruits T-cells to eliminate cancer cells that express CD33, a receptor that is
expressed on the majority of acute myeloid leukemias (AMLs) and is present on other hematologic malignancies. AMV-564 is bivalent for both CD33 on AML cells and CD3 on T-cells, forming a T-cell activating complex in the presence of target cancer cells. By maintaining the avidity for antigen as found
in typical monoclonal antibodies, AMV-564 mediates potent and efficient tumor cell lysis. AMV-564 also offers pharmacokinetic advantages over smaller, monovalent bispecific constructs due to a molecule size that exceeds renal clearance limits. Amphivena is currently completing IND-enabling studies to advance AMV-564 into clinical development as a treatment for AML.
Disease: acute myeloid leukemia (AML)
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On June 1, 2015, Amphivena Therapeutics, a developer of cancer immunotherapies, announced positive data from several preclinical studies characterizing its proprietary T-cell redirecting bispecific CD33/CD3-targeting antibodies as potential immunotherapeutics for the treatment of acute myeloid leukemia (AML). Study findings, which demonstrated potent and specific anti-AML activity for the novel antibodies, were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting. Amphivena also announced selection of a development candidate, AMV-564, based on these compelling preclinical data.
- A diverse collection of Amphivena’s novel T-cell redirecting, tetravalent, bispecific CD33/CD3-targeting antibodies were evaluated across a rigorous panel of in vitro and in vivo systems in order to identify an optimal candidate for clinical development. The studies, conducted in collaboration with leading researchers at the Fred Hutchinson Cancer Research Center and the Washington University School of Medicine, were designed to examine the antibodies’ stability properties, affinity for CD33 and CD3, and impact on T-cell activation and cytotoxicity against CD33+ AML cells.
- Key study findings for Amphivena’s CD33/CD3-targeting antibodies included:
- Mechanism-based, T-cell activation and proliferation was induced by the tetravalent, bispecific CD33/CD3-targeting antibodies. Importantly, the presence of CD33+ target cells was required for the T-cell activities, demonstrating the potential for minimal off-target safety issues for this
antibody platform.
- Potent and selective cytotoxic activity against CD33+ AML cell lines and 27 primary CD33+ AML specimens was observed at pM antibody concentrations. This activity was observed in newly diagnosed and relapsed or refractory AML samples, and was independent of disease stage. For the most potent CD33/CD3 antibodies, activity was independent of the level of CD33 expression.
- Robust tumor growth inhibition and delay in prophylactic and established AML xenograft models using human cancer cell lines and donor T-cells.
- Impressive activity in an AML patient-derived xenograft model with nearly complete elimination of leukemic blasts from all compartments, including bone marrow and spleen, despite the very low number of T-cells present in the patient sample.
(ASCO posters :
- Development Of A Bispecific Tetravalent CD33/CD3 TandAb For The Treatment of AML
- In vitro and in vivo killing of AML using tetravalent bispecific CD33/CD3 TandAbs
- The Therapeutic Potential of AMV564, A Novel Bispecific Bivalent (2×2) T-Cell Engager, for the Treatment of CD33-Expressing Hematologic Malignancies)
Is
general: Yes
