Date: 2015-05-27
Type of information: Publication of results in a medical journal
phase: non clinical
Announcement: publication of results in Science Translational Medicine
Company: Macrogenics (USA - MD)
Product: MGD006
Action
mechanism: bispecific antibody. MGD006 is a humanized Dual-Affinity Re-Targeting (DART) molecule that recognizes both CD123 and CD3. The molecule was designed to redirect T cells via their CD3 component to kill CD123-expressing cells, as shown pre-clinically. CD123, the Interleukin-3 receptor alpha chain, has been reported to be overexpressed on malignant cells in a wide range of hematological malignancies including AML and myelodysplastic syndrome (MDS). AML and MDS are thought to arise in and be perpetuated by a small population of leukemic stem cells (LSCs) that generally resist conventional chemotherapeutic agents. LSCs are characterized by high levels of CD123 expression that is low or absent in the corresponding hematopoietic progenitors and stem cell populations in normal human bone marrow.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On May 27, 2015, MacroGenics announced the publication of a nonclinical research paper on MGD006 in Science Translational Medicine. MGD006 is a humanized, Dual-Affinity Re-Targeting (DART®) molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, is expressed on malignant cells, including leukemic stem cells (LSC), in acute myeloid leukemia (AML) and other hematological diseases. The primary mechanism of action of MGD006 is its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cells. The recently published research shows anticancer activity in vitro and in mouse models together with favorable pharmacodynamic and safety profile in nonhuman primates. The paper titled "A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: Preclinical activity and safety in nonhuman primates," describes how MacroGenics' scientists engineered the MGD006 DART and demonstrated in vitro that the molecule can arm T cells from AML patients to reduce blast counts and is effective in eliminating AML cells implanted in mice. Furthermore, MGD006 administered to cynomolgus monkeys demonstrated potent pharmacodynamic activity in the form of near complete elimination of circulating CD123-positive cells at doses that were safe and well tolerated. MacroGenics continues to enroll patients in the dose escalation portion of a Phase 1 study of MGD006 for the treatment of AML. The Phase 1 dose-escalation study is designed to assess the safety and tolerability of MGD006 in patients with relapsed or refractory AML. In addition to the primary safety endpoint, secondary endpoints of pharmacokinetics and pharmacodynamic activity will be evaluated, as will a number of biomarkers examining the immunobiology of MGD006. The Phase 1 study was initiated at Washington University School of Medicine in St. Louis. In addition, Emory University and Providence Portland Medical Center are now recruiting patients and a fourth site is expected to commence patient recruitment in June.
