Date: 2014-12-10
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 6-9 in San Francisco, CA
Company: Macrogenics (USA - MD)
Product: MGD011
Action
mechanism: protein. MGD011, a humanized CD19 x CD3 bispecific DART protein, is being developed for the treatment of B-cell hematological malignancies. CD19, a lymphocyte-specific marker expressed from early B-lymphocyte development through mature memory B cells, is highly represented in B-cell malignancies. This makes it attractive for targeted interventions. MGD011 is designed to redirect T cells, via their CD3 component, to eliminate CD19-expressing cells found in many hematological malignancies. MGD011 has been engineered to address half-life challenges posed by other programs targeting CD19 and CD3. This product candidate has an Fc domain, which allows for extended pharmacokinetic properties and convenient dosing at a once-a-week or longer interval. In addition, MGD011 and the Company\'s other DART molecules that redirect T cells against cancer targets are manufactured using a conventional antibody platform without the complexity of having to genetically modify T cells from individual patients as required by approaches such as chimeric antigen receptor (CAR) T-cells.
Disease: B-cell hematological malignancies
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On December 6, 2014, MacroGenics, a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, announced the presentation of pre-clinical data for MGD011, a humanized CD19 x CD3 Dual-Affinity Re-Targeting (DART®) protein, at the 56th Annual Meeting of the American Society of Hematology (ASH), taking place in San Francisco, CA. These data demonstrate potent T-cell mediated anti-tumor activity in preclinical models. Liqin Liu , Ph.D., Senior Scientist at MacroGenics , presented a poster titled: MGD011, Humanized CD19 x CD3 DART® Protein with Enhanced Pharmacokinetic Properties , Demonstrates Potent T-Cell Mediated Anti-Tumor Activity in Preclinical Models and Durable B-Cell Depletion in Cynomolgus Monkeys Following Once-a-Week Dosing. The pre-clinical studies investigated the ability of MGD011 to mediate anti-tumor activity. These studies demonstrated potent anti-tumor activity in vitro and in mouse leukemia/lymphoma tumor models, with high complete response rates and no evidence of relapse over the study duration. MGD011, whose components cross-react with the corresponding cynomolgus monkey antigens, displayed prolonged pharmacokinetic properties in this species, consistent with that of a monoclonal antibody. Treatment with MGD011 induced durable, marked decrease in circulating B lymphocytes and profound B-cell depletion in lymphoid organs in cynomolgus monkeys following once-a-week dosing. MGD011 was well tolerated at doses up to 100 mcg/kg, the highest dose tested, with modest elevations in serum cytokines but no adverse findings. The results of these pre-clinical studies provide a strong rationale for the clinical development of MGD011 as a molecule for the treatment of B-cell malignancies. Macrogenics intends to initiate clinical development in 2015.
