Money will fund progression of DART-based autoimmune candidate to IND and viral pathogen antibody development.

Immunotherapeutics firm MacroGenics has been awarded three NIH grants totalling $9.8 million to fund further both the development of its Dual-Affinity Re-Targeting (DART) bispecific antibody scaffold platform and progression of its pipeline of infectious disease product candidates.

The DART platform has been developed to enable the design of dual specificity, antibody-like therapeutics that can target multiple epitopes. One grant will support preclinical development of MacroGenics’ B lymphocyte-targeting DART candidate to IND stage. The product is in development for the potential treatment of a range of autoimmune diseases including lupus, rheumatoid arthritis, and multiple sclerosis.

The two addition grants fall under NIH’s Partnerships for Biodefense Viral Pathogens initiative and will fund R&D focused on developing an antibody-based treatment for Chikungunya virus and a DART-based pan-Dengue virus immunotherapeutic for both prevention and treatment of Dengue virus infection.

MacroGenics is building a pipeline of candidates for the treatment of autoimmune disorders, cancer, and infectious diseases. In addition to its DART platform, the firm is exploiting its cancer stem like cell (CSC) technology to develop a new class of cancer-targeting mAbs and an Fc optimization technology to precisely engineer mAbs.

The CSC platform, acquired by MacroGenics through the 2008 buyout of Raven Biotechnologies, exploits a series of CSCs generated in vitro from a wide range of solid and hematological tumors. The company says it has created over 1,300 novel mAbs that target antigens on both CSCs and bulk tumor cells but display minimal binding to normal cells. The most promising are being developed into clinical candidates. MacroGenics is also exploring the use of CSC-binding antibodies for applications in compound screening and diagnostics.

The Fc optimization platform has been developed to engineer, screen, identify, and test Fc domains with customizable activity. The firm claims that engineering Fc regions to bind with optimum affinity to both activating and inhibitory receptors has allowed the design of more effective immune modulation and effector functions such as cytotoxic potency. The firm’s exclusive access to transgenic mice that express human Fc receptors is enabling the in vivo testing of antibodies that incorporate Fc domain variants, including potential cancer therapeutic candidates.

MacroGenics’ lead candidate is teplizumab (MGA031), a humanized mAb undergoing Phase III trials for the treatment of type 1 diabetes. Teplizumab is being developed in collaboration with Eli Lilly, as part of a deal signed in 2007 in which it obtained $41 million up front. Lilly gained exclusive, worldwide rights to the drug for autoimmune indications.

MacroGenics’ clinical-stage pipeline also includes a humanized mAb MGAWN1, which earlier this month started in a Phase II trial for the treatment of West Nile virus. Development of the antibody is being funded through a $50 million contract with the NIAID.

The firm’s preclinical-stage pipeline includes MGAH22, an Fc-optimized mAb that targets HER2, which is expected to start in Phase I trials during this year. Additional DART-based anticancer candidates are undergoing lead optimization.

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