MacroGenics uses an efficient method for exploiting cell lines' characteristics to rapidly raise monoclonal antibodies (mAbs) targeting cell surface proteins. The company’s proprietary methods for generating mAbs reactive to protein targets on the cell surface consistently yields a much higher percentage of cell surface-directed antibodies compared with approaches using conventional methods of immunization. In our primary screen, we confirm that antibodies generated through our immunization procedure recognize an antigen expressed on the cell surface. After identifying mAbs that bind to cell-surface antigens on a chosen cell line, we apply proprietary high-throughput tissue screens and "focused proteomics" approaches to assess those proteins' biological function and relevance to disease, rapidly narrowing the candidates to those most likely to be suitable for disease targeting. Using our proprietary CellArray™ technology, MacroGenics can within days, assess the prevalence of the targeted antigen on a large number of cell lines and patient samples. We integrate our proprietary high-throughput screens, automated CellArray system and focused proteomics approaches to prioritize those suitable for preclinical development. This time-efficient process contrasts with the many months or years required to express, purify protein and raise antibodies against a target identified in a genomics-based screen. To date, we have created over 30 cell lines, which support our immunization efforts. Our antibody library includes approximately 1,500 purified antibodies, which interact with a broad range of both validated and novel targets.
MacroGenics’ protein engineering approach incorporates two complementary strategies. We rely on a rational design approach, in which our scientists use their detailed knowledge of the structure and function of proteins to make desired changes. The second strategy is known as "directed evolution
" and is based on the application of random mutagenesis to a protein, and a selection regime is used to pick out variants that have the desired qualities. Based on these strategies, we have developed a significant library of Fc variants which allow us to improve an antibody’s functional activity through modulation of both activating and inhibitory Fc receptors. Furthermore, we have created our own proprietary platform for multi-specific antibodies, which is referred to as our DART platform. Both of these platforms have been configured in a “plug-and-play” format, so that we can quickly utilize them for specific antibodies. Finally, MacroGenics has significant in-house capabilities for humanization of antibodies, and routinely completes humanization in two months.
Internal GMP Manufacturing
MacroGenics operates its own cGMP manufacturing facility which utilizes disposable Wave Bioreactors, a system which allows for rapid and cost-effective production of therapeutic antibodies. Our company was an early adopter of single-use technologies which are redefining upstream and downstream processing of biopharmaceuticals today. The bioreactor requires no in place cleaning or sterilization, providing the ultimate ease of operation and protection against cross contamination. Using our cGMP manufacturing facility, MacroGenics has produced clinical supply for four separate antibody programs, and is already planning for additional expansion of its manufacturing capacity.
Clinical & Regulatory
Our company has the capability to support all clinical and regulatory activities from early stage development through license application submission, product approval and beyond. MacroGenics is leading the development of our most advanced product candidate, teplizumab, which recently completed the enrollment of a pivotal clinical trial conducted at sites across 14 different countries. We are currently supporting three active clinical programs. These programs include Phase 1, Phase 2, and Phase 3 trials and require routine regulatory interactions worldwide.