Bispecifics have the potential to overcome some of the shortcomings of monoclonal antibodies, which are often associated with inadequate or insufficiently durable responses and, in cancer in particular, the emergence of drug resistance. By hitting two different targets simultaneously, drug developers hope not only to overcome these shortcomings but also—in the case of cancer— to activate cellular immune responses against malignant cells, to improve the delivery of toxic payloads or to aid the delivery of agents across the blood-brain barrier. “Ideally, we want to see biology that would not be achievable without a bispecific,” says Jane Dancer, chief business officer at Cambridge, UK-based F-Star. Bispecifics also offer a commercial hedge against the biosimilars wave that is starting to sweep over some first-generation monoclonal antibody products. But bispecific developers have to solve manufacturing and clinical development teething problems before they—and their customers—can reap the benefits from the technology.
The deal with Pfäffikon-based EngMab, which has an additional CHF 150 ($151) million attached in development and regulatory milestones, and up to CHF 2.25 ($2.26) billion more in sales-based milestones, is not Celgene's first foray into bispecific antibodies. The big biotech already has a collaboration with Zymeworks, of Vancouver, British Columbia, Canada, based on the latter firm's Azymetric platform. The recent buyout will, however, accelerate Celgene's progress toward clinical trials thanks to EM901, the main molecule driving the deal. The bispecifc antibody is based on the CrossMAb technology developed by Basel, Switzerland–based Roche. It targets B-cell maturation antigen (BCMA) and the T-cell co-receptor CD3 (BCMA × CD3), and will be the subject of an investigational new drug filing in late 2017. BCMA, as the name suggests, is expressed on terminally differentiated plasma cells and has become a key target for developers of both bispecific antibodies and chimeric antigen receptor (CAR-) T-cell therapies for multiple myeloma. By acquiring EngMab, Celgene, of Summit, New Jersey, now has a foot in both camps—it already has an alliance with Bluebird Bio, of Cambridge, Massachusetts, to develop a BCMA-directed CAR-T cell therapy.
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