A privately held biotechnology company that develops next generation antibody therapeutics, MacroGenics, Inc., and France’s largest privately-held pharmaceutical company, Servier, entered into an option for a license agreement for the development and commercialization of MGA271, MacroGenics’ proprietary product candidate.

MGA271 is a first-in-class, Fc-optimized monoclonal antibody that targets B7-H3 and is currently being studied in a phase I clinical trial for the treatment of solid tumours.

MGA271 is a next generation monoclonal antibody which incorporates multiple complementary mechanisms of action including enhanced immuno-stimulatory properties and targeting of tumour vasculature. The B7-H3 target is overexpressed in several malignancies requiring innovative therapeutic approaches. “Following very promising pre-clinical results, we will work together to define the clinical indications and the best drug combinations and to identify early biomarkers predictive of response,” said Stéphane Depil, MD, PhD, in charge of Oncology Research & Development at Servier. “Today’s announcement underscores Servier’s commitment to develop novel targeted therapies that address significant unmet medical needs for cancer patients,” added Emmanuel Canet, MD, PhD, president Research & Development at Servier. “MGA271 is a novel immunotherapeutic with a compelling product profile and the potential to treat a broad spectrum of solid tumours. We have been deeply impressed by both the excellence of science being conducted by MacroGenics and their world-class antibody development capabilities. We are looking forward to building a long-term strategic collaboration with MacroGenics.”

Under the terms of the agreement, MacroGenics retains full development and commercialization rights to MGA271 in the US, Canada, Mexico, Japan, Korea and India, while Servier has an option to obtain an exclusive license covering the rest of the world. Prior to the exercise of Servier’s option, both parties will fund and conduct specified research and development activities. MacroGenics will receive a $20 million upfront payment. If Servier exercises its option upon completion of the phase I study and its expansion cohorts, MacroGenics will receive an option exercise fee which, combined with the up-front and early development milestone payments, will total $60 million. In addition, MacroGenics could receive up to an additional $390 million in clinical, regulatory and commercialization milestone payments. Finally, MacroGenics may receive tiered, double-digit royalties on future net sales. Both parties will share the clinical development costs following the option exercise.

“We are delighted to enter into this collaboration with Servier. It will significantly broaden and accelerate our clinical plans for MGA271, enabling us to further investigate the multiple solid tumour types for which MGA271 may have activity,” said Scott Koenig, MD, PhD, president and CEO of MacroGenics. “This important collaboration highlights the rapidly growing excitement surrounding the B7 family of immune regulators in oncology immunotherapy as well as our Fc engineering platform.”

“Servier is a world-class pharmaceutical company with a long history of successful innovation and a dedication to research for the benefit of patients,” Dr Koenig continued. “They have an expansive global footprint and are an ideal partner to maximize the potential of MGA271.”

MGA271 is currently being tested in an open-label, multi-dose, single-arm, dose-escalation phase I study in patients with refractory B7-H3-expressing neoplasms. The trial employs a companion diagnostic for B7-H3 which will enable prospective screening of patients for expression of the target antigen. Enrollment of the first dosing cohort has been completed. Clinical investigators include Dr Howard Burris at Sarah Cannon Research Institute, Dr Roger Cohen at Hospital of the University of Pennsylvania/Abramson Cancer Centre and Dr Keith Flaherty at Massachusetts General Hospital.

MGA271 is a humanized IgG1/kappa monoclonal antibody that recognizes human B7-H3, a novel member of the B7 family of immune regulators.  B7-H3 is an attractive target for immunotherapy, as it is over-expressed in a variety of solid tumours, including prostate, pancreatic, renal cell, ovarian, colorectal, gastric, bladder, and non-small cell lung cancers as well as melanoma. MGA271 has been Fc-optimized using MacroGenics’ proprietary Fc-engineering platform to further augment its tumour killing activity. The product’s Fc region imparts increased affinity for the human activating Fc-gamma receptor IIIA (Fc-gamma RIIIA, CD16A) and decreased affinity for the inhibitory Fc-gamma RIIB (CD32B).

MacroGenics is a private, venture-backed biotechnology company that focuses on the discovery, development and delivery to patients of novel biologics for cancer, autoimmune disorders and infectious diseases.

Servier is the leading independent French pharmaceutical company with its main therapeutic products used to treat diabetes, cardiovascular disease, CNS disorders, oncology and rheumatology.