Date: 2013-08-20
Type of information: Licensing agreement
Compound: enoblituzumab (MGA271)
Company: Servier (France) Macrogenics (USA - MD)
Therapeutic area: Cancer- Oncology
Type agreement: licensing development commercialisation
Action mechanism: monoclonal antibody. Enoblituzumab (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 tumors, 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 tumor 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).
Disease: solid tumors
Details: * On December 1, 2011, MacroGenics, a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer and autoimmune diseases, and Servier have 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 1 clinical trial for the treatment of solid tumors. Under the terms of the agreement, MacroGenics retains full development and commercialization rights to MGA271 in the U.S., 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.
MGA271 is currently being tested in an open-label, multi-dose, single-arm, dose-escalation Phase 1 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 Center and Dr. Keith Flaherty at Massachusetts General Hospital.
Financial terms: MacroGenics will receive a $20 million upfront payment. If Servier exercises its option upon completion of the Phase 1 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.
Latest news: * On October 28, 2015, MacroGenics announced that Servier has given MacroGenics notice that it will not exercise its option to license regional rights for enoblituzumab (MGA271), a clinical-stage monoclonal antibody targeting B7-H3, a member of the B7 family of immune regulators. As a result, MacroGenics now controls worldwide rights to all programs within its B7-H3 franchise. Enoblituzumab is currently being evaluated in patients with a variety of tumor types in three clinical studies, including a monotherapy trial as well as in combination with either ipilimumab or pembrolizumab. In October 2015, MacroGenics provided an overview of initial clinical data from the ongoing monotherapy trial of enoblituzumab. Results presented to date suggest that enoblituzumab is well tolerated and tumor regression has been observed in heavily-treated patients across different tumor types, including prostate and bladder cancer, as well as in melanoma patients who have progressed following treatment with one or more checkpoint inhibitor therapies. In addition, evidence of T-cell immunomodulatory function has been observed in patients treated with enoblituzumab. Data from the ongoing monotherapy trial will be presented as a late-breaking abstract session at the 2015 Society for Immunotherapy of Cancer (SITC) Annual Meeting on November 7, 2015 .
* On August 20, 2013, MacroGenics, has announced that the first patient has been dosed in a Phase 1 dose expansion cohort trial of MGA271. This milestone triggers a $10 million payment to MacroGenics from its partner, Les Laboratoires Servier. The dose expansion portion of this Phase 1 clinical trial of MGA271 is designed to further evaluate safety and pharmacokinetics at a weekly dose of 15 mg/kg. The dose expansion portion of the trial also includes an early evaluation of the potential anti-tumor activity of MGA271. MacroGenics plans to enroll 45 patients within three cohort groups: two with specific tumor types of 15 patients each, and a third cohort composed of other B7-H3-expressing tumor types. MacroGenics is enrolling patients in the United States and expects to complete the Phase 1 trial in 2014. Servier has indicated that it intends to evaluate MGA271 in 45 additional cancer patients representing additional tumor types beginning in the fourth quarter of 2013.
In the dose escalation portion of the Phase 1 clinical trial, 26 patients were enrolled, representing 15 different types of tumors. Ten patients received additional cycles of MGA271 treatment and all have had stable disease at the first tumor re-assessment. The most frequent adverse events in the trial were mild or moderate infusion reactions. No dose-limiting toxicity was observed.
