MacroGenics, Inc., a clinical-stage biopharmaceutical company, and Takeda Pharmaceutical Company Limited announced the conclusion of their License and Option Agreement for MGD010.

MacroGenics has regained the worldwide rights to MGD010, a bispecific molecule targeting CD32B and CD79B. Takeda’s decision comes earlier than the predefined expiration of its option exercise period and follows Takeda’s recently announced therapeutic area re-prioritization. Takeda’s decision was not based on the ongoing phase 1 study with MGD010. MacroGenics plans to continue to advance the development of this product candidate based on the positive study results reported to date.

"We presented promising interim data from our ongoing phase 1 study of MGD010 in an oral presentation at the Annual European Congress of Rheumatology (EULAR 2016) in London this past June," said Scott Koenig, M.D., Ph.D., president and CEO of MacroGenics. "We view Takeda’s early decision to not exercise its option as an opportunity for MacroGenics. This enables us to further develop MGD010 on our own or explore future strategic partnering opportunities with this programme."

“We have enjoyed collaborating with MacroGenics on this development project,” said Takeda’s Emiliangelo Ratti, Global Head Central Nervous System Therapeutic Area Unit. “While our re-prioritization on key therapeutic areas has resulted in a change of direction for Takeda’s role in this program, we look forward to MacroGenics’ continued progress with MGD010 as a potential new therapy for patients suffering from B-cell mediated autoimmune and inflammatory disorders.”

In May 2014, MacroGenics entered into an agreement with Takeda regarding MGD010. Under the terms of that agreement, Takeda received an option to obtain an exclusive worldwide license for MGD010 following the delivery of a data package, including data from a completed, pre-defined phase 1 study. Takeda has given formal notification it does not intend to exercise this option, allowing MacroGenics to control worldwide development and commercialization rights to MGD010. To date, MacroGenics has led all MGD010 product development activities. Takeda and MacroGenics are also parties to a separate research collaboration that was entered into in September 2014.

MGD010 is a humanized DART molecule that simultaneously targets CD32B and CD79B. CD32B is a checkpoint molecule expressed on B lymphocytes that, when co-ligated with CD79B, a component of the B-cell antigen receptor complex, delivers a co-inhibitory signal that dampens B-cell activation. In normal conditions, B cells utilize CD32B as one of the key negative regulators to ensure that tolerance to self is maintained and autoimmune disorders do not occur. MGD010 exploits this mechanism and triggers this inhibitory "immune checkpoint" loop for the inhibition of B-cell function, an approach that may be useful for the treatment of patients with autoimmune disorders. In pre-clinical studies, MGD010 was shown to modulate the function of human B cells without B-cell depletion in a variety of in vitro and in vivo models. MacroGenics believes this molecule can block those B cells that are activated to produce the pathogenic antibodies and promote the autoimmune process.

Interim data from a first-in-human, double-blind, placebo-controlled phase 1 study in which a single dose of MGD010 is intravenously (IV) administered to healthy subjects were presented at the EULAR 2016. Initial data from the first 49 subjects showed that MGD010 was well tolerated at all dose levels and no serious adverse effects were reported. In addition, MGD010 demonstrated linear pharmacokinetics and dose-dependent selective binding to B lymphocytes without persistent B-cell depletion. The data also showed: (1) a dose-dependent downregulation of B-cell receptor-induced signaling together with down-modulation of B-cell receptor expression among circulating memory and naïve B cells, (2) a decrease in expression of the costimulatory CD40 molecule and (3) a decrease in circulating immunoglobulin M levels, each consistent with the targeted action of MGD010. MacroGenics is currently completing the enrollment of an additional 24 healthy subjects in a final segment of the Phase 1 study, in which subjects will be assessed for immune modulation by MGD010 following Hepatitis A vaccination.

MacroGenics is a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases.