Incyte will partner with MacroGenics to develop its Phase I cancer immunotherapy candidate MGA012, a monoclonal antibody designed to inhibit programmed cell death protein 1 (PD-1), through a collaboration that could generate up to $900 million-plus for MacroGenics, the companies said today.

Incyte has acquired exclusive worldwide rights to develop and commercialize MGA012 in all indications. The companies’ global collaboration and licensing agreement also gives MacroGenics the right to develop its pipeline candidates in combination with the anti-PD-1 checkpoint inhibitor.

“We believe the addition of MGA012 to our clinical pipeline is important to fulfilling our long-term development strategy in immuno-oncology,” Incyte CMO Steven Stein, M.D., said in a statement. “This collaboration with MacroGenics will allow us to rapidly explore the potential clinical benefit of developing MGA012 as a monotherapy and also combining anti-PD-1 therapy with several of our existing portfolio assets.”

Incyte’s immuno-oncology effort has been anchored by epacadostat, an orally bioavailable small-molecule inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1) under development in eight cancer indications. The furthest advanced of these is unresectable or metastatic melanoma, for which epacadostat is being assessed with Merck & Co.’s Keytruda® (pembrolizumab) in a Phase III trial (NCT02752074). Epacadostat is the subject of five combination trials with Keytruda and two with Bristol-Myers Squibb’s Opdivo® (nivolumab).

Also in Incyte’s cancer immunotherapy pipeline are four candidates under study for clinical proof of concept, all designed to fight solid tumors: a first-in-class, oral arginase inhibitor being co-developed with Calithera Biosciences; INCSHR1210, a PD-1 inhibitor licensed in 2015 for up to $795 million-plus from Jiangsu Hengrui Medicine; and the antiglucocorticoid induced tumor necrosis factor receptor (GITR) agonist INCAGN1876 and the anti-OX40 agonist INCAGN1949, both licensed from Agenus.

MacroGenics president and CEO Scott Koenig, M.D., Ph.D., added: “We look forward to exploring the combination of MGA012 with multiple molecules in our own portfolio, including DART® [Dual-Affinity Re-Targeting] molecules for redirected T-cell killing, antibodies with enhanced effector function, and ADCs [antibody–drug conjugates], potentially to provide improved patient benefit.”

MGA012 is being assessed as a monotherapy across four solid tumor types, with enrollment having been completed in the dose escalation portion of MacroGenics’ 125-patient Phase I study (NCT 03059823).

Data to Emerge Next Month

The study has an estimated primary completion date of December 2018. Data from the study’s dose escalation portion have been accepted for poster presentation at the Society for Immunotherapy of Cancer (SITC) 32nd Annual Meeting, to be held November 8–12 in National Harbor, MD.

MacroGenics’ pipeline of seven oncology candidates is led by margetuximab, an Fc-optimized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2).

Margetuximab is now the subject of the Phase III SOPHIA trial (NCT02492711) in patients with HER2+ metastatic breast cancer, comparing the candidate plus chemotherapy to Genentech (Roche)’s Herceptin® (trastuzumab). Margetuximab is also in Phase II study in gastric cancer.

The rest of Macrogenics’ oncology pipeline consists of MGA012 and five other Phase I candidates: enoblituzumab (MGA271; solid tumors), flotetuzumab (MGD006 or S80880; acute myeloid leukemia and myelodysplastic syndrome), MGD007 (colorectal cancer), MGD009 (solid tumors), and MGD013 (solid tumors and hematological malignancies).

Incyte agreed to pay MacroGenics $150 million upfront, up to $420 million in payments tied to achieving development and regulatory milestones, and up to $330 million tied to achieving commercial milestones. Should MGA012 be approved and commercialized, MacroGenics would be eligible to receive royalties, tiered from 15% to 24%, on future sales of MGA012 by Incyte.

Incyte will oversee global development of MGA012, with MacroGenics retaining rights to develop combinations of its pipeline candidates with MGA012. Commercialization rights for combination therapies would be split, with Incyte allowed to commercialize MGA012 and MacroGenics, any of its pipeline candidates used in such combos.

MacroGenics will also retain rights to manufacture a portion of both companies’ global clinical and commercial supply needs of MGA012—which the company plans to do at its commercial-scale GMP facility, expected to be fully operational in 2018.

The deal is expected to close in the fourth quarter of 2017, subject to early termination or expiration of any applicable waiting periods under the Hart–Scott–Rodino Act and customary closing conditions.

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