AstraZeneca and Orca Pharmaceuticals said today they will partner to develop retinoic acid–related orphan nuclear receptor gamma (RORg) inhibitors under a three-year collaboration designed to develop new treatments for a broad range of autoimmune diseases.
The development partnership could generate up to $122.5 million in upfront and milestone payments to Orca—and possibly more, since AstraZeneca has the option to acquire the Orca compounds at the end of the collaboration.
AstraZeneca will gain access to RORg inhibitors developed by Orca. Researchers from both companies will then identify lead compounds for progression into clinical study, as well as the autoimmune condition for which the lead compounds are best suited.
RORg helps convert CD4+T cells into T-helper 17 (TH17) cells that produce cytokines that drive immune response. Excessive activity of TH17 cells and other RORg t-specific (RORgt) immune cells, however, have been tied to autoimmune conditions that include inflammatory bowel disease, psoriasis, arthritis, and multiple sclerosis. Inhibiting RORgt cells offers an opportunity to restore normal TH17/T regulatory (“Treg”) balance and achieve selectivity in autoimmune disease treatment, Orca reasons.
Psoriasis is the indication for the lead program of Orca, which was established in 2013 to commercialize discoveries by Dan Littman, M.D., Ph.D., Jun Huh, Ph.D., and colleagues at New York University; Drs. Littman and Huh are among the company’s founders and advisors.
In addition to discovering the role of RORg in the development of TH17 cells, the NYU colleagues showed that RORγt activity can be inhibited by small molecule compounds that could be developed into drugs, and that these compounds were effective in animal models of autoimmune diseases.
Orca aims to achieve proof of concept in psoriasis with an orally available inhibitor in 2016. Among investors in Orca are BioMotiv, the for-profit accelerator aligned with the Harrington Project for Discovery & Development; and NYU Innovation Ventures.
Maarten Kraan, Ph.D., head of AstraZeneca’s respiratory, inflammation and autoimmune diseases innovative medicines unit, noted in a statement that respiratory, inflammation, and autoimmune diseases constituted one of the pharma giant’s three key therapeutic areas: “We are delighted to be partnering with Orca Pharmaceuticals in this hot area of immunology science to help us create potentially best-in-class chemical assets and candidate drugs for patients who currently do not have any oral medicines available to treat their chronic conditions.”