CAMBRIDGE, Mass., Sept. 17, 2020 /PRNewswire/ -- Dogma Therapeutics ("Dogma") has reached an agreement for the acquisition of its oral PCSK9 program by AstraZeneca.  Dogma will receive upfront as well as downstream payments linked to global regulatory and commercial milestones.

​

The pursuit of a convenient, oral PCSK9-based therapy has been the singular focus of Dogma scientists for nearly a decade.  PCSK9 is widely considered the exemplary target accredited by human genetics, as variants found in humans establish the needed directionality of a therapeutic.  Both from a patient convenience standpoint and the potential for combination therapy, there is a need for widely-accessible oral therapies for the millions of people at risk for cardiovascular events.

Through a series of comprehensive hit-finding and validation efforts, the Dogma team discovered small molecules that directly bind to a novel binding pocket in PCSK9.  Dozens of high-resolution x-ray structures of Dogma inhibitors bound to PCSK9 allowed rapid optimization to picomolar affinity with exquisite physicochemical attributes and robust LDL-C lowering when dosed orally in preclinical models of hypercholesterolemia.

"We have built a robust data package that highlights the cholesterol-lowering and safety potential of our oral PCSK9 program," noted Dogma CEO Brian Hubbard, Ph.D.  "This agreement with AstraZeneca meets our strategic goal to accelerate access to patients unable to meet target LDL-C.  I would like to especially thank our scientific partners - Charles River Laboratories, Viva Biotech, Anji Pharmaceuticals, and our CRO partners - for their commitment to this project and their world-class problem solving."

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said: "Raised LDL cholesterol is a key risk factor for cardiovascular disease and is estimated to cause 2.6 million deaths worldwide every year. Whilst PCSK9 is a well validated target for lowering LDL cholesterol it has been a hugely challenging target to inhibit with small molecules. This agreement with Dogma Therapeutics offers us the opportunity to develop the first small molecule, orally bioavailable PCSK9 inhibitor, for patients at risk of cardiovascular disease."

Since inception, Dogma has developed a highly collaborative research model that leverages scientific expertise across the globe. This collaborative model was first created with Charles River, a leading, full-service drug discovery and early-stage development company, who, with its global, integrated drug discovery and safety assessment platform, has worked on 85% of drugs approved by the FDA in 2019. In tackling this previously considered 'small molecule undruggable' target, Charles River scientists and project leads contributed medicinal and computational chemistry, structural biology, biophysics, cell biology, ADME, and PK/PD expertise. "Charles River has played an integral role in the launch and progression of Dogma with their compelling drug discovery expertise and knowledge," noted Hubbard. 

"Our team is extremely proud to have worked closely with Dogma throughout the development of its oral PCSK9 inhibitor program," said Birgit Girshick, Executive Vice President, Discovery & Safety Assessment at Charles River. "This ground-breaking project could prove transformational in the management of hypercholesterolemia and cardiovascular disease."

​