Dogma Therapeutics and AstraZeneca Enter Global Acquisition Agreement for Oral PCSK9 Inhibitor Program

VCBeat (WeChat ID: vcbeat) has learned that on September 17, 2020, Dogma Therapeutics (“Dogma”), a biopharmaceutical company incubated and invested in by Viva Biotech, reached an agreement with AstraZeneca for the acquisition of global rights to its oral PCSK9 program. AstraZeneca will pay Dogma an upfront payment, as well as milestone payments upon the achievement of global regulatory and commercial milestones.

The Dogma scientific team remains committed to developing a convenient, orally available PCSK9 inhibitor. Leveraging WuXi Biologics’ globally leading structure-based drug discovery platform, the Dogma team successfully optimized the affinity of their compounds for the PCSK9 protein to the picomolar range. Preclinical studies have demonstrated that multiple oral small-molecule inhibitors developed by Dogma significantly reduce LDL-C levels within weeks. Dr. Ye Zhixiong, Chief Scientific Officer at WuXi Biologics, stated, “Since investing in and incubating Dogma Therapeutics in 2017, WuXi Biologics has collaborated closely with the Dogma team on the PCSK9 project, which has been a highly valuable experience for our team. The successful development of an oral small-molecule PCSK9 inhibitor will greatly address the clinical needs of patients with cardiovascular disease.”

Following the rapid validation of the PCSK9 target through human genomics, two PCSK9 antibody drugs, Repatha and Praluent, have received FDA approval for market launch. In recent years, large-scale clinical trials have demonstrated that PCSK9 antibody therapies can reduce the risk of cardiovascular disease by 15–20%, establishing PCSK9 as the most reliable lipid-lowering drug target since statins. However, PCSK9 antibodies are associated with high costs and require administration via injection. Furthermore, the extensive binding interface between antibodies and PCSK9 poses significant challenges to the development of non-antibody inhibitors targeting this site. To date, only a few cases of small-molecule compounds that indirectly inhibit PCSK9 have been publicly reported.

Dr. Brian Hubbard, CEO of Dogma, stated, “The Dogma team has accumulated robust experimental data demonstrating the efficacy of our oral PCSK9 inhibitor program in lowering cholesterol, as well as its favorable potential safety profile. The acquisition agreement reached with AstraZeneca will accelerate the development of this program, bringing new treatment options to patients requiring low-density lipoprotein cholesterol reduction more rapidly. I would like to express my gratitude to Dogma’s scientific partners—Charles River Laboratories, Viva Biotech, Angiopharm, and other CRO partners. Their dedication to the project and world-class capabilities have been instrumental to Dogma’s success.”

Regarding this acquisition, Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated: “Elevated levels of low-density lipoprotein cholesterol (LDL-C) are a key risk factor for cardiovascular disease, causing approximately 2.6 million deaths worldwide each year. While PCSK9 has been validated as an effective target for lowering LDL-C levels, developing small-molecule inhibitors against PCSK9 remains highly challenging. This successful acquisition agreement with Dogma provides AstraZeneca with the opportunity to develop bioavailable, first-in-class oral small-molecule PCSK9 inhibitors, which are expected to reduce the incidence and severity of coronary artery disease in patients with hyperlipidemia.”

WuXi Biology’s mission is to become the cradle of global innovative biotechnology companies. The company has developed a highly scalable business model that combines the traditional Cash-for-Service (CFS) model with its proprietary Equity-for-Service (EFS) model. The Group’s CFS business provides world-leading structure-based drug discovery services for preclinical innovative drug development by global biotech and pharmaceutical clients. Its services cover the full spectrum of early-stage drug discovery needs, including target protein expression and structural studies, drug screening, lead compound optimization, and the identification of clinical candidates. The Group’s EFS business also provides drug discovery and incubation services to high-potential biotech startups worldwide.

As of June 30, 2020, Viva Biotech had provided drug discovery services to 495 biotechnology and pharmaceutical clients worldwide, studied over 1,300 independent drug targets, delivered more than 17,000 protein complex structures to clients, and invested in and incubated a total of 56 biopharmaceutical start-ups.

Dogma Therapeutics has discovered multiple orally bioavailable small-molecule PCSK9 inhibitors, which have been validated in multiple preclinical studies. Through high-resolution X-ray structural analysis, the Dogma team successfully optimized the affinity of the compounds for the PCSK9 protein to the picomolar level.