dogma
\ˈdȯg-məˈ\
noun - something held as an established opinion
Drugging the Undruggable
The pharmaceutical industry has struggled to identify small molecule inhibitors of PCSK9 function. This has been explained by the expansive but flat binding interface between PCSK9 and the LDL receptor, spanning nearly 800 square angstroms. To date, only monoclonal antibodies have been able to target this region of PCSK9.
Dogma Therapeutics has discovered bona fide small molecule inhibitors of PCSK9 function that are orally bioavailable across multiple preclinical species. Guided by dozens of high-resolution x-ray structures of our molecules bound to PCSK9, we have utilized structure-based design to achieve picomolar affinity.
Real World Validation of PCSK9
Proprotein convertase subtilisin/kexin type 9 (PCSK9) represents a complete illustration of how human genetics can guide target selection. Beginning with the discovery of a multi-generational family with familial hypercholesterolemia (FH) with no identifiable abnormalities in their LDL receptor (LDLR), a gain-of-function mutation in PCSK9 was discovered that increased serum cholesterol and caused cardiovascular disease. Subsequent studies identified individuals with loss-of-function mutations in PCSK9 with lower rates of coronary heart disease (CHD). A 32-year old woman who completely lacked functional PCSK9 had an LDL-C level of 14 mg/dL and was perfectly healthy. With this data, Dogma Therapeutics was launched to discover oral PCSK9 inhibitors that could mimic nature's experiment.
Our Team
Brian Hubbard
Chief Executive
Michael Serrano-Wu
Chief Scientist
Virendar Kaushik
Co-Founder
Doug Daniels
Co-Founder
Contact Us
Bringing together a team of experienced and innovative drug developers (ready to re-think what's possible) is requisite to help patients get greater access to PCSK9-targeted therapy. Reach out to us to learn more.