©2019 by Dogma Therapeutics

dogma

dȯg-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.

We have 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.

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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, the race was on to discover 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

Cute Happy Dog

Partner With Us

Bringing together a team of experienced and innovative drug developers who are ready to re-think what's possible is requisite to help patients get greater access to PCSK9-targeted therapy.  We are actively seeking clinical development partners who share our vision.