Dogma Therapeutics

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.