J. Guy Breitenbucher, PhD
Organic Chemist by training with 26 years managing drug discovery projects resulting 14 compounds entering clinical trials.
Skills
About
Drug discovery leader with 27 years of experience successfully managing drug discovery and development projects from concept to clinic. My project experience spans a wide range of target classes (Kinases, GPCR’s, PPIs, PDEs, Ion Channels, Enzymes) and indications with 14 compounds entering clinical trials. My primary therapeutic focus in the last 15 years has been CNS and pain. I specialize in solving complex drug discovery problems common in lead optimization and drug development, including issues with; formulations, DMPK, structure biology, pharmacology, biomarkers, IP, and safety. I pride myself on having an excellent eye for compounds which overcome key project challenges. Although I specialize in direct hands-on project management of drug discovery, I also have experience with scientific diligence and licensing, portfolio management, outsourcing management, and team building.
Work experience
Director of Pain Chemistry
Led Pain drug discovery chemistry for J&Js San Diego research facility. Managed a team of 12 chemists on 8 different projects focused on pain and inflammation across a number of target types (ion channels, GPCRs, kinases, protease/hydrolases). Delivered 7 compounds into clinical development.
Head of Discovery Chemistry
Built, mentored, and managed department of 53 scientists and technicians across 9 drug discovery projects. Delivered 5 clinical compounds focused on a variety of CNS indications. Managed all aspects of drug discovery chemistry from Lead identification through early CMC.
VP Chemistry
Led a $300 M joint research collaboration between Convelo and Genentech to discover small molecule drugs which facilitate remyelination for the treatment of MS. Managed chemistry, DMPK and preclinical studies at external CROs and coordinated project activities with Genentech and Convelo teams.
Education
California State University, Long Beach
UC Riverside
UC Berkeley
Publications
Case STUDIES
PDE1 inhibitors for the Treatment of PD
The PDE1 program at Dart Neuroscience was originated from genetic studies which supported PDE1's role in memory and cognition. The program progressed from HTS screening and a significant structure biology effort to preclinical development in record time (18 months from screen to candidate). The program was beset with a number of safety and PK/PD issues which were expertly solved by the project team resulting in the first PDE1 clinical candidate which reached Phase II development for Parkinson's MCI.
FAAH Inhibitors for the Treatment of PTSD
I led the Fatty Acid Amide Hydrolase (FAAH) project within Janssens CNS/Pain franchise. I put together and managed the original collaboration between labs at Scripps Research Institute and Janssen. This led to a 3 year drug discovery project resulting in the discovery and development of JNJ5279. This compound was developed for PTSD and reached Phase III clinical development. We worked through many issues along the way including: PK/PD using ABPP techniques for evaluation of selectivity. Structure biology investigations into covalent binding. Development of a PET ligand for clinical POM. Multiple issues with IP in a crowded chemical space. I found this to be one of the most satisfying programs I have worked on because of the number of scientific challenges and because of the ultimate clinical success of the program.
Remyelination Stimulators
Initially as a consult and later as VP chemistry I worked with the Convelo biology team to develop compounds which inhibited the steroid synthesis pathway through the inhibition of the enzyme EBP. Inhibition of EBP resulted in robust enhancement of remyelination in OPCs and in animal models. We were able to take these findings and form a $300 M collaboration with Genentech to further develop these compounds to pre-clinical candidates. I managed the external chemistry, DMPK and IP estate as well as managing the project collaboration activities. We worked through a number of chemistry, PK/PD, DMPK and safety issues along the way to the development of viable candidates.
