Brian Cathers Email & Phone Number

Developing a new therapeutic mechanism - small molecules to selectively eliminate extracellular proteins

New York, New York, Us

South San Francisco, California, Us

Created industry leading pipeline focused on sickle cell disease (SCD). Expanded research capabilities to include translational science, genetics and multi-omics approaches to better understand our drugs and the phenotypic variability observed in SCD. Improved upon voxelotor (Oxbryta) with 10-fold more potent next-generation drug (GBT021601) and launched red cell health biomarker effort aimed at defining measurable and meaningful endpoints to improve the relevance, cost, speed and availability of tools used to assess severity or progression of disease and response to therapy.

Summit, New Jersey, Us

As the Co-Leader and Head of Drug Discovery for the Protein Homeostasis Thematic Center of Excellence, working with an amazing team, I created a pipeline of targeted protein degradation projects that led to multiple drugs currently in development (CC-92480 (mezigdomide, myeloma), CC-99282 (lymphoma), AR-LDD (PROTAC, prostate cancer), and CC-91633 (CK1alpha degrader, AML/MDS)).

Summit, New Jersey, Us

As Director of Biochemistry and later Sr. Director of Biochem and Structural Biol, I led a large group of scientists responsible for protein production and crystallography, enzymology, target validation, and the development of enzyme and cell assays in support of drug discovery efforts for all small molecule and antibody based project teams at the San Diego site. In 2011 the Cereblon Research Unit was formed within my department where I led the pioneering efforts in the field of molecular glue protein degraders. Following the association of cereblon (CRBN) with thalidomide by Hiroshi Handa’s group in 2010, my team uncovered that the mechanism of action of thalidomide and the IMiD drugs (lenalidomide/pomalidomide) was not due to inhibition of the CRBN E3 ligase but rather via recruitment and ubiquitin mediated degradation of non-native substrates aiolos and ikaros. Elucidating that neosubstrates were recruited to the IMiD-modified surface of cereblon led to the first crystal structure of a substrate bound E3 ligase, recognition of the novel structural degron substrate recognition element, an expansion of the spectrum of substrates that could be targeted beyond the Ikaros family, and the subsequent discovery and development of the first intentional molecular glue drug CC-90009 (targeting GSPT1). Senior Director, Biochemistry and Structural Biology Oct 2013 – Nov 2015Director, Biochemistry Mar 2011 – Oct 2013Associate Director, Molecular & Medical Sciences Jan 2008 – Mar 2011Group Leader, Lead Discovery Aug 2006 – Jan 2008Sr. Scientist II, Lead Discovery Mar 2006 – Aug 2006Sr. Scientist I, Lead Discovery Feb 2004 – Mar 2006

Built a very strong group at NewBiotics responsible for enzyme target discovery and validation, molecular modeling, drug/substrate design, assay development, enzyme and substrate characterization, protein purification, in vitro metabolism, and analytical chemistry/structure elucidation (LC and LC/MS) support for Medicinal Chemistry. Responsible for MOA studies as well as analytical method development and transfer to the fill-finish vendor for the drug substance, NB1011. Successful completion of a Phase I/II trial in colorectal cancer patients resulted in the acquisition of NewBiotics by Celmed Biosciences.

Us

Lead Enzymologist - Cathepsin S project in asthma/inflammation (partnered with Aventis Pharmaceuticals). - Successfully determined the mechanism of action for a problematic lead series and steered the project away from these false positives.Elucidated the mechanism of action of slow, tight binding inhibitors of cathepsin S and developed the experimental techniques to differentiate between potent, slow binding inhibitors and irreversible contaminantsLead Enzymologist - Histone Deacetylase as an anti-cancer target - Invented a high-throughput, fluorescence-based assay

Austin, Tx, Us

Mechanistic evaluation of dGTP analogues as selective telomerase substrates/inhibitorsDevelopment and evaluation of G-quadruplex DNA interactive molecules as anti-cancer agents.Development and validation of scientific technology and preparation of SBIR used to establish the biopharmaceutical company Cylene, San Diego, CA (initially Cyternex, San Antonio, TX).

Phd, Medicinal Chemistry

Bs, Chemistry, Minor In Mathematics