Bioorganic chemist by training with 30+ years experience in big and small pharma. Expertise in drug discovery including both FBLD and DEL, cheminfomatics, new technology development, library design and medicinal chemistry from screen to clinic.
I have more than 30 years of direct experience in developing small molecule therapeutics in the pharmaceutical industry. I have discovered and optimized numerous small molecules for therapeutic targets including ion channel modulators, transport inhibitors, GPCR agonists and antagonists, and many kinase inhibitors. I am an inventor on over 20 patents for a variety of targets and indications.
I have led drug discovery projects from compound hit identification to IND and first-in patient (FIP) with one of the resulting drugs, elagolix, recently approved by the FDA. I have managed collaborative programs for a variety of indications including neuropathic pain, anxiety, hormone dependent and independent prostate cancer, multiple myeloma and rare lysosomal storage diseases. I have worked with CADD software in structurally enabled discovery projects for more than 10 years and have used commercial packages to successfully invent lead compounds starting when the software was first commercialized. I have invented nanomolar potency lead compounds using fragment based lead discovery (FBLD) and solid phase DNA encoded libraries. I have been written government grants for multiple agencies, mostly in the US. To date, four of my US SBIR grants have been funded by NIH.
In summary, I have a demonstrated record of successful and productive research in the biopharmaceutical industry discovering and developing drugs with a wide range of target mechanisms. I have made substantial progress on extremely difficult projects including those without a known target, those without any previous compound knowledge, those with unusual readouts and those with extremely slow assay cycles. I prefer collaborative environments with cross-functional teams and have made inventive contributions in nearly every project I have been involved in. I have worked as the only chemist in a company setting, have managed both internal and external chemistry resources and am always ready to engage my colleagues in other disciplines to explain my particular challenges in an active program.
Chemistry lead for multiple projects including two that went into humans. Helped select elagolix as a development candidate; that compound was approved in the US in 2018.
Responsible for hit-to-lead activities involving 1959’s screening platform, a combination of solid phase synthesis using DNA encoding with a microfluidics activity based assay. Developed and supervised new DNA friendly chemistry, generated advanced library designs, was chemistry leader for company collaborations with 1859's clients.
Provide consulting services for drug discovery clients including invention of novel compounds, medicinal chemistry, grant writing, cheminformatics and technology review.
While at Bioblocks, a San Diego based CRO, I collaborated with one of our clients to develop a series of lead compounds for a non-standard drug target. In two years, we went from weak screening hits with poor pharmaceutical properties to high potency compounds with cell activity and a successful in vivo proof of concept study. The lead compound was accepted for development by the Multiple Myeloma Foundation. During the project, the actual target of the active compounds was in question and the site of action was unknown. I participated in modeling studies that proposed a binding site on the likely target and a mode of action that was subsequently proved by X-ray crystallography. Details of some of the lead compounds have been published in a peer-reviewed journal, including crystal structures (PDB 4PL3, 4PL4, 4PL5) of advanced compounds. Doi: 10.1038/ncomms5202.
At Neurocrine Biosciences, I directed a program exploring selective norepinephrine reuptake inhibitors (sNRI) for neuropathic pain. In two years, we went from initial concept to phase I trial. Although compounds in this drug class had been known for 30 years, we applied modern drug discovery principles to generate high quality clinical compounds, with better stability and fewer metabolic issues than previous candidates from several companies. The first compound met its target profile in Phase 1. This work has been published in a series of papers culminating in doi: 10.1016/j.bmcl.2008.10.013.