Unleashing the synergistic potential of HDAC inhibitors and targeted therapies requires an intimate understanding of the molecular interactions of HDACs with their co-repressors and their effect on signaling pathways. The founders of Syndax have dedicated their careers to elucidating these or related mechanisms and have extensive experience in translating bench science into commercial potential.
Dr. Evans is Professor in the Gene Expression Laboratory and March of Dimes Chair in Molecular and Developmental Biology at the Salk Institute for Biological Studies in La Jolla, California. Dr. Evans is an authority on hormones, both their normal activities and their roles in disease.
A major achievement in Evans’ lab was the discovery of a large family of receptors that respond to various steroids, vitamins A and D, and thyroid hormones. Molecular and genetic analysis of the nuclear hormone receptor family carried out in the Evans lab has also uncovered the molecular mechanism for receptor-regulated gene expression, leading to the identification of several novel enzyme cofactors, including histone deacetylases, histone acetyltransferases, and methyltransferases.
Dr. Evans is a member of the Institute of Medicine, the National Academy of Sciences, and the American Academy of Arts and Sciences. He is an investigator of the Howard Hughes Medical Institute and winner of the 2004 Albert Lasker Award for Basic Medical Research. In addition to Syndax Pharmaceuticals, Dr. Evans has been a cofounder of several companies, including Ligand Pharmaceuticals, X-Ceptor, and Xenopharm, while serving on the scientific advisory board of a number of biotechnology companies. He received his BA in Bacteriology from University of California–Los Angeles and his PhD in Microbiology and Immunology from UCLA; he was a postdoctoral fellow at Rockefeller University.
Dr. Ordentlich is Director of Scientific Affairs and Strategic Relations at Syndax with responsibility for the scientific rationale and direction of nonclinical efforts related to the company’s projects.
Prior to cofounding and joining Syndax, Dr. Ordentlich was a scientist at the Salk Institute in La Jolla, California, working with Dr. Ronald M. Evans to identify small molecules as potential therapeutics and evaluating synergistic combinations of histone deacetylase inhibitors and nuclear receptor ligands.
Dr. Ordentlich spent five years at X-Ceptor Therapeutics, a drug discovery company focused on the identification and therapeutic application of novel and selective modulators of nuclear hormone receptors, where he led a group in assay development, high-throughput screening, and lead optimization.
Dr. Ordentlich did his postdoctoral fellowship with Dr. Ronald M. Evans, investigating the molecular mechanisms involved in nuclear hormone receptor signaling. His work, along with that of Dr. Michael Downes and other members of the Evans laboratory, led to the identification and characterization of several proteins involved in nuclear receptor regulation including histone deacetylases 5 and 7 (HDAC5 and HDAC7) and novel isoforms of the co-repressors SMRT and SHARP.
Dr. Ordentlich received his BA in Biochemistry and PhD in Immunology from the University of Pennsylvania.
Dr. Downes is a Staff Scientist in the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California. Dr. Downes has extensive experience spanning over 14 years of research in the nuclear receptor field. Early work centered on understanding the roles of nuclear hormone receptors (NHRs) in muscle differentiation and progressed to studying the molecular mechanism of NHR-mediated repression.
Dr. Downes, in conjunction with Dr. Peter Ordentlich, isolated the first novel full-length clones of the co-repressor SMRT and an RNA-binding co-repressor associating factor, termed SHARP. Subsequent characterization of these co-repressors led to the identification of HDAC5 and HDAC7.
Dr. Downes recently developed a novel chemical tool, termed fexaramine, as a specific agonist of the bile acid receptor FXR. The development of fexaramine allowed the determination of the first structure of the active conformation of the receptor, providing insight into the interactions of the natural low-affinity bile acid ligands.
Dr. Downes received his PhD in Biochemistry at the University of Queensland, Australia.
Richard Heyman is Senior Vice President of Drug Discovery at Kalypsys, Inc. In 1999, he co-founded X-Ceptor Therapeutics, a drug discovery company that focused on the identification of new therapeutic agents targeting nuclear receptors for the treatment of metabolic diseases. He was Chief Scientific Officer and Senior Vice President of Research at X-Ceptor, and on acquisition of that company by Exelixis in 2004, he was appointed Senior Vice President of Metabolic Diseases and site head for the San Diego research site.
Prior to founding X-Ceptor, Dr. Heyman held the position of Vice President of Nuclear Receptor Discovery at Ligand Pharmaceuticals and was responsible for multiple-drug- discovery- programs, including the successful discovery and development of Panretin (alitretinoin) and Targretin (bexarotene), retinoids approved for the treatment of cancer.
Dr. Heyman has more than a dozen issued patents and has coauthored over 100 scientific publications. He received his BS in Chemistry from the University of Connecticut and his PhD in Pharmacology from the University of Minnesota.
Dr. Weber joined Domain in 2001 as a partner, where he specializes in creating companies around promising new pharmaceutical products. He has been the founding CEO of multiple biopharmaceutical companies in the Domain portfolio, including Acea Pharmaceuticals, Ascenta Therapeutics, Calixa Therapeutics, Cytovia, Domain Antibacterial Acquisition Corporation, NovaCardia, Novacea, Novalar Pharmaceuticals, Ocera Therapeutics, Orexigen Therapeutics, Sonexa Therapeutics, Syndax Pharmaceuticals, Tobira Therapeutics, and Tragara Pharmaceuticals. He currently serves as interim CEO of Calixa Therapeutics and Sonexa Therapeutics, two seed-stage biopharmaceutical companies.
He is Chairman of the Board at Ascenta Therapeutics, Ocera Therapeutics, Orexigen Therapeutics, Sequel Pharmaceuticals, Syndax Pharmaceuticals, and Tobira Therapeutics. He was Chairman of Peninsula Pharmaceuticals until the company was sold to Johnson & Johnson in 2005, Chairman of Cerexa until the company was sold to Forest Laboratories in January 2007, Chairman of NovaCardia until the company was sold to Merck in September 2007, and a board member of Conforma Therapeutics and Cabrellis Pharmaceuticals until they were sold to Biogen-IDEC and Pharmion, respectively. In addition, he is a board member of BioVascular and DiObex.
Until 1995, Mr. Weber was a tenured Professor of Pharmacology at the University of California at Irvine. He has over 20 years of drug discovery and development experience and has been a consultant to biotechnology and pharmaceutical companies. He is the inventor or co-inventor of over 40 patents and patent applications, and he has published over 130 papers in scientific journals.
