Today
Kalytera forms scientific advisory board
2021-03-08 10:22 ET - News Release
Mr. Robert Farrell reports
CLARITAS ANNOUNCES FORMATION OF NITRIC OXIDE SCIENTIFIC ADVISORY BOARD
Claritas Pharmaceuticals Inc. (formerly Kalytera Therapeutics Inc.) has formed a scientific advisory board that will work closely with Claritas's management team to develop nitric-oxide-based therapeutics to treat diseases and disorders with significant unmet medical need. The SAB will be led by Dr. Garry J. Southan, an internationally renowned expert in the biology, biochemistry, and chemistry of nitric oxide.
A synthetic chemist by training, Dr. Southan has an extensive experience and publication record in nitric oxide synthase (NOS) and in the chemistry of NOS inhibitors, nitric oxide adducts, and nitric oxide donor compounds. He has successfully identified, synthesized, and characterized a wide variety of novel NOS inhibitors as well as nitric oxide donor compounds. He is also the author of invited reviews and more than 100 peer-reviewed scientific publications and 25 patents, and an invited speaker at international meetings on the topic of NOS inhibitors and nitric oxide donors.
For his post-doctoral studies, Dr. Southan spent 3 years with the Nobel Laureate Sir John R. Vane, FRS at the William Harvey Research Institute in London, England to study the biochemistry of nitric oxide and nitric oxide synthases. Dr. Southan worked with Sir John Vane at the time when interest in nitric oxide as a vascular mediator was developing. As the only recognized chemist in the William Harvey Research Institute, he was required to explain why certain compounds prolonged the effects of "endothelial derived relaxing factor" (EDRF) on ex-vivo tissues. In the course of these studies, he showed that EDRF is in fact nitric oxide, and, subsequently, that nitric oxide associated with these hydroxyguanidine compounds to stabilize its activity. While investigating this interaction, he isolated and ultimately characterized a novel class of resonance-stabilized compounds formed by the reaction of nitric oxide and nitric oxide-related species with hydroxyguanidines. These compounds decompose in solution to release nitric oxide and nitrous oxide. Nitric oxide is produced in vivo by the NOS family of enzymes. Using 15N labeled substrates and high-resolution mass-spectrometry, he was able to confirm that nitric oxide synthase utilizes the hydroxylated guanidino nitrogen of N-hydroxyarginine for the generation of nitric oxide. At the same time, he discovered novel classes of inhibitors of nitric oxide synthase and nitric oxide generation, which had beneficial effects in models of inflammation and ischemic/reperfusion disease.
Dr. Southan's studies on nitric oxide synthase inhibitors continued when he was invited to help establish a research laboratory in the Division of Critical Care at the Children's Hospital in Cincinnati, Ohio. His work there focused on finding therapies for some of the more intractable diseases and infections in the pediatric intensive care unit based on novel inhibitors that were selective for the inducible NOS isoform (iNOS). Many of the inhibitors he discovered were made available to the research community and were used in the study of the physiological and pharmacological actions of nitric oxide. Hundreds of articles have been published using his isothiourea-based inhibitors alone.
Dr. Southan later worked at the National Cancer Institute in the laboratory of Larry Keefer, a leading group in the development of novel nitric oxide adducts. In addition, he studied other forms of nitric oxide and its downstream biological products in order to find deactivators of reactive oxygen/nitrogen species such as superoxide, peroxynitrite and nitroxyl.
Following his research at the National Cancer Institute, Dr. Southan co-founded Inotek Pharmaceuticals Corporation, where his initial responsibility was to provide novel pharmacological tools for the study of inflammatory, reperfusion and related diseases. His basic research on poly(ADP-ribose) polymerase ("PARP") inhibitors led to development of several clinical compound candidates. Six of his compounds, targeting different mechanisms, were taken through the investigational new drug (IND) process and into clinical trials. He was responsible for the pre-clinical chemistry and provision of GMP materials for the clinical trials. One of these compounds (INO-1001) was the first PARP inhibitor to enter clinical trials and was subsequently licensed to Genentech for $600 million in 2006.
Dr. Southan then took a position at Radikal Therapeutics for 12 years, as Senior Vice-President of Research, where he led the analytical and bioanalytical chemistry divisions. During this time, he was responsible, in conjunction with Dr. Prakash Jagtap, for the invention of R-107, a novel nitric oxide donor and peroxynitrite decomposition catalyst, as well as other new chemical entities regulating diseases involved with vascular tone, inflammation, and reactive oxygen species. Dr. Southan was awarded numerous grants and contracts to study and develop R-107, supported initially by the National Institutes of Health and later by the Biomedical Advanced Research and Development Authority (BARDA).
Upon the licensing of the R-107 COVID-19 program to Claritas Pharmaceuticals, Dr. Southan became an independent consultant to the pharmaceutical industry where he brings three decades of experience in drug discovery and development in the field of nitric oxide and free radical biochemistry.
"The scientific guidance of Dr. Southan will be invaluable as we focus on bringing nitric oxide therapies into the clinic for the benefit of patients," stated Robert Farrell, President and CEO of Claritas. "The potential of nitric oxide in various disease settings has been extensively validated in multiple small and large animal studies. Nevertheless, the use of nitric oxide has been limited due to the fact that it is a gas that is difficult and impractical to adminsiter. We are excited to work with this world-class expert in nitric oxide pharmacology as we move forward with R-107 to transform nitric oxide therapy into a practical and easily administered treatment for multiple diseases and disorders."