Scientific Core - Pharmacology and Drug Development

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Scientific Support Core: Pharmacology and Drug Development Key Personnel: Diane E. Heck, Ph.D., Core Co-Director; Preclinical Efficacy Team Lauren M. Aleksunes, Pharm.D., Ph.D., Core Co-Director, Preclinical Science Group, Preclinical Efficacy, ADME and Toxicology Team Patrick Sinko, R.Ph., Ph.D., Co-leader, ADME and Toxicology Focus Team, Regulatory Affairs Robert Casillas, Ph.D., Co-Leader, Preclinical Efficacy Focus Team, Translation to Advanced Development Jules Mitchel, Ph.D., Director, Translational Group, Regulatory Affairs Team Neal Simon, Ph.D., Leader, Translation to Advanced Drug Development Team Core Summary/Abstract The Rutgers CounterACT Center Pharmacology and Drug Development Core facilitates the development of therapeutics for treatment of skin, cornea and lung injury resulting from exposure to two high priority chemical threat agents, sulfur mustard and nitrogen mustard. This Core have been working closely with Center investigators to identify, characterize and prioritize drug candidates, evaluate the toxicological profile and pharmacokinetic properties of lead drug candidates, and determine optimal drug delivery approaches, with the aim of generating data to support Investigational New Drug (IND) applications and clinical trials. The Core is organized into four focus teams, each serving a specific function critical to drug development: Preclinical Efficacy, ADME and Toxicology, Regulatory Affairs, and Translation to Advanced Drug Development. The current pipeline coordinated by the Core includes modulators of inflammatory targets including matrix metalloproteinases (doxycycline) TNFα (anti-TNFα antibody), and COX-2/cholinesterase (AIDNX, NDH4338) that will reduce injury and/or promote healing of the lung, cornea, or skin following exposure to mustards. Drug products are rapidly progressing with several approaching readiness to transition to advanced development including clinical studies. These include drug products that have led to pre-IND meetings with the FDA office on Counter-Terrorism and Emergency Coordination Staff (CTECS) and the FDA’s Center for Drug Evaluation and Research (CDER). One product, Simponi® (a fully humanized anti-TNFα antibody marketed by Janssen Pharmaceuticals), has transitioned to advanced development with BARDA funding. Working with Argentum Biomedical, the Core has also spearheaded efforts refining a dermal minipig model for advanced development of Silverlon®, a burn dressing that has recently been approved by the FDA for use against mustard skin injury. The Core partners with contract research organizations and pharmaceutical companies, as well as federal regulators to ensure the timely and efficient progression of products. In this renewal application, we propose the advancement of a number of first generation drug products (TNFα antagonists, doxycycline, and an NSAID prodrug) towards regulatory approval. We will continue with refinement of the minipig model for label expansion of Silverlon®. This will be important for advanced development of other dermal countermeasures. We will also work with Janssen Pharmceuticals to refine a sulfur mustard vapor inhalation model of lung injury. Additional chemical entities in the pipeline continue to be investigated as second generation drug products with improved efficacy. Greater utilization of the Core is anticipated in the next 5 years as the Center is moving a number of products into advanced development as countermeasures for mustard toxicities.