Scientific Core - Pharmacology and Drug Development

科学支持核心：药理学和药物开发 关键人员： 黛安·E Heck博士，核心联合总监;临床前疗效团队 劳伦M. Aleksunes，药学博士，博士，临床前科学组，临床前疗效，核心联合总监， ADME和毒理学团队 帕特里克辛科，R. Ph.，哲学博士、法规事务部ADME和毒理学焦点团队共同负责人 罗伯特·卡西利亚斯博士，临床前疗效重点团队共同负责人，转化为高级开发 朱尔斯·米切尔博士，法规事务团队翻译组总监 尼尔·西蒙博士高级药物开发团队翻译负责人 核心摘要/摘要 Rutgers CounterACT中心药理学和药物开发核心促进了 用于治疗由暴露于两种高优先级化学品引起的皮肤、角膜和肺损伤的治疗剂 威胁剂硫芥和氮芥这个核心一直与中心密切合作， 研究者识别、表征和优先考虑候选药物，评估毒理学特征， 的药物动力学特性，并确定最佳的药物输送方法，与 目的是生成数据，以支持研究性新药（IND）申请和临床试验。核心是 组织成四个重点团队，每个团队都履行对药物开发至关重要的特定职能：临床前 疗效、ADME和毒理学、法规事务和高级药物开发翻译。的 目前由核心协调的管道包括炎症靶点的调节剂，包括基质金属蛋白酶， 金属蛋白酶（多西环素）TNF α（抗TNF α抗体）和考克斯-2/胆碱酯酶（AIDNX，NDH 4338） 这将减少损伤和/或促进肺、角膜或皮肤在暴露于MUR后的愈合。药物 产品正在快速发展，有几个接近准备过渡到高级开发 包括临床研究。其中包括导致与FDA办公室进行IND前会议的药品 反恐和紧急协调工作人员（CTECS）和FDA药物评估中心 研究（CDER）。一种产品，Ekoni®（由Janssen销售的完全人源化抗TNF α抗体） 制药），已在巴尔达的资助下转向高级开发。与Appltum合作 在生物医学方面，核心还率先努力完善皮肤迷你猪模型，以进行高级开发 Silverlon®是一种烧伤敷料，最近已被FDA批准用于对抗芥末皮肤损伤。 核心与合同研究组织和制药公司以及联邦政府合作， 监管机构，以确保产品的及时和有效的进展。在这次更新申请中，我们建议 许多第一代药物产品（TNF α拮抗剂、多西环素和NSAID）的进展 前药）以获得监管批准。我们将继续完善标签的迷你猪模型 Silverlon®的扩展。这将是重要的其他皮肤对策的先进发展。 我们还将与Janssen Pharmceuticals合作，完善硫芥蒸汽吸入肺损伤模型。 管道中的其他化学实体继续作为第二代药品进行研究， 提高功效。随着该中心正在向一个 许多产品进入高级开发阶段，作为芥子气毒性的对策。

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.