Scientific Core - Pharmacology and Drug Development

科学支持核心：药理学和药物开发 主要人员： Diane E.Heck，博士，核心联合主任；临床前疗效团队 Lauren M.Aleksunes，Pharm.D.，Ph.D.，临床前科学组核心联席主任，临床前疗效， ADME和毒物学小组 帕特里克·辛科，R.Ph，博士，ADME和毒物学焦点小组联合负责人，监管事务 罗伯特·卡西利亚斯，博士，临床前疗效焦点团队联合负责人，向高级开发转化 朱尔斯·米切尔博士，法规事务团队翻译小组主任 尼尔·西蒙，博士，高级药物开发团队负责人 核心摘要/摘要 罗格斯中和中心药理学和药物开发核心促进了 治疗接触两种高优先级化学品所致皮肤、角膜和肺损伤的治疗方法 威胁物质硫磺芥末和氮芥末。这一核心一直与中心密切合作 调查人员对候选药物进行识别、表征和优先排序，评估毒理学特征，并 先导候选药物的药代动力学特性，并确定最佳给药途径，与 目的是生成数据以支持研究新药(IND)申请和临床试验。核心是 被组织成四个重点小组，每个小组服务于对药物开发至关重要的特定职能：临床前 药效、ADME和毒理学、管理事务和高级药物开发的翻译。这个 目前由Core协调的流水线包括炎症靶标的调节剂，包括基质 金属蛋白酶(多西环素)、肿瘤坏死因子α(抗肿瘤坏死因子α抗体)和COX-2/胆碱酯酶(AIDNX，NDH4338) 这将减少接触芥末后的损伤和/或促进肺、角膜或皮肤的愈合。药效 产品正在快速发展，有几个产品即将过渡到高级开发 包括临床研究。其中包括导致与FDA办公室召开IND前会议的药物产品 关于反恐和紧急协调人员(CTECs)和FDA的药物评价中心 和研究(CDER)。其中一种产品是Simponi®(由扬森销售的一种完全人源化的抗肿瘤坏死因子α抗体 PharmPharmticals)，已经在BARDA的资助下过渡到高级开发。使用阿根廷 在生物医学方面，Core还带头努力完善用于高级开发的真皮微型猪模型 Silverlon®是一种烧伤敷料，最近被FDA批准用于治疗芥末皮肤损伤。 与合同研究组织和制药公司以及联邦政府的核心伙伴 监管机构确保产品的及时和高效的进展。在此续期申请中，我们建议 一代药物(肿瘤坏死因子α拮抗剂、多西环素和非甾体抗炎药)的研究进展 前药)获得监管部门的批准。我们将继续改进用于标签的微型猪模型 Silverlon®的扩展。这将对进一步开发其他真皮治疗药物具有重要意义。 我们还将与Janssen Pharmceuticals合作改进硫磺芥末蒸气吸入肺损伤模型。 管道中的其他化学实体继续作为第二代药物产品进行调查 提高了疗效。预计在未来5年内，随着中心将 一些产品进入高级开发阶段，作为应对芥末毒性的对策。

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.