Development of a novel lipase inhibitor for the treatment of acute pancreatitis

治疗急性胰腺炎的新型脂肪酶抑制剂的研制

• 批准号: 10210392
• 负责人: Gabi Hanna
• 金额: $ 7.84万
• 依托单位: LAMASSU PHARMA INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-07 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10210392
• 关键词: Academia; Adipose tissue; Agreement; Animal Experimentation; Animal Model; Automobile Driving; Award; Businesses; Cardiovascular system; Cessation of life; Clinical; Clinical Research; Clinical Trials; Collection; Data; Development; Disease; Disease Progression; Dose; Emergency department visit; Entrepreneurship; Etiology; Failure; Foundations; Goals; Hospitalization; Hypertriglyceridemia; In Vitro; Investigational Drugs; Investigational New Drug Application; Kidney; Laboratories; Lead; Light; Lipase; Lipolysis; Liquid substance; Lung; Medical; Modeling; Necrosis; Organ failure; Pancreatitis; Pathway interactions; Patients; Pharmacologic Substance; Pharmacology Study; Phase; Production; Prognostic Marker; Research; Risk; Safety; Scientist; Seminal; Severities; Severity of illness; Source; Systemic Inflammatory Response Syndrome; Toxic effect; Toxicogenetics; Toxicokinetics; Toxicology; Translational Research; Translations; Triglycerides; United States; Visceral; Work; acute pancreatitis; clinical development; clinical efficacy; clinically relevant; commercialization; data modeling; effective therapy; efficacy study; experience; gastrointestinal; in vivo; inhibitor/antagonist; innovation; meetings; novel; novel therapeutic intervention; novel therapeutics; pre-clinical; preclinical efficacy; prevent; programs; safety study; systemic toxicity; therapeutic lead compound; tissue injury

Project summary/abstract This proposal seeks the development of a novel therapeutic for acute pancreatitis, which is a major unmet medical need with no effective treatment. Our approach builds upon a body of clinical and preclinical data that strongly implicate lipolysis and lipotoxicity as major driving factors in converting mild acute pancreatitis to severe acute pancreatitis, which is defined by sustained organ failure. In addition, this work is supported by data demonstrating that inhibition of lipase activity abrogates the organ failure and indicators of systemic inflammatory response syndrome (SIRS) found in clinically relevant models of severe acute pancreatitis. Our status as a company is that we have a lead compound that has been validated in preliminary safety studies, and multiple preclinical efficacy models with outstanding efficacy. We further have in place an expert team in the fields of preclinical and clinical translational research, pancreatitis research and treatment, entrepreneurship, business development, pharmaceutical partnering, and clinical trials. Our primary goal is to rapidly, efficiently, and diligently advance this therapy through the translational pathway. In light of our strong feasibility data, we are submitting this as a Direct-to-Phase 2 proposal, which will allow us to most rapidly and efficiently move this compound forward into clinical trials (planned at the conclusion of this award). The current gap in moving this treatment into clinical trials is to complete the safety studies needed to submit an investigational new drug (IND) application. As such, the next phase of development is to complete the IND- enabling safety studies. The objectives of this proposal are the completion of the following specific aims: Aim 1: Complete dose range finding, ADME, in vitro safety and 7-day toxicity and toxicokinetics (TK) studies. Year 1 milestones: 1) completion of dose range finding, ADME, genetic toxicology, 7-day toxicity and toxicokinetic studies, 2) completion of pre-IND submission and pre-IND meeting. Aim 2: Complete in vivo toxicology and safety pharmacology studies. Year 2 milestones: 1) completion of GLP toxicology and safety pharmacology studies, 2) IND submission. At the completion of this proposal, we will have an IND-ready asset, with a committed, experienced, and successful clinical development team ready to take it through clinical trials.

项目概要/摘要 该提案寻求开发一种治疗急性胰腺炎的新疗法，这是一个重大未满足的问题 需要医疗但没有有效的治疗方法。我们的方法建立在大量临床和临床前数据的基础上 强烈表明脂肪分解和脂毒性是轻度急性胰腺炎转变为主要驱动因素 重症急性胰腺炎，其定义为持续的器官衰竭。此外，这项工作得到了支持 数据表明，脂肪酶活性的抑制消除了器官衰竭和全身性指标 在重症急性胰腺炎的临床相关模型中发现炎症反应综合征（SIRS）。我们的 作为一家公司，我们拥有一种已在初步安全研究中得到验证的先导化合物， 以及多个临床前疗效模型，疗效突出。我们还组建了一个专家团队 临床前和临床转化研究、胰腺炎研究和治疗领域， 创业、业务发展、制药合作和临床试验。我们的首要目标是 通过转化途径快速、有效、勤奋地推进这种疗法。鉴于我们的实力 可行性数据，我们将其作为直接进入第二阶段的提案提交，这将使我们能够最快速、最 有效地将这种化合物推进临床试验（计划在该奖项结束时进行）。目前的 将这种治疗方法纳入临床试验的差距是完成提交临床试验所需的安全性研究 研究性新药（IND）申请。因此，下一阶段的开发是完成 IND- 开展安全研究。本提案的目标是完成以下具体目标： 目标 1：完整的剂量范围发现、ADME、体外安全性以及 7 天毒性和毒代动力学 (TK) 研究。第 1 年里程碑：1) 完成剂量范围查找、ADME、遗传毒理学、7 天毒性和 毒代动力学研究，2) 完成预 IND 提交和预 IND 会议。 目标2：完成体内毒理学和安全药理学研究。第 2 年里程碑：1) 完成 GLP毒理学和安全药理学研究，2）IND提交。 完成该提案后，我们将拥有可进行 IND 准备的资产，并拥有忠诚、经验丰富且 成功的临床开发团队已准备好进行临床试验。