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: 10009653
• 负责人: Gabi Hanna
• 金额: $ 149.88万
• 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/10009653
• 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.

项目摘要/摘要 该提案寻求开发一种新型的急性胰腺炎治疗性，这是一个主要的未经元素质 没有有效治疗的医疗需求。我们的方法建立在临床和临床前数据的基础上 强烈暗示脂解和脂肪毒性是将轻度急性胰腺炎转化为的主要驱动因素 严重的急性胰腺炎，由持续器官衰竭定义。此外，这项工作得到了 数据表明，抑制脂肪酶活性可消除器官衰竭和全身指标 在严重急性胰腺炎的临床相关模型中发现的炎症反应综合征（SIRS）。我们的 作为一家公司的状态是，我们有一个铅化合物，该化合物已在初步安全研究中得到验证， 以及具有出色功效的多个临床前功效模型。我们进一步建立了一个专家团队 临床前和临床翻译研究，胰腺炎研究和治疗领域， 企业家精神，业务发展，药物合作伙伴和临床试验。我们的主要目标是 快速，有效且努力地通过翻译途径来促进这种疗法。鉴于我们的坚强 可行性数据，我们将其作为直接访问2的建议，这将使我们能够迅速迅速 有效地将这种化合物转发到临床试验中（该奖项结束时计划）。电流 将这种治疗方法转移到临床试验中的差距是完成提交所需的安全研究 研究新药（IND）应用。因此，下一阶段的发展是完成索引 启用安全研究。该提案的目标是完成以下特定目的： AIM 1：全剂量范围发现，ADME，体外安全性和7天的毒性和毒性（TK）（TK） 研究。 1年里程碑：1）完成剂量范围发现，ADME，遗传毒理学，7天的毒性和 有毒动力学研究，2）完成预性提交和预定时间的会议。 目标2：完整的体内毒理学和安全药理学研究。 2年里程碑：1）完成 GLP毒理学和安全药理学研究，2）IND提交。 该提案完成时，我们将拥有一个订立，经验丰富的和经验丰富的资产 成功的临床开发团队准备通过临床试验进行。