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.
Acute pancreatitis is a major unmet medical need in the United States, resulting in over 250,000 hospital admissions per year with no available treatment. We propose development of a new treatment approach that will mitigate the systemic toxicity and organ failure that causes lengthy hospitalization, organ failure, and death.
