Theraly Fibrosis, Inc — Department of Health and Human Services SBIR Phase I: 150

Description

Project Summary The goal of this project is to advance a new treatmentTLYas the firstdisease modifying agent that addresses two critical physiological and pathological features of chronic pancreatitisCPfibrosis and severe painCP is a progressive inflammatory disorder of the pancreaspredominantly caused by alcohol abuseCP leads to pancreatic fibrosis and eventually irreversible destruction of the pancreas structure and functionAlcohol related CP patients suffer from severe abdominal pain and increased risk of pancreatic cancer and diabetesHoweverthere are no therapeutic agents that either address CP progression or eliminate recurrent pain associated with CPresulting in a significantly underserved patient populationTLYis a long actingPEGylated recombinant human TRAIL that selectively eradicates activated pancreatic stellate cellsaPaSCthe key mediators of CP that induce fibrosis and painwhile leaving normal cells unharmedIn our preclinical studieswe found that systemically administered TLYto alcohol induced CP rat models simultaneously ameliorated pancreatic fibrosis and CP associated pain as well as restored pancreatic function without causing any toxicityThe key objectives of the project involve the translation of TLYfrom the research stage to completion of an IND application to the FDAIn the first phase of the projectPhase Imanufacturing of TLYfor pre clinical developmentwill include optimization and scale up of the existing manufacturing process to produce sufficient amount of TLYmaterialIn additionconfirmatory pharmacology studies using the newly produced TLYin an alcohol induced CP model and an initial toxicity assessment will be completed in rodents and non human primates in order to enable further safety testing in GLP toxicology studiesThe effects of alcohol on the pharmacokineticsPKof TLYin vivo will also be investigatedAssay development for PK and antidrug antibodiesADAtesting will be done to support sample analysis from PKpharmacology and toxicity as well as formulation stability studiesIn the second phase of the projectPhase IIcGMP TLYwill be produced using the final production methods for additional testing in GLP toxicity and future use in Phaseclinical studiesThis will include technical transfer of the scaled process to qualified manufacturing sitewith subsequent manufacturing of clinical materialLong term stability testing and clinical formulation development will also be initiatedOnce TLYis producedthe final IND enabling GLP toxicology studiessub chronic and chronicin rodents and non human primates will be completeda clinical protocol will be createdAt appropriate stages of this projectrequests will be filed for early advisory meetings with FDA to seek advice on adjustments to development strategyAs the final outcome of aforementioned studies an IND application will be filed to enable Phaseclinical studies in patients with alcohol induced CPUpon completion of project be successfula highly innovative new drugTLwill be ready for entry into clinical trials