NuPeak Therapeutics, Inc. — Department of Health and Human Services STTR Phase I: NHLBI

Description

Abstract NuPeak Therapeutics Incis a biotechnology companyC corporationdesigned to deliver a first in class smallmolecule kinase inhibitorSMKIfor therapeutic use in humansThe present Project is aimed at an inhibitor for treatment of respiratory airway disease especially due to asthma and COPDwhich remain leading causes of morbidity and mortality in the U Sand worldwide despite current therapeutic approachesMoreoverthere is growing recognition that these diseases are linked to obstruction of the airways with inflammatory mucusIn that contextwe identified a novel typeimmune response that activates mitogen activated protein kinaseMAPKto drive airway progenitor epithelial cellsAPECsto mucous cells in cell and animal modelsThis mechanism was validated in patients with excess mucus production due to asthma and COPD by our lab and by otherssuggesting the therapeutic benefit of a MAPKor combined MAPKinhibitor that also blocks the conventional immune responseHoweverto our knowledgeno MAPKor MAPKinhibitors are yet availableAccordinglywe obtained the first x ray crystal structure of MAPKand used structure based drug design to develop the first MAPKinhibitorsPreliminary Studies define proprietary chemical analogs that form the basis for our approved and pending patents for MAPKand MAPKinhibitors and uses thereofAmong these compoundswe identify a lead Compoundwith highly favorable qualities for enzyme inhibitionMAPKICnMMAPKICnMbinding mechanismDFG outand kineticsslow Kon and Koff and low KDxMkinome selectivityand physical chemical propertiesMoreoverCompoundeffectively and safely blocks ILstimulated inflammatory mucinMUC ACproduction at low nontoxic concentrationsICnMcell therapeutic indexin primary culture human airway epithelial cellsFurtherCompoundexhibits excellent microsomal stability and cell permeability in vitro and pharmacokinetic characteristics in vivo for oral dosingIn additionCompoundsafely attenuates inflammatory mucus production after ILchallenge in a pig in vivo model and after respiratory viral infection in pig and mouse in vivo modelsThuswe propose a Phase I STTR program for investigators at NuPeak and Washington University to advance Compoundto the next phase of pharmacology and toxicology testingAimand ChemistryManufacturingand ControlCMCinformationAimneeded for IND publicationNuPeak will operate with the entrepreneurial resources of the BioGenerator venture fund and a quick start license from Washington University under patents that cover the synthesis and use of MAPKand MAPKinhibitorsincluding Compoundand back ups such as CompoundThe commercialization strategy will be based on establishing initial pharmacology toxicology and chemistry manufacturing controlCMCinformation in PhaseSTTRthen final testingIND publicationand Phasesafety clinical trials in healthy humans in PhaseSTTRand then more advanced clinical trials and FDA approval in PhaseSTTR Relevance Excess airway mucus production is one of the most common maladies of mankindand the condition may be life threatening for patients with chronic lower respiratory diseases such as asthma and chronic obstructive pulmonary diseaseCOPDAt presentthere are no specific and effective drugs to control excess airway mucus productionThe proposed development of an anti mucus drug will thereby address an unmet need for a major public health problem