SBIR/STTR Award attributes
ABSTRACT Alzheimerandapos s diseaseADis one of the largest global public health crises facing us todayyet there are no effective therapies available to preventdelayor slow AD progressionDominant approaches based on a set of prevailing core hypotheses about druggable pathways and targets have failedThereforethere is a need for novel and alternative pathways distinct from those pursued over the past two decadesOur strategy is to target a particular form of dysregulated neuroinflammationinjurious proinflammatory cytokine overproduction that is a key contributor to synaptic dysfunctionneurodegeneration and cognitive decline in diverse neurodegenerative diseasesWe seek Fast Track SBIR funding for a first in humanFIHstudy of MWSRMMWa novelCNS penetrantorally bioavailablesmall molecule drug candidate that selectively suppresses stressorinduced proinflammatory cytokine overproductionMWameliorates synaptic damage and cognitive impairment at low doses in diverse animal models where proinflammatory cytokine dysregulation is established as a contributor to neurologic injury or susceptibility to neurologic injuryMWis chemically and metabolically stabilehas no liabilities in investigational new drugINDenabling safety pharmacology and toxicology screens following ICH FDA guidanceThese include respiratory and cardiovascular safety pharmacology screensrat and dogday repeat administration toxicology studiesand genotox analysesFurthera MWanalog developed for the more demanding i vroute of administration has been substantially de risked in a phaseb clinical trialOverallMWis a highly de risked and promising candidate for clinical development as an oral formulation for the treatment of AD or related disordersAimPrepare regulatory and other processes for a FIH SAD trialThe tasks include preparation and regulatory approval of required clinical trial documentsand the validation of methods for measurement of MWin human plasmaAimConduct a single ascending doseSADphasea trial of MWThe SAD study will determine safety and tolerability and maximum tolerated dose of MWas well as its pharmacokineticPKprofile in a SAD paradigm in healthy adult volunteersPlasma cytokine levels will be measured to provide baseline data for a future exploratory pharmacodynamicPDendpoint in phaseba clinical trialsAimPrepare regulatory and other processes for a multiple ascending doseMADphaseb trialWe will design a multiple ascending doseMADclinical study of MWin healthy volunteersincluding a cohort of elderly healthy subjectsThis project will advance clinical development of a promising drug candidate that could have disease modifying effects not only in AD but also in a number of other CNS disorders where proinflammatory cytokine dysregulation is part of the pathophysiology progression mechanism NARRATIVE Our project addresses an urgent and critically important priority of the National Plan to Address Alzheimer s Diseaseto develop effective disease modifying therapies to preventdelayor treat Alzheimer s diseaseWe are developing a promising small molecule drug candidate that targets detrimental brain inflammation and that attenuates cognitive impairment and disease progression in Alzheimer s animal modelsOur proposed study will perform the first human trial of this new drugto demonstrate safety in healthy adults as a prerequisite for future trials in elderly individuals with cognitive impairment
