Scale-up and Synthesis of a Tau Oligomer Inhibitor to initiate IND enabling studies for AD and ADRD

PROJECT SUMMARYSBIR RRFast Track ApplicationFOA NumberPASThe long term goal of this program is to develop a disease modifyingsmall molecule drug for Alzheimer s diseaseADand AD related dementiasADRDwith tau pathologyThere is a critical unmet need for a disease modifying drugDMDfor ADChronic treatment strategies require safeeffectiveand economically feasible approaches such as small molecule drugsThis program is progressing to fill this need with a DMD thatif successfulwill have a tremendous impact on the more than five million Americans who currently have ADprojected to bemillion byand their caregiversand will help reduce the current cost of $billionprojected to be $trillion byto our nationThe Company is developing a small molecule DMD for AD that targets the initial step in tau aggregation leading to the formation of tau oligomersthe toxic tau aggregates responsible for neuronal loss and impairment of memory formationWe hypothesized that by targeting the first step in tau self association all forms of tau aggregates should be reducedIn factwe have demonstrated proof of concept in vivoin a blinded study independently performed by Peter DaviesPh Da thought leader in the field of tau biology and therapeutic discoveryThe lead compound from our program inhibited tau aggregation in transgenic mice expressing human tauhtaubest representing tau aggregation in ADImportantlythe lead has good CNS drug like properties and has demonstrated a good safety profile in preliminary safety screens in vitro and in vivoHerewe propose to advance this lead compound to IND enabling studiesDuring Phase I of the project our subcontractorAlbany Molecular ResearchIncAMRIAlbanyNYwill develop scale up methodsanalytical methods and synthesizeg of our lead compoundPhase I milestoneThe program will be overseen by our Chemistry and Manufacturing Controls ConsultantEdward CheesmanPh DThis material will then be used by our subcontractorToxikonIncBedfordMAto carry out a single dose rat PK study andday non GLP preliminary toxicology study in ratPhase I milestoneSuccessful completion of the Phase I milestones will justify moving the program into Phase IIthat includes carrying out all GLP genetic toxicity testingsafety pharmacology and general toxicology studies in two speciesrat and dogOligomerix will manage the projectqualify the in vitro efficacy of the synthesized compoundand analyze and report the dataThroughout the programOligomerix will work with a regulatory consultantJoseph KozikowskiMDto develop a regulatory strategy and to have a pre IND meeting with the FDAThe proposed Aims will enable advancing the lead compound into pre clinical development and will define the pharmacokinetic and toxicology studies that need to be performed to complete the IND package for the FDADeveloping a DMD for inhibition of tau oligomerization provides a crucialnoveland viable approach to addressing the devastating impact of AD and ADRD PROJECT NARRATIVE There is a critical unmet need for a disease modifying drug for ADof the ten leading causes of death in the United Statesonly AD cannot be preventedslowed or curedThis program is highly important because it is progressing to fill this need with a small molecule disease modifying drug thatif successfulwill have a tremendous impact on the more than five million Americans who currently have ADprojected to bemillion byand their caregiversand will help reduce the current cost of $billionprojected to be $trillion byto our nationAlzheimerandapos s AssociationAlzheimerandapos s Disease Facts and FiguresThe proposed study will carry out initial scale up and safety testing toward moving our lead compound into clinical testing