APT THERAPEUTICS, INC. — Department of Health and Human Services SBIR Phase II: 105

Description

Principal Investigator Program DirectorLastFirstMiddleChenRidong AbstractThere remains a crucial unmet medical need in acute ischemic strokeAIStreatmentApproximatelyofpatients die within one year andare permanently disabledmaking AIS the fourth leading cause of death and the leading cause of adult disability in the USA with an estimated cost range of $billion annuallyRecombinant tissue plasminogen activatorrt PAis the only drug approved by the FDA for restoring cerebral blood flow and improving patientandapos s functional outcome with no survival improvementCurrentlyonlyof AIS patients receive rt PA as its use is limited by narrow time window of administrationup tohours post symptomandfold increased intracranial hemorrhageRecentlyendovascular treatment with retrievable stents has been shown to improve the outcomes in small subpopulation of patients with proximal vessel occlusionThe failures of numerous neuroprotective therapies in clinical trials suggest that neuroprotection alone without restoration of tissue perfusion may not be adequate for treatment of strokeThusdeveloping the combinational therapy of rt PA and or retrievable stents with human apyrase as a safe adjunctive antithrombotic that also will attenuate reperfusion and rt PA related hemorrhagic transformation will be of great importance for stroke patients that promises to extend the time window and improve clinical outcome and survivalAPTis a proprietary and optimized human apyrase which is a homolog of CDAdministration of multi functional APTscavenges pro thrombotic ADP and pro inflammatory ATPwhich are both released at sites of thrombosis and injuryHenceco administration of APTwith rt PA will prevent thrombotic reocclusion and maintain vascular integrity necessary to prevent hemorrhagic transformationThe efficacy and safety of APTin combination with rt PA has been demonstrated in the clinically relevant models of thrombo embolic strokeadult and aged animalsin two independent laboratories as recommended by the Stroke Therapy Academic Industry Roundtablefunded by a Phase II SBIR grantRNSThereforethis CRP project is well positioned to successfully advance APTto INDSpecificallywe proposeDevelop APTproduction process and validate IND enabling study plan with FDAEstablish protocols for manufacturing cGMPCurrent Good Manufacturing Practicedrug product for toxicology and IND filingEvaluate APTfor safety in nonclinical toxicology studiesandPrepare and file IND applicationWith the successful filing of INDwe will perform Phase I clinical trials of APTto obtain safetypharmacokineticand pharmacodynamic biomarker data in healthy volunteers and then Phase II and III trials for stroke patientsThe long term goal of this project is to market APTas combination treatment with r tPA to provide a highly effective and safe acute therapy for AIS with at least ah treatment windowThis treatment regimen could be used by emergency room physicians and even in a mobile stroke unit to achieve faster prehospital treatment with rt PA for overof AIS patients to improve functional outcomes as well as survivala dramatic increase from theof AIS patients currently treated with r tPA which does not provide survival benefit Principal Investigator Program DirectorLastFirstMiddleChenRidong NarrativeThe efficacy and safety of combining an optimized human apyrase with r tPA has been demonstrated unequivocally in several relevant models of thrombo embolic strokeincluding in the stroke model of aged ratsWith a strong interdisciplinary drug development teamwe propose to complete activities necessary to enable IND filing