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Novel Mitochondrial DNA Repair Enzyme for Heart Failure

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44HL139195-01
Agency Tracking Number: R44HL139195
Amount: $296,503.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NHLBI
Solicitation Number: PA16-302
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-08-05
Award End Date (Contract End Date): 2019-06-30
Small Business Information
Mobile, AL 36608-2814
United States
DUNS: 968503164
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (251) 654-1252
Business Contact
Phone: (251) 654-1252
Research Institution

Previous studies have demonstrated that heart failure triggers and sustains increases in oxidative
stress inducing mitochondrial DNA mtDNA damage that then propagates myocardial injury
resulting in cardiac dysfunction and myocardial cell death Fortunately mtDNA injury is reparable
via endogenous base excision repair BER mechanisms The rate limiting step within BER is
the amount of glycosylase present Here we offer the novel therapeutic Exscien III to catalyze
and enhance mtDNA repair by trafficking to the mitochondria the glycosylase necessary to
overcome this first and rate determining stage and thereby disrupt the propagation of myocardial
disease Exscien III is an innovatively engineered and patented three part fusion protein
construct consisting of a TAT sequence to facilitate cell uptake a mitochondrial import sequence
to direct the therapeutic into the mitochondria and a functional glycosylase to help effect mtDNA
repair Exscien s research variation of the protein also contains an HA tag for experimental
immunological localization
Preliminary in vivo studies at LSU s Cardiovascular Center of Excellence have demonstrated
significant cardioprotective action using Exscien III in murine models of acute myocardial
infarction AMI and heart failure HF The protein significantly attenuated myocardial infarct size
and improved left ventricular function following myocardial ischemia and reperfusion in mice
Administration of Exscien III following the onset of severe HF attenuated myocardial fibrosis and
left ventricular dilatation while improving left ventricular function in a murine pressure overload HF
model To further advance this fusion protein as an ameliorative therapeutic for HF we seek to
conduct a phased developmental program Phase I perform large animal efficacy dosing and
disposition testing of Exscien III Phase II utilize the results of Phase I to demonstrate efficacy
of Exscien III first as a therapy to prevent progression to HF following AMI and secondly as a
therapy to treat progressive HF in swine compromised with reduced ejection fraction
If successful the evidence would form the foundation of an IND application to the FDA Our
commercialization objective is to develop the drug in house as far as feasible including planned
early clinical trials before ultimately out licensing to a large pharmaceutical interest With an
estimated worldwide diagnosis of progressive heart failure in excess of million this therapy
offers substantial commercial potential and has already attracted large pharma interest PROJECT NARRATIVE
In this Fast Track proposal Exscien Corporation will perform pre clinical development of its novel
mitochondrial repair protein which has demonstrated the ability to restore fundamental cellular
metabolic function and if suitably administered will directly influence disrupt a root pathway for
cardiac disease progression and heart failure This proposal represents a first in class
therapeutic approach

* Information listed above is at the time of submission. *

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