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CN-105 Improves Functional Outcome After Intracranial Hemorrhage

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41NS108821-01
Agency Tracking Number: R41NS108821
Amount: $227,501.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 106
Solicitation Number: PA17-303
Timeline
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-09-30
Award End Date (Contract End Date): 2019-08-31
Small Business Information
3105 CONE MANOR LANE
Raleigh, NC 27613-6606
United States
DUNS: 078673636
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 ROBERT FREMEAU
 (919) 681-8087
 rtf@galactose.mc.duke.edu
Business Contact
 ADAM LAWLER
Phone: (252) 558-2037
Email: alawler@aegiscn.com
Research Institution
 ELEMENT GENOMICS, INC.
 
20 ROUNTREE LANE
BAHAMA, NC 27503-9692
United States

 Domestic nonprofit research organization
Abstract

ABSTRACT
Intracerebral hemorrhageICHis a devastating form of cerebrovascular disease with no FDAapproved treatmentsIt is generally accepted that ICH induced neuroinflammatory responses
mediate development of cerebral edemaintracranial hypertensionand secondary neuronal
injuryOne promising strategy for ICH neuroinflammatory modulation is through the
downstream effects of apolipoprotein EapoEPrevious studies from our lab and others have
demonstrated that endogenous apoE modifies neuroinflammatory responses by downregulating
glial activation and release of pro inflammatory mediators making it a compelling target for
therapeutic developmentHoweverthe therapeutic potential of the intact apoE protein is
limitedas it does not cross the blood brain barrierTo address this limitation AegisCN
developed CNaamino acid peptide that mimics the polar face of the apoE helical
domain involved in receptor interactionsIn well established preclinical models of ICHCNimproves shortand long term neurobehavioral and histological outcomesdecreases cerebral
edemaand increases neuronal survivalOur preclinical work with CNhas led to the
successful completion of an IND and translation to early clinical studiesCNdemonstrated
an excellent clinical safety profile in Phasehealthy volunteer single and multiple dose
escalation safety and PK studies andas recommended by the FDAwe have initiated a
multisite open label safety study in patients with ICHCNandapos s efficacy in preclinical ICH
models is firmly establishedas are its neurorestorative and anti inflammatory effects in other
preclinical models of acute brain injuryHoweverthis knowledge alone is insufficient for
therapeutic translationTo bridge this gapthe objective of this application is to define the
effects of genderageand chronic hypertension on long term neurobehavioral outcomes in
preclinical ICH relevant paradigms and to identify surrogate imaging and biochemical markers
of CNtarget engagement and efficacyWe will complete the following milestonesEstablish a greater thantreatment effect of CNvsvehicle treatment on
vestibulomotor deficitrotorod latencyat Dayin a rat model of ICH with comorbid
hypertensionEstablish treatment effects on vestibulomotor function as a function of age and
gender to inform clinical translationCompletion of these milestones will facilitate translation into
an adaptive randomized clinical trial for patients with acute ICH through PhaseSTTR funding NARRATIVE
Each yearapproximatelypatients in the US suffer from intracerebral hemorrhageICHa common form of cerebrovascular disease with high mortality and poor long term cognitive and
physical recoveryThere are no FDA approved pharmacologic treatments improving functional
outcomes in ICHOne promising therapeutic strategy is modulation of ICH induced
neuroinflammation responsible for secondary neuronal lossWe have identified CNa
proprietary neuroprotective peptidewhich improves long term histological and functional
outcomes in well established preclinical models of ICH as well as demonstrating an excellent
clinical safety profile with reproducible pharmacokinetics and brain penetration in Phasehealthy
volunteer studiesThe primary goal of this proposal is to define the critical parameters necessary
to advance CNinto a fully informed adaptive Phaseb randomizedcontrolled clinical trial
for acute ICH treatment

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

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