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Small Molecule Anti-Inflammatories for Ocular Graft Versus Host Disease

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41EY029185-01
Agency Tracking Number: R41EY029185
Amount: $218,692.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NEI
Solicitation Number: PA17-303
Timeline
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-06-01
Award End Date (Contract End Date): 2019-05-31
Small Business Information
59501 CARY
Chapel Hill, NC 27517-8320
United States
DUNS: 079455871
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 VICTOR PEREZ
 (919) 681-8680
 victor.perez@duke.edu
Business Contact
 SCOTT COUSINS
Phone: (919) 452-5931
Email: scott.cousins@eyedesis.com
Research Institution
 ELEMENT GENOMICS, INC.
 
20 ROUNTREE LANE
BAHAMA, NC 27503-9692
United States

 Domestic nonprofit research organization
Abstract

PROJECT SUMMARYABSTRACT
Ocular graft versus host diseaseOGVHDis a severe ocular surface inflammatory diseaseOSIDoccurring
in patients undergoing allogenic hematopoietic stem cell transplantationHSCTOGVHD is characterized by
dry eyemeibomian gland dysfunctionconjunctival scarringlid margin scarringkeratopathyand corneal
ulcerationcausing significant ocular morbidity and vision loss for affected patientsPresentlythere are no
effective disease modifying therapies for OGVHDThe purpose of this STTR Phase I grant application is to
develop novel and effective therapies for the treatment of OGVHD and potentially other OSIDsThe current
proposal represents a collaborative effort between Eyedesis Biosciencesa biotechnology company focused
on developing calciumcalmodulin dependent protein kinase kinaseCaMKKtargeted therapies for ocular
diseasesand scientists at Duke University School of MedicinePreliminary data demonstrate thatOGVHD is associated with infiltration of T cells and macrophagestwo types of inflammatory cells in which
CaMKKhas been previously shown to modulate and amplify effector functionthe Eyedesis team has
developed a proprietary library of small molecule inhibitors of CaMKKSMICsselected candidate SMICs
have been confirmed to inhibit CaMKKactivity in vitrothe major histocompatibility mismatch mouse
model reproduces clinical findings and pathologic features of OGVHDlocal ocular application of the tool
compound CaMKKinhibitor STOin this OGVHD model reduces severity of OGVHD findings as
compared to control treated mice in preliminary in vivo studieswithout signs of apparent drug toxicityThismonth Phase I STTR will fund feasibility studies crucial to the development of novel SMICs invented by
EyedesisDuring STTR Phase I fundingthe study team will work to demonstrate thatnovel SMICs are potent inhibitors of T cells and macrophage CaMKKand effector function in vitrothese molecules are potent CaMKKinhibitors without significant off target activitythese molecules are well tolerated when applied topically to the eyeandtopical administration of SMICs is efficacious in treating OGVHD in a mouse modelThe key deliverable will be the identification of at least one candidate SMIC for topical therapy for OGVHD that
meets these goals and is suitable for moving forward into formal pre IND formulation developmentSuccessful
realization of the Phase I milestones will justify additional development of SMICs in Phase IIincludingclinical formulation for topical administrationandperformance of IND enabling studiesi eGLP toxicology and formal pharmacokinetics studiesPROJECT NARRATIVERELEVANCE
The goal of this project is to develop new drugs to treat ocular graft versus host diseaseOGVHDOGVHD is
a severe ocular surface disease that occurs in patients undergoing bone marrow transplantationwhen their
new donor immune cells begin to attack their front of the eye tissues and tear glandsThere are no effective
treatments for OGVHDand patients have significant paindiscomfortand vision lossThis new class of drugs
will attempt to target inflammatory cells in the eye that cause OGVHDThis project is a collaboration between
Eyedesis Biosciencesa drug development company and Duke University scientistswho will work together to
develop new treatments that could be effective not only for OGVHD but also other ocular surface diseases

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

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