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Identification of novel small molecule inhibitors of Arf6 for the treatment of…

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2013 / SBIR
Agency Tracking Number:
R43EY022516
Solicitation Year:
2013
Solicitation Topic Code:
NEI
Solicitation Number:
PA12-088
Small Business Information
NAVIGEN, INC.
383 Colorow Drive SALT LAKE CITY, UT 84108
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2013
Title: Identification of novel small molecule inhibitors of Arf6 for the treatment of va
Agency: HHS
Contract: 1R43EY022516-01A1
Award Amount: $150,640.00
 

Abstract:

DESCRIPTION (provided by applicant): Age-Related Macular Degeneration is the most common cause of legal blindness in people over 60, affecting an estimated 1.6 million patients. Additionally, over 400,000 diabetic Americans are diagnosed each year with vision-threatening retinal edema and/or neovascularization. The main therapeutic strategies that have been successful to date have focused on reducing the signals from the destabilizing pathways. This is the basis of anti-VEGF therapies which are costly biologics administered by intraocular injection, typically once monthly. Navigen seeks to explore an alternative and innovative approach to treating the pathologic angiogenesis and endothelial hyperpermeability of the retinal and choroidal vascular beds. Our approach restores the balance toward vascular homeostasis by stimulating vascular stabilization signals. Through its work on guidance cues, the laboratory of Navigen's scientific co-founder, Dr. Dean Li, identified a novel endothelial- specific receptor, Robo4, that when activated by its cognate ligand, Slit2, stabilizes the endothelium and inhibits pathologic cytokine- and growth factor-induced angiogenesis and vascular leak by inhibiting the activation of ADP-ribosylation factor-6 (Arf6). These findings suggest that Robo4 activation, and specifically inhibition of Arf6, provides vascular stabilization signals that actively instruct the endothelium to maintain cell- cell junctions and limit vascular leak and invasion. Our preliminary data and the published literature support the relevance of Arf6 in vascular eye disease. This proposal outlines a strategy to identify novel small molecule inhibitors of Arf6 and to test these in in vitro models of vascular eye disease. By adopting an approach based on identifying small molecule inhibitors of Arf6, we anticipate that potential market advantages include: a small molecule for which topical or oral administration are feasible; a broad based approach to blocking VEGF and other cytokine mediated leak and angiogenesis,and a distinct biochemical pathway that may either replace or augment current anti-VEGF centric therapies. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Age-Related Macular Degeneration is the most common cause of legal blindness in people over 60, affecting an estimated 1.6 million patients. Additionally, over 400,000 diabetic Americans are diagnosed each year with vision threatening retinal edema and/or neovascularization. There is abundant evidence that small G protein ADP ribosylation factor 6 (Arf6) is of therapeutic interest in vascular eye disease; however, no small molecule inhibitors exist to this highly relevant target. The goal of this Phase I SBIR project is o identify clinically and commercially viable structural classes of Arf6 inhibitors that are effectiv at reducing the pathologic angiogenesis and hyperpermeability associated with vascular eye diseases.

Principal Investigator:

Kirill Ostanin
801-587-1456
kostanin@nvgn.com

Business Contact:

Brandi Simpson
801-587-1401
bsimpson@nvgn.com
Small Business Information at Submission:

NAVIGEN, INC.
383 Colorow Drive SALT LAKE CITY, UT 84108

EIN/Tax ID: 120853586
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No