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Novel Long-Acting Inhibitors of Vascular Endothelial Growth Factor (VEGF) for Treatment of Intraocular Vascular Disorders

Award Number: R01EY031345
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Novel Long-Acting Inhibitors of Vascular Endothelial Growth Factor (VEGF) for Treatment of Intraocular Vascular Disorders - ABSTRACT Neovascularization is a key feature of ischemic retinal diseases and the wet form of age-related macular degeneration (AMD), all leading causes of severe vision loss. Vascular endothelial growth factor (VEGF) inhibitors have transformed the treatment of these disorders. Currently, three anti-VEGF drugs are widely used in the USA for ophthalmological indications, bevacizumab, ranibizumab and aflibercept. Millions of patients have been treated with these drugs worldwide. After five-year treatment with these drugs, about half of neovascular AMD patients had good vision, i.e. visual acuity 20/40 or better, an outcome that would have been out of reach before anti-VEGF agents were available. However, in real-life clinical settings, many patients do not experience the same degree of benefit observed in clinical trials, in part because they receive fewer anti-VEGF injection. So, there is an urgent need to discover and identify novel long-acting VEGF inhibitors. We hypothesized that the ability to bind heparan sulfate proteoglycans in the vitreous may be a strategy to promote intraocular retention, ultimately leading to a reduced burden of intravitreal injections. We designed a series of VEGF receptor 1 variants and identified some with strong heparin-binding characteristics and ability to bind to the vitreous. Preliminary data indicate that some of our variants have longer duration and greater efficacy in animal models of intraocular neovascularization than current standard of care. Our proposal represents the first systematic attempt to exploit the functional diversity associated with heparin-affinity of a VEGF receptor. We anticipate that it will result in the discovery and development of more effective and durable VEGF inhibitors for intravitreal administration.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	5	12/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $449,788 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	5	4/9/2024	NON-COMPETING CONTINUATION	$449,788
														Subtotal = $449,788

Issue Date FY: 2023 ( Subtotal = $449,788 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	4	4/3/2023	NON-COMPETING CONTINUATION	$449,788
														Subtotal = $449,788

Issue Date FY: 2022 ( Subtotal = $436,292 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	3	4/18/2022	NON-COMPETING CONTINUATION	$436,292
														Subtotal = $436,292

Issue Date FY: 2021 ( Subtotal = $481,890 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	2	3/17/2021	NON-COMPETING CONTINUATION	$481,890
														Subtotal = $481,890

Issue Date FY: 2020 ( Subtotal = $448,365 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Vision Research	000	1	3/27/2020	NEW	$448,365
														Subtotal = $448,365

Grand Total All Awards = $2,266,123

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Novel Long-Acting Inhibitors of Vascular Endothelial Growth Factor (VEGF) for Treatment of Intraocular Vascular Disorders

Award Number: R01EY031345

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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