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Developing a therapeutic for adRP using Wave1A, a stereopure ASO

Award Number: R01EY038401
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Developing a therapeutic for adRP using Wave1A, a stereopure ASO - Retinitis pigmentosa (RP) is an inherited retinal dystrophy (IRD) affecting 1 in every 4,000 people in the US. It is a devastating orphan disease with no approved treatment/cure for any causative mutation that eventually results in blindness. It is characterized by progressive bilateral degeneration of rod photoreceptors, initially causing night blindness and progressing to tunnel vision. In later stage disease dysmorphic cones persist but lack normal function. The most common cause of autosomal dominant RP (adRP) results from mutations in rhodopsin and accounts for ~25-40% of all adRP cases. A single amino acid substitution, p.P23H ((P23H) occurs in ~1/3 of North American adRP patients. Cure/treatment requires the elimination of mutant RHO expression without impinging or WT RHO expression. There is an urgent unmet medical need to develop effective treatments to delay/prevent rod degeneration in adRP while safe and effective cures are in development and testing. To meet this challenge, we partnered with Wave Life Sciences and developed a stereopure antisense oligonucleotide (SPASO) therapeutic, Wave1A for P23H adRP. When delivered into the vitreous, Wave1A diffuses through the retinal layers and enters cell nuclei where it binds specifically to its target, hP23H RHO mRNA. Binding recruits endogenous RNAse H, which cuts the hP23H RHO mRNA and prevents the translation of mutant and toxic hP23H RHO protein. Preliminary data show Wave1A early treatment (P3) has efficacy and safety in a transgenic pig model of adRP that harbors multiple copies of a complete hP23H RHO transgene. As the only large animal model of P23H adRP, it can be used to test therapeutic strategies for human adRP. Pigs offer similarities to humans: eyes, similar in size and vitreal volume to humans; similar photoreceptor spatial distributions; high densities of rods in the periphery and of cones in the central retina. Preliminary data also indicate that Wave1A is a novel approach for the treatment of later-stage hP23H adRP, although efficacy declines after ~4 months post-injection due to natural ASO degradation. In Aim 1 we propose experiments to define the efficacy of a single dose of Wave1A and its relationship to Wave1A bioavailability. In Aim 2, we will determine an optimized repeat dosing regimen to maintain rod structure and function indefinitely. The successful completion of this experiment will define the timing and efficacy of a long-term therapy using Wave1A to prevent rod degeneration/dysfunction indefinitely and with that cone structure/function. Finally, these preclinical results will set the stage for IND-enabling safety, pharmacology, and toxicology studies and an IND filing.


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 = $807,123 )
2026	2026	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Vision Research	000	1	7/14/2026	NEW	$807,123
														Subtotal = $807,123

Grand Total All Awards = $807,123

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Developing a therapeutic for adRP using Wave1A, a stereopure ASO

Award Number: R01EY038401

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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