Presentation Summaries from the 10th Annual Retinal Therapy Innovation Summit

The Retinal Therapy Innovation Summit (RTIS), hosted by the Foundation Fighting Blindness and the Casey Eye Institute at Oregon Health & Science University (OHSU), is the must-attend event for researchers and companies seeking the latest news on emerging therapies for inherited retinal diseases (IRDs) and dry age-related macular degeneration (AMD).

The 10^th annual RTIS was held on May 2, 2025, two days prior to the 2025 meeting of the Association of Research in Vision and Ophthalmology (ARVO), in Salt Lake City. The RTIS featured 28 presentations from retina experts from around the world. More than 400 industry professionals were in attendance for the sold-out event. While the ARVO meeting is the world's largest eye research conference, the RTIS provides a special focus on clinical development and trials for retinal disease therapies.

For the first time, the RTIS included presentations on emerging small molecule treatments in addition to gene and stem cell therapies, which have traditionally been the focus of the meeting.

RTIS co-organizers were Casey's Paul Yang, MD, PhD, and Renee Ryals, PhD, and the Foundation’s Amy Laster, PhD, Michelle DiVincenzo, and Chris Adams.

Summit sponsors:

• Premier: Casey Eye Institute at Oregon Health & Science University.
• Innovator: Alkeus Pharmaceuticals, Belite Bio, Restore Vision, Sepul Bio, and Spark Therapeutics.
• Luminary: Astellas, Atsena Therapeutics, Beacon Therapeutics, BlueRock Therapeutics, and Johnson & Johnson.
• Patron: Apellis, EyePoint Pharmaceuticals, InFocus Clinical Research, Kiora, MeiraGTx, Nanoscope, Opus Genetics, PYC Therapeutics, REGENXBIO, and Roche.

KEYNOTE: Addressing Barriers to Translating the Foundation’s Preclinical Research

Amy Laster, PhD, Foundation Fighting Blindness, presented the recent advances, the unmet needs and opportunities for advancing retinal disease therapies into and through clinical trials to regulatory approval. Her summary was based on the Foundation’s landscape and gap analysis published in Translational Vision Science & Technology (December 2024). Noting that significant progress has advanced the field in the past five years, Dr. Laster noted significant challenges remain. Some of the opportunities to address those unmet needs included:

• Identification of the genetic cause of unsolved inherited retinal disease (IRD) cases
• Assessment of vision in advanced disease
• Repurposing of approved drugs
• Optimization of donor tissue for transplantation
• Understanding drusen development in age-related macular degeneration (AMD)

Dr. Laster also reviewed the Foundation’s recently released five-year science strategic plan, which proposes $139 million in research funding from 2025 through 2029 and emphasizes three pillars: a comprehensive research portfolio, collaboration with partners and stakeholders, and community education. The plan addresses many of the aforementioned needs and also prioritizes:

• Development of clinically meaningful endpoints for IRD therapy clinical trials
• Development of therapies for late-stage retinal disease
• Exploration of IRD genes and variants across diverse populations
• Mitigation of immunological triggers in diseases and treatments
• Development of better IRD and dry age-related macular degeneration (AMD) models

SESSION 1: RETINAL GENE & RNA EDITING

Moderator: Chad Jackson, PhD, Foundation Fighting Blindness

Gene Editing for CEP290-Related Retinal Dystrophy

Mark Pennesi, MD, PhD, Retina Foundation of the Southwest, presented results from the Editas Phase 1/2 clinical trial for EDIT-101, a CRISPR/Cas9, gene-editing therapy for people with Leber congenital amaurosis 10 (LCA10) caused by the IVS26 mutation in CEP290. In 2022, the company reported that some of the 14 patients enrolled in the trial responded to the treatment, however, Editas decided not to continue development of the therapy.

Six patients had improvement in full-field sensitivity (FST), which measures overall retinal sensitivity of rods and/or cones. Four patients had improvements in best-corrected visual acuity (BCVA). Also, four patients were better able to navigate a mobility course in different lighting conditions. Eleven patients had improvement in at least one measure.

Dr. Pennesi noted that some patients reported subjective improvements, and the trial was evidence that LCA10 was a treatable disease.

EDIT-101 was the first CRISPR/Cas9 therapy applied directly to the human body.

Precision Base Editing as a Therapy for Stargardt Disease

Bence György, MD, PhD, Institute of Molecular & Clinical Ophthalmology Basel (IOB), discussed his emerging CRISPR/Cas9 base editing therapy for the G1961E mutation in ABCA4, which is a relatively common mutation in people with Stargardt disease. The mutation is a single nucleotide (letter) change in ABCA4 where, at a specific location, a G is changed to an A. The base-editing therapy changes the A back to a G.

Dr. György said that the therapy transfected targeted cells in a large animal model, human retinal organoids derived from stem cells, and a donated human retina kept alive for several weeks. The treatment transfected rods, cones, and retinal pigment epithelial (RPE) cells.

Dr. György is seeking to move the base editing therapy into a clinical trial.

He noted the base editing approach could potentially be used for other IRDs caused by single nucleotide changes.

Optimizing Prime Editing for PRPH2 Mutations

Renee Ryals, PhD, Casey Eye Institute, OHSU, reported on her team’s development of a prime editing therapy for two common mutations in the gene PRPH2 – c.828+3A>T and c.514C>T – which lead to macular and pattern dystrophy, respectively. Prime editing has the benefit of addressing a variety of mutations and can edit relatively large regions of DNA.

Dr. Ryals’ approach uses lipid nanoparticle for delivery of the prime editor. Lipid nanoparticles have the benefit of delivering cargo of larger size and minimized risk of an immune reaction by host retinal cells.

The team’s emerging treatment transfected 40 percent of rods and cones in a large animal. The investigators are working to improve transfection and will evaluate suprachoroidal delivery (an injection into the choroid, the vasculature underneath the retina) through a partnership with Clearside Biomedical.

The project is funded by the Foundation’s Brint Family Translational Research Program.

Advancing PRPF31-Related Retinitis Pigmentosa Treatment: Key Insights from the VP-001 Phase 1B Study

Lesley Everett, MD, PhD, Casey Eye Institute, OHSU, reviewed results from Phase 1/2 clinical trials in Australia and the US conducted by PYC Therapeutics for VP-001, its emerging therapy for people with retinitis pigmentosa 11 (RP11) which is caused by mutations in the gene PRPF31.

VP-001is an antisense oligonucleotide (ASO or AON), a tiny piece of synthetic genetic material, that is designed to downregulate the gene CNOT3 which, in turn, increases expression of PRPF31. The treatment is injected into the vitreous, the soft gel in the middle of the eye.

Eighteen people have been dosed in the PYC trials, many of whom received multiple doses. Therapeutic levels of VP-001 (30 or 75 µg) led to vision improvements for trial participants as measured by a low-luminance visual acuity (LLVA) test and microperimetry, which captures light sensitivity at multiple points in the retina. One patient said they saw airplanes in the sky for the first time after treatment.

A Phase 3 clinical trial is planned for later this year.

Dr. Everett is the recipient of a career development award from the Foundation.

Developing a Therapeutic for P23H RHO adRP Using Wave1A, a Stereopure ASO

Maureen A. McCall, PhD, University of Louisville, presented her research on an ASO from Wave Life Sciences for the treatment of retinitis pigmentosa (RP) caused by the P23H mutation in the gene RHO. Wave’s ASO is designed to knock down the mutated RHO copy by cutting the mRNA (genetic messages) it expresses. The other, wild type (unaffected) copy of RHO continues to express normally.

Dr. McCall showed in a P23H pig model that repeat dosing provided durability for several weeks, structural improvements, as well as improvements in retinal sensitivity as measured by an electroretinogram (ERG). An initial dose of 50 µg with repeat dosing of 25 µg worked well. The goal: Repeat dosing every 12 weeks or longer.

AON RNA Therapies for IRDs: Lessons Learned and the Road Ahead (Combined with Sepul Bio’s Sponsor Presentation)

Zuhal Butuner, OD, Sepul Bio, presented lessons learned from clinical trials of AON RNA therapies and the road ahead. (Bart P. Leroy, MD, PhD, Ghent University Hospital, was originally scheduled to present but couldn’t attend the Summit.)

Dr. Butuner first discussed the Phase 1/2 and Phase 3 ILLUMINATE clinical trial results for sepofarsen, an AON treatment originally developed by ProQR for people with LCA10 caused by the IVS26 mutation in CEP290. Vision improvements were observed in both clinical trials. However, sepofarsen did not meet its ILLUMINATE primary endpoint, which was change in BCVA for patients in their treated eye compared to the control group which had neither eye treated. However, the treated eye of patients had significant vision improvements. The treated eye often performed significantly better for patients when compared to their untreated eye. Many patients are pleased to continue to receive compassionate use of sepofarsen.

ProQR subsequently licensed their IRD assets – sepofarsen and ultevursen for USH2A (exon 13 mutations) – to Labatoires Théa which created a business unit called Sepul Bio to continue clinically developing both emerging AONs.

Using learnings from ILLUMINATE Sepul Bio plans to launch its Phase 3 HYPERION clinical trial for sepofarsen later in 2025.

Due to time limitations, Dr. Butuner was unable to review LUNA, Sepul Bio’s Phase 2b clinical trial currently underway for ultevursen. Sepul Bio is using key insights from the Foundation’s RUSH2A natural history for design of LUNA.

The RD Fund previously invested in ultevursen when it was a ProQR asset.

SESSION 2: SMALL MOLECULES TO THE RESCUE

Moderator: Angela Bowman, PhD, Foundation Fighting Blindness

Rhodopsin Misfolding in adRP: A Multi-Variant Corrector Approach

Jason Comander, MD, PhD, Mass Eye and Ear, Ocular Genomics Institute, Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, reviewed his project that used high-throughput screening of all variants in RHO to identify all the mutations that lead to protein misfolding. This information will help the company Octant which is developing OCT-980, a molecule to treat RHO protein misfolding. The company is planning to launch a clinical trial for OCT-980 in early 2026.

In 1989, RHO was the first IRD gene identified, a breakthrough made possible in part by Foundation funding for the Berman-Gund Lab. Mutations in RHO are the most common cause of autosomal dominant RP (adRP).

Through deep mutational screening, Dr. Comander tripled the number of known misfolding variants for RHO that show evidence of being mutations (i.e., disease-causing).

Hundreds of these mutations appear to be amenable to treatment with OCT-980. OCT-980 showed benefit in an RHO (P23H) mouse model.

Targeting Photoreceptor Metabolism to Halt Dry and Wet AMD

Thomas Wubben, MD, PhD, Ocutheia, Inc., presented his company’s emerging therapy for preventing advanced age-related macular degeneration (AMD). He began his talk by noting that photoreceptors have the highest metabolism of any cell type in the body. He added that photoreceptor loss, due to metabolic dysfunction, precedes loss of retinal pigment epithelial (RPE) cells in geographic atrophy (GA), the advanced form of dry AMD.

Dr. Wubben said that pyruvate kinase (PK) is a master regulator of photoreceptor metabolism. PK is regulated by the PKM2 protein and dysregulated in AMD. Ocutheia’s OCU-568, delivered by intravitreal injections, is designed to boost PK activity.

A first-in-human trial for OCU-568 is planned for early 2026. The company plans to enroll patients with wet AMD in one eye (fellow eye) and intermediate dry AMD in the other (treated eye). The goal is to prevent the eye with intermediate AMD from converting to late-stage disease.

Repurposing Disulfiram to Improve Vision in Retinal Degeneration

Michael Telias, MsC, PhD, University of Rochester, discussed the potential for the drug disulfiram, used to treat alcohol abuse, for improving vision in people with IRDs. His previous research showed that excess retinoic acid from degenerating photoreceptors and retinal remodeling leads to hyperactivity in retinal ganglion cells. That hyperactivity creates “visual noise” or “visual static” that makes vision worse for those affected.

Disulfiram blocks retinoic acid and shows improved vision for mice with RP.  Two clinical trials of disulfiram are underway – at the University Washington (Russ Van Gelder, MD, PhD) and University of Rochester (Alex Levin, MD).

Dr. Telias said that long-term safety of oral disulfiram is unknown. Therefore, genetic therapies to inhibit retinoic acid might be a better long-term approach.

Effect of Oral N-acetylcysteine in Patients with Retinitis Pigmentosa

Peter A. Campochiaro, MD, Wilmer Eye Institute, Johns Hopkins University School of Medicine, presented his team’s research into N-acetylcysteine (NAC), an FDA-approved drug for acetaminophen overdose, for mitigating oxidative stress and thereby potentially preserving vision in people with RP. Dr. Campochiaro and other researchers have shown that oxidative stress is increased and damaging in IRDs such as RP.

Animal studies have shown that loss of rods increases oxidative stress and accelerates loss of cones. NAC was effective in preserving photoreceptors in mice with RP. A 30-patient NAC trial called Fight RP determined the optimal dosing regimen for the current Phase 3 NAC Attack trial which has almost completed enrollment for 483 patients at 33 sites (US, Europe, Mexico, Canada).

The National Eye Institute (NEI) is providing approximately $20 million in funding for NAC Attack.

Nacuity’s Gene Agnostic Therapy for Retinitis Pigmentosa Using NPI-001

Halden Conner, Nacuity, reviewed his company’s development of N-acetylcysteine amide (NACA), a modified form of NAC that was developed to be more potent and require smaller doses than NAC.

Mr. Connor expects Nacuity to report results in June for 42 Usher syndrome patients who have been enrolled for at least 24 months in a Phase 2 NACA clinical trial in Australia. If results are positive, Nacuity plans to launch a Phase 3 NACA clinical trial in the US in the first quarter of 2026.

The company is also developing a slow-release intravitreal implant to prevent cataracts for patients who receive vitrectomies.

The RD Fund is an original investor in Nacuity.

Tinlarebant: A Promising Oral Treatment for Macular Degeneration

Hendrik P.N. Scholl, MD, Belite Bio, Inc., discussed Tinlarebant, a drug designed to block the uptake of vitamin A into the retina for people with Stargardt disease and GA. While vitamin A is essential for vision, processing of vitamin A leads to the accumulation of toxic byproducts in these conditions. Tinlarebant is designed to block the RBP4 protein to reduce vitamin A uptake, and resulting toxins, in the retina.

The Phase 3 DRAGON clinical trial is evaluating the oral drug in 104 adolescent (12-20 years-old) patients with Stargardt disease (ABCA4 mutations). An interim analysis by the DRAGON data safety and monitoring board (DSMD) found that Tinlarebant appears to be safe and well-tolerated, and visual acuity was preserved for most patients. The DSMB also suggested that the company submit data for further regulatory review for potential drug approval.

Dr. Scholl was the principal investigator for the Foundation-funded ProgStar study for evaluating the natural history of disease for Stargardt disease patients. Data from ProgStar was used to design DRAGON.

The company’s international Phase 3 PHOENIX clinical trial for GA will soon reach its enrollment goal of 500 patients.

Harnessing Innovative Science to Create a Breakthrough Advancement That Could Potentially Transform Stargardt disease (Sponsor Presentation)

Michel Dahan, Alkeus Pharmaceuticals, said the company plans to submit a new drug application (NDA) to the FDA this year for gildeuretinol for the treatment of Stargardt disease. The drug is a modified (deuterated) form of vitamin A designed to metabolize with significantly less dimerization than natural vitamin A. Dimerization is the process that leads to accumulation of toxic byproducts in the retinas of people with Stargardt disease.

The emerging therapy has been evaluated in five clinical trials. In the TEASE-1 clinical trial for 50 patients (12-70 years old) with advanced Stargardt disease, glideuretinol slowed the growth rate of atrophic lesions (areas of cell loss) by 21.6 percent.

TEASE-3 was launched for young patients with early structural signs of Stargardt disease but without visual complaints. All five patients enrolled in TEASE-3 for at least 24 months (and as long as seven years) had stable visual acuity.

 In the company’s two-year SAGA clinical trial for GA, gildeuretinol showed slowing of lesion growth but didn’t meet the trial’s primary endpoint.

Restore Vision, Inc. (Sponsor Presentation)

Yusaku Katada, MD, PhD, Restore Vision, reviewed his company’s launch of a clinical trial in Japan for RV-001, a gene-agnostic optogenetic therapy for people with advanced RP.

Dr. Katada said that RV-001 expresses a chimeric, hybrid (animal and microbial) rhodopsin protein to bestow light sensitivity to surviving bipolar cells. The company believes the approach will provide vision in a broad range of lighting conditions. RV-001 uses an AAV for delivery of the protein expressing DNA. RV-001 is administered by intravitreal injection.

The company plans to expand the trial globally.

SESSION 3: NATURAL HISTORY STUDY AND ENDPOINTS

Moderator: Todd Durham, PhD, Foundation Fighting Blindness

Regulatory Endpoints and Trial Design: REDI to Inform Clinical Trials for Retinal Degenerations

Jacque Duncan, MD, University of California, San Francisco, reviewed the Regulatory Endpoints and Trial Design for IRDs (REDI) Working Group, a project organized by the Foundation’s Clinical Consortium and led by Rachel Huckfeldt, MD, PhD, Mass Eye and Ear, Harvard Medical School. The REDI Working Group is using data from Consortium-led natural history studies (NHSs) to develop and compare new candidate endpoints for clinical trials of IRD therapies – endpoints that can potentially be validated by the FDA and other regulators.

Endpoints under consideration include: static perimetry, microperimetry, and FST. Longer term (seven- and nine-year) data from the Consortium’s ongoing Rate of Progression in Usher Syndrome 2A (RUSH2A) NHS may help determine if these measures can serve as effective and validated endpoints.

SESSION 4: STEM Cell Therapies

Moderator: Alicia Kemble, PhD, Foundation Fighting Blindness

CLARICO: A Phase 1/2a Interventional Study of OpCT-001, an iPSC-derived Photoreceptor Precursor Cell Therapy for Primary Photoreceptor Disease

Byron L. Lam, MD, Bascom Palmer Eye Institute, University of Miami, presented an overview of BlueRock Therapeutics’ Phase 1/2a CLARICO clinical trial for OpCT-001, a photoreceptor replacement therapy for people with primary photoreceptor disease caused by RP, Usher syndrome, or cone-rod dystrophies. The two-year, dose-escalation trial will enroll up to 54 patients.

The photoreceptor precursors in the trial are derived from allogenic induced pluripotent stem cells (iPSCs). (The allogenic cells are mature cells from one unaffected human that isn’t in the trial.) The therapeutic approach came out of the Foundation-funded lab of David Gamm, MD, PhD, University of Wisconsin-Madison.

BlueRock is using a group of patients in the Foundation’s Uni-Rare Study, a 1,500-patient NHS, as the control group in the trial.

The goal of the initial study is to evaluate safety, efficacy, and the profiles of patients who can potentially benefit most from the treatment.

Therapeutic Approaches for Macular Degenerative Diseases

Alessandro Iannaccone, MD, Astellas Pharmaceuticals, reviewed the company’s therapeutic approaches for macular diseases. IZERVAY™ is its FDA-approved, C5 inhibitor that blocks the damaging complement system for people with GA. In clinical trials, the treatment slowed the growth of atrophic lesions (areas of cell loss). IZERVAY is delivered by monthly intravitreal injections.

A Phase 2b clinical trial for IZERVAY is underway for people with Stargardt disease.

Asetllas’ ASP7317 is an RPE cell replacement therapy derived from human embryonic stem cells (hESCs) in a Phase 1b clinical trial. Some modest improvement in BCVA has been observed with the low dose of the treatment. Mean improvement of more than two lines on an eye chart has been observed with the medium dose. Patients have also reported subjective improvements, as well.

The company is also developing an RPE cell therapy derived from universal cells (cells that are invisible to the immune system of the recipient).

Functional and Safety Outcomes of hESC-Derived RPE Patch in Retinitis Pigmentosa Patients

Christelle Monville, PhD, I-Stem, University of Evry Paris-Saclay, reviewed her institution’s Phase 1/2 clinical trial of RPE cell replacement for people with forms of RP that cause RPE cell loss. Derived from hESCs, the RPE cells are embedded in gelatin to create a patch that’s injected through a beveled cannula.

Dr. Monville showed results for seven RP patients (LRAT, MERTK mutations). Overall, the treatment was safe and well-tolerated. Most patients had stable visual acuity. Most patients had improvement in their nystagmus (roving eye movements associated with central vision loss). Some patients reported subjective improvements.

An AMD trial is planned.

The team is also planning to develop a patch that will include both RPE cells and photoreceptors.

Interim Results of Safety & Efficacy from a Phase 1/2a Clinical Trial of Allogeneic Retinal Pigmented Epithelium (RPE) Cells in Dry Age-Related Macular Degeneration (AMD) with Geographic Atrophy

Rajani Battu, MD, PhD, Eyestem Research, Pvt, Ltd, discussed her company’s goal of creating a platform for scalable and affordable cell therapies.

Based in Bangalore, India, the company conducted a Phase 1 clinical trial for its EyeCyte RPEä cell therapy for people with GA. The RPE cells are made from iPSCs, which are derived from the mature cells from an unaffected human donor(s). Nine patients have been treated thus far. The first six patients from the first two cohorts (low and medium doses) had an average improvement in BCVA of three lines on an eye chart over four to six months. One patient had six lines of improvement. Patients also reported subjective improvements.

The company is planning Phase 2 clinical trials in India and the US.

SESSION 5: RETINAL GENETIC AUGMENTATION

Moderator: Ben Shaberman, Foundation Fighting Blindness

Update on Bota-vec Safety and Efficacy Data in Patients with RPGR-XLRP

Michael Clark, MD, Johnson & Johnson, reviewed the results of his company’s Phase 3 LUMEOS trial of its gene therapy (bota-vec) for XLRP (RPGR mutations). The primary endpoint in LUMEOS was the effect of bilateral treatment on patients’ performance in a vision-guided mobility assessment (VMA), i.e., performance in navigation of a maze under reduced lighting.

Though bota-vec did not meet its primary endpoint in LUMEOS, some patients did show a response to the treatment with improvement in the VMA. A responder was someone who navigated the VMA under reduced lighting that was two lux levels lower than VMA lighting prior to treatment. Some patients also had improvements in low-luminance visual acuity (LLVA) and static perimetry which measures retinal sensitivity at different locations (loci) in the retina.

All patients treated in LUMEOS had at least one treatment emergent event, most of which were mild or moderate.

In LUMEOS, 95 patients were randomized to receive a bilateral high or low dose of the treatment or assigned to a control group which is eligible for deferred treatment. The company reported results at 52 weeks after treatment for 55 treated patients and 30 controls. Johnson & Johnson has not announced its next steps for bota-vec.

Beacon Therapeutics: Transforming Lives with Pioneering Ocular Gene Therapy

Lance Baldo, MD, Beacon Therapeutics, reviewed clinical trials for the company’s XLRP (RPGR mutations) gene therapy known as AGTC-501 (laru-zova) which expresses a full-length RPGR^ORF15 protein for transduction of both rods and cones. The treatment has been well-tolerated in 44 patients across three clinical trials.

In the 14-patient, Phase 2 SKYLINE clinical trial, the eight patients receiving the high dose had sustained efficacy, as measured by microperimetry, at 24 months after treatment.

Dr. Baldo also said that patients enrolled in the Phase 2 DAWN clinical trial had improvements in LLVA. A presentation on the preliminary, six-month DAWN results was made on May 6 by Mark Pennesi, MD, PhD, Retina Foundation of the Southwest, at the ARVO meeting. The DAWN trial was comprised of two groups: 12 patients who received a high dose of AGTC-501 and three who received a low dose. (Six-month data weren’t available for one high-dose patient.) Treatment-emergent adverse events were generally non-serious and mild or moderate. The average improvement in LLVA for the second eyes of patients was 16 letters or about 3 lines on an eye chart. Improvements in microperimetry were also observed.

Beacon is actively enrolling in its Phase 2/3 VISTA clinical trial for laru-zova.

The company is also in preclinical development for dry AMD and cone-rod dystrophy gene therapies.

The Foundation funded earlier, preclinical research for the XLRP gene therapy that became AGTC-501.

Advancements in IRD Gene Therapy: From the Bench to the Clinic

Kenji Fujita, MD, Atsena Therapeutics, first reviewed results from the Phase 1/2 clinical trial for ATSN-101, a gene therapy for people with LCA1 (GUCY2D mutations). A total of 15 patients (12 adult, three pediatric) were dosed in one eye with ATSN-101. The nine patients receiving the high dose had significant vision improvements in FST and performance in navigating a multi-luminance mobility course. Improvements in vision were maintained through at least 24 months after treatment.

Through a partnership with Nippon Shinyaku, the company is planning a Phase 3 clinical trial for ATSN-101.

Next, Dr. Fujita reviewed results for Part A (nine adult patients) of the Phase 1/2 clinical trial for ATSN-201, an emerging gene therapy for X-linked retinoschisis (XLRS) which is caused by mutations in RS1. Three doses were evaluated. Four of six patients had closure of schises, the characteristic splitting of retinal layers associated with XLRS. Vision improvements per microperimetry measures correlated with the structural improvements.

ATSN-201 uses AAV.SPR, an innovative capisd developed by Atsena co-founder Shannon Boye, PhD, to spread the gene therapy more broadly across the retina than other, commonly used AAV delivery systems.

The RD Fund is an original investor in Atsena.

First-In-Human Gene Therapy for RDH12 Retinopathy

Ruifang Sui, MD, PhD, Peking Union Medical College Hospital, first explained that mutations in RDH12 can lead to a variety of IRDs including: LCA, RP, early onset retinal dystrophy, macular dystrophy, and cone-rod dystrophy.

Her team evaluated a gene therapy for RDH12 in retinal organoids (retinas in a dish). They chose intravitreal administration for the subsequent 10-patient (LCA, RP), dose-escalation clinical trial in China to minimize impact on the fragile retina and its macular region.

The gene therapy was generally well-tolerated. Some patients had significant improvements in BCVA and LLVA.

Dr. Sui said that early intervention was best for LCA (RDH12) patients.

Treating Severe Retinal Degenerations with Gene Therapy: Gene Augmentation for LCA5 as a Model

Tomas S. Aleman, MD, Scheie Eye Institute, University of Pennsylvania, explained that a severe retinal disease can be treatable if some retinal structure (i.e., photoreceptors) remains. He showed promising results (vision rescue) for a preclinical (mouse) study of LCA5 gene therapy.

Opus Genetics, a company founded by the Foundation and an RD Fund investment, launched a Phase 1b/2a dose-escalation clinical trial for the OPGx-LCA5 gene therapy. Dr. Aleman reported results for the first three patients treated. Adverse events were mild and resolved. Improvements in cone-mediated FST and pupillometry were observed. Gains in visual acuity were also observed. Formed vision was possible for the first time for some of the patients. Improvements were also shown for other measures including microperimetry and navigation of a multi-luminance mobility course.

Two additional pediatric patients were recently dosed in the trial.

SESSION 6: ARTIFICIAL VISION

Moderator: Natsumi Takahashi-Vitiello, PhD, Foundation Fighting Blindness

An Update on KIO-301, a Novel Small Molecule Approach to Vision Restoration for Inherited Retinal Diseases

Eric Daniels, MD, Kiora Pharmaceuticals, presented results from his company’s Phase 1b ABACUS clinical trial in Australia for KIO-301, a chemical (a photoswitch) that is designed to bestow light sensitivity to ganglion cells in people who have lost most or all their photoreceptors to RP and other IRDs. A total of 12 patients were treated. Three dose levels were evaluated. The treatment, delivered by intravitreal injection, was safe and well tolerated. People with little or no light perception at baseline had improved light perception after treatment. People with better baseline vision (e.g., able to count fingers or see hand motion before treatment) had improved visual fields, improved mobility, and visual acuity as measured by the Berkeley Rudimentary Vision Test (for people who are unable lines on a standard ETDRS eye chart).

The company is planning a 36-patient, multiple-dose, ABACUS-2 Phase 2 clinical trial at five sites in Australia. Kiora is also planning to dose choroideremia and Stargardt disease patients.

The Foundation funded preclinical research conducted by Richard Kramer, PhD, for related photoswitch molecules.

Optogenetic and Prosthetic Vision Restoration Trials

José-Alain Sahel, MD, University of Pittsburgh Medical Center, UPMC Vision Institute, reviewed optogenetics, an approach to harness bipolar or ganglion cells for vision in retinas that have lost all or most of their photoreceptors in people with advanced retinal diseases such as RP and AMD.

He then discussed a clinical trial for GenSight’s GS030 optogenetic therapy which combined a gene therapy to bestow light sensitivity to ganglion cells and goggles to boost the light signal coming into the eye. GS030 enabled patients to identify objects on a table.

Dr. Sahel also reviewed an artificial retinal prosthesis called PRIMA which includes a microchip with tiny light sensitive electrodes (378 pixels) that is implanted subretinally. The system includes special glasses that capture images and wirelessly power the microchip.

Now being developed by Science Corporation, the system led to improved baseline visual acuity by four to eight lines on an eye chart for people with GA in feasibility trials.

The company is now conducting a 38-patient, international pivotal trial for people with GA. The mean improvement in visual acuity thus far has been nearly five lines. One patient had nearly 12 lines of improvement.

The primary use of the system has been for reading.

Development of Next Generation Optogenetic Gene Therapies for Retinal Degeneration

Peter Francis, MD, PhD, Ray Therapeutics, presented the company’s emerging optogenetic therapies for people with advanced retinal diseases including RP, Stargardt disease, choroideremia, and GA.

RTx-15, its therapy for outer retinal conditions (RP, choroideremia, XLRS, cone-rod dystrophy) has moved into a Phase 1/2, dose-escalation clinical trial. RTx-15 is delivered through an intravitreal injection and bestows light sensitivity to retinal ganglion cells. The treatment has a broad range of light sensitivity (e.g., ambient light). No glasses or goggles are needed.

Moving into a clinical trial at the end of 2025, RTx-021 is designed for people with macular diseases including GA and Stargardt disease. The therapy is delivered by intravitreal injection for transfecting surviving bipolar cells.

Ray has established the Vision Research & Assessment Institute (VRAI) to “set the highest standards in the clinical evaluation of low vision.” The VRAI team will include world-leading low vision experts for development of validated endpoints and reducing test-retest variability.