Investing In Cures Summit: Collaboration is Driving Development of the Next Treatments and Cures for Retinal Degenerative Diseases

The Foundation Fighting Blindness and the Retinal Degeneration Fund (RD Fund) hosted their annual Investing in Cures Summit (ICS) on March 21 and 22, 2025 in Tampa to highlight the strong progress in development of treatments and cures for the entire spectrum of retinal degenerative diseases. ICS convened nearly 200 stakeholders — including researchers, companies, investors, donors, and families — who heard from three dozen presenters about the accelerating advancement of therapy-focused research to save and restore vision for the millions affected by inherited retinal diseases (IRDs) and age-related macular degeneration (AMD).

“As we stand at the forefront of transformative progress in the development of treatments and cures for blinding retinal diseases, the work of the Foundation and the RD Fund has never been more critical,” said Karen Petrou, chair of the Foundation’s Board of Directors. “This Summit served as a testament to the power of collaboration that has enabled the Foundation and the retinal disease community to reach this promising juncture. Through thoughtful dialogue, strategic partnerships, and shared insights, we are forging the path forward to new discoveries and improved outcomes for the blind and low vision community.”

Friday Dinner Keynote Address: The Drug Development Journey
Jerry Cagle, PhD, senior vice president emeritus, Alcon R&D

Dr. Cagle, a renowned scientist with more than three decades of ophthalmology drug development experience at Alcon, delivered an insightful primer on the therapy development process for the Friday preconference dinner. His presentation provided the ideal background for understanding and appreciating the dozens of therapies in development discussed the next day at ICS. His key takeaway: Therapy development is never a slam dunk. It can take as long as 20 years (sometimes longer) for a potential treatment to be discovered, tested in cell and/or animal models, evaluated for safety in a large animal, and then moved into a clinical trial. He noted that 87 percent of the cost of therapy development is for clinical trials. If an emerging therapy performs safely and efficaciously in the human trial, the sponsoring company submits a new drug application (NDA), a 10,000-page document telling the story of the drug’s development journey, to the US Food and Drug Administration or another regulatory agency. Biologic license applications, or BLAs, are submitting for gene or cell therapies (i.e., therapies that are derived from living sources). His presentation on the challenges underscored the remarkable progress being made for retinal disease therapy development with 50 clinical trials now underway.

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Chad Jackson, PhD, senior director of the Foundation’s preclinical translational research program, served as the ICS emcee extraordinaire on Saturday with Jason Menzo, the Foundation’s chief executive officer, providing opening remarks.

Menzo underscored ICS’s goal of bringing together the many participants in the therapy development ecosystem to share their knowledge, experience, and perspectives.

“No single group can advance the field by itself,” said Menzo. “We are here at ICS for the unique opportunity to learn, grow, and connect.”

Rusty Kelley, PhD, MBA, managing director of the RD Fund, the Foundation’s venture philanthropy arm, discussed the RD Fund’s role in mitigating risk for clinical development of emerging therapies for IRDs and dry AMD. The RD Fund invests in companies developing emerging therapies that are near or in early-stage clinical trials — a stage characterized by high risk that most investors are reluctant to fund. As a philanthropic fund, returns are invested back into retinal research.

Since its inception in 2018, the RD Fund — with its exceptional team of scientific advisors and Foundation Fighting Blindness clout — has attracted significant venture capital investment for its portfolio companies. The RD Fund itself has deployed $86 million for investments in 17 companies. Those investments have impressively attracted $850 million from 45 venture firms.

Dr. Kelley noted that RD Fund portfolio companies have collectively achieved 33 regulatory and clinical milestones thus far, including the launch of 11 clinical trials with a few additional trials expected to start in this calendar year. Many of these companies have secured orphan drug designations, rare pediatric disease designations, and fast-track approvals, all of which are critical to rare disease therapeutic development.

“We have a hyper-focused strategy that leverages an outstanding Board of Directors and the Foundation’s Scientific Advisory Board to help select and diversify our portfolio investments,” said Dr. Kelley. “This is a powerful model. A multiplier effect occurs when the Fund and philanthropic partners converge with great science and our industry and investment partners.”

Amy Laster, PhD, the chief scientific officer at the Foundation, provided an overview of the numerous, impressive achievements of the Foundation over the past five years which included $105 million in funding for 120 grants at prominent research institutions around the world.

Some of those dollars funded career development awards (CDAs) for up-and-coming clinical researchers to further their careers and keep them in the challenging inherited retina disease field. Historically, 90 percent of CDA recipients have remained in IRD clinical research.

Foundation funding also drove the development of human retinal organoids — i.e., retinas in a dish — which have emerged as in invaluable tool for understanding disease pathways and screening emerging treatments.

Dr. Laster also noted the Foundation’s funding for clinical development of dual vector gene therapies to address the challenge of large gene delivery. Multiple companies now have dual vector genetic therapies for IRDs in or approaching clinical trials.

In recent years, the Foundation has boosted investment in several natural history studies (NHSs) to identify new endpoints for evaluating therapies in clinical trials. The largest of these NHSs is Uni-Rare which is enrolling 1,500 IRD patients affected by a vast majority of the mutated genes associated with the conditions.

Looking towards the future, the Foundation is strongly focused on clinical trial endpoint development led by the Regulatory Endpoints and Trial Design for IRDs (REDI) working group which was established by the Foundation in collaboration with researchers and industry to develop new clinical trial endpoints for emerging IRD therapies that can be validated by the FDA. The goal is to boost the chances that future therapies will move through trials successfully and gain FDA approval.

Dr. Laster said that new priorities include development of new IRD animal and cellular models and improving the understanding and controlling of inflammation associated with retinal gene therapies.

Advancements in IRD Gene Therapy: From the Bench to the Clinic
Moderator: Katherine High, MD, Chief Executive Officer, RhyGaze

Dr. High opened the gene therapy panel session by reflecting on the challenges in development of LUXTURNAÒ, the first FDA-approved gene therapy for the eye or any inherited condition. Dr. High and Jean Bennett, MD, PhD, co-founded Spark Therapeutics, a spin-out of Children’s Hospital of Philadelphia (CHOP), which commercialized the landmark, vision-restoring gene therapy for people with Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP) caused by biallelic mutations in RPE65. She said that while vision improvements for most clinical trial participants were dramatic, the team needed to develop a new, clinically meaningful endpoint — a maze called the multiluminance mobility test (MLMT) —  for approval of the gene therapy by the FDA. Dr. High thanked the Foundation for funding trial equipment and genetic testing for trial participants. The Foundation also provided $10 million in funding for preclinical research that helped move the gene therapy that became LUXTURNA into a clinical trial.

Jayashree Sahni, MD, PhD, chief medical officer at AAVantgarde Bio, reviewed her company’s emerging IRD gene therapies designed specifically for delivery of large IRD genes. The company, a spin-out of the Telethon Institute of Genetic Medicine (Italy), was founded by Alberto Aurrichio, MD, a longtime recipient of research grants from the Foundation. The company has moved its dual vector adeno-associated virus (AAV) into a Phase 1/2 clinical trial for Usher syndrome type 1B (USH1B) which is caused by mutations in the gene MYO7A. The MYO7A genes are delivered in two halves and recombined in targeted cells. The company is planning a clinical trial of its dual AAV vector gene therapy for Stargardt disease (ABCA4 mutations) which employs protein trans splicing (connecting to protein halves) to overcome the large gene delivery challenge.

Ash Jayagopal, PhD, MBA, chief scientific at Opus Genetics, said the company was founded to provide a sustainable engine for development of IRD gene therapies, overcoming barriers for advancing them into clinical trials. The company currently has seven programs. Its most advanced program is a gene therapy for LCA5 currently in a Phase 1/2 clinical trial. The emerging gene therapy was originally developed by Jean Bennett, MD, PhD. The condition causes, early severe vision loss. Results have been reported for three adults thus far in the LCA5 trial with restoration of clinically meaningful vision improvements on up to five measures including visual function as captured by a virtual reality (VR) assessment. The trial has begun dosing kids. Opus is also planning to launch a clinical trial in the second half of 2025 for people with IRDs caused by mutations in the BEST1 gene. The Foundation launched Opus in 2021 and funded preclinical research for both LCA5 and BEST1. Opus was launched by the Foundation and is currently an investment in the RD Fund portfolio.

Kenji Fujita, MD, chief medical officer at Atsena Therapeutics, reviewed the company’s two clinical-stage IRD gene therapy programs. The most advanced program is moving into a Phase 3 clinical trial for people with LCA1 (GUCY2). Nippon Shinyaku has acquired a commercial license (US and Japan) for the LCA1 gene therapy. High-dose patients in the LCA1 Phase 1/2 had robust improvements in photoreceptor sensitivity (as measured by full-field sensitivity testing) and in their ability to navigate an MLMT. Dr. Fujita also reviewed early results for Atsena’s Phase 1/2 gene therapy clinical trial for X-linked retinoschisis (XLRS) which is caused by mutations in RS1. Nine adult patients were dosed in Part A of the XLRS Phase 1/2. Resolution of the retinal-layer splitting associated with XLRS was reported for the first few participants. Nine adult and three pediatric are now being dosed in Part B.  The XLRS gene therapy uses a specially designed AAV delivery system (AAV.SPR) to deliver healthy copies of RS1. The gene therapy spreads laterally across a larger area of retina than other AAV systems and can reach the fragile fovea which is crucial for sharp central vision. The Foundation provided 13 years of research funding to Atsena co-founder Shannon Boye, PhD, for gene therapy development. Atsena is an RD Fund portfolio company.

Lance Baldo, MD, chief executive officer at Beacon Therapeutics, reviewed the progress in the company’s Phase 3 gene therapy clinical trial for X-linked RP (RPGR mutations). Known as VISTA, the trial has enrolled about half of its target enrollment. Beacon expects to report results in 18 months. The company reported preliminary clinical evidence from the Phase 2 DAWN and SKYLINE trials evaluating the efficacy, safety, and tolerability of the XLRP gene therapy. This evidence includes emerging data from DAWN showing improvements in low luminance visual acuity (LLVA), which provides support for the measure as a clinically meaningful endpoint. The Foundation funded earlier preclinical research for Beacon’s emerging XLRP gene therapy.

Shankar Musunuri, PhD, MBA, chief executive officer at Ocugen, reported on its three clinical programs for its gene-modifying gene therapies. Its most advanced program is for OCU400 which is in a Phase 3 clinical trial for RP. OCU400 is a one-time therapy injected underneath the retina to deliver copies of the NR2E3 gene that may improve regulation of multiple functions in the retina including: photoreceptor maintenance and development, metabolism, phototransduction, inflammation, and cell survival. OCU400 uses an AAV to deliver NR2E3 copies into the recipients’ photoreceptors. Phase 3 enrollment will be completed soon. Ocugen also has clinical trials underway for its modifier gene therapies for people with geographic atrophy (GA) associated with advanced dry AMD and Stargardt disease. These emerging therapies — OCU410 for GA and OCU410ST for Stargardt disease — are designed to deliver copies of the RORA gene to retinal cells to improve lipid metabolism and reduce inflammation. The company has reached an alignment with FDA on Phase 2/3 pivotal confirmatory clinical trial for OCU410ST for Stargardt disease. The company has completed dosing in its Phase 2 for OCU410 for GA.

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Small Molecule Approaches for IRDs
Moderator: Matthew Albert, MD, PhD, vice president, Octant Bio

Dr. Albert opened the session by discussing the pros and cons of small molecule therapies which are usually taken orally. He noted that oral administration makes them accessible. Drug production is also relatively scalable. The molecule needs to be small enough to penetrate the blood-retina barrier (BRB) to reach the back of the eye.

Dr. Albert also discussed Octant’s emerging drug, OCT980, for addressing mutations in the gene RHO which cause autosomal dominant RP. These mutations often lead to misfolded proteins which don’t move through cells or function properly. That results in retinal cell stress and disease. OCT980 corrects the misfolding and has demonstrated promising results in preclinical studies. Dr. Albert likened proteins to paper airplanes. If they aren’t folded correctly, they don’t fly. He noted the drug might be extendable to other diseases characterized by protein misfolding.

Michel Dahan, the chief executive officer at Alkeus, discussed gildeuretinol, the company’s emerging oral treatment for Stargardt disease (ABCA4). The condition is caused by the accumulation of toxix byprodcuts (vitamin A dimers) in retinal pigment epithelial (RPE) cells which support photoreceptors in the retina. Gildeuretinol is a modified form of vitamin A which is metabolized with fewer vitamin A dimers than dietary vitamin A. The molecule has reduced the growth of lesions (areas of cell loss) in a few Stargardt disease clinical trials. In a small group of young Stargardt disease patients, it prevented the onset of vision loss for several years. The company is planning to submit a new drug application (NDA) for gildeuretinol to the FDA soon and is seeking guidance for an approval pathway in the EU. The molecule also slowed lesion growth in a clinical trial for people with GA. Alkeus has benefited from grants from the FDA and the National Eye Institute.

Zuhal Butuner, OD, MSc, MBA, the chief medical officer at Sepul Bio, a division of Théa, reviewed her company’s emerging antisense oligonucleotide (AON) therapies acquired from ProQR. AONs are tiny bits of genetic material which bind to mRNA to overcome disease-causing mutations. mRNA are the genetic messages that cells read to make proteins critical for cell health and function. Ultevursen, the company’s emerging AON therapy for USH2A (exon 13) mutations is now in a Phase 2b clinical trial. Ultevursen previously received funding from the RD Fund when the treatment was being developed by ProQR. Data from RUSH2A, the Foundation’s natural history study for patients with USH2A mutations, has also been used in the therapy’s development. Théa also acquired sepofarsen, an AON for LCA10 (CEP290-IVS26 mutation), from ProQR. Sepofarsen led to vision improvements in previous clinical trials but did not receive regulatory approval because the primary trial endpoint was not met. A total of 67 patients were in sepofarsen trials and half of those patients continue to receive the treatment. Another sepofarsen clinical trial is planned. Sepul Bio’s AONs are delivered by intravitreal injections every six months.

Cindy Elden is co-founder and president for the Usher III Initiative, a nonprofit dedicated to finding cures for Usher syndrome type 3A (USH3A) which is caused by mutations in CLRN1. Elden and her late father, Dick, founded the organization 25 years ago. Her dad taught her not to accept the “tragic narrative” of the USH3A diagnosis. Thanks to the company’s sustained efforts, a promising small molecule for stabilizing CLRN1 moved into a Phase 1 safety clinical trial in Australia. No major safety issues have been observed. Elden said a strategic partner is needed to move the molecule into Phase 2. The molecule may have applications for treating other conditions such as cancer and neurodegenerative diseases. The Foundation’s Brint Family Translational Research Program funded preclinical development of the molecule.

Dry AMD/Geographic Atrophy (GA) Landscape Overview
Jim Handa, MD, chief of the Retina Division, professor of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University

Dr. Handa opened the session by noting that AMD affects about 300 million people globally with 15 million affected in the US. That’s nearly twice the prevalence of Alzheimer’s disease. He said that the retina is a complex ecosystem with the choriocapillaris/choroid (vasculature), retinal pigment epithelial (RPE) cells, and photoreceptors all affected in AMD. Early symptoms include problems with dark adaptation and perceiving contrast. Central vision is affected later. Disease-related changes happen slowly with aging and smoking as the greatest risk factors. Diets high in fat and with a high glycemic index increase risk. Genetic variations associated with the complement system (the innate immune system) also contribute to risk. Many cellular components are impacted in AMD including: mitochondria (cells’ power supplies), lysosomes (cells’ cleanup system), and Bruch’s membrane which controls the exchange of oxygen, nutrients, and waste between the RPE and the choroid. In AMD, lipid deposits known as drusen accumulate and cause degeneration of RPE, Bruch’s, and the choroid. Oxidative stress and inflammation are elevated and destructive. Researchers need to better understand how the numerous disease pathways interact. The over-the-counter AREDS2 supplement modestly reduces risk of advanced AMD. SYFOVREÒ and IZERVAYÔ, two recently approved treatments, slow progression of GA but more treatments are needed.

Novel Approaches for Dry AMD/GA
Moderator: Jim Handa, MD, chief of the Retina Division, professor of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University

Karsten Schmidt, PhD, chief scientific officer at BioJiva, reported on his company’s emerging oral therapy for AMD. Docosahexaenoic acid (DHA) is a fatty acid that’s important for neural cell health — it can protect neurons (including retinal cells) from inflammation and oxidative stress. It can also make cell membranes more flexible. DHA is prevalent in cold water fish, other dietary sources, and supplements. However, DHA can be harmful when oxidized. BioJiva’s therapy is a modified form of DHA (deuterium added) to make it oxidation resistant. The company plans to seek authorization to launch a clinical trial for its therapy in May 2025. Also, Maureen McCall, PhD, University of Louisville, received a grant from the Foundation’s Brint Family Translational Research Program to test BioJiva’s modified DHA therapy for preserving cone photoreceptors in pig models of RP.

Laura Carter, PhD, chief scientific officer at Character Bio, discussed her company’s emerging therapies for dry AMD. CTX114 is a treatment designed to slow the progression of GA by inhibiting the complement system (innate immune system) which is overactive and damaging to RPE cells in AMD. CTX203 is a lipid regulator (targeting drusen development) designed to prevent advanced AMD. Both approaches are delivered by intravitreal injections and will be moving into clinical trials soon. On March 25, 2025, Character Bio received $93 million in Series B funding to support its early CTX114 and CTX203 clinical trials.

Ying Kai Chan, PhD, is co-founder and chief executive officer at Cirrus Therapeutics. Co-founded with Andy Dick, MBBS, the company is a spin out of the University of Bristol (UK). They are developing a gene therapy that expresses the IRAK-M protein which protects RPE cells. Dr. Chan noted that IRAK-M levels decrease with aging. He said the protein protects against oxidative stress, inflammation, and mitochondrial dysfunction. The company is close to selecting the optimal therapeutic candidate. Next, they will begin studies to prepare for a clinical trial.

Ramanath Bhandari, MD, is chief executive officer at RevOpsis Therapeutics. His company has two emerging therapies for AMD moving toward clinical trials. RO-104 targets three different pathways (VEGF-A, VEGF-C, and Ang-2) for halting the growth of damaging, leaky blood vessels associated with wet AMD. Current FDA-approved wet AMD treatments target one or two pathways. The company’s other potential treatment targets two GA pathways as well as VEGF-A to also prevent wet AMD.

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Gene Agnostics: Broad Spectrum Therapeutic Strategies to Address Retinal Disease
Moderator: Paul Bresge, chief executive officer, Ray Therapeutics

Bresge spoke about RTX015, Ray’s optogenetic therapy, which is now in a Phase 1/2 clinical trial for people with advanced RP (vision of 20/200 or worse). He said the company has raised $114 million and has Phase 3 trial design alignment with FDA. Ray has built their own vision testing facility which includes evaluations using a mobility course and a virtual reality system. Low and medium dose groups have been dosed, and they are now administering the high dose. The therapy has been administered without safety concerns. The company will be enrolling choroideremia patients soon and Stargardt disease patients by the end of the year. They plan to enroll GA patients at the end of 2026.

Sam Barone, MD, chief medical officer at Nanoscope Therapeutics, reviewed the company’s optogenetic therapy clinical trials. The company will be submitting a biologics license application (BLA) for MCO-010 to the FDA by mid-2025. MCO-010 restored some vision for RP patients in its Phase 2b clinical trial. Dr. Barone spoke of one 60-year-old trial participant who could see cars and houses after treatment. An avid rock climber, he could also see the colors of holds for his hands when climbing. The company is also planning to enroll patients this summer in a Phase 3 clinical trial of its optogenetic therapy for Stargardt disease. Dr. Barone also spoke about a Phase 2 trial participant with Stargardt disease who could read her phone and use a cash register better after treatment. The company is also developing MCO-020 for GA. MCO-020 uses a laser instead of an AAV to get the therapeutic gene into the retina.

Dan Chung, DO, MA, is the chief medical officer at SparingVision. He explained that mutated genes in RP and Usher syndrome usually affect rod photoreceptors. However, cones die in later stages of disease. Foundation-funded researchers in Paris identified a protein secreted by rods that is important for cone survival. They aptly named the protein rod-derived cone viability RdCVF and developed a gene-agnostic gene therapy that expresses RdCVF to preserve cones in a broad range of patients with RP and related conditions. The therapy also serves as a powerful antioxidant. SparingVision will complete enrollment in their Phase 2 clinical trial (PRODYGY) of RdCVF this summer. They hope to move into a Phase 3 trial that will enroll patients with a broader range of genetic profiles. They are considering FST or EZ area (which measures the population of remaining photoreceptors) as endpoints. They may need to monitor patients for as long as 24 months to determine if the treatment is preserving vision. The company is also developing a gene therapy to restore phototransduction to cones that are dormant in people with advanced retinal disease. They hope to move that into a clinical trial clinic in the second half of 2025. The RD Fund is an investor in SparingVision.

Halden Connor, chief executive officer at Nacuity, discussed NACA, his company’s emerging, gene agnostic, oral treatment for people with RP, Usher syndrome, and related conditions. NACA is a modified version of N-acetylcysteine (NAC), a strong FDA-approved antioxidant that was originally developed for acetaminophen overdose and other conditions. NACA was designed to be more available to the retina than NAC and preclinical studies at Johns Hopkins University (JHU) for NACA provided compelling evidence for potential efficacy in humans. A 48-patient, Phase 2 clinical trial of NACA for people with RP associated with Usher syndrome will be reporting results in June 2025. If the data are promising, Nacuity plans to launch a Phase 3 clinical trial for NACA in the US at the end of 2025. The RD Fund is an investor in Nacuity. The Foundation funded preclinical studies at JHU for NACA.

Cell Therapies: The Future of Vision Restoration
Moderator: Carter Cliff, MD, PhD, co-founder, Agnos Therapeutics

Dr. Cliff discussed Agnos’ emerging, gene agnostic cell therapy for rescuing photoreceptors in people with retinal diseases. The cellular treatment, in preclinical development, is designed to work by delivering therapeutic proteins through cytoplasmic transfer (i.e., cell-to-cell transfer) to the patients’ remaining photoreceptors. Agnos was founded by Mandeep Singh, MD, PhD, Johns Hopkins University, and Eugene DeJuan, MD, University of California, San Francisco.

Patrick Jiang, MBA, chief executive officer at InGel Therapeutics, discussed his company’s emerging cell therapy for mid-stage RP. The treatment consists of purified rod photoreceptors contained in a hydrogel that mimics the vitreous. The rod-derived cells secrete neurotrophic factors to help cones survive or reactivate. The gel helps cells survive when injected through a syringe and protects them from immune system reactions. A clinical trial for the treatment is starting in Shanghai, China. A US trial is planned for 2026. The approach was developed by Michael Young, PhD, Mass Eye and Ear.

Lenore von Krusenstiern, MD, PhD, is senior vice president of clinical development at BlueRock Therapeutics. Their emerging therapy consists of photoreceptor progenitors — photoreceptors that haven’t fully matured. The progenitors are developed from induced pluripotent stem cells (iPSC), which are derived from mature skin or blood of human donors. The mature cells are genetically tweaked to revert to a primitive, stem cell state and then coaxed forward to become photoreceptor (cones and rods) progenitors. The progenitors are designed to mature and integrate into the host retina. The treatment was licensed from Opsis, a company co-founded by the Foundation-funded, stem cell pioneer David Gamm, MD, PhD, University of Wisconsin-Madison. The therapy is for people with photoreceptor-based diseases such as RP, Usher syndrome, and cone-rod dystrophy. A dose escalation clinical trial has begun. Initially, patients with advanced vision loss (legal blindness) will be enrolled. Patients with wider ranges of vision loss will be enrolled thereafter. BlueRock is using the Foundation’s Uni-rare natural history study to identify clinical trial participants.

Jeff Stern, PhD, MD, co-chief executive officer at Luxa Bio, reviewed his company’s RPE stem cell treatment for people with GA. He and his wife, Sally Temple, PhD, identified RPE stem cells in the mature human retina. For their clinical trial, they obtained RPE stem cells from recently deceased donors and expanded them to make 100s of millions of therapeutic cells. In people with GA, the loss of RPE cells leads to the subsequent loss of photoreceptors. The Luxa therapy is designed to replace lost RPE cells thereby preserving or restoring dormant photoreceptors. Six people have received the RPE stem cell therapy in the company’s Phase 1/2 clinical trial. The three people with more advanced vision loss upon enrollment had vision improvement of 22 letters on an eye chart after receiving a low dose of the cells. The three patients with better vision had three letters of improvement with the low dose. (Five letters is equal to one line on an eye chart.) The trial is now injecting people with a medium dose of the therapy.

Genetic Medicines: Expanding the Addressable Patient Populations through Advances in Gene Editing
Moderator: Bence György, MD, PhD, assistant professor, University of Basel

Dr. György reviewed his emerging base-editing therapy for the G1961E mutation in ABCA4, a mutation that is the cause of about 10 to 20 percent of Stargardt disease cases.  The mutation is a single letter change in a specific nucleotide or base (genetic location) where a G is changed to an A. Dr. György’s emerging therapy uses CRISPR/Cas9 gene-editing to correct the mistake by changing the A back to a G. The base-editing treatment has been tested in retinal organoids, retinal explants, and non-human primates (NHPs). At a relatively low dose, the treatment made the correction with excellent efficiency in NHPs. Dr. György is seeking an industry partner to advance the treatment. He is also working on addressing other IRDs caused by single-point mutations with based-editing.

Gerard Caelles, chief business officer at SpliceBio, discussed SB-007, his company’s emerging protein-splicing therapies for Stargardt disease (ABCA4) which has moved into a Phase 1/2 clinical trial called ASTRA. Protein splicing is suitable for IRDs caused by genes that are two large to deliver in one AAV vector. Protein splicing with SB-007 involves delivery of the ABCA4 gene in two halves, using dual viral vectors, to cells in the retina. Once in the cells, each gene half makes half of a protein. SB-007 uses a special biochemical process called protein splicing to bond the two protein halves to make a full-length, functional protein. SpliceBio used data from ProgStar, the Foundation-funded natural history study for Stargardt disease, to better understand patients’ disease course and potential trial endpoints. The company is also conducting its own natural history study, POLARIS. Caelles said the company also has two other protein splicing therapies in development for IRDs.

Robert Bell, PhD, chief scientific officer at Ascidian Therapeutics, reviewed ACDN-01, the company’s emerging RNA exon-editing therapy for Stargardt disease (ABCA4 mutations). ACDN-01 is in a Phase 1/2 dose-escalation clinical trial. The treatment is delivered in a single AAV vector. Dr. Bell explained that mRNA (derived from DNA) is the blueprint for making proteins that are critical to cell health and function. ACDN-01 edits exons, the regions in mRNA that contain the code that cells read to make proteins. ACDN-01edits (rewrites) about half of the exons in ABCA4 mRNA which the company believes can address about 70 percent of Stargardt disease patients. The company has a therapy development program for patients with ABCA4 mutations not addressed by ACDN-01. Dr. Bell said that ACDN-01 is the first RNA editing of any kind in humans. Ascidian used data from ProgStar to inform clinical trial design.  

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Fireside Chat: Policy in Action
Moderator: Jason Menzo, chief executive officer, Foundation Fighting Blindness
Guest: Joel White, president and founder of Horizon Government Affairs

White and Menzo discussed how Congressional and White House policies could impact drug development and ophthalmology regulatory approvals. White said that it was important for the Foundation and the community to focus on policy, not politics. The community needs to ask Congress to prioritize federal funding for vision research. While the Foundation receives 98 percent of its revenues from non-governmental sources, researchers leverage Foundation funding to receive large grants from the National Eye Institute (NEI) that fuel industry’s development of treatments and cures.  Foundation funding de-risks research so the NEI will fund it. NEI cuts would have a dramatic impact on therapy development.

White noted that the current continuing resolution for the federal government’s budget, which runs through September 30, 2025, calls for level funding of the NEI and the Advanced Research Projects Agency for Healthcare (ARPA-H), the latter of which is funding whole eye transplantation (WET). The Foundation plays a lead role in the WET project.

White and his team are helping the Foundation communicate the benefits of eye research to Congress. He added that the best strategy for community outreach is to visit House Members when they are in their local districts for recesses.

Panel Session: Investing in Retinal Therapeutics
Moderator: William J. Link, PhD, founder and managing partner, Flying L Partners
Rusty Kelley, PhD, MBA, managing director, RD Fund
Owen Smith, partner, 4BIO Capital
Leonard Feiner, MD, PhD, principal, Bain Capital
Elisa Petris, PhD, MBA, partner, Syncona Investment

4BIO Capital invests globally in biotech with a focus on emerging therapies that target severe, rare genetic conditions. The venture capital firm has invested in SparingVision and Ray Therapeutics. Smith said that financing challenges are ongoing for small biotechs but won’t last forever. These start-ups need to do more with less. He added that the RD Fund has been a good strategic partner because they understand patients and retinal diseases.

“We've been fortunate to partner with the RD Fund since we invested in Sparing Vision in 2020. What impressed me was the passion and the curiosity, but also the willingness to help better understand disease, help to connect investors with people who are patients, clinicians, or researchers in the space, and highlight the unmet need,” said Smith. “I would describe the RD Fund as a real strategic partner to have around the table with our investments and they have contributed huge value in a way that I haven't seen with any other patient advocacy groups to date.”

Syncona is a leading life science investor based in the UK. Their companies develop treatments that deliver patient impact by working in close partnership with world-class academic founders and experienced management teams. They are current investors in Beacon Therapeutics and were previous investors in the retinal gene therapy companies Nightstar and Gyroscope. Dr. Petris said that bigger companies were moving away from ophthalmology. She said that preclinical researchers seeking investment need to build a good business case, understand patient populations, have a good clinical development plan, and identify good endpoints for clinical trials.

"We've certainly had many, many interactions with the RD Fund, particularly around clinical trial recruitment and access to real thought leaders. There's been a real collaboration there. I think being able to speak to the Fund has helped us as investors to understand the landscape and how the environment is evolving,” said Dr. Petris.

Bain Capital Life Sciences pursues investments in pharmaceutical, biotechnology, medical devices, diagnostics, and life science tool companies across the globe. Dr. Feiner, a retinal specialist, said that Bain invests in more mature companies. Current ophthalmology investments include Atsena, Alkeus, and EyeBio. Bain likes to invest when a lot of risk has been taken off the table, i.e., signs of efficacy are evident. He acknowledged challenging economic conditions in the biotech space. He also lauded the RD Fund’s “tacit knowledge of diseases and regulatory pathways.”

The RD Fund provides an invaluable service to the companies they partner with. They have a lot of tacit knowledge about regulatory pathways. They understand prevalence and incidence of disease in a deep way because of My Retina Tracker,” said Dr. Feiner. “They're advocating financially for priority review vouchers which are a critical part of financing companies that are dealing with rare indications given how expensive it is to run those trials.”

Flying L Partners has been involved in building, leading, and funding high impact technologies for more than 30 years. The firm focuses primarily on the ophthalmic space. They adhere to the principle that if it is better medicine and better business, then value will be created.  Dr. Link expressed hope for therapy development for rare diseases. “Money follows success,” he said. He also discussed the forthcoming “transformative” campaign led by CCS Fundraising to expand funding for the RD Fund. He noted the important role of venture philanthropy in driving the development of breakthrough treatments for rare conditions.

The RD Fund has deployed $86 million, investing in 17 companies, since its inception in 2018. Its current investments include leading IRD gene therapy developers such as Atsena Therapeutics and Perceive Bio which is developing a complement-targeting gene therapy for GA. Dr. Kelley noted that companies need to be especially creative in financing development of therapies for ultrarare IRDs.

Donor-Based Venture Philanthropy Drives Innovation
Speakers:
Judy Taylor, senior vice president, chief philanthropy officer, Foundation Fighting Blindness
Natalie Skinner, managing director, CCS Fundraising

With an introduction from Taylor, Skinner said that CCS is a strategic management firm that helps nonprofit organizations drive transformational change through fundraising. They work with about 700 organizations a year on transformative fundraising campaigns. CCS is working with the Foundation to help the RD Fund build capital and accelerate its impact.

Skinner explained that venture philanthropy takes charitable gifts and invests them into companies developing breakthrough treatments. The goal is not just to give money away, but to strategically fund innovations that can have a real and lasting impact. Unlike traditional philanthropy, where gifts are given without expectation of financial returns, venture philanthropy reinvests any returns into new projects, creating a sustainable cycle of funding to drive treatments.

Skinner said that the RD Fund drives innovation by supporting research and clinical trials that might not receive traditional funding. It bridges the gap between early-stage research and getting treatments to market by providing capital and strategic oversight. The RD Fund stands out as a differentiated investment model, attracting top-tier co-investors, including blue-chip firms and leading biotech experts. It leverages a world-class advisory network, ensuring investments are guided by scientific and industry leaders. And it offers a unique blend of philanthropic capital and venture capital discipline, maximizing both mission-driven impact and financial sustainability.

Skinner said that without the RD Fund, there’s no guarantee that market forces alone would prioritize rare IRD treatments. Furthermore, without the RD Fund, significant co-investment capital would not be unlocked. For every $1 the RD Fund invests, it attracts $7–$8 from private capital. Without the Fund, this multiplier effect disappears, and significantly less total funding would flow into advancing treatments.

Skinner’s call to action to attendees: “Think about the difference you want to make in this world, philanthropy — especially venture philanthropy — creates a legacy and drives meaningful outcomes and impact. If you want to be a part of this groundbreaking movement in venture philanthropy, and if you know others would too, please talk to Jason Menzo or Rusty Kelley. Your expertise, insights, and support will be game-changing.”

Charting the Course: Summit Rundown and What’s Next
Closing Remarks by Mark Pennesi, MD, PhD, Retina Foundation of the Southwest

Dr. Pennesi said that he’d wanted to be an IRD specialist since the age of 19. Though he had been counseled to avoid the IRD field because there were no treatments for patients, the lack of therapies was precisely why he wanted to be a part of it — to help develop treatments for the patients who needed them.

Through career development and individual investigator awards, the Foundation played a pivotal role in his early career. Now midway through his career, he’s had five different fellows receive Foundation funding. It’s important, he noted, to keep attracting clinical research talent to the challenging IRD field.

Dr. Pennesi lauded the Foundation’s no-cost genetic testing program and patient registry. When he started in the field 15 years ago, only about 30 percent of people opted for genetic testing. Today, virtually all his patients get genetically tested and about 70 percent get a conclusive result from it.

Dr. Pennesi also spoke highly of Foundation-funded natural history studies which are helping the research community identify better endpoints to boost success of clinical trials.

On the treatment development front, Dr. Pennesi spoke of the miraculous vision restoration that his LCA2 patients (RPE65) have experienced. He’s excited about the potential that emerging gene therapies are showing for LCA1 (GUCY2D), LCA5 (LCA5), X-linked RP (RPGR), and X-linked retinoschisis (RS1). With gene-editing and -splicing therapies moving into trials, the repertoire for genetic therapies is expanding, he said. Dr. Pennesi is also encouraged by the development of gene agnostic approaches for saving and restoring vision, noting there are five clinical trials underway for emerging optogenetic treatments that are providing evidence of meaningful vision restoration for people with the most advanced vision loss.

Though cell therapies have not advanced as far as genetic treatments, Dr. Pennesi noted that replacement approaches, though challenging to develop and implement, are moving into trials.

In closing, he said that only one IRD trial was underway in his clinic when he started his career 15 years ago. Today, his clinic at the Retina Foundation of the Southwest in Dallas has 27 clinical trials underway for IRDs.