The 2026 Investing in Cures Summit (ICS) brought together 185 patients, caregivers, donors, scientists, clinicians, and industry leaders in Boston, Massachusetts, for a two-day gathering organized by the Foundation Fighting Blindness and the RD Fund. Held under the theme Illuminating the Future: Where Insight Meets Innovation, the summit offered a rare opportunity to witness the full arc of inherited retinal disease (IRD) research, from foundational science to late-stage clinical breakthroughs, in a single room.

What emerged over the course of the weekend was a picture of a field that has moved decisively from hope to evidence. Novel therapies are in or approaching pivotal trials. Individuals who were functionally blind have regained meaningful vision. A new generation of precision genetic technologies and gene-agnostic approaches is broadening the horizon for patients who cannot be served by single-gene strategies. And the RD Fund, the Foundation's venture philanthropy arm, has demonstrated a 10x return of donor dollars into outside capital, with multiple portfolio companies now in the public markets or approaching FDA approval.

Friday Evening, March 6

Welcome Remarks

Jason Menzo, CEO, Foundation Fighting Blindness

Warren Thaler, Foundation Board Member

CEO Jason Menzo opened the evening by welcoming attendees from across the patient, philanthropic, and scientific communities, noting that nearly a third were attending a Foundation event for the first time. He invited the room to build new connections, reflecting that while an IRD diagnosis can feel isolating, the ICS community represents a global network of people who refuse to accept that blindness is inevitable.

Menzo paused to honor two individuals whose contributions define the Foundation's history. Founder Gordon Gund, whose presence in the room was greeted with sustained applause, was recognized as the person without whom none of this work would have been possible. Menzo also shared a tribute to Board Chair Karen Petrou, who had passed away two weeks earlier on what would have been her birthday. Rather than a moment of silence, he asked the room to raise a glass to the word she said often: “Onward!”

Board member Warren Thaler, a longtime friend and colleague of Gordon Gund who came to the Foundation without any personal connection to blindness, offered brief remarks on why people like him give their time and resources. “If you hear the story, it can make stuff happen,” he said. “Please help us spread the message.”

Keynote: The State of Genetic Medicine, and the Promise Left Behind

Jim Wilson, MD, PhD, Founder, GEMMABio; Professor, University of Pennsylvania

Keynote speaker Dr. Jim Wilson, one of the founding figures of modern AAV gene therapy, delivered a wide-ranging address tracing genetic medicine from his earliest days to the urgent challenges the field faces today. Wilson began by sharing how he came to gene therapy through Jean Bennett, MD, PhD, whom he supervised as a medical student during his residency at Massachusetts General Hospital. When Bennett arrived at his Penn lab in 1993, announcing she was going to cure blindness, Dr. Wilson said, “I basically said, ‘How can I help?’”

From that starting point, Dr. Wilson traced the field through landmarks the room knew well, the LCA2 (RPE65) trial that became LUXTURNA®, the development of spinal muscular atrophy (SMA) therapy, and the cascade of genetic interventions now underway. What has most impressed him, he said, is how profoundly different outcomes are when you correct a gene at its root rather than treat symptoms. He described children with Angelman syndrome gaining the ability to say “Mama” after genetic intervention, and babies with SMA regaining motor function within months of treatment. “Who would have predicted that until we did the experiment?”

“I don't remember in the history of medicine where we had fundamental solutions to diseases that could fundamentally change the trajectory... and we as a society are not developing them.”

But Dr. Wilson's keynote was also a call to action. He named a hard truth he called “the great abandonment”: the reality that pharmaceutical companies have largely stepped back from ultra-rare disease gene therapy because individual markets are too small and the one-time treatment model doesn't generate recurring revenue. He described a growing health equity crisis, “too rare or too poor,” where the universe of diseases that science can treat is expanding faster than the business models to fund their development. Dr. Wilson closed by describing his new ventures, GEMMABio (which has treated its first patients in clinical trials) and Rare Therapeutics (designed to ensure every ultra-rare disease patient can access transformative gene therapy), and suggested the Foundation Fighting Blindness is uniquely positioned to help break through these systemic barriers.

Saturday, March 7

Welcome and Why This Moment Matters

Jason Morris, Incoming Board Chair, Foundation Fighting Blindness

The Saturday program opened with remarks from Jason Morris, newly appointed Board Chair, following the passing of Karen Petrou. Mr. Morris spoke personally, sharing that his 23-year-old son Jack was diagnosed with an IRD at age five and now has approximately 10 degrees of vision remaining. “Vision loss is not abstract,” he said. “It affects independence, mental health, opportunity, and the daily reality of entire families.”

Mr. Morris acknowledged the governance strength of the Foundation, crediting the succession planning that allowed for a smooth transition in leadership. He thanked Gordon Gund for over 50 years of refusing to accept a world without treatments for blinding diseases, and challenged the room: “Progress only matters if it reaches people, and that requires continued action and continued funding.”

Venture Philanthropy at Work: Impact Meets Innovation

Rusty Kelley, PhD, MBA, Managing Director, RD Fund

Dr. Rusty Kelley, Managing Director of the RD Fund, presented a comprehensive picture of the Foundation's venture philanthropy arm over seven years into its mission. The RD Fund sits at the intersection of traditional philanthropy and venture capital, channeling not-for-profit donor dollars into for-profit investments that turn science into therapies. Financial returns are recycled back to the Foundation to further the mission.

In seven years, the RD Fund has committed $95 million across 18 portfolio companies, co-investing with more than 50 top-tier investment firms. Those companies have attracted over $1 billion in outside capital, a 10x multiplier on every donor dollar invested. Twelve international clinical trials have been supported, with more than 350 patients treated. Five trials have achieved clinical proof of concept, including four gene therapy programs demonstrating functional benefit and one gene-agnostic strategy slowing disease progression.

Dr. Kelley highlighted the breadth of the portfolio, spanning early- to late-stage vision loss, gene-specific and gene-agnostic approaches, IRDs, dry AMD, and geographic atrophy. New portfolio additions Agnos Therapeutics and Beacon Therapeutics have broadened the portfolio into a cell-based renewal strategy and a major XLRP (X-linked retinitis pigmentosa) program. Opus Genetics, founded by the Foundation and RD Fund, has completed a public company merger and is valued at over $500 million.

Session 1: A History of Innovation

This session explored advances in AAV genetic technologies for inherited retinal diseases, highlighting translational progress, clinical outcomes, and strategies to enhance durability and safety.

Moderator: Rusty Kelley, PhD, MBA, RD Fund

Atsena Therapeutics

Shannon Boye, PhD, Chief Scientific Officer, Atsena Therapeutics

Dr. Shannon Boye opened the scientific program with a journey tracing the entire arc of modern ocular gene therapy, from her earliest graduate school experiments to Atsena's Phase 3-ready pipeline. She began by grounding the room in the fundamentals: gene therapy delivers a healthy copy of a gene into the retina via adeno-associated virus (AAV), allowing cells to produce a protein they could not make on their own.

“We have children who can see snowflakes for the first time, young adults who can read without assistance, adults who can ski again. The testimonies are real and growing.”

Dr. Boye's path began at the University of Florida, where she trained under Dr. Bill Hauswirth and developed her first gene therapy constructs for LCA1. After years of working with pharmaceutical partners who ultimately shelved their programs, “On any given Tuesday, upper management can say we don't want to be in this therapeutic area anymore,” she and her husband, Sanford Boye, MSc, founded Atsena Therapeutics with foundational support from the RD Fund.

Atsena's lead program for LCA1 (GUCY2D) has now fully enrolled its Phase 1/2 trial, 15 patients treated, with some having data beyond five years. Results include a clean safety profile with no serious adverse events related to the gene therapy, and compelling functional gains. One young patient saw snowflakes for the first time. Another woman can navigate outside at night for the first time in her life. Another was able to read the labels on her children's Halloween candy. Scientifically, some patients have shown 10,000-fold improvements in retinal sensitivity. Atsena plans to move into a Phase 3 pivotal trial in 2025, targeting FDA approval in 2028.

Atsena's key differentiating technology is AAV.SPR, a proprietary AAV vector engineered to spread multiple millimeters beyond the injection site. This matters because conventional vectors only transduce (deliver the gene into) cells immediately adjacent to the subretinal bleb. To treat the fovea with conventional AAV, surgeons must inject directly under it, a risky procedure in patients with already fragile retinas. AAV.SPR allows peripheral injection while gene expression spreads to the critical foveal region.

This same technology is driving Atsena's XLRS (X-linked retinoschisis) program, where 15 adult patients and several pediatric patients have been treated. Structural improvements, closure of the foveal schisis cavities that characterize the disease, are being observed, with corresponding functional gains. The FDA has indicated the program may qualify for a streamlined pivotal trial based on Phase 1/2 data, with enrollment beginning imminently. Atsena is also advancing a dual-AAV program for Usher syndrome type 1B (MYO7A), which is IND-ready.

Opus Genetics

Ben Yerxa, PhD, President, Opus Genetics

Dr. Ben Yerxa, the Foundation's former CEO and creator of the Investing in Cures Summit, told the story of Opus Genetics with unusual candor, describing near-financial-collapse, the implosion of Silicon Valley Bank, staffing down to a single employee, and an 11th-hour merger that transformed the company into a publicly traded biotech with an over $500 million fully diluted market cap.

The journey began in 2018, with Dr. Jean Bennett at the University of Penn, therapy programs for ultra-rare conditions, including LCA5 (affecting roughly 170 people in the U.S.), and a potential transaction fell apart when the underlying pharmaceutical company changed its mind. The RD Fund served as Opus's anchor investor through its founding, providing $10 million of a $19 million seed round and ensuring the Foundation held 75% control of the company. The explicit goal: build a company oriented around patients.

The scientific results justified the persistence. Opus dosed its first LCA5 patient, a 26-year-old man functionally blind since age two, in August 2023. Thirty days post-treatment, he could read the large E on the eye chart. The second patient, Lindsey Rambo, later appeared on Good Morning America as a "medical miracle." The company went 3-for-3 on early efficacy signals. Despite multiple near-bankruptcy moments, an 11th-hour merger with Ocuphire Pharma (a company holding $30 million in cash following a Phase 2 failure in diabetic retinopathy) gave Opus a path to the public markets. Since going public, the company has raised multiple rounds of institutional capital, landed major investors including Perceptive Advisors, and is now covered by 13 analysts, all with buy ratings.

Opus's pipeline spans LCA5 (with Regenerative Medicine Advanced Therapy, a priority FDA designation to expedite the development and review of innovative cell therapies, tissue engineering products, and gene therapies meant to treat serious conditions and pivotal enrollment underway), Best disease (BEST1 mutations, with first patient data at the Macula Society driving significant investor interest), autosomal dominant RP (RHO mutations), and additional programs to be announced. Dr. Yerxa's advice to the room on fundraising: "Never turn money away."

Beacon Therapeutics

Lance Baldo, MD, CEO, Beacon Therapeutics

Dr. Lance Baldo, CEO of Beacon Therapeutics and a former head of ophthalmology at Genentech, introduced his company as a new member of the RD Fund portfolio. Beacon is an ocular gene therapy company focused on both rare and prevalent retinal diseases. Its lead asset, laru-zova, targets X-linked retinitis pigmentosa (XLRP), a progressive, devastating condition affecting approximately 10,000 people in the U.S. with virtually no treatment options.

XLRP is caused by mutations in the RPGR gene. Laru-zova delivers a full-length, codon-optimized RPGR construct subretinally, enabling the missing protein to localize to the connecting cilium of photoreceptors and allowing dormant cells to begin functioning again. In the open-label DAWN Phase 2 study, patients have achieved 5, 10, 15, and sometimes 30 letters of visual gain on low luminance visual acuity testing, consistent and robust across treated subjects.

The Phase 2/3 VISTA trial has enrolled 75 subjects across three arms (high dose, low dose, and untreated control), is fully blinded, and completed enrollment in July 2025. Top-line data are expected in the second half of 2026. Beacon deliberately elevated low luminance visual acuity and detailed mapping of central vision to primary endpoint status, learning from challenges other programs faced with mobility testing as a primary measure. Dr. Baldo credited the FDA for collaborative engagement on trial design, noting the agency's explicit compliment on the rigor of Beacon's trial design. He closed by thanking the RD Fund and Goldman Sachs as Beacon's two most recent investors: "You are the company you keep."

Session 2: Navigating Endpoints for Effective Clinical Trials

Experts discussed how endpoint selection drives trial success, balancing scientific rigor, regulatory alignment, and commercial relevance to bring sight-saving therapies to market faster.

Moderator: Todd Durham, PhD, SVP Clinical and Outcomes Research, Foundation Fighting Blindness

Alkeus Therapeutics

Carlos Quezada-Ruiz, MD, Chief Medical Officer, Alkeus Therapeutics

Dr. Carlos Quezada-Ruiz, a retina specialist and veteran drug developer who previously worked at Genentech, presented Alkeus Therapeutics' approach to Stargardt disease, the most common inherited macular dystrophy, affecting approximately one million people worldwide. Alkeus's lead compound, gildeuretinol (deuterated vitamin A palmitate), addresses the disease at its biological root.

Mutations in ABCA4 disrupt how vitamin A is metabolized in the retina, causing toxic byproducts to accumulate and ultimately killing photoreceptors. By substituting a single hydrogen atom with a heavier element called deuterium, Alkeus makes vitamin A more stable and resistant to forming the dimers responsible for Stargardt progression. The result is a once-daily oral tablet, a treatment modality that Quezada-Ruiz described as potentially the "holy grail" for a disease like Stargardt, where surgical or injectable approaches carry meaningful risk.

More than 400 patients have now received gildeuretinol acetate across early, moderate, and advanced disease stages, with follow-up data extending as long as seven years. The safety profile has been clean, and clinical signals are emerging: statistically and clinically significant stabilization of low luminance visual acuity, and slowing of atrophic lesion growth. Alkeus is now launching a Phase 3 trial in approximately 230 patients with advanced Stargardt, using atrophic lesion growth as the structural primary endpoint and low luminance visual acuity as a key secondary, a design aligned with the FDA and international regulators. An interim analysis provision could accelerate filing.

On the broader topic of endpoint strategy, Dr. Quezada-Ruiz offered a direct message: engage with regulatory agencies early and often, without fear. "The agency is not here to tell us no. It's to try to figure out what's rational for our objective and work with us on whether it's feasible."

Sepul Bio

Zuhal Butuner, OD, MBA, Chief Medical Officer, Sepul Bio

Dr. Zuhal Butuner, CMO of Sepul Bio (a unit of Laboratoire Théa), presented two RNA-based programs targeting LCA10 and Usher syndrome type 2A. Unlike gene therapy, which delivers a corrected copy of a gene, RNA therapy works at the messenger RNA level. It is transient, requiring repeat dosing approximately every six months, but avoiding the permanent modifications associated with gene editing.

Dr. Butuner shared a hard-won lesson from the field. Sepul Bio's LCA10 program (Sepofarsen) showed compelling efficacy in early trials, noting a carpenter who lost his sight in his teens was able to return to carpentry after treatment, yet the trial failed to meet its primary endpoint in Phase 3. Approximately 50 patients have remained on Sepofarsen through a compassionate use program since then. "It worked, but we didn't hit the primary endpoint. And that's frustrating." The failure, she explained, was partly driven by too few patients per cohort and too much variability across a heterogeneous disease, compounding the limitations of standard visual acuity measurement at very low vision levels.

This experience is now shaping a more rigorous approach. For its Phase 3 LCA10 program, Sepul Bio is working with Dr. Todd Durham and the Foundation to validate the Freiburg Visual Acuity Test, a tool offering more precise measurement at very low vision levels than the standard ETDRS chart. While the FDA has not yet accepted this measure for trial efficacy, Dr. Butuner plans to present validation data alongside the Foundation to make the case. For their Usher syndrome type 2A program, enrollment is approaching target at 65 of 90 patients, with strong confidence that remaining patients in screening will complete the cohort.

Fireside Chat: From Baseline to Finish Line – Measuring Success in Clinical Trials

Rachel Huckfeldt, MD, PhD, Mass Eye and Ear

Mark Pennesi, MD, PhD, FARVO, Retina Foundation of the Southwest

Moderator: Todd Durham, PhD, Foundation Fighting Blindness

The session concluded with a frank discussion featuring two clinician-scientists working at the intersection of clinical trials, natural history, and regulatory science. Their central message: endpoint selection is not an afterthought; it defines the trial. A measurement that fails to capture real-world benefit can doom a therapy that works.

The conversation addressed the gap between statistical significance and clinical meaningfulness, the challenge of standard visual acuity charts at very low vision levels, the value of natural history data in anchoring trial design, and the cultural shift required to bring regulators, clinicians, and patient advocates into alignment before a trial begins rather than after it fails. The Foundation's RUSH2A Natural History Study was cited repeatedly as a model; its data have now served multiple companies in designing eligibility criteria and aligning endpoints with validated disease progression patterns.

Dr. Huckfeldt and Dr. Pennesi both emphasized a simple truth that is often ignored in practice: success requires shared definitions. When clinicians, sponsors, regulators, and patients are not aligned on what meaningful change looks like from the outset, even compelling data can fail to translate into approved therapies. The Foundation's role in building that alignment, through natural history studies, endpoint validation, and regulatory advocacy, was named as one of its most valuable contributions to the field.

Session 3: Rewriting Vision: The Next Frontier of Precision Genetic Therapies

As genetic technologies mature, precision approaches are redefining what is possible in retinal therapeutics. Emerging platforms and translational insights are enabling more tailored, durable, and scalable genetic interventions for retinal disease.

Session 3 Moderator: Alicia Kemble, PhD, RD Fund

Amber Bio

Jacob Borrajo, PhD, Founder & CEO, Amber Bio

Dr. Jacob Borrajo, who trained at the Broad Institute at MIT, founded Amber Bio after a graduate school insight that now shapes the company's entire platform. Analyzing ClinVar (a database of disease-causing genetic variants), he found that of approximately 6,000 genes associated with genetic disease, about 2,000 have 10 or more pathogenic variants in patient populations. The one-by-one model of gene therapy cannot scale to reach these patients.

Amber Bio's answer is an RNA splice editing platform that corrects disease-causing mutations at the RNA level. Rather than editing the DNA itself, their CRISPR-based system intercepts and corrects the flawed genetic message the cell receives, fixing the instruction before it can cause damage. Dr. Borrajo described testing 12 variants in the lab, expecting failure, and then watching cells finally turn bright green on the fourth plate. "I felt this sense of wonder and excitement, thinking, this approach that people said is impossible actually seems to be working." That experiment became the founding insight of Amber Bio.

The lead program targets USH2A (Usher syndrome type 2A), estimated to cover approximately 60% of USH2A patients with mutations in exons 1 through 13. In small rodent models, the platform achieves 70% RNA editing efficiency in non-human primates, approximately 50%, well above the ~18% threshold shown to be sufficient to rescue the disease phenotype in humans. An Investigational New Drug (IND) filing is planned for 2027 with a first-in-human trial targeting 2028.

Amber Bio is also integrating AI and large language model tools to accelerate the design of new RNA editors, moving development cycles from years to months, and exploring whether "zero-shot design" (where an AI-designed molecule works on the first attempt) is achievable. The company's investors include Andreessen Horowitz, Lilly Ventures, Hummingbird, and the RD Fund.

Ascidian Therapeutics

Murray Abramson, MD, MPH, Chief Development Officer, Ascidian Therapeutics

Dr. Murray Abramson brought a personal and institutional perspective to Ascidian's platform. A former faculty member at Duke who led global clinical operations at Biogen, where he witnessed SMA therapy transform a fatal pediatric disease, he joined Ascidian after his own family's experience with ALS deepened his conviction that clinical acceleration is a moral imperative.

Ascidian has developed an RNA exon-editing platform, delivered via AAV, capable of replacing large segments of mutated RNA—up to ~3.7 kb per edit—enabling correction of a broad range of mutations within large genes such as ABCA4. In Stargardt disease, this approach has the potential to address approximately 60–70% of patients across mutation types. The company’s lead program has received FDA IND clearance, and the STELLAR Phase 1/2 trial is currently enrolling across multiple U.S. sites with low-, mid-, and high-dose cohorts, including pediatric patients. In non-human primates, the platform has demonstrated ~30% restoration of target protein expression at six months, exceeding the ~10–20% levels shown in preclinical models to be sufficient for phenotypic rescue.

Ascidian's single-vector approach differentiates it from dual-vector strategies: manufacturing is simpler, surgical injection volume is reduced, and there is no need to co-deliver two AAVs to the same cell. The company also holds a large collaboration with Roche for CNS applications beyond the eye.

Session 4: Panel Discussion: Advances and Challenges in Retinal Cell Therapies

This session highlighted the therapeutic potential of cell-based approaches while addressing the scientific, regulatory, and translational challenges that influence their path to patients.

David Gamm, MD, PhD, Opsis Therapeutics (Moderator & Speaker)

Mandeep Singh, MD, PhD, CEO, Agnos Therapeutics

Sally Temple, PhD, R&D Director, Luxa Bio

The afternoon panel addressed one of the most scientifically compelling and logistically complex frontiers in retinal medicine: using transplanted cells to restore vision. Dr. David Gamm noted the Foundation's involvement in an ambitious ARPA-H-funded whole eye transplant program before the discussion turned to the nearer-term reality of cell-based therapies.

Dr. Sally Temple, whose work on neural stem cell biology spans decades, described the unique challenges of cell therapy in the immune-privileged eye, including the careful balance between immune suppression needed to protect transplanted cells and the risks that suppression entails. Dr. Mandeep Singh of Agnos Therapeutics, a new RD Fund portfolio company, discussed early-stage work on cell-based renewal strategies with the potential to rebuild rather than simply preserve retinal tissue.

The panel reached a shared conclusion: the path forward for cell therapy likely involves combination approaches, pairing gene therapy or neuroprotection with cell replacement to create a therapeutic environment hospitable to regeneration. The field is also navigating the challenge of endpoint design in pivotal trials, where the subtler functional gains that patients experience after cell therapy may not be captured by standard visual acuity measures designed for different treatment paradigms.

Session 5: Gene-Agnostic Approaches

This session highlighted therapeutic strategies that work across many retinal diseases by acting on common biological drivers rather than specific genetic defects.

Session 5 Moderator: Preeti Subramanian, PhD, VP Preclinical Research, Foundation Fighting Blindness

Zhongmou Therapeutics

David Gao, PhD, CSO, Zhongmou Therapeutics

Dr. David Gao presented Zhongmou Therapeutics' optogenetics program for late-stage retinitis pigmentosa, a gene-agnostic approach specifically designed for patients whose photoreceptors have already degenerated and who cannot benefit from gene replacement. Rather than restoring a missing gene, optogenetics reprograms surviving retinal cells (primarily ganglion cells) to become light-sensitive by introducing a channelrhodopsin protein via a single intravitreal AAV injection.

Zhongmou's proprietary channelrhodopsin has been engineered for high light sensitivity, designed so that patients can respond to natural light without the goggles or external devices required by earlier optogenetic approaches. The company conducted a 12-patient clinical trial in China using an investigator-initiated trial mechanism, treating patients with late-stage RP across multiple dose levels with a sham control arm. Results: 70–80% of treated patients achieved BCVA improvement greater than 0.3 log units; average improvement was approximately 0.6 log units, equivalent to four to five lines on an eye chart. One patient who had been forced to leave college due to her vision loss enrolled in an MBA program after treatment. Another rode a bicycle alone for the first time.

An IND has been cleared in the U.S., with a Phase 1/2 trial expected to dose its first patients within months. While the program begins in late-stage RP, the biology suggests potential applicability to earlier-stage disease and other indications, including Stargardt, where early signals from the Chinese trial were also encouraging.

Nacuity Pharmaceuticals

Jami Kern, PhD, Chief Clinical Officer, Nacuity Pharmaceuticals

Dr. Jami Kern presented Nacuity's gene-agnostic approach to retinitis pigmentosa, targeting oxidative stress, one of the shared biological drivers of photoreceptor death across many forms of retinal degeneration. As rods die in RP, the retina becomes hypoxic, triggering a vicious cycle of oxidative damage that accelerates cone death. NACA (N-acetylcysteine amide), taken twice daily as an oral tablet, is a potent antioxidant designed to penetrate cells efficiently and interrupt this cycle.

Nacuity's Phase 2 proof-of-concept trial enrolled 49 participants with RP associated with Usher syndrome. After two years, patients receiving NACA experienced nearly 50% slower photoreceptor loss compared to placebo, a treatment effect consistent across the study population. "Cutting the rate of cell loss in half is not incremental. It's meaningful." Based on this data, the FDA granted Nacuity Breakthrough Therapy designation, in addition to previously granted Orphan Drug and Fast Track designations.

"Behind every data point, there's a person. A person adjusting to night blindness, a teenager whose field of vision is narrowing, a parent wondering how long they'll be able to see their child's face clearly."

Dr. Kern credited the Foundation Fighting Blindness explicitly, not only for funding, but for the RUSH2A Natural History Study data that allowed Nacuity to design eligibility criteria, putting them in the best position to demonstrate a treatment effect. Confirmatory trials are now being planned, with enrollment expected to start within months and expansion to the U.S. and Europe. All but three of the Phase 2 participants elected to continue on their assigned treatment for three additional years when given the option, a meaningful signal of patient confidence.

SparingVision

Kali Stasi, MD, PhD, Chief Medical Officer, SparingVision

Dr. Kali Stasi, a cornea surgeon turned gene therapy CMO, joined SparingVision after a career that included faculty work at Penn, a Wharton business degree, and leadership roles at Novartis and several biotechs. Her experience at Novartis, where an RLBP1 gene therapy program with compelling efficacy was ultimately canceled, leaving a drug that had to be discarded as patients emailed her for access, has sharpened her focus on what separates science from medicine that actually reaches patients.

SparingVision has two gene-agnostic programs targeting cone photoreceptors. SPVN06 is a subretinal AAV therapy that delivers DNA of two distinct isoforms of the NXNL1 gene, rod-derived cone viability factor (RDCVF) and RDCVFL, to rods, protecting them from the oxidative and metabolic damage that drives degeneration in RP and potentially dry AMD. Its Phase 1/2 trial (PRODIGY) has now completed enrollment of 33 patients, with two and a half years of safety data showing no serious adverse events. Efficacy data are expected in approximately one year, supported by AI-powered machine learning analysis alongside standard statistical methods.

The second program, SPVN20, targets dormant cones, degenerating cells that cannot transduce light, having lost their outer segments, but persist in a structurally altered, weakened state. By delivering a novel ion channel (GIRK1) via intravitreal AAV, SparingVision aims to reactivate phototransduction in these cells, restoring rather than merely preserving visual acuity in more advanced disease. A Phase 1/2 trial (Nirvana) is underway in Europe, with no adverse safety signals observed. The two programs are designed to be complementary, SPVN06 protecting vision in earlier-stage disease, SPVN20 potentially restoring it in later stages, with future co-administration possible.

Session 6: Therapeutic Strategies Spanning IRDs and Dry AMD

An overview of the current therapeutic landscape across inherited retinal diseases and dry AMD, highlighting key modalities, shared biological themes, and platform approaches with potential to translate across rare and prevalent retinal indications.

Harvard Medical School: The Science of Cone Survival

Connie Cepko, PhD, Bullard Professor of Genetics and Neuroscience, Harvard Medical School

Dr. Connie Cepko, a foundational figure in retinal developmental biology, offered the summit's most expansive scientific presentation, a 20-year retrospective of her lab's quest to understand why cones die when rods are lost and what can be done to save them.

The central puzzle: cones don't carry the disease genes responsible for most RP. So why do they degenerate? Dr. Cepko's lab discovered that cones begin dying when rods in their immediate neighborhood are lost, suggesting environmental rather than intrinsic causes. Investigating gene expression changes across four different mouse models of RP, they identified three common pathological processes at the moment of cone death: metabolic failure (cones are not receiving adequate glucose), oxidative damage, and inflammation from activated microglia.

To determine whether these processes are causal, the lab delivered 84 different AAVs expressing 47 different genes across three mouse models. Seven emerged as candidates for gene-agnostic neuroprotection. Highlights include NRF2, a transcription factor that simultaneously combats oxidative damage and inflammation; several secreted anti-inflammatory factors that regulate microglia-neuron interactions; CD47 ("don't eat me"), which protects cones from microglial engulfment; and three metabolic strategies ensuring cones receive adequate energy through improved glucose or lactate supply. NRF2 was also tested in two oxidative damage models thought to mimic AMD. In one model, it completely protected the RPE and the photoreceptors that depend on it.

"I don't think curing, for that number of disease genes, for small numbers of people, is really going to be doable in terms of the funding models. So that's why we took the approach of prolonging vision."

Dr. Cepko framed her lab's strategy explicitly: keep photoreceptors alive long enough for curative gene therapy or editing to reach them, and serve patients whose disease gene has not yet been identified or cannot yet be targeted. She also raised the possibility that these findings could have implications well beyond the retina. The three drivers her lab identified, metabolic disruption, oxidative stress, and inflammation, appear as common threads across many neurodegenerative diseases, including AMD, glaucoma, and potentially vascular dementia.

Closing Remarks

Rethinking What's Possible in Retinal Disease

Amy Laster, PhD, Chief Scientific Officer, Foundation Fighting Blindness

Dr. Amy Laster closed the scientific program with a synthesis of the day's themes organized around three imperatives.

First, the toolkit: the field has moved from single-mechanism thinking to platform thinking, from one gene, one therapy to approaches capable of reaching broad patient populations regardless of genetic background. AAV gene therapy has matured. RNA editing and exon editing are expanding coverage. Cell therapy is moving from concept to clinic. Gene-agnostic strategies are now showing clinical proof of concept.

Second, proving benefit: even the most elegant science can be stalled if it can't demonstrate its value in the right clinical framework. Endpoint selection defines a trial from the outset, shaping feasibility, timeline, interpretability, and whether a positive result becomes an approved therapy. Dr. Laster called on the field to treat endpoints as innovations, to be pursued with the same rigor as biology.

Third, scaling up: real progress requires shared infrastructure. The Foundation's My Retina Tracker® Registry, natural history studies, scientific advisory board, and preclinical research funding have quietly underpinned many of the advances heard throughout the day. Connecting rare and common retinal conditions accelerates discovery and broadens trial networks. Progress happens through coordination, not in silos.

Her charge to the scientific community: prioritize long-term, durable approaches from day one. Bring patients and regulators into conversations earlier. Invest in the talent pipeline. Share failures as openly as successes. "Every month we save in this collective timeline matters to patients and families watching their vision change in real time."

Closing Remarks: The Road Ahead is Paved with Opportunity

Jeffrey Freed, MBA, Foundation Board Director; Chair, Audit & Risk Committee

Jeffrey Freed, Foundation Board Director and himself a person living with RP diagnosed in 2007, closed the summit with news that brought the room to its feet. He announced a $50 million matching gift challenge from the Gordon and Laura Gund Foundation, the largest philanthropic commitment in the RD Fund's history.

Every new or increased commitment made to the RD Fund will be matched dollar for dollar by the Gund Foundation, up to $50 million in additional funding. Given the RD Fund's existing 10x multiplier of donor dollars into outside capital, the effective leverage of the match rises to 20–30 times philanthropic investment. Freed set a first milestone: $10 million in donor commitments by June 2026.

Gordon Gund, in brief remarks following the announcement, reflected on how far the mission has come from the Foundation's founding 55 years ago. "A day like today was way beyond our thought process at the time. I know if it wasn't for days like today and the results that we heard about, no one would want to fund this. And I think we've got a lot to be proud of."

Key Takeaways

• Gene therapy is delivering on its promise. Multiple programs, LCA1, XLRS, LCA5, and XLRP, are approaching pivotal trials, with patients demonstrating real, measurable visual gains. FDA approval timelines of 2028–2030 are being discussed realistically for the first time across multiple programs simultaneously.
• Platform technologies are taking on genes that are too large for single-gene approaches. RNA splice editing (Amber Bio), exon editing (Ascidian), and AI-accelerated design are moving the field toward scalable platforms capable of addressing broad swaths of the genetic landscape, covering 60–70% of patient populations within a single disease rather than one mutation at a time.
• Endpoints define the trial. The day's most consistent theme: endpoint selection at the study's outset determines whether a therapy that works can prove it works. The field must invest in validating new measures, including low luminance visual acuity, the Freiburg Visual Acuity Test, and innovative microperimetry tools, with the same commitment as it invests in the science itself.
• Gene-agnostic approaches are gaining clinical validation. NACA (Nacuity) achieved FDA Breakthrough Therapy designation for slowing photoreceptor loss by ~50% over 2 years. Optogenetics (Zhongmou) is entering U.S. trials with striking early results in patients with RP. SparingVision and Harvard's Dr. Connie Cepko are building a scientific and clinical rationale for neuroprotection strategies that can complement gene-specific approaches at every stage of disease across indications.
• The RD Fund model is working and growing. $95 million committed across 18 companies, nearly $1.5 billion raised by portfolio companies, 12 clinical trials supported, 350+ patients treated, and a 10x multiplier on donor dollars. Gordon and Laura Gund Foundation's $50 million matching gift challenge now has the potential to grow that leverage to 20–30x.

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Angel Partners

Nacuity Pharmaceuticals • Octant • Ora Clinical • SparingVision