Recording Available: Insights Forum | Friday, December 12, 2025

Foundation Fighting Blindness
Insights Forum Transcript
December 12, 2025

Amanda Bement, Development Operations Specialist:

Hello everyone, and thank you for joining today's Insights Forum. Before we get started, I would like to briefly review a few details for this call. Currently, all participant lines are muted and without video. Please be aware that all controls are at the bottom of your Zoom window, and this control bar may collapse when it is not in use. If you would rather prevent the controls from hiding automatically, you can use the following keyboard shortcuts to change your always show meeting controls options. If you are using a Windows computer, you can press the Alt key, and if you are using a Mac keyboard, press Command and Backslash at the same time.

Today's presentation is being recorded and is available with closed captioning. To activate closed captioning, please select show captions at the bottom of the screen on your Zoom toolbar. Please note that on today's call, our speakers do have their videos live. However, all of their comments will be provided verbally and there are no slides. Throughout the call, you will be able to ask questions via the Q&A feature at the bottom of the Zoom window. We will address these questions towards the end of the call. If we do not get to your question live, we will follow up over the next week or so, so please make sure to include your name in your question. You can also submit a question by sending an email to info@fightingblindness.org. I would now like to turn the call over to our chief executive officer, Jason Menzo.

Jason Menzo, Chief Executive Officer:

Thank you very much, Amanda, and good morning, everyone. Thank you for joining us today. My name is Jason Menzo and I'm the CEO here at the Foundation Fighting Blindness, and we are so glad to welcome you to our quarterly Insights Forum meeting. Through these calls, we connect with our global community to share updates on our strategic priorities and initiatives. We spotlight progress across the field and the development of treatments and cures to advance and treat blinding retinal diseases, which is really our mission as an organization. For today's call, we will start with Jeff Klaas, our Chief Strategy and Innovations Officer, who'll share some year-end perspectives and upcoming opportunities for engagement with our community. Then Peter Ginsberg, our Chief Operating Officer, will highlight a few new corporate partnerships, summarize recent industry developments, and provide a snapshot of recent financial performance, plus fiscal year 2026 budget targets.

And then after Peter, Dr. Amy Laster, our Chief Scientific Officer, will provide an update on our Science award programs and natural history studies. And then after Amy, I will share some takeaways from many impactful stories I've heard from our community over the past year and the progress that we're making against our mission. Then to wrap up our formal remarks, I'm thrilled to have Dr. Rachel Huckfeldt with us today. Many of you know Dr. Huckfeldt. She is a recognized retinal specialist and clinician scientist at Mass Eye and Ear and an associate professor of ophthalmology at Harvard Medical School. She is a particularly special individual to our team, and she also serves as co-chair of the Foundation Fighting Blindness Clinical Consortium, which is an international network advancing clinical trials for inherited retinal diseases. Dr. Huckfeldt is going to provide a summary of the clinical landscape of therapies in development and what's coming down the pipeline for treating inherited retinal disease and macular degeneration.

And then as always, after Dr. Huckfeldt's comments, we will open up the call for Q&A. In addition to the speakers that I just mentioned, we will also have Chris Adams, our Vice President of Marketing, and Dr. Rusty Kelley, Managing Director of our Retinal Degeneration Fund with us to participate in the Q&A session at the end of the call. So with all that said, I'm excited to get things kicked off, so I'm going to throw it over to our chief strategy and innovations officer, Mr. Jeff Klaas.

Jeff Klaas, Chief Strategy and Innovation Officer:

Thank you, Jason. And good morning, everyone. I'm pleased to join you today on the Insights Forum. We are in the holiday season, and my primary goal today is to simply say thank you. The amazing progress that you'll hear about on today's call came from significant hard work over many years. And here's the main message, you did this, not just the Foundation, not just the scientists, researchers, and medical professionals, you, the volunteers, the donors, the corporate partners, and the families. You made this progress possible and that's why you show up on these calls. Together, we are accelerating research and changing lives. And at the end of the year, it's the perfect time to renew your commitment to making a difference, to volunteer, to donate, participate. Your involvement is fundamental to our success.

That commitment really came through in this year's Giving Tuesday campaign. We raised over $125,000, representing a 40% increase over the last year. This includes more than 500 individual donors with strong participation by our Board of Directors, our Visionary Circle members who are making annual gifts of $1,000 or more. Let's keep that momentum going.

One of the best ways to engage with our community is to attend the United in Vision's 2026 conference. This groundbreaking global event unites the Foundation Fighting Blindness Visions Conference, and the Retina International World Congress in Fort Worth, Texas. On Friday and Saturday, June 12th and 13th, more than 1,000 participants from around the world, patients, families, researchers, clinicians, advocates, and industry leaders will come together to spark collaboration, innovation, and hope.

We have a dynamic program planned with expert-led sessions, interactive exhibits, and workshops designed to empower and inspire. Whether you're seeking practical insights to navigate vision loss and update on cutting-edge therapies, global networking opportunities, or simply to gather with community committed to lasting impact, United in Vision's 2026 promises to be an unforgettable experience. Please register today and be part of this special event.

In addition to attending events like United in Vision, there are many other ways to stay involved with the Foundation. You can served as a chapter leader, organize Vision Walk teams, host do it-yourself or DIY fundraisers, or contribute to local educational programs. In addition to one-time donations, multi-year commitments and legacy giving directly support research for treatments and cures. So please go to our website, fightingblindness.org, to find the opportunity that works best for you.

And as we look ahead, I want to frame our journey with three simple words, review, renew, and recommit. Review the lives touched this year, the breakthroughs achieved, the hope restored. Renew your connection to our mission, whether it's through time, energy, advocacy, or generosity. Recommit to the road ahead. Because while we've come far, we are not finished. Our mission is now more urgent than ever. And on that final note, I'll turn the program over to Peter Ginsberg, our Chief Operating Officer.

Peter Ginsberg, Chief Operating Officer:

Thank you, Jeff, and good morning, everyone. I'd like to begin our industry and financial summary today by recognizing a couple of our key corporate sponsors providing critical support for important Foundation initiatives. First of all, we've expanded our collaboration with Théa, a global ophthalmology company. Théa has two late stage programs being developed by its dedicated business unit, Sepul Bio. One is sepofarsen, which is an antisense RNA therapy for treating Leber congenital amaurosis Type 10, which is a rare genetic disorder that causes severe vision loss in childhood. And the second program is ultevursen, which is also an RNA therapy, and it targets a specific mutation in the gene that causes Usher syndrome 2A.

We've also initiated a broad partnership with AAVantgarde Bio. AAVantgarde's mission is to restore visual function and halt disease progression for patients with inherited retinal disorders by next generation therapies. AAVantgarde is currently conducting Phase 1/2 trials for its gene therapies targeting Usher syndrome Type 1B, and also Stargardt disease. We really greatly appreciate Théa and AAVantgarde's support of the Foundation and our mission.

Additionally, we've seen pharmaceutical companies becoming increasingly active in our field. Eli Lilly, which is the largest global drug company by market value, recently acquired global rights to MeiraGTx's gene therapy program for Leber congenital amaurosis Type 4. And in October, Lilly announced its acquisition of Adverum Biotechnologies and its intravitreal gene therapy for age-related macular degeneration. Also, Novartis acquired Tourmaline, which is developing a late stage therapeutic for thyroid eye disease.

We're also encouraged to see financings for retinal disease-focused companies, including Opus Genetics, AAVantgarde Bio, and Belite Bio. We're really excited by the momentum being generated by companies in our field, most of which are either partnered with and/or have received funding from the Foundation.

Now, moving on to our financial update. We completed our fiscal 2025 on June 30th and our audited financial statements are now available on our website in the About section under Financials and Governance. For fiscal 2025, our unrestricted net fundraising revenue was $39.1 million, and operating expenses were $20.7 million, yielding a net fundraising surplus of $18.4 million, enabling us to fund even more research than originally budgeted. The combination of that surplus with funds previously committed means that the Foundation was able to invest more than $31 million in retinal disease research and educational programs in our fiscal 2025. I just want to repeat that. The Foundation invested more than $31 million in retinal disease research and educational programs last year. We're excited about the potential of that retinal disease research. On top of that, in fiscal 2025, the RD Fund invested $7.8 million in promising emerging retinal disease companies.

For the current year, which is fiscal 2026, we're targeting $37.9 million in unrestricted fundraising revenue against $24.4 million in operating expenses for a $13.5 million net fundraising surplus. For the first four months of fiscal 2026 through October, we're behind on our budgeted fundraising plans, but we hope to close that gap between calendar year-end fundraising activity this month and then during the second half of the fiscal year. I'm now pleased to turn the call over to Dr. Amy Laster, our Chief Scientific Officer for a research update. Amy?

Dr. Amy Laster, Chief Scientific Officer:

Thank you, Peter. I'd like to cover several topics today, including our progress toward our five-year Science Strategic Plan and a status update on our clinical consortium and natural history studies underway. In fiscal year '25, going back to Peter's comments, in addition to funding more than 90 ongoing programs, we awarded 19 new research grants across five programs totaling $9.7 million. This strategically helps to diversify our research portfolio addressing early, intermediate, and late stages of retinal diseases. We have advanced our efforts in identifying and validating clinical trial endpoints and strategically identifying gaps and opportunities for research for a large fraction of inherited retinal diseases. So looking ahead to fiscal year 2026, we are committing $15.1 million specifically for earlier stage discovery and preclinical research awards, which then fuel the later stage clinical programs. This is an impactful level of investment. However, there is still more to do.

We are seeing a significant increase in the number of grant requests. This means more researchers are entering our field, but there is not enough funding to support all of their promising projects. So there is a sense of urgency in all of our fundraising initiatives because we want to support as much promising science as possible.

In addition to the grants we provide for scientists and research projects, the Foundation also funds natural history studies, which collect mutation-specific data, and this helps to understand disease progression and to enable researchers and therapy developers to identify new and reliable clinical trial endpoints, as well as to inform clinical trial designs for emerging IRD therapies. These studies are coordinated through the Foundation's Clinical Consortium, which is a network of more than 40 clinical sites of excellence with standardized protocols, equipment, and clinical IRD experts. These studies provide important data that helps companies and researchers determine how to advance therapies through clinical trials to get products to our community. I'd especially like to thank Dr. Huckfeldt for serving as the Co-chair of the Consortium.

Now, let's run through a quick update on our natural history studies that continue to progress on schedule. RUSH2A is focused on mutation in the Usher 2A gene that caused either Usher syndrome Type 2A or non-syndromic retinitis pigmentosa. This study has followed more than 100 patients for over four years, and we're now extending that to a total of nine years. And so as we announced the last month, the four-year data are now available for access by the research community through our coordinating center.

RUSH1F is focused on Usher syndrome Type 1F. In this study, the patient visits remain on track with the baseline dataset being prepared for publication now.

Pro-EYS, another natural history study, is focused on retinitis pigmentosa caused by mutations in the EYS gene. Most participants have now completed their final 48-month visit with data analysis underway to inform regulatory endpoint recommendations and to support publication on the baseline genetics and progression.

GYROS is a study that focused on patients with gyrate atrophy, and the recruitment and baseline closeout in this study are complete with grading of the endpoints scheduled to begin later in this calendar year.

And finally, Uni-Rare, which is a broad study that targets more than 1,500 participants who have one of the 300 rare mutated genes that have not been well characterized in the clinic to date. In this study, we're continuing to recruit participants with a goal to fully enroll the remaining longitudinal natural study cohorts by the middle of next calendar year.

If you are interested in participating in one of these natural history studies or one of the many other clinical trials in process, I encourage you to sign up for our patient registry, which is called My Retina Tracker Registry. By being a part of our Registry, you and your affected family members may have the opportunity to be connected with upcoming clinical trials. At last count, there are more than 50 clinical trials being conducted globally. With the Foundation's continued research funding, we do expect that number to continue to grow in the coming years. If you haven't already completed genetic testing to confirm your diagnosis, we encourage you to talk with your retina specialist about the foundation's genetic testing program, which offers individuals with a clinical diagnosis of an IRD access to high quality genetic testing, genetic counseling, and connection to our Registry at no cost to the patients in the United States. You can find more information on how to participate in our Registry at myretinatracker.org.

As you'll hear today from Dr. Huckfeldt, there are multiple life-changing treatments already making an impact for clinical trial participants. As Peter mentioned, there are several companies with positive clinical trial data and successful funding transactions. Belite Bio recently announced positive Phase 3 results for its oral therapy, tinlarebant in Stargardt's disease, which met the primary efficacy endpoint, which showed a 36% reduction in lesion growth compared to the placebo. The company plans to file a new drug application, or NDA, with the United States FDA in the first half of 2026.

Opus Genetics reported sustained vision improvement in adult and pediatric patients in its gene therapy program for LCA5. The company also began enrollment in its clinical trial for macular degeneration due to mutations in the BEST1 gene.

Finally, AAVantgarde Bio progressed its dual AAV gene therapies with clinical testing initiated in Stargardt's disease and encouraging early safety and efficacy signals in clinical testing for RP secondary to Usher 1B due to mutations in the MYO7A gene.

Together, these achievements highlight major advances in inherited retinal disease therapies, spanning oral drugs, gene therapies, and novel delivery platforms. This success is the result of many years of donations making clinical research come to fruition. This is the moment to act. I'd now like to turn the program over to our CEO again, Jason Menzo.

Jason Menzo, Chief Executive Officer:

Thank you so much, Amy, Peter, and Jeff. Great updates from all of you. As we come together at the close of the year, it's now my turn really, to take a few minutes, pause, and reflect not just on the strategies and the priorities or the numbers, but more importantly, on the people that are touched by our mission. Our year-end reviews are often focused on data, the number of trials, the milestones, and the metrics. While all of those are super important and they truly help move our mission forward, really what matters most are the lives of the people who are affected that sit behind these numbers. And so I wanted to take a few minutes and just reflect on the year that is closing now in 2025.

This year, I've had the privilege of traveling and meeting so many of you at our walks, our conferences and community events across the country and even all over the globe. I've shaken hands, I've shared lunches, I've listened to stories, and in all cases, I've learned some really, really impactful things that have stuck with me. I want to share a few of them with you now.

For example, earlier this year, I was at our San Francisco Vision Walk. It's called our Bay Area Vision Walk. And after the walk was over, a young woman, I think she was college age, came up to me and she introduced herself. She was excited to chat. What I found out was that just six weeks before, she was diagnosed with an inherited retinal disease. And then about a week or two after her initial diagnosis, it was confirmed that she did indeed have a rare form of Leber congenital amaurosis caused by the gene, RPE65. At the time, she didn't really know much about our community. She didn't know anything about the Foundation Fighting Blindness, but she dove in and she learned a lot about it very quickly.

The story has an awesome, awesome ending because a few weeks after she was diagnosed with RPE65, she was scheduled to have a gene therapy treatment. And so think about that just for a second. In her case, her journey, went from initial diagnosis to treatment in just a few weeks. Many of the people in our community, that journey has stretched for many, many years and decades, but in this case, the entire process was compressed to just a few weeks. I said this to our team earlier this week. In my mind, I saw the future in that conversation with her, because her experience is truly what we aspire for everyone who's diagnosed with an inherited retinal disease. A future where a diagnosis leads directly to a confirmation via genetic testing and then a treatment in short order. That was a really special experience. It was a really special moment that stuck with me, and it informs the way I think about how our field is evolving and what the future really looks like for individuals in our community.

Another example came from a visit I had actually a couple of weeks ago, just at the end of October. I took a trip up to Pittsburgh. I was up in the Steel City and I met a young family. They have four young daughters, all under 10, and two of their daughters have Stargardt's disease and two do not. I was standing there where I was at the Vision Walk and the mom and dad are standing there, we're talking, and the girls are all smiling and happy, and they were excited because we just finished the walk. It was great to talk to them. The energy, the love and the optimism in this family unit was just awesome. Talking to mom and dad in that moment, what came across in the conversation was that they knew that there were multiple treatments that were in development for Stargardt. They had real hope that by the time their girls were a little bit older and the condition of Stargardt continued to advance, that some of the therapies that are in development are going to be available for their girls. Their positivity about the future was awesome, but it was also justified because they're exactly right, that there's so much progress happening in our field that their hope is not just hope, there's actually reason to believe. That was a really fun and great experience.

And then really, the last one that I want to wrap up my comments with is a story that was recently shared with me by a young mother. Her name is Lindsey. We heard earlier in Amy's comments about the clinical trial at Opus Genetics for LCA5. I want to tell you a little bit about Lindsey's story. She's affected with LCA5. Her journey really does remind us why we're here today. She was initially diagnosed with, and I'm using air quotes as I say this, a disease of the retina as a baby, and she wore glasses starting at just 10 weeks old. At 16 years old, she was told that she had cone-rod dystrophy, with a prognosis of going completely blind.

In her 20s, through genetic testing, Lindsey was diagnosed with more detail. She was diagnosed with Leber congenital amaurosis caused by mutations in the LCA5 gene. And for many years, she had been dealing with the challenges of living with an invisible disability and the daily reality of vision loss, yet her story was not defined by these limitations. It was defined by her resilience. Through her connection to the Foundation Fighting Blindness, Lindsey found information, support, and hope.

And now you flash forward a decade later, in September of 2023, Lindsey became the second participant in a groundbreaking gene therapy trial for LCA5. A lot of times, we hear language like that, a clinical trial, a name of a gene, and this example tells the story of a real person who was actually one of the participants in this trial. She received the treatment and her central vision has improved dramatically since.

As I said a minute ago, the study was being conducted by Opus Genetics, which is an IRD-focused biotech company that was internally conceived here at the Foundation Fighting Blindness and launched by our RD Fund. When I met Lindsey, she shared that about a month after surgery, she looked out her window in her kitchen and she was able to clearly see her kids playing in the yard. And importantly, and this was the key thing for her, was that she was able to distinguish the faces of her kids from the other kids that were playing outside. She said she's never been able to do that before. It was just a little moment, but it was everything. And in her words, she said, “It changed my life because of this.”

Those words capture the heart of our mission, real cures and treatments are happening today. It's not just hypothetical. It's not just someday in the future. It's real. It's tangible, and change to people's lives are happening, as Jeff said, because of you, the people who are helping to support this mission, and of course, folks like Dr. Huckfeldt, who are doing the research and advancing the programs to the clinic and into the clinic.

In fact, Lindsey had this great opportunity to share her experience on Good Morning America just a few weeks ago. Our own Ben Shaberman sat down with her and in one of the upcoming episodes of the Eye on the Cure podcast, she goes deeper in telling her story. If you listen to the Eye on the Cure podcast, this'll be a very special episode coming up. And if you don't listen to the Eye on the Cure podcast, you should subscribe to it. You can subscribe to it on any podcast platform, Apple, Spotify, et cetera.

So as Jeff said earlier on this call, really your generosity is what makes all of this possible. Every gift fuels the research, sustains the programs, and ensures that there'll be more stories like these that I just shared in the future. Together, truly we are bringing hope into focus and moving closer to a future where blinding disease are treatable, they're curable, and the journey can be shortened from decades to weeks. So today, I say thank you. I say thank you for showing up, for believing, for making this possible for your generosity, both in terms of time and your financial contributions to our mission. Each year, the number of lives changed grows larger and larger, and hope becomes a reality for more and more families. And each year, we move closer to the day when treatment is not the exception, but the expectation for all of those in our community.

The number of potential treatments in development has been increasing exponentially just in the last couple of years alone, and to provide a summary on that progress and the status of the many clinical trials for inherited retinal diseases and age-related macular degeneration, I'm thrilled to have Dr. Huckfeldt as our guest speaker today. As I mentioned earlier, Dr. Huckfeldt is the associate professor of ophthalmology at the Harvard Medical School, a leading expert in inherited retinal diseases such as retinitis pigmentosa, Stargardt disease. And she has dual training in neuroscience and ophthalmology, which brings a rare depth of insight to the diagnosis and treatment of inherited retinal diseases. And as I mentioned, she is really at the forefront of translating genetic discoveries into sight-saving research. With that, Dr. Huckfeldt, I'll turn it over to you.

Rachel M. Huckfeldt, MD, PhD, Associate Professor of Ophthalmology, Harvard Medical School:

Thank you so much, Jason, for that kind introduction, but also sharing those wonderful stories about why this work is so important. I just want to comment that as a clinician scientist focused on inherited retinal disorders, I have benefited from all of the work and the support of FFB for over 15 years, I think at this point. And across all my activities, I see on a daily basis the impact of the Foundation. I am grateful to everybody who allows this work to happen. I want to call out the Clinical Consortium that Amy mentioned. It is a really wonderful thing that the Foundation has had the vision and the commitment to start and support the Consortium, and the work has been very impactful. And of course, I get to be here today talking to you about clinical trials and emerging therapies, which is one area where the Foundation's contributions have been very impactful.

As I was preparing for this call last night and counting the number of trials on my list of ongoing trials, I hit a number similar to what Jason shared with you, and it's a real testament to progress. To put that in more of a less abstract form, I recently had the pleasure of seeing one of the very first patients that we ever treated with a gene therapy at Mass Eye and Ear. It was really staggering to reflect over the decade since we treated him, our very first clinical trial, how much growth there has been in this area. So I get 15 minutes to talk to you today and it's unrealistic to go through all the trials trial by trial, but what I'd like to do is really talk to you about the kinds of strategies and approaches that are being tested, and I'm going to highlight areas that I'm particularly excited about.

I do have a few disclaimers. I'm only going to share information that is publicly available. I'm sure that some of you may know more about particular trials than I do, which is wonderful. And also, with all of the trial activities that are currently underway, I'm sure I'm going to unintentionally miss something that I will regret not including. So take that for what it's worth.

I'd like to give you a little bit of a roadmap. I'm going to spend most of my time with you talking about emerging therapies for inherited retinal disorders, or IRDs, but then at the end, we will come back to dry age-related macular degeneration, or AMD. And then thinking about therapies for IRDs, I'd really like us to think about them in two broad categories. And the first is therapies that are designed to target the light sensitive rod and cone photoreceptors to improve their function and improve their health and survival. We can talk about both genetic and neuroprotective therapies in this regard.

And then the second broad group is therapies that are targeted for stages of inherited retinal disorders, where it really makes more sense to think about how can we restore and improve vision without necessarily relying on the remaining light sensitive photoreceptors? And so I would put approaches like optogenetics, stem cells, and retinal chips or implants into the second category.

Let's start with genetic therapies. That's where our field has really been catapulted forward. And these start with the premise that if we understand the precise genetic reason for someone's retinal disease, then we should be able to address their disease at a genetic level. You already heard about Luxturna, or voretigene, in this call, and this was really the first proof of concept that this approach was not just feasible, but transformative. And so like Luxturna, our field has continued to use some of the same strategies.

Many of our therapies that we'll be talking about today use an adeno-associated virus, or AAV, as a delivery truck to bring genetic information to the retina. And most of what I'll be telling you about under the umbrella of genetic therapies is delivered with a surgery where a small volume of a genetic therapy is actually placed under the retina. And what I'd like to first comment on is something you heard about on a personal level from Jason, and that is that on the one hand, we had this remarkable success of Luxturna, but then what is equally important is that we have had three different programs in recent years show us that Luxturna was not a one-off. So you heard about the Opus LCA5 program from Jason. I would add Atsena's LCA1 or GUCY2D program, as well as the MeiraGTx and now Eli Lilly LCA4 or AIPL1 program into that category.

These are all gene replacement, or you can call that gene augmentation programs for various forms of labor congenital amaurosis. Where like Luxturna, we get to hear these pre and post-treatment stories from people that they never fail to give me chills because it's the kind of transformation we want. And so beyond the importance of these three programs and trials to the individuals that have been able to participate in them, they are ongoing proof and foundation for our field that this is an approach to take.

What has also been exciting though is to see the same kind of subretinal gene augmentation or gene replacement therapy brought into a larger scope of inherited retinal disorders. And one of those, of course, has been retinitis pigmentosa, or RP. And as I suspect many folks on this call are aware, a particular form of X-linked RP has been the focus of multiple companies working on gene augmentation therapies. The particular gene is called RPGR, but I'll just refer to the condition is XLRP.

And again, going for concept as much as facts, I think it was so important that all three companies that have worked in this space over time have all shown the potential for improvement in vision in various ways in people with RP and gene therapy. And I want to spend a moment on that because when these trials were getting started pre-2020, I came into it with cautious expectations. It would be great if we could slow the rate of progression, maybe stop people where they were, improvement would be icing on the cake. And so to see these three different programs all show some form of improvement in their outcomes for X-linked RP, it's been a big deal in terms of shaping expectations about what's possible.

Most recently, Johnson & Johnson finished a Phase 3 trial for X-linked RP, whereas they announced last spring, the trial missed its primary endpoint, but had many positive results on secondary outcome measures. As one example of this, half of the participants at the end of one year could read two lines smaller on the eye chart under certain conditions. That's a big deal. That's improvement that we don't see unless there's a therapy that brings it.

And now Beacon Therapeutics is working on a Phase 3 trial again for the same condition, X-linked RP. So we are hoping for their success and hoping that we will have a FDA-approved therapy one way or the other for X-linked RP in the years ahead.

I want to highlight one other ongoing or upcoming Phase 3 trial for a gene augmentation therapy, and that is for the condition, X-linked retinoschisis. This is like X-linked RP, also a condition that tends to affect males more than females. And this particular program is funded by the company, Atsena.

What I want to highlight is that although they are using an AAV like many other trials, this AAV, again, the delivery truck, it's been engineered to be a little special. It can be delivered under the retina a little distant from the place that we want it to act. And as we think about the risk of delivery and trying to make the delivery process as safe as possible, the early signs of efficacy that has been seen in the earlier stages of this program is a big deal and again, speaks to what could be possible in the future.

As I think about gene augmentation therapies, I also want to stress that a gene being a rare cause of disease does not mean that it's not a studied cause of disease and potential gene therapy. Going to rattle off a list of other newer indications that are in first-in-human gene therapy trials. They include the Bardet-Biedl syndrome gene, BBS10, BEST1 causing a particular form of macular disease, RDH12, approaching clinical trials for a form of leber congenital amaurosis, and the gene that causes Bietti crystalline dystrophy. Again, rare indications, but rare does not mean that there's not hope or potential for treatment.

Up to this point, everything I have mentioned has had the ability... All the genes have had the ability to fit into this delivery truck we use, the adeno-associated virus. And on the one hand, this virus is really good at what it does. On the other hand, it has a fundamental flaw, and that fundamental flaw is that you can think of it as a pickup truck, not an 18-wheeler, which is to say that it has a limited cargo capacity for the amount of genetic material that we can put into it. Turns out many of the genes that are the most common causes of inherited retinal disorders are quite large, and they're too large for us to be able to simply put the whole gene into this adeno-associated virus. And so another area of real progress over the last few years has been how we handle big genes. I'm going to focus on this first with the Stargardt gene, ABCA4, and then the Usher 1B gene, myosin7A.

And so what has truly been exciting for me in the last year or two is to see an emergence of multiple first-in-human genetic therapies being brought to clinical trials for Stargardt disease. These trials are possible, again, because of new technical ways to address this challenge of big genes and a limited capacity viral vector. So right now, there are three companies, SpliceBio, AAVantgarde, BeyondGene, that are handling this issue in various ways, splitting the ABCA4 gene in half and engineering their gene therapy so that at the end of the day, whatever mechanism they use, you get a full-length protein with the hypothesis that that full-length protein will slow down the rate of Stargardt progression.

Another company, Ascidian, is taking a slightly different approach. They are doing what I think of as RNA replacement, where they are substituting the first half of the gene and any misspellings it contains with a correctly spelled alternate half at an RNA level. And so again, technical details maybe don't matter, but just phenomenal to have all of these new approaches not only emerge, but emerge and be promptly brought to clinical trials in the last few years.

I said I would mention myosin7A for Usher 2B as well. I think the company, AAVantgarde, has already been mentioned multiple times. Like some of these companies working in the Stargardt area, including AAVantgarde, they are bringing some of these same approaches to handling big genes to the RP that accompanies myosin7A variants. Again, wonderful to see solutions to these technical challenges posed by bigger genes.

There are other ways to do that too, to address big genes. I want to stress that these alternate ways are also active in clinical trials. You already heard during this call about Théa and their business company, Sepul. The nucleic acid medications that Sepul is testing are a little bit different from gene augmentation therapies. Rather than a virus that permanently delivers genetic material to a cell, Sepul's therapies are introducing a medicine that interferes with the process of DNA becoming RNA, becoming protein, again, with the goal of having the protein at the end of the day, being functional and helping to restore vision or slow progression. It's wonderful to see Sepul's two drugs continue in clinical trials. I also want to note, again, under the arm of different ways of delivering genetic therapies, a RNA therapy being tested by the company, PYC Therapeutics, that is taking the innovative approach of rather than replacing a gene, in this case the gene, PRPF31, they're using an RNA therapy to allow the volume on PRPF to be turned up so that more PRPF31 is made.

And I know I'm getting technical, but I think the big picture is I am impressed by the number of new technical and molecular strategies that are being brought to clinical trials, and it's making me very optimistic. There are challenges though. We know that for RP, for example, there are many more genes that cause RP than genes for which there are therapies and trials. It's also possible that some of you on this call may be listening to me and thinking, "But my doctors haven't identified my RP-causing gene yet." And so both of these issues really emphasize that sticking to a gene by gene approach for developing therapies is shortsighted and just not sufficient to make sure that we eventually have treatments for everybody. And if we take a step back to medicine more broadly, we like to have multiple ways of treating the same problem. So if you have high blood pressure that's not fully treated by one kind of medication, you know your doctor will add a second class of medication. That's what we would love to have for inherited retinal disorders as well.

And so I conceptually think of all those drugs that are not gene-specific as falling under the umbrella of being neuroprotective. And what I mean by that is any kind of drug that acts downstream of the genetic variant and the genetic problem to try to compensate for that genetic problem. Neuroprotective medications can be oral, they can be genetic, one is stem cell-based, and they can be specific to one gene or gene independent.

I want to talk about oral and gene-independent therapies first, and there are two that I am certainly paying attention to. One is called N-acetylcysteine, another is called N-acetylcysteine amide. The first of those, N-acetylcysteine is currently being tested in a really impressive nearly 500 patient trial being run by Johns Hopkins to see if this molecule slows down the rate of change in RP. This is a very ambitious, very well-organized trial that we will start seeing more data on in the years ahead.

N-acetylcysteine amide is kind of a sister molecule, also a pill, also has the potential to be gene agnostic for RP, meaning it doesn't matter why someone has RP, perhaps this improves the health of the retina. That recently had some favorable results in a small trial in Australia. I think many things to pay attention to there.

Neuroprotective strategies though, they can be gene specific. And so I say that thinking about the Belite trial that has already been mentioned in this call for Stargardt disease. Indeed, there are at least three therapies being tested for Stargardt disease that are oral medications that interfere in a good way with some of the pathways that go awry when somebody has Stargardt disease. Belite is clearly advancing and progressing well. You heard about their plans for applying for drug approval to the FDA. I think Alkeus is approaching that point as well. In the next year, year and a half, I really look forward to seeing what comes down the pike in this regard.

I want to highlight one other gene-specific oral potential therapy that is being developed by a relatively new company to this field called Octant. Octant is moving to trials soon with an oral medicine that is geared at treating Rhodopsin-associated RP. RHO, as many of you may be aware, is one of the most common forms of dominant RP, certainly in North America, but globally too. It's exciting to see an oral therapy being tested for this particular indication.

When we think about gene-independent neuroprotective therapies, some of them may work by genetic means. There are two companies that are currently testing surgically-delivered genetic therapies to ask, do these therapies slow down the rate of change or improve retinal health?

One of those is being tested by the French company, SparingVision. They are testing a gene and a protein called rod-derived cone viability factor asking, this gene, if given to the retinas of people with RP, does it protect cones and their health?

A company called Ocugen is testing a gene therapy that also is hypothesized, and some data to show this, modifying the health of the retina, in this case by tweaking some of the pathways that are important in rods and cones for health in the setting of RP. It's exciting to see our field move beyond a very narrow gene-specific focus to thinking about what are therapies that could be broadly applicable.

I'll just mention, because I think many of you are aware of it, the company, jCyte, is using stem cells also with a neuroprotective purpose in mind, asking what neuroprotective factors do stem cells injected into the jelly of the eye release that may be beneficial for the health of the retina? And my understanding is that they are continuing on in clinical trials.

Realizing I talk too long, which is always the case, I want to shift gears as we finish to think about vision restoring technologies and thinking about stages of inherited retinal disorders where light sensitive photoreceptors have decreased in number, to an extent, that we need to think about other ways to restore vision without necessarily relying on the photoreceptors. I'll just briefly discuss three different types of therapies in this regard.

The first is optogenetics. Optogenetics asks the question, can we restore vision by making light insensitive layers of the retina light sensitive? And just as a reminder, the retina is a stack of layers. Only the first layer, the rods and cones, is light sensitive. The function of the other layers of the retina is to convey the electrical signals started by the rods and cones to the brain. So what if we, again, put special proteins or genes in those other layers of the retina that can make them light sensitive to start that process of electrical activity one step later?

There's multiple companies working in this area. We saw the first proof of concept a few years ago, and then we've seen a real evolution of the kinds of genes and proteins that are used, whether or not special accompanying glasses are needed as part of this therapy. I think we will see a lot of activity in this area over the next year or two.

I get asked all the time, why can't we have an eye transplant? And it's a great question. We have cornea transplants. I think eye transplants are coming, but for right now, my thought is why fix everything? Let's just fix what we need to. And so we don't need an eye transplant, we need a photoreceptor transplant.

This area of study has been active for a long time. I think we are picking up a little bit right now with two companies, BlueRock and Sumitomo gearing up for... BlueRock is already in clinical trials, but moving into clinical trials of subretinal stem cell transplantation for RP.

And then finally, the idea of a retinal chip or implant is not a new idea. Many of you may remember the Second Sight Argus implant. And then we've had a period of quiet without much activity on that front. In that regard, I was very encouraged earlier this fall about a month or two ago to see a new paper in the New England Journal of Medicine, the premier journal, that described subretinal implants for people with blurry vision due to age-related macular degeneration. So on the one hand, not RP or genetic retinal disease, AMD, but this to me underscores that technology is going to bring types of improvement and therapies that we can't even begin to envision right now, and that some of these therapies will be broadly relevant to all kinds of retinal diseases.

I said I would end with AMD, I'm going to do that quickly. Compared to two years ago, if you live in the United States and you have advanced AMD causing thinning of the retina called geographic atrophy, your retina doctor now has potential therapies for you. We have two FDA-approved treatments that are injected into the back of the eye to help with that kind of thinning. What's exciting is that there is a very rich pipeline of other trials that are being tested in various stages of clinical trials to also help with dry AMD. Some of them address the immune system, others of them address oxidative stress. There's just myriad strategies being brought to that, and of course, stem cells as well. And so I think the potential for treatment changing therapies in that area is rich in the years ahead too. So I'm going to end. I apologize for going a little bit longer than I meant to. I think it reflects my enthusiasm and optimism about what is underway.

Jason Menzo, Chief Executive Officer:

Well, Dr. Huckfeldt, first of all, no apology needed. That was incredible. And this is Jason back speaking now. For those who don't know, we've had 40 some odd questions that have been chatted in either before the call or even during the call. We've got more questions this Insights Forum than I think we've ever had ever. I would venture to say 75% of the questions were answered just in what you were discussing. And so you did an awesome job covering an incredible amount of content in a very simple and easy to follow summary. So that was fantastic and thank you very much. I know everyone on the phone certainly appreciated and enjoyed that.

What I'm going to do now, we've got just a few minutes left in the call, I want to remind the audience that everyone who submitted a question, whether the question was sent in when you registered... Which again, we have 40 some questions that were submitted when you registered. We've had a dozen or so that have been chatted in during the call. Every question is reviewed by Foundation Fighting Blindness staff, and whether we actually answer your question here on the call or not, we will follow up and get an answer to every question that's asked. Don't be alarmed if we don't cover your questions specifically on the call.

There are a couple that we didn't touch on though, so I definitely want to make sure we have an opportunity to touch on those. With that, before we jump to them, now I'm going to invite all of my colleagues to come back off of mute and come on camera. I'm going to ask Amanda to restate the instructions how to ask a question so that way, even if we don't get to the questions here, we can at least capture them to follow up, and then we'll dive into a couple final questions here today.

Amanda Bement, Development Operations Specialist:

This is Amanda. There are several methods that you can use to ask your questions. You can submit them through the Q&A feature that's at the bottom of your Zoom screen. And again, just make sure you include your name in that so that we can follow up afterwards, as Jason mentioned. You can also send an email to info@fightingblindness.org, and we'll follow up in the next week. Back to you, Jason.

Jason Menzo, Chief Executive Officer:

Awesome. Thank you. There were a couple very specific questions. Actually, there were a ton of questions specifically about particular genes or very specific groups of inherited retinal diseases. And there's a couple exciting programs that we have in place that I want to make sure that folks hear about. Amy, the first question I'm going to pose to you is actually around a particular gene called PRPH2. It's one of the more prevalent genes in our space. There were a number of questions about what's happening in PRPH2, what is the Foundation doing around PRPH2? And I thought you could talk a little bit about some of the programs we have in that regard. And then also CRB1, where I know we have a big program in that regard as well. So if you could speak to both of those.

Dr. Amy Laster, Chief Scientific Officer:

Thank you, Jason. This is Amy. I'll start with PRPH2, or peripherin, or you may hear it as RDS. There is no active late stage therapeutic trial for PRPH2, but as Jason mentioned, we have launched and partnered with the Nixon Vision Foundation to target PRPH2 research awards. And these are designed to advance gene-specific and gene agnostic strategies, as well as the natural history study of understanding PRPH2, which is, again, a necessary prerequisite, if you will, for clinical trials. I will say, and people may be aware, there is a personalized N of 1 antisense oligonucleotide effort that is active and it's for a single PRPH2 variant. That information is posted on clinicaltrial.gov. We do not have any details if it's expanded or there'll be additional individuals enrolled in that, but we will ensure that our community stays aware.

I do want to note before I talk about CRB1 that the Foundation together, again, with the Nixon's Vision Foundation, we are hosting a free in-person workshop, and this is going to bring together individuals and families affected by PRPH2 and associated retinal diseases, along with researchers, clinicians, and industry partners, September 9-11, 2026, and that will be held in La Jolla, California. We just sent out a Save The Date and we'll make sure everyone on this call gets that as well.

And now let me just jump over briefly to CRB1. There are many academic and foundation-backed programs. I want to call out specifically one. We have a $2.5 million multi-team project. It's led by Dr. Kay at Duke University, which is really tackling CRB1-related diseases due to causing either LCA or RP. And this, again, multi-institution team, it's using a variety of disease models to understand why the photoreceptors die and to really identify some ways to stop or slow down degeneration. And so it has a key goal of understanding where exactly the damage starts. Can we test some gene therapy approaches to restore the structure that is ultimately the result of the disease and really build some tools that can be used to monitor disease and to design future clinical trials? With that, I will stop. Thank you, Jason.

Jason Menzo, Chief Executive Officer:

Awesome. That's great. Thanks, Dr. Laster. So we've got just a minute or so left, but I do want to address one other area of questions, and we can do it, I think, fairly briefly. But a large number of people in our community are affected with age-related macular degeneration. Obviously, a lot of folks on the call, that's what brings them to our community. Dr. Huckfeldt, I wonder if you could speak a little bit to the difference between dry age-related macular degeneration and then the more advanced form that we refer to as GA and where a lot of the treatments are targeting GA. And so I'm going to pose that to you. And then Rusty, I'll pose to you on follow-up to that to wrap the call up a little bit within our portfolio within the RD Fund of how we're approaching different strategies for treating different stages of AMD.

Rachel M. Huckfeldt, MD, PhD, Associate Professor of Ophthalmology, Harvard Medical School:

Thanks for the question. Geographic atrophy, or GA, represents an advanced form of dry age-related macular degeneration. So up to the point of having geographic atrophy, dry AMD is characterized by having little bumps or drusen underneath the retina. So Jason, without saying it, explicitly, I think you're pointing out a big problem, which is that all of our current therapies for dry AMD wait until there's already significant damage with the thinning and the loss of light sensitive cells that represent geographic atrophy. I know that figuring out how to intervene earlier is a major focus of the dry AMD community, and I hope we have advances in that area in the years ahead.

Jason Menzo, Chief Executive Officer:

That's great. And Rusty, can you speak just at a high level to some of the approaches in our portfolio for the RD Fund?

Dr. Rusty Kelley, Managing Director of the RD Fund:

Yeah, happy to do so. Thanks, Jason. It's a pleasure to be on this call with Rachel as well. Yeah, so the foundation, with all of its granting programs in concert with the RD Fund is targeting a number of mechanisms that would address some of the pathology that Rachel just mentioned. We have a couple of products on the market that address complement. And in fact, we have one portfolio company, Perceive Bio, founded by Greg Hageman and many others, to address a genetic cause of AMD that relates to complement factor H. It's very exciting. That program is in the clinic.

We also have a program founded by Napoleone Ferrara, who is one of the pioneers of the wet AMD success, is now studying dry AMD through trying to gain a better understanding of the vasculature that support the retina. Some believe that that is a key sequelae or the etiology of dry AMD is more related to the ability to get an appropriate blood supply that would stop the growth of the lesions that are caused by the drusen deposits that Rachel just mentioned.

But we have a significant list of new opportunities that we're in diligence with that tackle all sorts of mechanisms of dry AMD. It's a great time to be in this field. These include inflammation, immune modulation, not just complement, which is obviously very popular, but also the mitochondrial intermediate metabolism, oxidative stress, neuroprotection, cell death. And of course, we're also trying to target these diseases, as we are with IRD, via the more advanced therapies of optogenetics and cell-based therapies as well.

Jason Menzo, Chief Executive Officer:

Thank you, Rusty. Well, listen, I want to say thank you to Dr. Huckfeldt, to my colleagues, and to all of you for putting this wonderful program on, and especially to all of the folks that are listening in and dialing in from all over the world. We have participants on these calls from all over the world, and it really is a reminder of how this is a global community that is pushing this mission forward to advance treatments and cures for blinding retinal diseases, including IRDs and AMD, as we've discussed so much today. I wish you all a very happy holidays. I wish you all a happy new year. I'm going to throw it over to Amanda just to wrap the call up. Actually, before I do that, Amanda, anyone who is seeking more information about the Foundation Fighting Blindness, go to fightingblindness.org. Earlier in the call, we referenced an email address that you can send questions into as well. So if you missed your chance during this call, the email address for inbound is info@fightingblindness.org. Over to you, Amanda.

Amanda Bement, Development Operations Specialist:

Thank you, Jason. We would like to thank everybody for participating in today's call. As a reminder, there will be a transcript and audio recording of today's call within the next week or so on our website, which I will repeat for you, wwww.fightingblindness.org. Also, be sure to follow us on Facebook, Twitter, LinkedIn, Instagram, TikTok, and Threads, to stay informed on the latest news and activities from the Foundation. You can like and share Foundation posts on your own social media channels to help spread the word all throughout the month. If there is any other information that you might need, please do reach out to us by sending an email to info@fightingblindness.org. Thank you all and have a great day.