Recording Available: Insights Forum | Wednesday, June 24, 2026

Foundation Fighting Blindness
Insights Forum Transcript
June 24, 2026

Maddie Mossman:

Hello, everyone, and thank you for joining today's Insights Forum. My name is Maddie Mossman, and I'm part of the Foundation's VisionWalk team. Before we get started, I would like to briefly review a few details for the call. Currently, all participant lines are muted and without video.

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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, Maddie. And good morning, everyone. My name is Jason Menzo, and I'm the CEO here at the Foundation Fighting Blindness. We're so glad to have you join us for our quarterly Insights Forum. These calls allow us to engage directly with our community to outline strategic priorities, spotlight advances across the field, and highlight the ways in which we are advancing our mission to speed new treatments and cures for blinding retinal diseases.

For today's agenda, we have Mr. Jeff Klaas, who is Our Chief Strategy and Innovation Officer, who's going to highlight strategic event updates, the expansion of our development leadership team and community engagement opportunities.

Then Mr. Peter Ginsberg, who is our Chief Operating Officer, will provide a snapshot of our recent corporate partnerships and industry developments and also summarize our fiscal year 2026 financial performance to date. And then after Peter, Dr. Amy Laster, who is our Chief Scientific Officer, will share an update on our science initiatives, recent medical conferences and clinical news. And there's a lot of clinical news that she's going to be sharing.

And then after Amy, I will come back on to reflect on key accomplishments from this past fiscal year and share the priorities guiding our work moving forward into fiscal year 2027. And then to wrap up our remarks, we're very pleased to have on the call today, Dr. Eric Pierce, our guest speaker.

Many of you know Dr. Pierce. He is a global thought leader in the retinal space, and truly one of the most trusted and groundbreaking researchers focused on advancing our mission. It's particularly special to have Dr. Pierce join us today because just last month he was awarded the Foundation's highest honor as the recipient of the Llura Liggett Gund Award, which is presented to an individual whose work has fundamentally reshaped the inherited retinal disease research space. Dr. Pierce is going to share his perspectives on the future of precision medicine for inherited retinal diseases.

And then as always, after Dr. Pierce's comments, we will open the call up for questions and answers. And as Maddie said, you can chat your questions in. And if we don't get to your questions today, we'll follow up with you offline.

In addition to the speakers I just mentioned, we have Chris Adams, our Vice President of Marketing, Dr. Todd Durham, our Senior Vice President of Clinical and Outcomes Research, and Dr. Alicia Kemble, our Senior Venture Associate for the Retinal Degeneration Fund, all with us today to participate in the Q&A discussion later.

Before I turn the call over to Jeff, though, I do want to take a moment and recognize and celebrate our very own Maddie Mossman, who you just heard a minute ago, who is not only hosting today's call, but will also be the new host of our Eye on the Cure podcast. I welcome you all to please tune in to Maddie's first episode hosting the Eye on the Cure podcast, which will air next week on July 1st. And she'll be interviewing Dr. Patrick Starapoli, who is a NASCAR driver and practicing retinal specialist at the Retina Consultants of Texas. It's great to kick off the new generation of Eye on the Cure with Maddie next week.

Let's get into the program and turn things 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 am pleased to join you today on the Insights Forum to highlight the progress and priorities shaping our work. Today's call brings together several important updates that reflect both the momentum of our mission and the strength of our community.

We'll start with key takeaways from our United in Vision 2026 conference, which was held earlier this month in Texas.

Nearly 700 members of the blind and low-vision community attended, and more than half were participating in their first Foundation Fighting Blindness event, an encouraging sign of our growing reach and ability to connect with new individuals and families with information, support, and hope.

United in Vision was a powerful reminder of what this community can achieve together. The conference opened with an inspiring keynote from Paralympic gold and bronze medalist and world record holding swimmer, Anastasia Pagonis, whose message of resilience and authenticity set the tone for a weekend focused on progress and possibility.

Attendees also learned about the latest advances in gene therapy and emerging treatments, along with innovative technologies that are helping reshape the future for people living with inherited retinal diseases.

Mental health and emotional wellbeing were also highlighted throughout the conference and reinforced our Mental Health Awareness Month outreach in May. Through new resources, community stories, and expanded awareness efforts, visits to our mental health resource center increased nearly 300% over last year, underscoring the importance of providing ongoing support and resources for individuals and families navigating vision loss.

As we work on ways to meet our community's needs, I'm pleased to share that we've added a new team member to support these efforts. Daniel Widner joined the Foundation as our new Vice President of Community Development. Daniel spent more than a decade at the American Cancer Society supporting community-based fundraising and volunteer engagement, advancing through progressively senior leadership roles.

Most recently, he served as Vice President and Senior Executive Director of Development for the greater San Francisco Bay Area, working closely with field teams, volunteers, and donors across multiple markets in support of community fundraising and signature events. We're excited to have Daniel on our team and look forward to having him share some of the team's priorities on a future Insights Forum.

Speaking of fundraising and signature events, I'm thrilled to report that our New York Night for Sight Gala held in May, raised an incredible $800,000 and brought together more than 350 supporters, thanks to the efforts of our honorees, our committee members, and our community. As we wrap up our spring event season, prepare for upcoming events across the country, including VisionWalks, Scramble for Sight golf events, and Night for Sight celebrations, the Foundation will expand our portfolio of events this fall. We extend our sincere gratitude to everyone who helps make these impactful fundraising events possible. We also encourage you to get involved with an event by reaching out to your community manager or send a note to events@fightingblindness.org.

And finally, I would like to close with a call to action to participate in our National Day of VisionWalk, which will be held on October 31st, 2026. This will be a virtual interactive event that brings our entire community together no matter where they live. Participants will be able to walk in support of the Foundation, connect with others across the country, and be part of a shared day of awareness and action. This event is a great opportunity for people who don't have a local vision walk in their area to get involved, meet others, and feel connected to the mission. Registration and additional details will be available on our website this summer.

Thank you for your belief in this mission and for the generosity you bring, not only through your financial support, but through your presence, your advocacy, and your hope. Because of you, more lives are being changed each year. More families are seeing real progress and the future we've all been working toward is coming into view. Together we're moving closer to the day when treatments are not rare breakthroughs but routine possibilities.

I'll now turn over the program to Peter Ginsberg, our chief operating officer.

Peter Ginsberg, Chief Operating Officer:

Thanks, Jeff. And good morning, everyone. I'd like to begin our industry and financial summary today by recognizing some of the corporate sponsors that provided important support for our United in Vision conference. As Jeff noted, the conference was a really remarkable gathering of our community. Our corporate partners played a key role in enabling the Foundation to put on what was our largest conference ever.

Our United in Vision gold partners were Amgen, Astellas, BlueRock Therapeutics, Genentech, and Sepul Bio by Thea. Our silver partners were Alkeus Pharmaceuticals, American Airlines, Atsena Therapeutics, Belite Bio, EyeBio, which is a Merck subsidiary, Ray Therapeutics, and Regeneron. We also had 10 bronze corporate partners. We're deeply grateful to these industry leaders for their outstanding partnership and steadfast support of our mission.

Now I'd like to highlight recent news related to the Foundation's venture investing arm, the Retinal Degeneration Fund, or RD Fund. We've added two new companies to our portfolio.

First, Agnos Therapeutics is developing AGN-001, which is a gene-agnostic allogeneic photoreceptor cell therapy designed to preserve vision across a wide range of autosomal recessive rod-cone dystrophies. Agnos aims to provide a treatment option for the vast majority of IRD patients who currently lack mutation-specific therapies.

Our other new investment is in Salution Health, an AI‑enabled regulatory and clinical strategy company that helps innovators accelerate ophthalmic therapeutic development. Combining deep regulatory and clinical expertise with a proprietary agentic AI platform, Salution supports drug development teams through trial design, regulatory submissions, and commercialization.

I'm also pleased to report that we just announced a $1 million commitment from A Race Against Blindness to advance gene-agnostic therapeutic approaches for IRDs. A Race Against Blindness was founded in 2023 by Stephen and Kristina Johnston after their son was diagnosed with retinitis pigmentosa caused by Bardet-Biedl syndrome. Since then, the family nonprofit has directed millions of dollars toward research with a focus on pediatric inherited retinal diseases. The commitment directs $775,000 to the RD Fund and $225,000 to a Foundation research award. Importantly, this RD Fund award will be matched dollar for dollar through the Gordon and Llura Gund Foundation Challenge. And Jason will discuss that challenge later in today's call.

Some other important industry news that I wanted to report. First, MeiraGTx acquired bota-vec from Johnson & Johnson through an asset purchase agreement, regaining full rights to the late-stage XLRP gene therapy. The company plans to move quickly toward global regulatory filings supported by its Phase 3 data and its existing role as the commercial manufacturer.

Also, Opus Genetics entered into a strategic financing agreement with Oberland Capital, securing access to up to $155 million in funding. This financing strengthens Opus' ability to advance multiple IRD gene therapy programs toward clinical trials, manufacturing readiness, and future regulatory milestones. Foundation Fighting Blindness and RD Fund founded Opus Genetics, and this large financing is a very important milestone for the company.

In other events, Amgen reported positive Phase 3 results for its subcutaneous version of TEPEZZA, its treatment for thyroid eye disease or TED. The subcutaneous on-body injector formulation showed efficacy comparable to the IV version, potentially expanding access and convenience for patients with moderate to severe active TED.

Also in the TED field, Viridian reported positive Phase 3 results for elegrobart, which is its subcutaneous IGF-1R inhibitor for chronic TED. The company plans to submit a biologics license application, or BLA, to the U.S. FDA in 2027.

What's most exciting across all of these developments is the momentum building in our field. For instance, there's the potential for as many as five inherited retinal disease therapies to achieve regulatory approval in the next two years, pending successful clinical results and regulatory review. While it may be overoptimistic to expect all five to be available to our community members in the near term, even the addition of two or three would have a great impact.

Finally, I'd like to conclude my remarks by providing our quarterly financial summary. As you may recall, the Foundation operates on a fiscal year that runs from July to June, and I'll report on our financials through May. For the first 11 months of fiscal 2026, our unrestricted fundraising revenue was $26.0 million versus expenses of $21.7 million, and our current projections for fiscal year 2026 ending later this month place us on track with our fiscal 2026 budget.

I'm now very pleased to turn over the call to Dr. Amy Laster, our chief scientific officer for a research update.

Dr. Amy Laster, Chief Scientific Officer:

Thank you, Peter. There are a number of key science topics that I want to cover today. I'm going to highlight our newly awarded grants, some development on the federal grant review process, additions to our natural history studies, and some takeaways from the recent Innovation Summit that we hosted prior to the annual ARVO Ophthalmology Research Meeting. I'll wrap up my comments highlighting some of the clinical announcements since our last form call.

I'm pleased to report that we expect to invest nearly $15 million in new research funding in our fiscal year 2026. We recently announced 13 new awards that span from individual investigator research awards to research awards that focus on disease models.

We're seeing a steady rise in the number of scientific and clinical proposals that are submitted. And this is really a clear sign that more investigators are entering the inherited retinal disease field with really strong ideas and momentum.

Unfortunately, the available resources haven't kept pace and it forces us to leave many promising projects without the funding that they need to move forward. And so this is why urgency really underpins all of our efforts. We want to ensure that as many high potential research projects as possible can advance towards meaningful impacts for the field and ultimately for patients.

These opportunities were on full display last month when we hosted our 11th Annual Retinal Therapeutic Innovation Summit ahead of the 2026 ARVO, or Association of Research in Vision and Ophthalmology Conference. With nearly 500 participants, the Innovation Summit continues to be the premier convening of industry leaders, clinicians and researchers to advance treatments for retinal diseases.

And then post the Innovation Summit, the ARVO Conference highlighted a field that's rapidly advancing towards precision, scalability, as well as clinical impact. And the convergence around artificial intelligence, RNA therapeutics, clinical trial design and endpoints, and enabling technologies really reflect a maturing research biomedical ecosystem that's focused on delivering meaningful outcomes for patients.

In addition to supporting scientists and research initiatives through our grants program, the Foundation also invests in natural history studies that gather mutation specific data to map how these diseases progress. These studies provide the important data that researchers and therapy developers need to design clinical trials for emerging IRD treatments and identify potential participants for these trials.

Our largest natural history study, Uni-Rare, targets more than 1,500 participants who have one of the 300 rare mutated genes that have not been well-characterized in the clinic today. We are excited to have a new collaboration with Octant, Inc. to expand the Uni-Rare study by adding a new cohort for people with IRDs caused by mutations in the RHO gene.

We are continuing to recruit participants across the range of mutations with a goal to fully enroll the remaining longitudinal natural history study cohort shortly. We strongly encourage community members to find out more about the Uni-Rare study to see if you or your family member is eligible to participate.

More information about this study and other ongoing clinical trials is available on our website on the Clinical Trials Pipeline page in the research section. On that page, you will see that there are now more than 60 clinical trials for retinal diseases underway.

I'd like to highlight some of the recent clinical news coming from some of these studies.

Alkeus recently reported that it has dosed the first patient in its global Phase 3 study evaluating gildeuretinol acetate for the treatment of Stargardt. Alkeus plans to enroll approximately 230 participants between the ages of eight and 45 who have advanced Stargardt disease, with about 55 planned sites across more than 11 countries.

Beacon Therapeutics presented new X-linked RP clinical data at ARVO and showing continued functional improvements in treated patients, including sustained retinal sensitivity gains.

Atsena Therapeutics presented updated XLRS and LCA1 clinical data at ARVO with safety and functional findings consistent with program advancements. And just this week, Atsena reported that it dosed the first patient in its Phase 3 pivotal trial of ATSN-201 for X-linked retinoschisis, with the top line results anticipated in the first half of 2028 and a potential FDA filing for approval in the second half of 2028.

Opus Genetics presented new LCA5 Phase 1/2 pediatric data at the AVRO Conference this year, showing continued improvement in cone-mediated vision and functional outcomes in treated patients.

VeonGen presented results from its ongoing Phase 1/2 study in its Stargardt program, in which VG-801 demonstrated a favorable safety profile with no dose limiting toxicities or serious adverse events reported to date in both adult and pediatric patients.

In addition to following trial listings and recent news, there's another important way to stay aware of clinical work happening in your specific disease or mutation. We encourage you to sign up for our patient registry called My Retina Tracker Registry. By being a part of our registry, you or your affected family member may have the opportunity to be connected with upcoming clinical trials. Please go to the research section of our website to find out more information.

I'd now like to turn the program back over to our CEO, Jason Menzo.

Jason Menzo, Chief Executive Officer:

Thank you very much, Amy. That was a great update. It is always so exciting at this stage of our Insights Forum calls to hear the latest updates in the clinic and the programs that are actually moving from the lab to the clinic and all of these great updates.

Since we're here at the end of our fiscal year, and I think everyone by this point in time knows, feel like we say this every year, we are on a unique schedule here at the Foundation Fighting Blindness that our new year starts on July 1st. And so this is really the end of our fiscal year 2026 right now.

With that in mind, I'd like to take just a few minutes to review some of our key accomplishments from this past year as well as some of our priorities for the year ahead. And I think it's really important to start this portion of the program by recognizing that fiscal year 2026 was a year that was marked both by extreme progress, which we heard some of just a few minutes ago, but also profound loss.

This past year, we mourned the passing of three key leaders of the Foundation whose contributions helped shape the Foundation and the mission, not only during their time with the Foundation, but also for years to come. I think everyone on this call at this point knows that earlier this year we lost Karen Petrou, who at the time was our Board chair. We also lost Ed Gollob, who is the past President of the Foundation Fighting Blindness and a Board member, particularly impactful at some of the early days of the Foundation's formation and early days of the Foundation making progress. And also Bill Carty, who is a recent Board member of the Foundation Board of Directors. And I do want to take a moment to just recognize their leadership, their advocacy and commitment, and how the impact that each of them made really continues to influence our work and will be felt for years to come.

Now, at the same time, this past year, the Foundation continued to build on incredible momentum across research, clinical development, community engagement, and fundraising activities. Today, the Foundation is driving more than a hundred active research projects worldwide across a broad range of therapeutic approaches, including gene therapy, gene editing, RNA editing, cell therapy, neuroprotection, optogenetics, other gene-agnostic approaches, and as we heard just a few minutes ago, also now artificial intelligence.

Our global clinical consortium continues to generate critical data that helps accelerate therapeutic development. As a matter of fact, we have six global natural history observational studies completed or in progress, and collectively, these natural history studies have generated data for more than a thousand individuals living with inherited retinal diseases, which are critical in helping researchers and industry partners better understand disease progression and prepare for future clinical trials.

As you heard from Amy, today there are more than 60 interventional clinical trials underway. These are trials, testing treatments in people. And this represents more therapeutic opportunities for patients truly than at any other point in time in history. The field could see as many as five new FDA approvals over the next 18 months, which is incredible, and it really speaks to the strength of the treatment pipeline and the momentum that we're seeing in the field.

The RD Fund continues to serve as a critical catalyst for therapeutic development. Since we launched the RD Fund in 2018, the fund has grown from an initial $73 million, to today, over $130 million under management and with nearly a hundred million of that deployed in investing in companies advancing our mission. To date, we've completed 19 investments, including two new investments in fiscal year 2026 alone. And the portfolio companies that we have invested in collectively have launched a dozen clinical trials. They've attracted more than a billion dollars (with a B) and follow on capital from for-profit venture capital investors.

And the most important thing is that through the RD Fund, the companies that we have invested in have treated now more than 400 patients with inherited retinal diseases or age-related macular degeneration. And that number is only going to climb and climb and climb over the months and years ahead.

Historically, every dollar that we have invested through the RD Fund has attracted $10 of additional outside investment. And these results continue to validate that the Foundation Fighting Blindness's venture philanthropy model and its ability to accelerate a path from scientific discovery in the lab to patient impact in the clinic and soon to be in the market.

To capitalize on this unprecedented momentum across the field, we recently launched a major $50 million campaign to expand the RD Fund. And to fuel this campaign, we're very happy to share today that Gordon and Llura Gund Foundation has issued a match/challenge and will match every dollar raised for the RD Fund campaign up to $50 million, creating a unique opportunity to accelerate future investments and attract even more additional capital to focus on the mission of driving treatments and cures for blinding retinal diseases.

This is really a special opportunity, particularly for high-net-worth individuals to make meaningful impact on our field. And I ask you, if you are interested or have someone in your network that might be interested in learning more about this opportunity, to please contact us at dev@fightingblindness.org. That's D-E-V @fightingblindness.org.

In addition to advancing research, we remain firmly committed to community engagement and advocacy. The Foundation serves as a trusted source of information, education, advocacy, and community engagement for those affected by retinal diseases. And in this past year alone, we had more than 10,000 of you participate in VisionWalks across the country. We hosted 70 different educational symposia across the country. We had more than a dozen national webinars and virtual programs. And we advanced multiple federal advocacy priorities, including support for a strong and independent National Eye Institute.

In total, more than two million individuals engaged with the Foundation Fighting Blindness through either in-person or digital activities this past year, and our online presence generated nearly 36 million impressions. And so as we enter fiscal year 2026 ... I'm sorry, fiscal year 2027 - it's going to take a second to get used to that - as we enter fiscal year '27, we really do have strong momentum.

And to recap, we have a hundred active research projects that we're funding. We have six natural history studies ongoing or completed. We have more than 60 active clinical trials in the field. We have as many as five potential regulatory approvals over the next 18 months. We have a growing RD Fund portfolio with more than $130 million under management, invested in 19 different investments making progress and advancing the mission. We have strong fundraising performance and organizational engagement. And we expect to raise more than $40 million in new capital this next year to fuel our advances faster than ever.

The opportunities before us really have never been greater, and with continued support from our stakeholders like all of you on this call, the Foundation is well-positioned to accelerate the development of treatments and cures in fiscal 2027 and beyond.

Before wrapping up, I just want to highlight some really exciting news for our space and particularly the IRD research community. You may have heard of the Breakthrough Prize, which is an award established nearly 15 years ago by a group of technology leaders to shine a light on scientific achievements that expand what's possible for patients for society. This is a really big deal. It's a high profile award.

I'm really excited to share that the 2026 winners of the Breakthrough Prize included three members of our research community, Dr. Jean Bennett, Dr. Albert Maguire, and Dr. Kathy High, in recognition of the impact of their pioneering work in gene therapy. As I think everyone knows by now, their groundbreaking research at the Children's Hospital of Philadelphia and at Penn Medicine led to the development of the first FDA-approved gene therapy for any condition, LUXTURNA, for the treatment of RPE65 associated retinal diseases.

This achievement really transformed a future for people, not only with this form of LCA, but also helped to define an entirely new therapeutic area with now several additional gene therapies having been FDA approved since that breakthrough moment. And this international recognition really comes as no surprise to our community. We've known the important work that Drs. Jean Bennett , Maguire and High have been doing for years. In 2021, Dr. Bennett received the Foundation's highest honor, the Llura Liggett Gund Award, and now with the Breakthrough Prize also reflecting the extraordinary impact of decades of dedication to advancing treatments and cures in our space.

Speaking of the Llura Liggett Gund Award, it really serves as a perfect segue to our featured guest speaker today who just happens to be the 2026 winner of this prestigious award. I think many on the call today know Dr. Eric Pierce, but for those who don't, he is the William Chatlos Professor of Ophthalmology at Harvard Medical School, where he also serves as the director of the Berman-Gund Lab for the study of retinal degenerations and is the director of the Ocular Genomic Institute at Massachusetts Eye and Ear.

Dr. Pierce's relationship with the Foundation spans more than 25 years. He has served as the chair of our scientific advisory board, helping shape research funding strategy and launching career development initiatives that have really supported a whole host of new generation of investigators. And so we're thrilled to have Dr. Pierce with us today.

Eric, I'll turn the program over to you.

Dr. Eric Pierce, Professor of Ophthalmology at Harvard Medical School

Jason, thank you so much, and thank you all for tuning in. As you may have heard, I gave a version of this talk at the Innovation Summit at the ARVO meeting when I received the Llura Liggett Gund Award. It's a great honor to receive this award. It's really been a pleasure to be part of the FFB family for the past 25 years, and I'm grateful to all of you and to Lulie and Gordon and the other members of the Gund family for all of your friendship and support over the years.

So in advance of that meeting, when I received the award, Chad Jackson asked me to talk briefly about the progress towards gene editing as treatments for inherited retinal degenerations. I'm going to do a short version of that talk to review briefly progress to date towards using gene editing to treat inherited retinal disorders and identify a couple of challenges that we've learned about as we deploy these approaches, and discuss briefly some future directions. I'm going to try to keep this short so there's more time for question and answers, because I understand there are a bunch of questions that have been submitted.

As Jason mentioned, I do my work at the Ocular Genomics Institute at Mass Eye and Ear Harvard Medical School. It's a great group of 14 colleagues all working towards developing therapies for inherited eye diseases, with a core group focused on inherited retinal degenerations. And we're really trying to change the paradigm of understanding and developing treatments for inherited diseases in general.

And in addition to the progress you've heard about so far in this call towards therapies for inherited retinal disorders, there's great progress in general in the field of medicine towards developing treatments for inherited disorders globally. There are now 17 approved gene therapies for rare inherited disorders, 11 antisense oligonucleotide therapies approved and many more in hundreds of clinical trials being studied.

I think these genetic medicines demonstrate the potential of genetic therapies and show that we've made a great start on turning our understanding of genetic causality of these diseases into precision medicines. And it's really helped identify a new field of genetics, which we're starting to call interventional genetics.

As you heard just now, there was a big milestone in our field with the development of gene therapy for RPE65 associated retinal degeneration, or LUXTURNA, that generated a lot of interest not just in our field, but across medicine in general. And as you've heard, there are many clinical trials in progress of additional therapies for inherited retinal disorders, including 16 of them for adeno-associated virus or AAV-based genetic therapies, or antisense oligonucleotide therapies, and one genome editing therapy in progress with many more coming. And we're hoping that some of these, which look very promising, as you've heard so far today, will be some of the next approved genetic therapies for inherited retinal disorders.

Progress is moving forward, but we're also learning from challenges encountered along the way, so I want to talk a little bit about that. The first gene editing therapy for inherited retinal disorders was developed for CEP290 associated leber congenital amaurosis or severe early-onset retinal degeneration. Turns out that the most common misspelling in a gene, the most common mutation in a gene causing severe early-onset retinal disease is a mutation in the CEP290 gene that basically turns the gene off.

We can't use regular gene therapy for CEP290 associated disease because the gene's too big for the adeno-associated virus vectors that are used for delivering therapeutic genes to the retina. So this is a great target for gene editing or CRISPR-Cas9 associated remediated gene editing approaches. The company, Editas, developed the genetic therapy called EDIT-101 to treat this disease. I consulted with them during that development and had the fortune to lead that trial when it came to clinical trials.

EDIT-101 is an AAV drug that delivers the gene editing reagents for the CRISPR-Cas9 approach to the retina to cutout that mutation and the CEP290 gene that prevents it from working and restore gene function. We treated 14 subjects in that trial, and I think the trial was a significant success. There was a good safety profile. And even though it was an early Phase 1/2 study focused primarily on safety, there was good evidence of efficacy, with eight of the 14 subjects showing clinically meaningful improvement in their vision, such as their cone function, their ability to detect light or their visual acuity, and 11 of 14 having measured or reported some improvement in their vision.

That's a win on many accounts. And what makes me realize therapy is effective was hearing what participants in the study said. One young woman who was treated when describing meeting one of her friends in one evening for dinner, said that with her untreated right eye, she was not able to see her friends' facial features but only their silhouette. But with her treated left eye, she could see everything on their face. That's quite a profound improvement.

And I think gene editing for this disease and for many other inherited retinal disorders has the potential to deliver that kind of improvement in vision broadly. This was also the first clinical trial ever using CRISPR-Cas9 gene editing therapies in vivo, in patients directly. So this is a milestone for biomedical research in general showing that gene editing can be used safely in vivo.

Unfortunately, Editas, the company that sponsored these studies, chose not to pursue driving this therapy towards Phase 3 style trials and eventual licensure. And I think that's because the expectations for improvements in vision that might be obtained were too high and because of perceived challenge in identifying an endpoint that the FDA would approve to use for this drug. And I think that's emblematic of some mixed results that have been obtained in the IRD field in general.

You've heard that there have been some recent successes in clinical trials of therapies or other genetic forms of disease, like RPGR and GUCY2D and retinoschisis, et cetera, LCA5. Hopefully those will be the next approved therapies. But there've also been some challenges, drugs that even in Phase 3 trials, although they worked well, didn't meet their primary pre-established endpoints and therefore are delayed in getting FDA approval.

So how do we increase our success rate in these therapies? How do we get more of the therapies that are being developed in labs around the world into clinical trials and then successfully approved by regulatory bodies? And I think there are a bunch of categories or possibilities of how to do that. And I know time is short, so I'm going to just go through the list of what I think the options are where to improve our success rates and try to finish up promptly.

Even though you may not want to hear this, I think we still need to continue to improve our understanding of the disease genetics and biology of inherited retinal diseases. Those of you who may know me won't be surprised to hear that. I think there are multiple reasons for this. I think we need to understand the genetics better so we can not only identify more people who are eligible for potential therapies, but also to go further into understanding the genetic contributions to disease so we can identify in advance who might respond to therapies best and therefore be the best subjects for treatment.

We also need to update clinical trial design. We need to identify and convince regulatory bodies of additional approvable endpoints, including better patient reported outcomes. The natural history data being collected in the FFB sponsored studies is critical to this. And we also need to develop and focus on something called surrogate biomarkers, which I'll talk very briefly about, and of course have realistic expectations in these studies. If we can make a severe disease less severe, we've made an important contribution and that should be an approvable drug.

So what do I mean by surrogate biomarkers? I'm mentioning that because the FDA recently put out what they call the plausible mechanism framework to develop individualized therapies that target specific genetic conditions with a known biologic cause. What that means is, for rare diseases, including many inherited retinal diseases, if we can identify the root genetic cause and develop a treatment that targets that and there's natural history data we can use for controls, we could potentially get FDA approval for a therapy with one well-controlled clinical study. But a key piece in achieving that is being able to demonstrate what the FDA called target engagement. Meaning, did the genetic drug actually do its genetic job and restore function of the target gene, for example?

We currently really can't do that in the inherited retinal disease space because we can't assay retinal cells directly. So we need surrogate biomarkers to tell if the target engagement has occurred. We did that for the CEP290 study that I mentioned by knowing that people's vision improved. But that's a secondary effect. How would we measure that the gene editing and the target photoreceptor cells actually took place?

So there are some wonderful research studies, some being supported by the Foundation Fighting Blindness directed towards developing these biomarkers so we can detect target engagement and potentially benefit from this hopefully new policy which the FDA will adopt to allow improved progress towards more therapies for rare genetic disorders.

There's a lot more to say on this, but I'm going to stop here so there's time for questions. I hope you all understand that genetic therapies show great promise for treating inherited rental disorders. And it's really a pleasure to see how the FFB has catalyzed this field moving more in this direction. Thank you all.

Jason Menzo, Chief Executive Officer:

Well, thank you very much, Dr. Pierce. And often times I feel like these calls we should schedule for two hours because there's actually so much to cover. We actually have more questions that were sent in advance for this call than we've ever had. I think it was like 50 or 60 questions were sent in. We're obviously not going to be able to get to all of them, but there are a few in particular that I want to make sure that we touch on here while we're all together. We've got about 10 or 15 minutes, so we'll be able to cover a handful of them for sure.

Maddie, why don't you go ahead and re-review the instructions for asking questions so anyone who is interested in asking a question can send it in. Even if we don't get it on the call, we'll follow up.

Maddie Mossman:

Thanks, Jason. There are several methods that you can use to ask questions. You can submit them through the Q&A function at the bottom of your Zoom screen. Please make sure you include your name so that we can follow up with you afterward. You can also send an email to info@fightingblindness.org, and we will follow up with you in the next week.

Jason Menzo, Chief Executive Officer:

Thank you very much, Maddie. I invite all of our team members to come off of mute and turn their cameras on, and we'll go ahead and jump in. First, I have a question for you, Dr. Pierce, and a second regarding a high level overview of what's happening clinically broadly for RP. And before I send that to you though, I want to make sure that everyone in the audience knows because there were a lot of questions about where can I find this information, what resources exist, how do I find out what the latest is with clinical trials other than these calls.

I want to point folks to our website. Fightingblindness.org has a wealth of information, but in particular the tab that is titled Living with Vision Loss has access to our Mental Health Resource Center, a whole host of resources for low vision, including a doctor directory and resources, and it can also direct you to local leaders in the community through our chapter network. So there's a ton of information there. And then also through the research tab of our website is where we have our Clinical Trial Pipeline. When we keep saying there are now 60 clinical trials, more than 60 clinical trials, every one of those are listed on our website and that's a great place to find that information.

Dr. Pierce, can you give a brief overview when we think about RP, which affects a large percentage of people on this call, what are the two or three things that ultimately excite you in terms of the landscape and what should people know about what's happening in terms of advances there?

Dr. Eric Pierce, Professor of Ophthalmology at Harvard Medical School

Well, to pick up on what I was just talking about with the gene editing, I think there's some very promising genetic therapies being developed for inherited retinal degenerations that fall in the RP or rod-cone degeneration category, which you're asking about.

In addition to genetic therapies, we continue to try to create and develop therapies that might be useful for groups of people with different genetic forms of inherited retinal disease. I think it's going to be hard to find therapies that are truly gene-agnostic, but I think it might be quite possible to find therapies that can work for a group of genes that share some common underlying disease mechanisms. Some of those are neuroprotective therapies like N-acetylcysteine, or NAC, which are showing varying results in several clinical trials. And then of course, there's this long-term goal, kind of holy grail, of developing a regenerative therapy with maybe the right stem cell recipe that might be beneficial for patients with more advanced disease.

Jason Menzo, Chief Executive Officer:

That's great. Thank you. A couple questions came in related to the statement that there are as many as five potential FDA approvals in the next 18 months or so. A couple of those are for RPGR or X-linked retinitis pigmentosa. Alicia, this is your first time on these calls, so welcome, but why don't you share a little bit about X-linked retinitis pigmentosa and our investment in Beacon and obviously the other company in that space, MeiraGTx?

Alicia Kemble, RD Fund Senior Venture Associate:

Thanks, Jason. So as Peter mentioned, MeiraGTx has recently acquired Johnson & Johnson's asset bota-vec for XLRP. And the company is planning to initiate a BLA filing immediately to the FDA. And that's a biologics license application, which, if approved, allows therapeutics to enter the market for commercialization. Although the Phase 3 LUMEOS trial conducted by J&J missed its primary endpoint, new and potentially flexible regulatory pathways for rare disease and a consensus among experts in the field supported by the Foundation, that the failure rested in the design of the primary endpoint and not efficacy could allow the company to gain approval.

Beacon Therapeutics, as Jason mentioned, is an RD Fund portfolio company and is advancing their XLRP asset laru-zova in a Phase 2/3 VISTA pivotal trial, with top line data expected to be reported in the second half of 2026. And upon reception of positive data, a BLA submission by the end of 2026 with a potential acceptance by the end of 2027 is expected.

Jason Menzo, Chief Executive Officer:

That's great. So there's two of the potential. And we want to be cautious in how we say this, these are far from guaranteed, but there are five potential approvals in the next 18 months, two of them for XLRP, MeiraGTx having one of those potential approvals, and Beacon Therapeutics to the other. So that's great. Thanks, Alicia.

Amy, let's come to you. Dr. Pierce a moment ago spoke about the possibility of what the future might hold with regards to gene-agnostic approaches. Maybe you could just provide a brief explanation. When we say gene-agnostic, what does that mean? What about cell therapy? What about therapies that are designed to slow down the progression, not necessarily halt the disease or reverse the disease, but maybe you could give a gene-agnostic overview.

Dr. Amy Laster, Chief Scientific Officer:

Thanks, Jason. Again, this is Amy. And as Jason is alluding to, when we say gene-agnostic, it's a treatment that can benefit individuals regardless of their genetic mutation? And so Dr. Pierce just mentioned NAC, or NACA, as one small molecule or drug that is being tested that may help to slow down the progression of disease. There are other treatments such as from SparingVision that may also have gene-agnostic benefits that are also in clinical trial.

And then there are two exciting approaches, which are the cell-based and optogenetic therapies, which are also gene-agnostic. They take really two very different paths to restoring vision. With cell-based therapies, essentially this is a form of cell replacements where you have researchers that are growing healthy retinal cells in the lab and then they place them in the eye, and I'm really simplifying this, with the goal of replacing or supporting cells that have been lost. Then on the other hand, you have optogenetic therapies, which is a different approach. So instead of replacing the cells, basically they're reprogramming the remaining cells within the retina to respond to light. It's essentially helping them to act like new light detectors.

In simple terms, these two gene agnostic approaches, one strategy is to replace damaged cells while the other rewrites the cells that are still there to restore light sensitivity. There are several companies that are exploring these strategies to benefit RP, Stargardt, Ushers, and they're on our Clinical Trial Pipeline page. I do invite you to go there and to see the clinical trials that are offered in this space.

Jason Menzo, Chief Executive Officer:

That's great. Thank you, Amy. And to your point, each of these strategies have different companies or projects, some of which are at the clinical stage, some are preclinical, some are very early. But the strategies that we're describing have many, in a lot of cases, many different shots on goal executing each of those strategies at different stages of development.

A couple questions came in, actually more than a couple, a lot of questions came in about age-related macular degeneration. We spent a lot of time today talking about RP or LCA or different IRDs. But Alicia, I'm going to come back to you. We have several investments through the RD Fund specifically targeting AMD, and maybe you could briefly give an overview of what those look like.

Alicia Kemble, RD Fund Senior Venture Associate:

Sure. The RD Fund currently has three companies in our portfolio with therapeutics to address dry age-related macular degeneration and its late-stage manifestation geographic atrophy. InVasc is a preclinically staged company developing a biologic, a leukemia inhibitory factor agonist, which promotes revascularization to atrophic lesions, so areas of cell death.

Perceive Bio is a clinical stage company developing an AAV gene therapy to target mutations in the complement factor H gene, which has been identified as one of the strongest known inheritable risk factors of AMD.

The third company has yet to publicly disclose their AMD assets, but be on the lookout because they may do so in the near future.

Jason Menzo, Chief Executive Officer:

That's great. Thank you, Alicia. We had several questions coming in about Stargardt in particular. And Dr. Pierce, one of the potential five approvals the next 18 months is a treatment for Stargardt disease we spoke earlier on this call, also about Alkeus, and there's obviously technology in development that are genetic in nature that are targeting Stargardt. Maybe just very high level, your thoughts on what the future holds for treatments for Stargardt.

Dr. Eric Pierce, Professor of Ophthalmology at Harvard Medical School

I think it's very exciting what's developed for ABCA4 associated retinal degeneration or Stargardt disease. As you mentioned, there's potential for small molecule therapies developed by companies like Alkeus. And genetic therapies and modern genetic and gene editing approaches are being deployed effectively for Stargardt disease with both dual AAV vector gene therapy approaches and RNA editing approaches now in clinical trials, which I think is very exciting.

Jason Menzo, Chief Executive Officer:

That's great. We are almost at time. And probably one of the most exciting questions that may be on a lot of folks' mind we haven't gotten to yet, but I'll just maybe tease with this. Between all of the mainstream media talking about companies like Neuralink or brain-computer interface or retina-on-chip, or through our partnership with ARPA-H in a whole-eye transplant potential, maybe just in 30 seconds, Dr. Pierce and then Amy. I know, loaded question, 30 seconds. What is exciting about the potential for really groundbreaking next-generation prosthetics, brain-chip interface, whole-eye transplant? What does the future really hold over the next several years in that regard, Dr. Pierce?

Dr. Eric Pierce, Professor of Ophthalmology at Harvard Medical School

So I'm most excited about the technology that Daniel Palanker and colleagues from Stanford developed called the PRIMA retinal prosthetic. I've been skeptical about retinal prosthesis for many years, and I think this has real potential.

Jason Menzo, Chief Executive Officer:

And Amy, maybe around whole-eye transplant, what are your thoughts on this topic?

Dr. Amy Laster, Chief Scientific Officer:

Again, this is Amy. We’ve been taking a leadership role in a very ambitious vision restoration effort. This is a multi-institutional whole-eye transplant program through one of the federal agencies, ARPA-H. The goal isn't just to transplant an eye, but to really restore vision by solving a lot of major challenges, like reconnecting the optic nerve. You got to preserve the donor tissue, advancing very intricate and detailed surgical and regenerative technologies.

While this is still in the preclinical phase, it is a very high-risk, high-reward effort that could transform what's possible for people who are blind, but also what is possible for nerve regeneration very broadly. This drives a lot of breakthroughs across neuroscience and the regenerative medicine feel more broadly, and that's what makes me super excited about the potential of this project.

Jason Menzo, Chief Executive Officer:

That's great. Thank you, Amy. Thank you to all of our speakers today. I'm going to leave all of you, our audience today, with three things. Number one, there's never been a more exciting time in this space. The advances that are happening are happening very rapidly. As you can tell, every quarter when we have an Insights Forum call, there's new news and new information and it's happening very, very quickly.

And so I really encourage everyone to stay in tune with our website, and in particular, not just the resources which are very important, including our Mental Health Resource Center, which is exceptional, but also the Clinical Trial Pipeline. And through there, you can not only identify what clinical trials are ongoing, but also have links directly to the companies that are conducting them.

Questions that we'll take offline around how do I navigate potentially seeing if I'm eligible for a clinical trial, or what do I do if I email the sponsor and they haven't emailed me back, or how do I find a clinician? The Foundation Fighting Blindness is proud to work individually with you to help shepherd you through those challenging experiences or times. So don't be shy about emailing us at info@fightingblindness.org, or certainly encourage you to get involved at a local level with our chapters. We have chapters all over the country and local leadership that can help guide and direct with local resources and navigate those tricky situations with regards to clinical trials.

With that, I do want to thank everyone for joining us today. And if we didn't get to your question, which is the vast majority of the questions that came in, we will get with you offline and make sure that everyone's questions are answered. Thank you, and have a great rest of your day.