Hello, and welcome to H.C. Wainwright's Fifth Annual Ophthalmology Virtual Conference. My name is Eduardo Martinez, and I'm a Biotechnology Equity Research Associate at Wainwright. I have the pleasure of introducing Mr. Craig Parker, CEO of Surrozen. Mr. Parker?
Thanks very much, Eduardo, and thanks H.C. Wainwright for the opportunity to participate in the conference. We'll be making forward-looking statements. Please see our SEC filings for a full discussion of our risk factors. Surrozen is really a science-driven leader and innovator in modulating the Wnt pathway, which I'll tell you more about. This is a novel and now clinically validated target for what I'll describe to you are some very large markets in ophthalmology. The relevance of the Wnt pathway and some of the early clinical proof of concept data has stimulated quite significant strategic interest in this approach, including by Merck, Roche, and Boehringer Ingelheim . As I mentioned, there's now clinical proof of concept in diabetic macular edema for targeting activation of the Wnt pathway for improving both visual acuity outcomes as well as retinal anatomy.
Because of the productivity of our approach, both our antibody expertise and our Wnt biology expertise, we've been able to generate quite a broad pipeline in ophthalmology development candidates that I'll tell you more about, all targeting highly prevalent retinal and corneal diseases with significant unmet need. One of the outcomes of our being very early to understand the importance of Wnt in both ophthalmology and broadly in other disease areas and applying our bispecific and multi-specific antibody technologies was a very broad intellectual property position for activating Wnt signaling with antibodies that bind the relevant receptors in the pathway. Importantly, our patent application has actually been cited as prior art in the EyeBio-Merck patent, which was then subsequently withdrawn.
I'll tell you about our being able to advance what we think is a best-in-class FZD4 targeted antibody with our partner, Boehringer Ingelheim into the clinic for retinal diseases. I'll describe the breadth of our pipeline in other disease opportunities as well. Let me tell you a little bit more about Wnt biology and its relevance in the eye, though. Wnt proteins activate diverse downstream signaling cascades that are involved in stem cell renewal, tissue homeostasis, and tissue regeneration through a complicated receptor-mediated signal transduction complex. This is a really fundamental and important biology. Others have tried to utilize recombinant versions of Wnt proteins as therapeutics, but this historically posed several challenges. Until our approach, this pathway was really considered undruggable. Our vision at Surrozen has been to target specific receptors in this pathway with antibody-based molecules that mimic natural proteins in activation of the Wnt/ beta-catenin signaling.
We discovered Wnt ligand mimetics that combine FZD and LRP binders in antibody-based formats that optimize the pharmacology. The role of FZD4 specifically in normal retinal development and in several rare diseases, Norrie disease, and FEVR have been well described in the literature and served as a foundation for our pursuit of a FZD4 targeted therapeutic. Importantly, there are other Wnt responsive tissues and cell types in the eye that represent intriguing therapeutic targets in diseases like endothelial cell dystrophy, geographic atrophy, glaucoma, and several inherited retinal diseases. As I mentioned, the productivity of our approach has resulted now in a broad preclinical pipeline of antibody candidates. The most advanced of those we out-licensed to Boehringer Ingelheim . I'll share some of the preclinical data for that molecule.
We took our learnings from that molecule and expanded the targets in our antibodies to include other clinically relevant targets like VEGF and IL-6. I'll show you some of the preclinical data that we've been able to generate with those antibodies. We've also approached some other tissues in the eye with SCN-113, which targets a different complex of FZD receptors that we think could have relevance in a corneal disease that I'll describe for you, and also in geographic atrophy, which I'm sure many of you know is one of the most prevalent macular degenerations. There are some, I think, really notable advantages of Wnt signaling in the eye and in ophthalmology. I'll show you data that shows we can not just reduce vessel leakage in the retina, but actually improve normal vessel function and improve the retinal barrier function.
We've also shown in a different disease model for GA that we can preserve retinal pigment epithelial cells, which are damaged in the disease, and photoreceptors. Finally, we've shown that we can proliferate endothelial cells, and that could have relevance in Fuchs dystrophy, as I'll describe for you. In building this pipeline, we've really built both antibody capabilities and also abilities to study these antibodies in preclinical models. Most of the data you'll see we've generated ourselves internally. We were quite early in identifying FZD4 as a relevant target. That is what drove our early intellectual property filings and now broad position with our patents. Importantly, our license with Boehringer Ingelheim has left us plenty of room to design and discover other molecules, again, that I'll describe for you and their relevance in retinopathies.
While we were the first to design and patent a highly selective FZD4-targeted Wnt mimetic, other groups have worked on first-generation approaches. Restoret, which many of you may know, evolved from technology developed by Dev Sidhu at the University of Toronto. The EyeBio molecule carried over Dev's diabody-based LRP binders into an IgG-based format. That's what's on the right. His library of selective diabody-based LRP and FZD binders was subsequently acquired by Roche, representing, as far as we know, the only other approach to creating selective antibody-based Wnt mimetics. Our initial work started in 2017 and resulted in a highly selective FZD4-targeted Wnt mimetic that we licensed to Boehringer Ingelheim . SCN-413 activates Wnt signaling more potently than Restoret by clustering FZD4 and LRP receptors in a 2:2 stoichiometry. SCN-413 directly upregulates endothelial cell tight junction proteins, reduces vessel leakage, and normalizes retinal vascular anatomy.
We then asked ourselves, how can we improve upon both some of the antibody engineering aspects of SCN-413, as well as incorporating other what are known to be clinically relevant targets in the eye? The two middle molecules that you see here, sorry, the second and fourth molecule that you see on this slide, describe our approach of incorporating both FZD activation and also VEGF inhibition. On the far right, FZD-targeted Wnt activation, VEGF inhibition, and IL-6 inhibition. In addition, we've incorporated state-of-the-art antibody technology approaches into these molecules to potentially reduce side effects and improve half-life. Let me tell you a little bit more about the data that we generated in the molecule that we out-licensed to Boehringer Ingelheim SCN-413. As I mentioned, this is a very novel mechanism to treat retinal vascular diseases that can both directly reduce leakage and potentially reduce VEGF production.
We do directly upregulate endothelial cell tight junction proteins, reduce vessel leakage, and normalize retinal vascular anatomy. The economics of the deal with Boehringer Ingelheim are just described here. We did this license several years before the molecule was going to be in the clinic and received $12.5 million upfront. You can see the other milestones that we expect to receive from BI. Some of the really exciting preclinical data that we were able to generate showed a compelling treatment effect in rabbit and rodent models of retinal vessel injury, demonstrating both suppression of vessel leakage, a large reduction on what are called neovascular tufts, and an effect superior to Eylea in reducing the avascular area in a mouse oxygen-induced retinopathy model. You can see in the central retina flat mount images that animals treated with SCN-413 had retinal vasculature nearly indistinguishable from uninjured animals.
This is really a fundamental effect of activating Wnt signaling in retinal vascular endothelial cells, this normalization of retinal vasculature. We both reduce vessel leakage, and we reduce any of the pathologic vessels that are a real clinical hallmark of diseases like neovascular AMD or wet AMD and diabetic macular edema. I mentioned that we wanted to try to improve on the SCN-413 molecule, which we did by adding both IL-6 inhibition and VEGF inhibition in SCN-8143 and in SCN-8141 by adding VEGF inhibition. What are the theoretical benefits of that? You can see in this survey from retinal specialists what they considered to be important potential advancements in next-generation therapies. Really foremost among those was potentially having fewer injections.
We think we've designed the antibody in a way that has the promise of delivering on that and certainly has the promise of improving the retinal anatomy, as I showed you in that previous mouse oxygen-induced retinopathy experiment. Here's some of the data we've been able to generate with SCN-8141. Again, this molecule potently reduces vessel leakage, normalizes retinal vascular structure and function in both a mouse oxygen-induced retinopathy model and a laser CNV injury model. We're trying to recapitulate both the important retinopathies clinically, both diabetic macular edema with one of these injury models and wet AMD with the other. You can see we have quite a potent and immediate treatment effect in both of these models in reducing vessel leakage and normalizing retinal vasculature. SCN-8143 adds IL-6 targeting moiety intended to address the inflammatory component of diseases like uveitic macular edema.
The same desirable effects on vessel leakage, vessel regeneration, and reperfusion are observed. We expect to advance SCN-8141 into the clinic approximately six months behind SCN-8141. In summary, FZD4 targeted Wnt signaling represents an exciting new mechanism to treat retinopathies by directly reducing vessel leakage and by normalizing retinal vascular anatomy throughout the retina, reducing areas of non-perfusion. The combination with additional clinically validated pathways like VEGF and IL-6 and state-of-the-art antibody technologies has the potential to create, we think, a step change improvement in clinical benefit for retinopathy patients. Let me tell you more about our programs in other areas of the eye. We've been looking at the opportunity to improve corneal function in a disease called Fuchs endothelial cell dystrophy. I'll show you preclinical evidence that we can proliferate healthy endothelial cells and matrix organization and even in human tissue stimulate recovery of corneal thickness and clarity.
This is a large market. There are a number of people who are treated with quite expensive and limiting transplant therapies. Additional market research we've conducted really shows that there is both a high unmet need and a high prevalence of this disease. The cornea is the structure at the front of the eye that allows light to be transmitted into the eye through the lens. It's actually responsible for an important part of focusing in addition to the lens. Over time, the cells on the inner lining of the cornea can develop these what are called guttata or guttae. These are spots that can ultimately inhibit vision and result in clouding of the cornea and an inability for the cornea to assist in focusing. We've established a model that recapitulates what happens in humans.
In this injury model in the mouse, the mice both experience corneal thickening, as happens in human Fuchs dystrophy, as well as a reduction of clarity in the cornea. Treatment with our FZD4 targeted antibody reduces quite rapidly the edema and also improves corneal clarity. We think this bodes well for the opportunity for SCN-113 to be efficacious in human Fuchs dystrophy. We didn't stop there, though. We wanted to answer the question of whether we could have that type of an effect in human cells, not just in a mouse model of corneal injury. Indeed, we've been able to show with different types of human explants that we can both activate Wnt signaling, proliferate corneal endothelial cells, and do that in a way that's superior to the one other approach that's been tried recently, which is a human-engineered fibroblast growth factor molecule, that's TTHX in this data.
You'll see that we have quite a demonstrably superior effect on proliferating corneal endothelial cells. Finally, let me tell you about an opportunity in a very highly prevalent disease, dry AMD and geographic atrophy. As many of you know, this is a very prevalent disease that can severely affect vision ultimately. It is not characterized by the kind of exudate or fluid that's seen in wet AMD, but it does result in loss of cells, ischemia, and loss of cells and atrophy throughout the retina as well as in the vision sensing regions of the retina like the fovea. Current therapy right now is really limited to complement inhibitors, which have very modestly slowed progression of the disease. The real holy grail for treating this disease is to be able to preserve those cells in the vision sensing layers of the retina.
Those cells include retinal pigment epithelial cells as well as photoreceptors. We've challenged ourselves to try to look for a Wnt-mediated effect in those cell types. This diagram shows you how these cell types are all interrelated in this outer nuclear layer. Those cell types, again, that have been shown to be Wnt- responsive include photoreceptors, as I mentioned, RPE cells, as well as Müller cells. This is data from a study where we injure that outer nuclear layer, and that includes injuring all these potential cell types. What the green fluorescent stain shows is that after treatment with SCN-113, so this is the same molecule as in Fuchs dystrophy, we're able to reduce the number of cells that are lost. We do have this photoprotective, neuroprotective effect in the vision sensing layers of the retina.
Finally, we've been able to show that another key cell type in the retina, these retinal pigment epithelial cells, can be proliferated with this same approach. You can see here that these cell types, RPE cells, upon treatment with SCN-113 or a different bispecific antibody, proliferate in culture. In summary, Surrozen has become an established scientific leader in Wnt. We've applied both Wnt biology and multi-specific antibody expertise to clinically diverse opportunities in ophthalmology, opportunities in highly prevalent diseases with very high need for new mechanisms and better vision outcomes for patients. We look forward to reporting our progress and clinical outcomes in 2025 and 2026. Thanks for your attention.