Targeted antibodies to treat serious tissue injury disease. Surrozen is traded on the NASDAQ under the ticker SRZN. Craig, the floor is yours.
Thank you very much. Thanks everyone for being here and anyone who's watching the Webcast. I'm going to continue with the previous theme of ophthalmology, not urology, but talk about some opportunities that are much earlier stage than the ones you just heard about. I think also provide a really exciting opportunity for clinical benefit for really large patient populations, particularly in ophthalmology. Surrozen is a science-based company in South San Francisco. We were started in 2016 by the preeminent biologists in a field called Wnt biology. This is really one of the fundamental pathways in cell biology that was previously considered undruggable. Our founders' inventions and inventions of the company itself have shown that we can target this pathway with bispecific antibodies and activate the pathway. This biology is very powerful, and particularly I'll describe in the retina in the eye, it's very powerful in improving and preserving anatomy of the retina in large diseases like wet AMD and diabetic macular edema. There's been some recent both strategic interest in this field of Wnt biology in the eye, as well as specific strategic activity and clinical activity. Merck acquired a company last year that was our one direct competitor for $1.25 billion upfront and a total of $3 billion. That was subsequent to this company demonstrating in diabetic macular edema patients that targeting this pathway can provide clinical benefit. We have multiple opportunities targeting this pathway that I'll show you. Importantly, because we're really the innovators and discoverers of this approach of using bispecific antibodies to target this pathway, we have quite broad intellectual property. That's an issued patent at this point with broad claims. We think some of the competitors would infringe our claims. Consistent with being one of the first in this field, we actually had an early asset that we outlicensed to Boehringer Ingelheim , again targeted for diseases like diabetic macular edema and wet AMD and potentially others. We hope that Boehringer Ingelheim will be in the clinic this year or next year with that asset. Although we've interrogated a number of different disease areas for this pathway, the eye turns out to be one that's particularly rich in opportunities for this pathway. This is called the Wnt pathway, stands for Wingless and Integration site. I won't go into the history of where those names come from. It's one of the fundamental pathways in biology. We now know that many of these tissues in the eye rely on this pathway, both during embryonic development and to maintain tissues in the eye. I'll talk more about wet AMD and diabetic macular edema. There are indeed other diseases like geographic atrophy, like glaucoma. There's a disease at the front of the eye called Fuchs endothelial dystrophy, where I'll show you some preclinical data that all are known to rely on this pathway for maintenance of important cell types for function in those tissues. There are also some rare disease opportunities. I won't talk about those, but we've been able to generate some data in some rare disease models showing that we can proliferate certain cell types that could be important in maintaining photoreceptors in those diseases. Our pipeline, we think, really provides some opportunities for both transformative clinical benefit as well as large patient populations. The first molecule that we outlicensed to Boehringer Ingelheim , as I said, we hope will be in the clinic this year or sometime next year. As a private company, Boehringer Ingelheim doesn't disclose a tremendous amount publicly, but they do disclose it at their booths at retinal conferences. You can see our molecule displayed quite prominently as part of their, what they call, eye health efforts. I'll tell you more about our lead candidates, which are SCN-8141 and SCN-8143, and then a little bit about this final candidate, SCN-113. What we're bringing to the table compared to the molecule that we outlicensed to Boehringer Ingelheim and to this direct competitive molecule at Merck is the addition of other known clinically relevant targets like VEGF and IL-6, harnessed with this known biology of Wnt signaling. I'll tell you more about both of those opportunities and some of the really exciting preclinical data that we've been able to generate that suggests the potential for major clinical benefit compared to alternative therapies that are available today. To describe some of these effects of Wnt biology on some of these tissues in the eye, I'll show you preclinical data that shows that we can not only prevent the kind of vessel leakage that's a hallmark of diseases like diabetic macular edema and neovascular AMD, but by activating this pathway in cells that line the vessels of the eye, we can normalize those vessels. We're not just reducing vessel leakage. We're actually addressing the underlying pathology of those malformed vessels. In other diseases like geographic atrophy, we have data showing that we can actually proliferate some of the cell types that lead to the loss of photoreceptors. I won't talk a lot about that area of geographic atrophy and dry AMD, but it's an incredibly prevalent disease with really a major need for improved therapies. Finally, I mentioned this front of the eye disease, where we know Wnt is important in preserving these cells. These cells maintain essentially what's referred to as the stroma of the cornea. It's what contributes to light transmission, and any perturbations in that tissue lead to loss of vision. I mentioned that we're science-driven. We actually have everything from antibody discovery capabilities of the company to cell biology to actually running some of the disease models that I'll show you some data for. I also mentioned that we were really the first in this area. We've published quite extensively. I think we've published 17 manuscripts in different disease areas and tissue types in this area and have filed something like 37 patent applications. While other companies like Merck are a bit ahead of us in the clinic, we feel like we really are the most science-driven company that really understands the fundamental biology contributing to these diseases and contributing to the design of these specific antibodies. Finally, we are targeting this lead molecule to be in the clinic in 2026. Just to give you an idea about what some of the other large strategics are doing in this area, there were two acquisitions last year, actually, in this area. I mentioned the Merck acquisition of iBio. They made that acquisition based on 26 patients' worth of data in diabetic macular edema. That program is now in phase III. They were able to go directly from a phase I/II study into phase III, which we would also hope to do. This is the structure of the molecule. I'll show you the structure of our molecule and some of the points of differentiation. Related to that, actually, it was an academic at the University of Toronto that discovered this antibody and outlicensed it to iBio. He had a library of other related compounds that Roche subsequently acquired. While Roche hasn't disclosed their actual antibody in this field, we expect Roche to also be a competitor in this field in the future. This has driven a lot of the clinical proof of concept from Merck and has driven a lot of strategic interest in the area of Wnt biology and retinal diseases. These are cartoons of the formats of some of our molecules. I just want to highlight again that what we've done is to take a molecule on the far left that we've licensed to Boehringer Ingelheim , the pharmacology of which is similar to the Merck molecule. It binds receptors called Frizzled and LRP, activates Wnt signaling, and reduces vessel leakage in these retinal vessels, where leakage and malformation is a hallmark of these diseases like wet AMD and diabetic macular edema. We've taken that molecule and we've added on VEGF inhibition. Many of you know this is already a $20 billion market of VEGF inhibitors today, globally, probably growing quite rapidly. While we think Frizzled IV is an important contributor to the disease, the biology and the iBio Merck data show that we think there could still be vessel leakage that could be addressed by VEGF. Our molecule really addresses both of those potential contributors, the middle molecule. Finally, the molecule on the far right, we know there are more inflammatory-driven diseases, where a cytokine called IL-6 contributes to some of the vessel leakage and the vessel malformation. We have another molecule. It's becoming quite complex now. This activates Frizzled signaling, inhibits VEGF, and inhibits IL-6. Rather than having those two candidates go directly against each other, our current strategy is to direct the far-right molecule to more inflammatory-driven diseases. You'll hear these referred to as non-infectious uveitis. Kodiak, excuse me, refers to them as macular edema secondary to inflammation. There's clearly a smaller patient population, but a category of retinal diseases and diseases of the uvea that are driven more by inflammation. That's where we're going to target this molecule, SCN-8143. I won't go into the details of the Boehringer Ingelheim agreement. I will tell you that that agreement is quite narrow. It leaves us the opportunity to work actually with the molecule we licensed to BI, as long as it's in a slightly different format, and also to work with other related molecules. Just to give you an idea about how powerful this biology is, this is data from the molecule we licensed to BI. This is a model in the mouse of retinopathy. We use high oxygen to damage the mouse retina. This model was actually derived from a disease from when we treat preemies with high oxygen because of their undeveloped lungs. It damages their retina. They're actually given anti-VEGFs for this treatment, but it led to the development of this mouse model where we can damage the retina in a way that looks like the human disease of diabetic macular edema. When we treat that with our molecule, you see this image in green in the middle, we get this normalization of blood vessels. The far right is just what the mouse retina looks like if it's undamaged. I think you can see to the naked eye anyway, treatment with this molecule results in a very normal-looking retinal vasculature, no vessel leakage. The bar charts, if you look on the far, or excuse me, the one on the left, that's a direct comparison to Eylea. If you treat these animals with Eylea, you can reduce the areas where there are these very darkly stained areas that are referred to as tufts. That's where there's vessel leakage. What Eylea does not do is restore normal vessels throughout the retina. If you measure that by what's called the avascular area, you can see that our molecule, which is in purple, almost completely reduces that avascular area where Eylea only has a partial effect on that avascular area. This is really important. What retinal specialists want to do when they treat these patients, whether they're DME patients or wet AMD patients, is to dry the retina. Drying the retina is not just reducing vessel leakage, but restoring normal vessel formation in the retina. At least the mouse models suggest that we have the potential for that clinical benefit over the currently available therapies. Every year, the American Society of Retinal Specialists does a survey of what the unmet need is. Some of you may have seen this before. This is actually last year's survey. This year's survey just came out recently. I'll point you to actually the fourth row here about what is the unmet need currently. Clearly, people would like to get fewer injections. That maybe goes without saying that it's not that pleasant to have to come into the retinal specialist's office every four to six weeks or eight weeks and get an injection directly into your eye. Importantly, people would really like to see this stable anatomy. That's what we think our biology directly addresses: restoring normal vessels, not just reducing vessel leakage. There's clearly an awareness that that's a need in the category. We think our biology is going to directly address that. To show you that our next-generation molecule, adding the VEGF inhibition produces that same kind of very potent, rapid restoration of vessels. These are the same sort of images of the retina in a mouse model of oxygen-induced retinopathy. This model is thought to be more of a model for diabetic macular edema. We also wanted to make sure that we worked as well in a model of wet AMD. The bottom is a model where you actually laser damage the mouse retina. It's where you see those spots. You can see in the far right of those three images, with treatment with our molecule, there isn't as much leakage around those spots. The central retinal vessels are actually not what you're looking at here. You're looking at the spots, and the spots are reduced, and you can quantify that. The effect here is actually roughly comparable to Eylea. We're getting this normal restoration of vessels. Finally, adding IL-6, while it's difficult to show an additive effect, we can clearly show that we're having this same potent effect on normal vessels. The bottom images really highlight that not only are we restoring normal vessels, we're restoring what are called tight junctions between those normal vessels. That's really important to this normal vessel function and what's referred to as the barrier function of these vessels, preventing leakage. We can quantify that we're reducing leakage. We can quantify that we're restoring normal vessels. This is really qualitative evidence that staining for particular proteins that are in these tight junctions, we're able to restore those. Those are our two lead candidates for retinopathies. We're going to have the first in the clinic in 2026. We're clearly still early stage, but these programs can go quite quickly. iBio has gone from starting a phase I to we've heard they've completely enrolled their first phase III in a couple of years. We'd be excited to be able to have some data probably within six or eight months of starting our phase I to demonstrating, we hope, an improvement in visual acuity, reduction in vessel leakage, drying of the retina, and of course, safety is really paramount in this population. Let me take the last couple of minutes to just show you data from our last molecule in our pipeline, which is a molecule that's targeted to slightly different Frizzled receptors. One innovation that we've really brought to this field is to be able to target different receptors in this pathway. There are 10 different receptors in this pathway. They're expressed in different tissues. This is something no one else has been able to do in this field to target specific receptors in the pathway. These are different receptors than we're targeting with the retinal molecules. These are referred to as Frizzled I, II, and VII subfamily receptors. I'll show you a little bit of data and tell you a little bit about this disease. There's a front of the eye disease that's quite prevalent. It's age-related. It's probably related to UV damage over time, where these cells on the back, so the inside of the cornea, sorry, I just said retina, on the inside of the cornea are destroyed over time. You develop these spots called guttae that interfere with vision. The way that's manifest to a front of the eye specialist is when he looks with an ophthalmoscope. Those are these images on the bottom right. He sees these cells that don't have a normal morphology and actually this very hazy cornea. As I said, this does lead to vision loss. It leads to vision loss in a minority of patients. There are a very small minority of patients who receive corneal transplants for this disease to help restore their vision. We've established a model for this disease where we actually damage the cornea of the mouse. We treat with our antibody. What these charts show is that we're able to reduce the thickness. This is actually what happens in the human, is when those corneal cells are lost, the cornea swells, and so light is not transmitted as effectively. A treatment in the human that would be considered effective would reduce that corneal thickness and improve the clarity of the cornea. We've shown that at least in a mouse model, that we can reduce that thickness in treatment and also improve the clarity of the cornea. The mouse happens to recover extremely quickly on its own without treatment, which is why you see these lines converge over time as the mouse has incredible healing powers, not just in its eyes, but in many organ systems. We are able to very rapidly, after treatment, show a reduction in that thickness. We are excited. Front of the eye specialists that we've talked to are excited about the opportunity for a therapy that wouldn't be transplant. Transplants are limited by the number of donors and by the size of the lesion that can be transplanted. There are many, many patients whose disease needs cannot be met with transplant. We've shown this also in cells from actual patients who have this disease. Finally, many of you may know a much more prevalent disease is dry AMD. There are two approved products for that that are minimally effective in slowing the progression of the disease. No one's been able to show improvements in visual acuity. This cartoon just shows all the layers of the retina that contribute to the preservation of photoreceptors and visual acuity. We've been able to show in a model injuring those layers that we're able to preserve cells in those layers. We know that we can directly affect important supportive cells. Some of those are called RPE cells, Muller-Glial cells. Importantly, we've shown that we can preserve cells in that photoreceptor layer after they're damaged in a mouse model. We think this really has great potential to directly improve visual acuity in patients with geographic atrophy. That's a much more challenging clinical setting. It took others 18 months to show a clinical benefit in that setting. One of the reasons we addressed retinopathies initially is the opportunity within weeks to see a benefit versus months or years in geographic atrophy. I will stop there and see if anyone has any questions. I'd be happy to.