Surrozen, Inc. (SRZN) Earnings Call Transcript & Summary

Yes, absolutely. So our DUET study is divided into two parts. The first part is a first-in-human dose ascending phase. And so participants will receive a single injection, and then they'll be observed for 3 months in ascending dose. We'd obviously start with both lower doses and if safety permits, we would then escalate to the top dose. This would be open-label. And our study is being performed in both parts in DME. And in this first part, the majority of these patients will likely have had previous VEGF or other treatments for DME. I think the main purposes of these two parts is to determine initial safety as well as the two doses that we'd like to take into the part two. We'd obviously get some initial efficacy data after single injection as well. And then that would transition to the part two portion, which is our dose expansion, randomized dose expansion with comparator. And so we would have 3 arms in this study: two dosing levels of SCN8141 randomized 1-to-1 compared to Vabysmo. The label dose, all 3 of these groups would be given 3 monthly injections of the drug and then observed for 4 months. And that dosing regimen is typical of a common clinical dosing regimen that one would see in clinical practice. The main endpoint for all of these again is safety and tolerability. And the second part again as was mentioned is about 60 patients total, so about 20 patients per arm. And so from an efficacy standpoint, it is not statistically powered to show statistical differences. However, we can get meaningful directional data on a number of endpoints, such as best corrected visual acuity, fluid and OCT metrics, as also other measures related to non-reportable retinal non-perfusion. And I think in particular what we've designed this study is hopefully to show in the second part is, again, how does SCN81 compare to a contemporary standard of care. And we think there are, I think, 3 ways of differentiation that we would like to see for the molecule. One, I think, is related to anatomic control or drying. And we think that this is a reasonable number of patients to see directionally to compare Vabysmo compared to SCN8141. The second is also an early look at the durability of the effect. As I mentioned, we will be observing these patients 4 months without treatment after the 3 monthly doses. And the third part is also related to this idea of retinal non-perfusion, is whether SCN8141 could help to reverse retinal non-perfusion, looking at some of these exploratory endpoints.

You know, I think for people who don't follow retinal vascular diseases and clinical development there, you know, it's important to highlight that the drugs that have been developed for retinal vascular diseases have a very rapid effect. And so I think one can get a pretty good idea about clinical benefit, like probably literally within days, but certainly within weeks, and at 12 weeks, I think you'll have a pretty good indicator about what the ultimate effect, the efficacy of the drug, can be in a relatively small study. And so for those of us in the industry and for investors, I think it's a really attractive therapeutic area because the opportunity to see clinical benefit really early and in a relatively small sample size have a pretty good idea about ultimately.

Efficacy is going to look like. And maybe one thing just to fall back on, and again, for those that are not familiar, is like, you know, what are really the key unmet needs in DME? And I think we've tried to address that, actually, with our 3 points of differentiation. I think #1 is better anatomic control. With our current standard of care, not all patients respond. In fact, there are numbers from studies that quote 50% to 60%, about 40% are suboptimal responders to our current therapy based on anatomical measures, and so agents which can improve drying is certainly a big unmet need. The second is durability and reducing treatment burden. I think current patients need to receive these injections as frequently as monthly, and so I think that's kind of a very clear value proposition. And then the third part is then, again, addressing this retinal non-perfusion, which is known as a clear driver of diabetic retinopathy, and we know our current treatments, our current anti-VEGFs, do not reverse this non-perfusion. So the potential to be able to revascularize or perhaps disease modify in the effect is also something of high interest in the field.

Great, thank you. The next area I'd like to talk about is your second candidate, SCN8143, which layers in IL-6 antagonism on top of the two targets from 8141 to reach uveitic macular edema alongside DME and wet AMD. How does the triple mechanism broaden the franchise, and how do you differentiate the two programs?

You want to start on that one? Sure. I think one thing is, I think in the field of retinal vascular disease, I think IL-6 has also been established as a key mediator of disease, and now there are a number of programs looking both at kind of IL-6 inhibition as a monotherapy or in combination and have shown some interesting results. And so I think the strategy there is that, you know, IL-6 again is more on an inflammatory axis. And again, that could cover another, I think, circle of the Venn diagram of retinal vascular diseases that may or may not be addressed by the other two, and so I think very excited about our molecule that we've created and its potential in retinal vascular diseases.

I mean, a foundation of our approach broadly, and it's very much true for 8143 and 8141, is these are diseases that we know have multiple contributors to the pathology of disease. And so while anti-VEGF therapy is very effective, I think the biology and biomarker studies, and then studies with some of these other monotherapy agents, have shown that there are these multiple contributors to the disease pathology, and so I think, you know, you'll hear at retinal conferences more and more people talk about multifunctional antibodies because of this growing evidence that there are these multiple contributors to the disease. So, you know, we think it just makes sense for these disease entities with multiple contributors to try to go after multiple pathways within one molecule, and as Dan said, but now there's growing evidence that IL-6 is an important contributor to certain patients with macular edema. There's a related inflammatory driven disease called uveitic macular edema, where IL-6 has been shown clearly to be a contributor to that. So that's sort of a natural fit for 8143. And then how they fit together with each other. I think as you know, 8141 is ahead of 8143. I think we don't have to make decisions early. We have the opportunity to look at evolving data from others, to see what the clinical data with 8141 looks like, and to really not have to decide on the relative positioning until we have a lot more information. Ultimately, it could be that going after all 3 of those pathways is the best for every retinal vascular disease. And if that's the way the landscape and our own data evolves, I think that's great for us. Great, thank you. The markets you're targeting are all large and continue to grow. Like you said, anti-VEGFs still leave considerable unmet needs for these populations. How do you think about the areas where your therapeutics could be most helpful in the current therapeutic landscape? Yes, so as you said, these are, you know, these are highly prevalent diseases if you include, you know, wet AMD and Diabetic Macular Edema and some of these other related diseases like uveitic macular edema. The current market for these for the anti-VEGF agents today is about $15 billion globally. I don't have to tell anyone who's a healthcare investor that the population is aging and for the most part these are age-related diseases. That's currently going to be a growing market. Dan's alluded to differentiation, the most recently launched drug, and now also I think it's market leader for, I don't know if it's true for both wet AMD and DME, but certainly for one of those is Vabysmo. And that product, I think, showed you how differentiation can translate to very rapid adoption by retinal specialists. So they showed somewhat better drying on a secondary endpoint in phase 3 trials. And that led to very rapid adoption, because I think retinal specialists are like, they're treating to fluid, they can visualize it very clearly with this OCT imaging, it's all part of normal clinical practice. And I think there are certainly opportunities to be the best agent for drying for some of these areas like retinal non-perfusion for durability. It could be that you hit all of those with this molecule with 8141. So again, really large growing markets with very clear evidence that retinal specialists are very quick to adopt products that have some differentiation. That makes sense, thank you. On the IP front, we recently saw some news that the Patent, Trial, and Appeal Board recently declined to institute Merck's Post-Grant Review of one of your core patents. Can you tell us a little bit more about the IP situation there and how it relates to your own product portfolio? Yes, so we have what we think is a broad issued patent for these SWAP-like molecules that are Frizzled binders and LRP5 or 6 binders. Merck filed an opposition to that called a Post-Grant Review. People can find those documents online at the USPTO website. And ultimately what's called the Patent Trial and Appeals Board chose not to institute that. When they make that decision, it's based on the low likelihood that they would win that opposition. So right now, one has to institute this PGR, or at least file for it, within 9 months of the patent issuing. That's long past now. So there isn't an opportunity for anyone else to challenge that patent through a Post-Grant Review process. You know, we are discoverers of this technology. The company was started around this technology and Wnt agonism, and we have a broad, we think, broad issued patent for this general approach and formats of antibodies or antibody-like molecules that bind Frizzled LRP molecules.

Great. And then beyond just the retinal vascular programs, I understand you also have earlier research in corneal endothelial disease, in RPE and photoreceptor protection, where you pointed to Wnt's relevance, including conditions like Fuchs Endothelial Corneal Dystrophy. How should investors think about the potential opportunity in some of these other disease spaces? Yes, so Dan can elaborate on, I think, this disease called Fuchs Endothelial Dystrophy and some of the other opportunities. The biology behind this is related to the Wnt pathway again. So we know that the Wnt pathway is involved in preservation of some of these cell types, in some cases differentiation of some of these cell types. Actually, Wnt has been implicated or demonstrated in other actually lower species to be involved in differentiation of different cell types into photoreceptors, so that's some potential relevance for disease like geographic atrophy. So fundamentally, the Wnt pathway is important in many of the cell types in the eye, so there is a pretty rich opportunity set just in ophthalmology for pursuing molecules that can modulate the Wnt pathway. Some of those cell types include cells in the cornea, so I'll let Dan describe that and what the disease is and what the opportunity is there.

Yes, we think this is a particularly interesting one. It's a disease called Fuchs Corneal Endothelial Dystrophy. And what is it? Yes, you can think of it as a window, and at the back end of that are is a monolayer of cells called endothelial cells, which are there essentially to dehydrate and pump out materials to keep that clear. So in the absence or dysfunction of these corneal endothelial cells, essentially the cornea gets steamy and you can't see. Just imagine you're in the shower, and imagine that's every day of your life. And one of the diseases is the Fuchs Corneal Endothelial Dystrophy, which is kind of a native disease, an age-related corneal endothelial degeneration. Now there are other ways to have corneal endothelial dysfunction, like for instance after surgery you also lose these endothelial cells. And currently the treatment for corneal edema is surgery to essentially transplant and replace those endothelial cells. That is quite effective, but you can imagine that's limited both by donor tissue as well as then risk benefits of going into surgery. And I think what we've shown is some really interesting science showing the Wnt pathway being important for proliferation of these corneal endothelial cells. So you can imagine, say, what if you had a drug that you could inject in the front or in the back of the eye that could endogenously regenerate these endothelial cells and clear the cornea? And I think we have some interesting preclinical data to suggest that's possible through manipulation of the Wnt pathway.

And I think represents a very interesting opportunity that we're looking into. So we have a candidate-ready molecule actually right now. We don't have, we're very well financed to run clinical trials for 8141 and 8143, but not as much for SCN113 as the designation for this molecule for Fuchs Dystrophy. So that's really just limited by capital at this point. But I think really compelling animal models, of course, corneal injury combined with all of the kinds of biophysical characterizations that you do for the molecule itself to prepare it for further development. And it's ready to go right now. All right. Great, looking forward to seeing more of that in the future. Thanks. Speaking of the future, finally, for investors just getting to know the story, what does Surrozen's success look like over the next 12 to 18 months, and what are the key milestones you think people should be paying attention to? So I'll talk a little bit about some of the development milestones and financial milestones. We filed our IND, I think, 8 or 9 days ago. We did a PIPE financing in March 2025. The second tranche of $95 million of that is due when our IND is open. So we would hope for that to happen quite soon. That's what would adequately finance us through clinical trials for the first two molecules. Dan mentioned Restoret, which is a Merck molecule. It's not being called Restoret anymore. MK3000 or Remig Gromig, I think is the molecule name. There's phase 3 data for that forthcoming. It's actually scheduled to be presented at the American Academy of Ophthalmology on October 10. There may be a press release before that. That's a Wnt only molecule. Remember our molecule is 8141, is Wnt agonism combined with VEGF antagonism. But that could be really important validation that the Wnt pathway alone has benefit that could be VEGF-like. Again, that would be really supportive of our thesis of combining these two best pathways. So that's relatively near-term. And then what we've said is we'll be treating patients by the end of this year and have data our own data in the second half of 2027 so obviously that's, you know, critical milestone for the company is to generate our own safety and potentially efficacy data in 2027, nominate 8143, and get that moving into the clinic as well. So those are some of the critical near-term milestones. Fantastic. I'll look forward to it. Well, great. Thank you so much for joining us here today. Thanks for having us. Thank you. This live transcript is auto-generated without human intervention or review.