Welcome, everyone, to the Piper Sandler Healthcare Conference. My name is Biren Amin. I'd like to welcome our next company with us. We have Surrozen, their CEO, Craig Parker, and their Chief Operating Officer, Charles Williams. Welcome, gentlemen. Maybe for those in the audience and on webcast that aren't familiar with Surrozen, can you just walk through the company's focus and its pipeline? Sure. We were founded, actually, in 2016 by the preeminent Wnt biologists in the world, and we'll tell you a little bit more about what Wnt biology is. There is a really fundamental pathway in cell biology that had really been considered undruggable previously. Some breakthroughs from our founders really enabled the idea of engaging this pathway with antibodies. In our case, these are bispecific, multivalent antibodies, and it is agonizing the pathway for tissue regeneration. The concept behind the company was to be able to design antibodies that, in a very tissue-selective way, could activate the pathway. This pathway is involved in, actually, both the development of many of the tissues in our body as well as the maintenance of the structure and function of many of the tissues in our body. There was a really compelling, fundamental biological concept of using this pathway for different diseases. We'll talk a lot about ophthalmology now. There's indeed, actually, human genetics behind targeting a particular element of this pathway for retinopathies. That was the foundation of the company. We're a very science-driven company. We do everything ourselves, from antibody discovery to the cell biology to some of the animal experiments in retinopathies. That's resulted in wholly-owned antibodies that are targeting a particular aspect of this pathway that's relevant in the vessels on the back of the retina. That's why we're right now focused on ophthalmology as a therapeutic area and retinopathies in particular, as this Wnt biology is known to be intimately involved in both the development of retinal vessels in the eye as well as the maintenance and function of retinal vessels in the eye. The lead program is, I think, SZN-8141, which is a bispecific targeting Wnt and VEGF. Correct. What was the rationale in developing a bispecific versus strictly just a Wnt agonist? We actually developed a Wnt agonist, solely a Wnt agonist, initially. We were one of the first. We were the first to file a patent in this field. We have a very broad intellectual property. We've published in this field. We ended up out-licensing a first Wnt-only molecule to Boehringer Ingelheim. We hope they'll be in the clinic sometime soon. Having seen now multiple different pathways be exploited for retinopathies, each of which seems to show some benefit, and there are clinical studies now that show additive benefit combining all these pathways, I think there's a really compelling argument that there are multiple contributors to the pathology of retinopathies and that you can achieve additive benefit by targeting multiple pathways. That's the concept behind our approach, which is to take our novel pathway, which is Wnt, and then also add on to that VEGF antagonism. We have a second molecule that takes both of those and adds on IL-6 inhibition as well because there is now clinical proof of concept that IL-6 is relevant in diabetic macular edema, uveitic macular edema. Again, there is really exciting evidence that you can get additive benefit by combining these pathways. I guess your first molecule that you developed, the Wnt agonist, solely, as you know, Merck is active in this area with the purchase of EyeBio, where they bought the company for about $1.3 billion upfront and then a biobucks of about $1.7 billion. Can you tell us what the learnings were from that EyeBio-Merck program and what you hope to achieve with your program? What have they seen in their clinical studies that give you confidence on this pathway? We have not seen a lot. We have only seen about 30 patients' worth of data, about 26 patients, of which was diabetic macular edema. The exciting data that I think compelled Merck to make the acquisition was a benefit that seemed to be as large as Eylea or VEGF inhibitors confer, which is about 10 letters of visual acuity gain. There is a measurement to show drying of the retina, which is how much you shrink the thickness of the macula. They shrunk it about as much as Eylea did, about 150 microns. That was actually unprecedented, that a pathway other than VEGF alone could achieve VEGF-like efficacy. It is a very small sample size, 26 patients, but really a first-ever VEGF-like activity without using VEGF. I think we are excited by that, that Wnt biology seems to confer that magnitude of clinical benefit. Again, 26 is a small sample size, but it seems to be very safe. As you know, covering ophthalmology companies, drugs have to be extraordinarily safe when you inject them into the eye. You can't have rates of infection or other vision-threatening adverse events. I think we and obviously Merck were encouraged that it seemed to have a very good safety profile. Good. We're, like everyone else, excited to see the phase III data from Merck, which will be roughly, I think, just after mid-year in 2026. Their design, they're dosing it every four weeks, correct? And that's the DME trial that's currently ongoing? They've started a separate study in Wet AMD as well? Yes. That's also every four-week delivery? Yes. Is that a single-agent therapy, or are they combining with anti-VEGF? In their DME studies, the regulatory requirement for those is that you do a non-inferiority or you're allowed to do a non-inferiority study head-to-head with an approved agent. That's what they're doing in DME, is Restoret alone versus an approved agent to show non-inferiority. In their Wet AMD study, they do have an arm that's a combination of Eylea plus restored. I think that's for the treatment experienced in DME and also for what's something called a branched retinal vein occlusion. I think there'll certainly be learnings for us from all of those studies that we can apply to our trial design. In any case, again, it's exciting that there's a magnitude of clinical benefit, that it's as good as VEGF, that other agents have shown additive benefit. Again, that's obviously our approach is to try to achieve some additive benefit with multiple pathways. Clearly, multiple pathways contribute to the disease because you can inhibit IL-6 alone, you can inhibit VEGF alone, you can activate Wnt, and each of those seems to have some benefit. When we talk about 8141 and the Wnt VEGF bispecific, that VEGF component, can you just talk about the potency? What is that closest to, the drugs that are currently on the market or in development? Because the sequences are published and off-patent, we actually use the sequences from Eylea, the VEGF trap portions of the sequences from Eylea. Like Eylea, two VEGF receptor components bind one VEGF molecule. That is really the same as Eylea, the same as others who have tried this approach, like Kodiak, for example, with their VEGF IL-6 molecule. If you target having the same concentration in the eye as Eylea, our molecule is a little bit bigger than Eylea molecular weight-wise. The 2 milligram equivalent would be something like 2.7 milligrams of our molecule in the eye. If you wanted to get to Eylea HD, 8 milligram equivalent would be something like 9.5 milligrams, 10 milligrams of our molecule in the eye. Where is this currently in terms of phase of development? When can we expect it to enter phase I? We have just indicated that we would be filing an IND in 2026. We will refine that as we get closer and have a little more to say about the specific trial design and when we would expect data. As of now, we have just said 2026 IND for 8141. 8143 is months behind that. I guess between now and the filing, what needs to complete in order for you to file that IND? Yeah. I mean, all the stuff that, as operators, we get excited about that aren't really disclosable. We're not doing the manufacturing. Lonza is doing the manufacturing. But there's scale-up, purification. That's all going well. Typical toxicology studies, what are called dose range finding studies, and then GLP toxicology studies. This is all very well-established precedent in the field of retinopathies. You do rabbits and non-human primates for the toxicology studies and intravitreal injections for the toxicology studies. We're in the midst of all that, but nothing to disclose except things are moving along well. In the animal studies, would you compare it to anti-VEGF alone, for example? In the efficacy studies, we actually do those internally at the company. For the efficacy studies, we use a mouse model. There are multiple different mouse models of retinopathy. I always love to brag about some of our research associates. You do these experiments in five to ten-day-old mouse pups. They're very small. Their eyes are really small. We have research associates who are able to do intravitreal injections in the eye of a five or six-day-old mouse, which is really remarkable to not damage the lens and get it into the intravitreal space. We do all those ourselves. We do compare in some of those studies to Eylea alone. We've shown that data before. We're superior to Eylea alone in some of those retinopathy models and some of the outcome measurements. We're superior to just activating Wnt alone, the combination. There is actually synergy in the combination. We have not published that data yet. It is very exciting that when you combine these two pathways into one molecule, there does not just seem to be an additive effect. There seems to be a synergistic effect. That is in models of retinal injury that are mimicking either DME or Wet AMD. That's improvement on a single agent potentially. Yes. Not just efficacy, but the field talks a lot about durability and the infrequency of injections. Yeah. Is that something that you think will translate into the clinic based on your animal model and the work that you've done there? The animal models are limited in their translatability for the duration because mice tend to recover completely if you don't treat them. This is true in many, many organ systems and tissues in the mouse. You can injure it. It very rapidly recovers on its own. The models just don't lend themselves to really understanding the true durability. The biology would suggest that you're normalizing both the anatomy and the function of retinal vessels. That should be long-lasting, right? This is a disease, at least in Wet AMD, that takes decades to develop. You would think that restoring normal vessels could have a durable effect, but we can't really understand that in the mouse models. What we know is that we can concentrate the drug to a level that we can put enough in the eye, sort of learning from the Eylea experience. If you put enough in the eye that several, even months later, you still have an active level of drug in the eye, we're quite confident that we can get to that. Now, will the tox studies enable that? Is that really the optimal dose? We don't know that yet. But just from the biophysical properties of the molecule, we know we can get enough in the eye that potentially you could have infrequent dosing. You probably will have good data before you go into IND filing on, I guess, the design of the phase I, what you hope to achieve in terms of target product profile. Is that a good assumption? Yes. Yes, for sure. Yeah. I mean, we'll know from tox studies what the maximum dose we could put in the eye is. Regardless of what that dose is, we'll obviously have developed the protocol, and we'll share some elements of that when the time is right about, are we doing DME? Are we doing Wet AMD? Are we doing both? Are we doing treatment naive patients, treatment experienced patients, all of the above? We'll share all that when it's more fully developed. You mentioned the maximum dose and the comparisons to Eylea. How do you think about drug concentration as it relates to delivery into the eye? Because you hear from time to time certain drugs are viscous. The injector has to stay in until the drug gets pushed out. Is that something that you think about right now before going into phase I in terms of the ease of delivery for the retina physician? Yeah. Absolutely. I think it's a critical element of the product profile. And it's one of the advantages of being a company that does all the science in the product is we've spent quite a bit of time working out which formats of the antibody not just have good activity in vitro and in vivo, but also have these really good biophysical properties. And so we actually do a lot of that work ourselves. Lonza repeats it. But we're very focused on things like viscosity, stability. We know that we can concentrate the drug to more than 100 mg/mL. So it's a very simple calculation. You can put 50 microliters -70 microliters in the human eye without causing elevated intraocular pressure. If you wanted to put more, there are ways to relieve that, but it's not really ideal. We have taken all that into account designing the antibodies, and it has very, very good properties, both 8141 and 8143, and particularly with respect to aggregation, stability, and viscosity. We do those rheology studies now ourselves. That's great. It's a lot of good progress. Yeah. I guess on the Wnt side, can you talk about, I guess there's two receptors in the RPE, LRP5 and LRP6. Which one of the two are you most binding to? Are you binding to both? What's the binding opinion? How does that potentially translate into clinical activity? How does that compare? I assume that this is basically similar characteristics to the Boehringer molecule in terms of the Wnt-only aspect? Yes. All right. We are going to get to go down the Wnt biology rabbit hole now. The co-receptors in this pathway are called Frizzled receptors and LRP receptors. There are two LRP receptors that are relevant, LRP5 and LRP6. We have published on this. It does not seem to matter for activating the signal, whether you are binding LRP5 or LRP6. What matters is whether that receptor is present in the tissue. They are both present in the retinal vascular endothelial cells. LRP5 is expressed at a higher level. Taking into account all these properties we look for, including the biophysical, we settled on LRP5 versus LRP6 for a lot of these issues, testing everything from viscosity to the activity in animal models. We bind Frizzled 4 and LRP5. We bind the same epitope on LRP5 with both arms of the antibody. The antibody is, both arms are identical on our antibody. Sorry, what was the other part of your question? I guess how does it, from the LRP5 / 6, do you bind to both? Yeah. So we don't bind LRP6 at all. Oh, you don't bind LRP6.[crosstalk] We're very specific to one epitope on LRP5. Some others have made the argument that that might make a difference. The discoverer of Restoret has published on this. With his diabodies, he believes that you should be binding two different epitopes on LRP. We've published in Cell Chemical Biology that that's not necessary, and we thought it was easier to just make a homodimeric antibody. Both arms exactly the same. In vitro, we have greater potency than the Merck molecule. Will that matter clinically? We don't know. We have not published this, but we have compared to the Merck molecule in some of these rodent models of retinopathy. We seem to be better. Is that the in vitro potency? Is it the configuration of the molecule? It could be difficult to tease out those aspects. Ultimately, the Wnt portion of our molecule is doing the same thing that Restoret's doing, but it seemed to be more potent in activating Wnt signaling. Of course, we have the VEGF component that the Merck molecule doesn't. That's right. I guess Boehringer, your partner, is moving forward in phase I. Maybe just talk about the economics of that deal and collaboration. Do you have exclusivity on the bispecific as well as the trispecific? Yeah. Chuck negotiated this deal, and I think it's quite unusual, so it's worth explaining. Yeah. Maybe I'll start with the financial economics, and then talk about the scope of the license. $12.5 million upfront. Total economics were about $500 million-$600 million in milestones, single-digit to low double-digit royalties. I mean, in terms of the scope of the license, we're actually able to use the same sequence that's in the 413 molecule that Boehringer Ingelheim licensed. That's what we do for both 8141 and 8143. Those are wholly owned molecules by Surrozen. No economics back to Boehringer Ingelheim. Extremely narrow license to BI for just that sequence in that format. And we can even use that sequence ourselves in other formats. That's great. Very unusual deal, actually. It actually de-risked 8141 and 8143 as they produce clinical data. Yeah. That was the idea. We wanted to reduce just the sequence liability anyway, which is why we used the Eylea VEGF trap sequences and used the 413 sequences as to we know that, obviously, Eylea's safe. We have some insights into what work that Boehringer Ingelheim had done, and we're confident in the 413 sequence. Now, I do want to touch on the trispecific, the IL-6 component. At AAO ophthalmology meeting, Roche presented some data on the Microbot. One trial positive, one trial negative. What are your read-throughs on that? There's clearly now significant room to be with the trispecifics such as your program. Yeah. I mean, I'll let others comment on the primary endpoint hitting in one study and not the other. I was at the presentation, but I don't know all the nuances of baseline characteristics that might have contributed to that. We're really encouraged, particularly in DME, which they summarized, but you can see all the data now on clin trials, that there's an additive effect with IL-6. So clearly, IL-6 alone has good activity in uveitic macular edema, which is a little bit different than diabetic. Or clinically, it's different. The etiology is very different than diabetic macular edema. I think it's encouraging that IL-6 has activity in UME alone. Kodiak had very good data in combination with VEGF and what they're calling [Mezzy], but it's UME or something broader than UME. And then IL-6 in diabetic macular edema clearly has an additive benefit on top of VEGF. I think it just strengthens the story that all of these different, whether they're cytokines or growth factors, are contributing to the pathology of the disease and that you can have an additive benefit with targeting multiple elements. How do you optimize for binding affinity across multiple?[crosstalk] Sorry, that was the other part of your question. Yeah. We set out to achieve the same both in vitro binding affinity as well as activity in activating the Wnt pathway or inhibiting VEGF as the individual components, which we've achieved. The Wnt part of the molecule looks the same as 413 in terms of the potency of Wnt activation. The VEGF part of the molecule, both binding affinity-wise and inhibiting VEGF, looks the same as Eylea on an equal molar basis. The same is true for the IL-6. We set out to basically try to achieve the exact same binding affinity and IL-6 inhibition as the individual antibody is able to achieve. We've been able to do that. Now, there's Kodiak out there developing a VEGF IL-6. You clearly have confidence that the trispecific could potentially be superior. Is that a fair assumption given how you've built 8143? Yes. I mean, I would say the strategy is based on people showing additive benefit with multiple components and that clearly multiple components are contributing to the disease. One of the other limitations of the animal models is we can't really interrogate the role of IL-6, nor can anyone else, because no one's antibodies cross-react with mouse IL-6. You will see from a lot of companies, including Roche, the rationale for pursuing IL-6 inhibition had to do with the observation that IL-6 is elevated in both the anterior and posterior chamber of patients with these diseases. There is no animal data on IL-6 inhibition because none of these molecules cross-react with mouse IL-6. We do not have preclinical data that says we have synergy or an additive effect. We have now clinical data that all these elements contribute to the disease and could have an additive effect. Craig, you mentioned IND, I guess, a few months after, several months after 8141. You clearly have a lot going on with both programs. Do you have the cash runway to resource both programs? Yeah. We ended the quarter with $80 million in cash. We did a $175 million pipe earlier this year. We got about $75 million of that upfront. We get about $100 million upon FDA acceptance of our IND. What it'll allow us to do is fund both of those programs through proof of concept data. Great. I guess we'll wait for the IND filing and more data out of the pipeline. Yeah. We look forward to disclosing more details about the trial design and the timing. I appreciate the opportunity to be here. Thank you for the invitation. Thanks for participating and looking forward to more interactions and more updates. Awesome. Thank you. All right. Thank you. All right. Thank you.