Welcome everyone to the next session. Thanks so much for joining us at the Cantor Global Healthcare Conference. It's my privilege to welcome Surrozen as our next participating company at the conference. I'm joined up here at the front by CFO Andrew Maleki and COO Chuck Williams. I'm Steve Seedhouse on the biotech team here at Cantor. Really exciting time for the company and really for the overall space that Surrozen is operating in, which, of course, we'll discuss. The company itself has made some exciting recent announcements with respect to advancement into the clinic. I think we should just start right off the top with the initial clinical program that you've designed and that you announced, the intent of that program, some of the decisions you made into that. Maybe you can just review what you announced. What you're planning to do here in the clinic with your lead molecule, which you can also introduce as well, Chuck. Great. Thanks, Steve, and thanks for having us. What we recently announced is that we'll be entering the clinic later this year. The DUET study is a two-part study. Part one is a single ascending dose, and we'll be enrolling both treatment-naive and treatment-experienced patients. Ultimately, the objective there is to study safety and tolerability and select two doses, which will enter part two of the dose expansion phase, where we'll have an active comparator Vabysmo. The primary endpoint will be at three weeks. We'll give three monthly doses of SZN-8141, and then we'll have four-month follow-up. Really the objective here is to tease out potential differentiation on a couple different fronts. One is on potential anatomical outcomes, so drying. Two is we do have some endpoints geared towards potential reperfusion, which is uniquely suited for the Wnt mechanism. Then three is really around potential durability given the four-month follow-up we have after the three loading doses that we're giving every month of 8141. In terms of timing, as I mentioned, we'll initiate the study later this year, and we will look to have some initial clinical data in the second half of 2027. Very good. There are a couple decisions with respect to dosing with the control arm, with respect to the endpoints you are measuring that I think you would have had various options on how to do this study, some more aggressive than others. Can you just talk about what you considered and ultimately contemplating the overall objectives of what you are trying to accomplish here early on, why you settled on what you did? Right. I think based on what we have demonstrated preclinically and the promise of combining both VEGF and Wnt, we think we have the potential to be best in disease. In terms of what we considered for the design, typically phase I-B/II-A studies have been open label, but the stands have shifted a bit. It has become more competitive. Ultimately we shifted to potentially considering an active control, and then the next question was: What compound do we compare 8141 to? Ultimately we landed on Vabysmo because we think that is the most commercially relevant product. It has demonstrated incremental improvements over anatomical outcomes relative to EYLEA. It is a multifunctional antibody. Ultimately we came to that conclusion that we would answer more questions than less by having an active comparator and by including Vabysmo. What about the prioritization of DME altogether? This molecule, given the VEGF Wnt dual activity, should be active in exudative disease, I guess, more broadly, but just maybe you can articulate mechanistically why certain paths are maybe lower-hanging fruit than others, and I guess, also taking the long-term view, where do you think development makes sense here? Right. DME, I think DME was prioritized, although we did allude in our public disclosure that we will be looking at other We do not need to wait for the DME data in particular, but looking at other indications like wet AMD. I would say principally, there has been more published literature around the role of Frizzled-4 and LRP5 and its role in DME. There is also literature to suggest that their Frizzled-4 is expressed on the choroid, so there is potential for it to be effective in wet AMD as well, and certainly Merck has a wet AMD ongoing trial, and we are looking at, which we will lay out at some later point around what our wet AMD trial would look like. Okay. Is it contingent in any way on what you see from the field, as it were, the Wnt field on wet AMD, or you're pretty confident, obviously, that at some point that program makes sense one way or another? Based on our preclinical data, we've demonstrated in the CNV model, which is the— Yeah. —wet AMD workhorse model that we're effective there. Certainly, we'll take data in from external competitors like Merck. Okay. But there are key differences between our molecule relative to theirs that I think are important to consider when thinking about wet AMD. Okay. Presumably this is I think it's 20 patients per arm in your initial study. Okay. Presumably this isn't formally powered statistically across all of these endpoints, let alone any of the endpoints, and there's some novel ones in here that you mentioned that I would love for you to expand on, particularly the assessments of reperfusion, which would be a novelty, I think, in DME, and something obviously that fits the mechanism, right? That's why you're exploring it in the first place. But maybe you can talk about, I guess, in lieu of a clear statistical result on some of these endpoints, what's a win across the board here on some of the efficacy assessments that you're looking at? Right. I think we wanted a comprehensive data set, and also that's why we included an active comparator to get a sense for a potential signal around differentiation to the market leader, and I think that can manifest itself in a couple ways. It could be improvements in anatomical outcomes or drying. It could be on durability, and it also could be on these reperfusion metrics that we've included as well, given, as you mentioned, Wnt is uniquely suited to potentially address that, which no other therapies currently on the market do. Do we have a clear bar precedent? Is there natural history data, particularly on reperfusion? Do we know what to expect from those images and from that endpoint for an interventional drug? So I think, unfortunately, from the development side and commercial side, none of these VEGF have demonstrated effectiveness— Right. —in reperfusing the retina. So there was a study, the ALTIMETER study, that dosed Vabysmo monthly for six months and definitively concluded there was no impact on non-perfusion. Again, that is where potentially our molecule is uniquely suited to address that. So the endpoints we are using are complementary measurements. One is OCT angiography, which will provide images to be able to measure potential non-perfusion, particularly in the retinal microvasculature. Then the other one is the ultra-wide fluorescein angiography, which will give us a broader measurement of the retina and be able to look at things like ischemic index as well as area of non-perfusion. Okay. These will be exploratory endpoints. I think the other thing to note too, Steve, is that we could potentially run a clinical trial with specific inclusion-exclusion criteria to further tease out this potential signal that is unique to the mechanism. I see. So if you find a signal in this study, but it appears only in certain patients, maybe that have large enough avascular area or something like this, a baseline, you pursue that. Correct. Yeah. Okay. Well, that's terrific. Maybe it'd be worth recapping some of the preclinical data in the Wnt field and with your dual-acting molecule in particular that gives you confidence that where VEGF or even where Wnt monoagonists have been unable to demonstrate reduction in avascular area, where this might be something that you could see in a clinic. Right. In the OIR model, we've demonstrated that we significantly reduce the avascular area, whereas in comparison to aflibercept, it's widely known that these VEGF do not have an impact on that. I think that's, again, where we could potentially differentiate. We've conducted multiple studies head-to-head with VEGF and demonstrated time and time again that we're significantly better than what they are able to demonstrate. In this case, the Wnt business end of your molecule, is it a potency thing? If in fact you are able to demonstrate this, is it because you have a more potent Wnt agonist arm of your molecule relative to maybe some legacy Wnts? Yeah. In terms of what Merck had demonstrated, it's not clear. They haven't published their actual Restoret preclinical data as it relates to avascular area. They did publish the precursor model, and it didn't have much of an impact on the avascular area. It's not really clear to us how much of an impact Restoret's going to have as it relates to non-perfusion. Remind me, in AMARONE, which was the original Restoret study, that being the Wnt monoagonist, do we know if they explored it or if there was any? Our understanding is they explored it, but we don't know that they published any data on it. Okay. In the 8141 initial clinical study, I was curious, this is maybe an easy clarification question, but you have two dose arms, then they're characterized as mid dose and high dose. There's no low-dose arm. [crosstalk] Yeah. You expect even that mid dose to be highly active, maybe even saturate the— No, I wouldn't read too much into that. I think it's just the objective of the SAD is really to identify two doses to move forward into that part two. That's the primary objective, whether it's defined mid or low. Okay. That's how we're thinking about it. Okay. I think you mentioned you're going to have three monthly doses in that dose expansion cohort after you've gone through the SAD. Is there a longer follow-up in those patients, and what are you expecting from a durability standpoint, just given the properties of the molecule? Maybe you can articulate resident time in the eye or half-life or durability of effect that you saw preclinically just to sort of frame what we might see in patients. Right. There will be four-month follow-up. What I can say, we have not published this, but we have Vabysmo-like PK. We feel pretty, again, we will have to prove this out in the clinic, but we feel pretty confident in the potential for the durability of this molecule. I think the other thing what we do not know is given the biological activity, right? Wnt plays a key role in retinal vascular development and vascular repair. Could that biological effect translate to longer duration and durability with our molecule? That is something we will take a look at in the clinic. Okay. Just back on the measurements of avascular area, because nothing has ever been able to show a sort of interventional efficacy or activity, I guess it is not clear to me how well vetted or standardized or established are those two measurements that you are taking? I think it is OCTA and fluorescein angiography. Is there sort of good natural history data here to sort of look to and know what a clinically meaningful change on those are? As you go from site to site in your clinical trial, is it sort of standardized how to even run these tests and assess for efficacy? Yeah, I would say that it is well accepted by the field, but they are certainly not as well validated as measurements like anatomical, like CST, for example. I think there is some variability in the measurements, but that is why we are also having a comparator arm to see if there are changes relative to Vabysmo as well to understand whether or not there is a signal. Okay. Is it being measured? Are those assessments being measured in all patients in the study, or is there going to be some subgroup that has— It will likely be a subgroup because some may not have sufficient ischemia to be able to detect a signal. It will be some subgroup, and then ultimately we will take a look if there is a signal and can then design a specific study to address. Okay. Generally speaking, based on your trial design, based on maybe some of the conversations you have had with the clinical trial sites, are you expecting the demographic, and how do you think the demographic that you enroll in this study, whether it is how treatment-experienced they are? Are you even allowing treatment-naive patients in the study? Is that possible even in this type of early study? Then just broadly the type of demographic you have, is it going to be comparable to contemporary studies? Is there anything you might flag that you are changing in the eligibility criteria that would be noteworthy when comes time to interpret the data? Yeah. In terms of the eligibility criteria or inclusion/exclusion criteria, we are not doing anything out of the ordinary. Okay. Much down the fairway as it relates to that. I think the only maybe slight difference is, although some companies have done this in the SAD, we will be enrolling both treatment-experienced and treatment-naive. The reason for that is really to accelerate enrollment, but in the part two, we will only be enrolling treatment-naive, which is pretty standard for trials at this stage development. Okay. Thanks for walking through some of the specifics there about your clinical study. Maybe want to spend the last half of the conversation just talking more broadly about the field and just perspective also on the broader approach of Wnt agonism and maybe a higher-level question, I guess, that still relates to your study in some regard. But it is a broader question of just the general level of safety risk you think for Wnt agonism and sort of novel mechanism like this. Obviously, we have the AMARONE data, and so we see what the safety profile is for Wnt mono agonism. But take us through your molecule and how much you have been able to discharge any sort of novel safety risk, whether it is inflammation or anything that would be unwanted in phase I and your comfort level with the anticipated safety profile for your molecule. Yeah. Well, I would say the Restoret molecule, albeit in 26 patients, was pretty clean from a safety and tolerability perspective. I would say secondly, we haven't seen anything in the preclinical battery of studies that we have done that would concern us. Keep in mind this is local administration, intravitreal targeting Fzd4, LRP5, obviously along with VEGF. So there is nothing that really concerns us at this point. Keep in mind also we have engineered an FcRn mutation into the antibody, which is the same mutation that Vabysmo has in its molecule, and really that is designed to eliminate the drug in the systemic circulation quicker to reduce any potential safety liabilities. Again, we will have to see what happens in the clinic, but there is nothing specific that we are concerned about. Okay. That FcRn mutation, that doesn't really have any impact on its— [crosstalk] No, it does not. No. It does not. No. Just systemic. Yeah, any theoretical unwanted. You don't want to agonize Wnt systemically if you don't have to, so you engineer that in. Why is that in Vabysmo? I think they've, for the same reason, just— Same reason. —systemic. Yeah. Just, yeah. Yeah. Okay. Can you just talk a little bit about the manufacturing of this molecule because it's a bifunctional molecule, I guess? But it's multi-specific. It's targeting a lot of things, complex molecule. What have you been able to do to sort of solve for streamlined manufacturing and get ready for the clinic, obviously, which you are now? Right. Lonza is our CMO. They have extensive experience manufacturing intravitreal ophthalmology therapeutics. We're not doing, again, anything out of the ordinary in terms of formulation, delivery, et cetera. I think we've mitigated all those types of risks that some have seen because they deviated from what historically has been done. Okay. When you think about just thinking about the broader landscape, Wnt is in this category, I would argue, and if you would rephrase it or reframe it, feel free to, but it's in these sort of novel orthogonal targets in retina. In the same sort of conversation I would say as things like IL-6, Tie2 sort of emerging in this regard. How would you say Wnt can sort of distinguish itself or what makes Wnt different as you prosecute your molecule in the clinic than some of those other mechanisms that others are pursuing? Yeah, I could speak to that. First talking about some of these other mechanisms, IL-6 is a very inflammation-driven mechanism. Ang-2, the Tie2 axis, is around vascular stability. Wnt is both vascular stability I'd say, and also reperfusion and vessel development. They all have distinct mechanistic rationales that are complementary to each other I'd say. I think the one thing to point out and what makes us more excited about Wnt versus these other mechanisms is some of the monotherapy data that we've seen to date. Wnt's the only one that's shown VEGF-like or close to VEGF-like efficacy. While when you look at IL-6 alone and DME Tie2 Ang-2, they haven't been VEGF-like and they've shown much weaker efficacy. We think the mechanism has the potential to be much more effective and potent. When you have VEGF, it's kind of like your foundational mechanism. Wnt is potentially the best thing to pair with it. Obviously, we think IL-6 is interesting, too. We have another molecule that adds IL-6 on top of it, but we see them as kind of complementary approaches. Yeah, I think obviously if 8141 is successful in the clinic, that trispecific becomes the interesting next question of what does IL-6 then add to that? Yeah. Is it even necessary? Maybe you can talk through that molecule you have, describe it, and just strategically how you plan to use that molecule, depending on some of the outcomes of your study and others. Yeah. 8143, that's our second wholly owned molecule. So that adds on IL-6 inhibition on top of Wnt agonism and VEGF inhibition. IL-6 has shown, I think, varying levels of efficacy across retinopathy. So I'll put first like uveitic macular edema, or some people term it UME, as one where it's most established as being effective. DME, there is an emerging evidence that at least in combination with VEGF, it has an additive benefit. Then I'd say wet AMD is probably third, where the evidence is more emerging there. But there's potential across the three mechanisms. So in terms of the molecule itself and where we take it, I think it depends a little bit on SZN-8141 and the data that we generate with that molecule. That'll be informative, as well as these external IL-6 data points that'll come in over the coming months and years. That'll be informative in terms of how we position 8143 compared to 8141. Okay. That saved us, I think, enough time to maybe cover it in sufficient detail, but obviously there's a big competitive readout coming up here in the BRUNELLO study, which is that Restoret phase III study in DME. I think for better or worse, folks are going to read through from the result of that study to Wnt as a class, which will have important implications for Surrozen. Would love if maybe you gentlemen could frame, I don't know, your expectations for that study, maybe in terms of different scenarios that could manifest. What do we know about when we're going to get the data and sort of what we should be looking out for? I think we have some information on that that you could cover, and yeah, we'll take it from there, but would love to sort of just talk through some of these scenarios with you both. Yeah. I think in terms of what it means for Wnt, it's potentially validating the mechanism, right? There are differences between our molecule. Most notably, obviously, we have the VEGF component of aflibercept attached to the Wnt component. Secondly, our Wnt molecule is three times more potent than Restoret. The second thing I'd say is that they're doing head-to-head against LUCENTIS, non-inferiority. I think probably the easiest thing for us is that they just show non-inferiority to LUCENTIS. I also think that if they show clinical activity and miss the primary endpoint, I think our thesis still holds, right? If you think about, as Andrew alluded to, these other mechanisms, Ang-2 tied to IL-6, they haven't demonstrated VEGF-like activity. In fact, they haven't demonstrated even about half of what VEGF has demonstrated. But when you combine those mechanisms, you've actually observed that there's a benefit over VEGF alone. Yeah. IL-6, I guess, falls into that category, right? Abicipar pegol alone failed, I think, even against LUCENTIS. Maybe it could have been EYLEA. As a monotherapy, but when combined, in that case, not in a bispecific, but the combination with VEGF, it added a benefit. I guess for your purposes, right, you're ahead of the curve in the bispecific with VEGF. Do we know when we're going to be getting the BRUNELLO data? When are you expecting it? Is it sort of any day now? I think maybe there's some medical meetings coming up also that we could see full data, but I'm not sure when to expect sort of top-line release. Yeah. October 10th, there's a presentation at AAO. We'll know that'll be the full data set there. There could be a press release that Merck puts out ahead of time that with no numbers, just says whether they hit the primary endpoint or not. We'll see what they do there. Would you be surprised if, you mentioned one scenario obviously is that it misses non-inferiority. I guess we have the AMARONE data. Would that be surprising to you, or did you see things in that data set? Do you see things in their molecule that have always made that a possibility? No, that study was pretty compelling in terms of the effect. Obviously, it was open label and in 26 patients. Again, you never know what's going to happen when you enter into a phase III. Again, I think if they do show clinical activity, I think our thesis is still intact given we're combining both VEGF and Wnt together. Yep. You've licensed another Wnt monoagonist, which is of course the Wnt business end of your molecule, and that's in the hands of BI, and they're, I think, still advancing that program. Can you just talk about that license agreement and the history there? Because that's a competitive dynamic, maybe there's not much you want to say, just given the fact that they're now a competitor and not necessarily just a collaboration partner. Any comments on that? Yeah, what I can say, that's the Fzd4 LRP5 monotherapy. What we know from them is that when we recently announced this, they achieved a milestone. They're in the clinic now. There's not much more that we know other than that, and that they're continuing to progress the molecule, and they're committed to doing so. Okay. Assuming BRUNELLO is successful and Merck advances that to market, is there any dynamic here to watch for from an IP standpoint? Do you think you're in a position of strength for Wnt agonists on the IP front, and any comment you would make there? From an intellectual property perspective, we have very strong intellectual property. We've filed over, I think, 25 applications. We have over eight issued patents. I think it really demonstrates our leadership in the field, given we've been working on this Wnt pathway since 2016. As you may have seen, we recently announced that the PTAB denied the PGR. This is a process by which once a patent is issued, and this particular patent claimed multivalent antibodies targeting Frizzled LRP5 or 6, a company can file a PGR to then submit expert testimony on why those claims aren't valid, and we have an opportunity to submit our expert testimony as to why we think they're valid. Ultimately, the PTAB determined that it wasn't reasonably likely that they would prevail in this particular case, so they denied the institution. In terms of next steps, we're evaluating our options, and the next potential opportunity to have a discussion would be once Merck launches. As you know, these things oftentimes get settled as well. Okay. Lastly, we'd just sort of circle back, and this, I guess, comes back to our original topic on the clinical study, but if there's anything else you would highlight pre-clinically or from a business development standpoint, would love if you could walk through the catalyst or sort of milestone path for Surrozen into the back half of this year and as we go into 2027. Yeah. I think one big one is the IND clearance that's coming up, and that triggers the second tranche of our PIPE financing. For those who don't know, we did $175 million PIPE in March of 2025, so an additional $95 million would come in upon clearance of that second tranche. That would enable us actually to fully run this DUET study that we've talked about and take 8143, our second program, into the clinic and get some initial clinical data there. That's a big milestone, and then ultimately starting the DUET study and initiating it this year is a key milestone for us, too. Getting that up and going as soon as possible. Terrific. We'll look forward to that. Obviously, we'll look forward to reconnecting maybe once we see BRUNELLO and get more implications with data in hand. I know it's hard to talk about scenarios that we don't know the outcome of yet. But Chuck and Andrew, thanks so much for being here. I appreciate the conversation and very helpful to walk through all that with you. Thank you. Thank you. Terrific. Thanks everyone online and in the room.