MediWound Ltd. (MDWD) Earnings Call Transcript & Summary

Good morning, and welcome to the MediWound KOL event. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the MediWound website following the conclusion of the event. I'd now like to turn the call over to Ofer Gonen, Chief Executive Officer at MediWound. Please go ahead, Ofer.

Thank you, Tara. Hi. Good morning, everyone, and thank you for joining us today. I'm Ofer Gonen, the CEO of MediWound, and I'm thrilled to welcome you to this important discussion about our innovative product, EscharEx. I'm especially excited to be joined by 3 of the top experts in the field of wound care: Dr. Vickie Driver, Dr. John Lantis and Dr. Robert Snyder. Throughout today's session, we will discuss the clinical data, market opportunity and the strategic vision behind EscharEx. All this will show you how this innovative product is poised to transform the future of wound care and to dramatically improve outcomes for large underserved patient populations. Next slide, please. Before we begin, I'd like to acknowledge that during today's presentation, we will be making forward-looking statements. Next slide, please. This is today's agenda. Dr. Snyder will start with summarizing our compelling Phase II data. Dr. Driver will walk us through the VALUE Phase III study design. Barry Wolfenson will reveal exciting data from recently completed third-party market research and analysis and Dr. Lantis will break down EscharEx's uniquely attractive commercial opportunity. We will conclude with an interactive panel discussion where you can engage directly with these experts and ask your questions. Next slide, please. So before we dive into the science and market of EscharEx, let me share a bit about the company behind it. MediWound is a global leader in next-generation enzymatic therapeutics, focused on nonsurgical tissue repair. The key points that I would like to highlight here are that our technology has been validated in 14 successful clinical trials and approved by both the FDA and EMA. We have an approved product, NexoBrid for severe burns that generated $20 million in revenue last year, and we have also a pipeline product, EscharEx, targeting the huge chronic wound market. We have our own cGMP manufacturing facility, and it is designed to fully support the global demand of our product. And lastly, we have attracted collaborations with major players in the global wound care industry, companies including Solventum, Molnlycke, Vericel and MiMedx. Next slide, please. So our 2 products are based on the same technological platform, the same API. NexoBrid on the left, it treats severe burns, and it is already approved in more than 40 countries, including the United States, Japan and all over the European Union. And EscharEx, on the right, it targets much larger chronic wounds market. Specifically, it addresses 2 type of wounds: Venous leg ulcers and diabetic foot ulcers. The venous leg ulcer Phase III study is scheduled to start imminently as we already submitted the IND to the FDA. Next slide, please. So the main goals for today are: The first one is to demonstrate that our Phase III study is strategically designed for success and to show that how EscharEx represent a transformative opportunity for MediWound and its investors. Thank you again for being here. Let's begin with Dr. Robert Snyder and the Phase II data summary of EscharEx, Dr. Snyder.

Thank you, Ofer, and good morning, everyone. I'm Dr. Rob Snyder. I'm Chief Medical Officer for MediWound. I'm also Dean, Professor and Director of Clinical Research at Barry University School of Podiatric Medicine. Next slide, please. So first and foremost, what is EscharEx? Well, it's a bromelain-based debriding agent. It's now in an investigational stage -- late stage of clinical development for venous leg ulcers. It's a mixture of proteolytic enzymes which are enriched with bromelain derived from the stem of the pineapple plant. It utilizes the same active ingredient as NexoBrid, which is FDA and EMA approved for removal of eschar in patients with wound -- with burns, and this is true not only of the adult population, but the pediatric population as well. We have Phase II trials in venous leg ulcers, diabetic foot ulcers and traumatic ulcers. And this has clearly shown superiority over the placebo hydrogel and nonsurgical standard of care, and we particularly looked at debridement of nonviable tissue and promotion of granulation tissue in patients with these very difficult-to-heal chronic wounds. Next, please. So these are the studies. They're very robust in nature, 2 of them are randomized. And what's important to note here is that the results of all these studies were consistent in the Phase II studies relating to debridement, wound size reduction and also wound bed preparation. Next, please. So let's look at the first study, the -- looking at primary endpoints. And first and foremost, let's look at the incidents of complete debridement in venous leg ulcers, diabetic foot ulcers and traumatic ulcers. EscharEx had 55% versus 29% in the placebo group, clearly showing significantly higher incidence of complete debridement. What was really important was the time to complete debridement, dramatically shorter in nature. Over 90% of patients who completed debridement with EscharEx were debrided within 7 days. Four to five applications were utilized. And of course, if you compare this to collagenase, collagenase normally takes anywhere between weeks to months to get the same result. Next slide, please. So let's turn our attention now to the chronic study and looking at the incidence of complete debridement. We looked at complete debridement within the daily treatment period of 2 weeks. And when you compare EscharEx to the gel vehicle, there's a dramatic difference, 63% versus 30%. And of course, the nonsurgical standard of care was a very distant third with about 13%. So clearly, EscharEx achieved a significantly higher incidence of complete debridement compared to both the placebo, which, of course, is the primary endpoint and the nonsurgical standard of care. Next slide, please. We then look at the incidence of wound bed preparation, and for purposes of this lecture wound bed preparation will be defined as complete debridement and complete coverage of the wound bed with granulation tissue. So we looked at wound bed preparation within the daily treatment period, again, over a 2-week period of time. And the results were extraordinarily dramatic. EscharEx, 50% and versus the gel vehicle, which was about 25.6% then, of course, the nonsurgical standard of care was a very distant third with less than 10%. So clearly, the incidence of wound bed preparation on the EscharEx was significantly higher versus the gel vehicle and the nonsurgical standard of care within the daily, 2-week visits. Next slide, please. We also looked at faster time for wound bed preparation. This is extraordinarily important. The estimated time for wound bed preparation with EscharEx was only 11 days; nonsurgical standard of care, 63 days; and the gel vehicle very far behind with 85 days. So clearly, EscharEx achieved wound bed preparation significantly faster than not only the gel vehicle but the nonsurgical standard of care. Next slide, please. So we then did a post hoc analysis looking at EscharEx versus SANTYL in a head-to-head study. And we looked first and foremost at the incidence of complete debridement in 2 weeks. This was just incredibly different. The EscharEx group, 63%; SANTYL was 0, really no complete debridement during this 2-week period. The mean time to wound bed preparation was 11 days for the EscharEx group and, of course, greater than 100 days for the SANTYL group. The time to wound closure was also dramatically different, the EscharEx group, 48.4% versus 76%. And patient reported pain was very, very minimal and when be compared SANTYL to EscharEx, we found no significant difference. Next slide, please. So we know that bromelain, through in vitro studies has a very significant effect on biofilm. So what we did was we did an open-label proof-of-concept study assessing the effects of bromelain-based enzymatic debriding agents on biofilm and also the microbiologic loads of not only venous leg ulcers, but also diabetic foot ulcers. And the results were really dramatic. The wound size was reduced by the end of 2 weeks by 35% and bio burden reduction by the end of treatment was 65%, complete debridement within 8 applications was 70% and biofilm reduction in those wounds that did have biofilm was 100%. And this was verified not only with biopsies before and after treatment, but also fluorescence and electron microscopy. Next slide, please. So as far as takeaways are concerned, EscharEx truly is a triple threat for wound bed preparation across 3 Phase II studies. EscharEx demonstrated efficacy in 3 basic areas: One, promoting rapid debridement; two, stimulating granulation tissue, of course, very robust granulation tissue; and thirdly, effectively disrupting biofilm and eliminating planktonic bacteria. So I'd now like to turn the floor over to Dr. Vickie Driver, who will discuss the Phase III trial and also discuss the importance of wound bed preparation. So Dr. Vickie Driver.

Thanks, Dr. Snyder. Really nice to be here today. It's an honor to be part of this program. I am a physician leader with 30-plus years of experience in this field of medical practice. I also serve on the Board of Directors for MediWound, have for many years. I've been very involved in clinical practice, clinical trials, including developing clinical trials internationally, implementation and oversight, but also physician education in this field, in particular. I run and have developed training programs. But I think even more importantly is I'm very closely aligned with the FDA and CMS because I chair the Wound Care Collaborative Community, which is strategic in its involvement to better design clinical trials in the U.S. I'm a full professor, but I'm -- moreover, I'm very dedicated to bringing worthy medicines and diagnostics to the bedside of the patient, which is why we're all here today to discuss just that. So next slide, please. When we think about this clinical trial Phase III, we have to start with the fact that this is a Phase III international, randomized, double-blind controlled, adaptive study with 2 co-primary endpoints: The incidence of complete debridement and also the incidence of complete wound closure, 2 critically important endpoints in clinical practice today. The secondary endpoints are also very, very important when we look at the patients in clinical practice, time to complete debridemont and time to complete wound closure as well as the incidence of complete granulation tissue, meaning it's completely red and beefy and we're ready to go to the next phase and also change in wound area, meaning length and width of the wound as it progresses over time. Two arms in this study, EscharEx versus placebo, 1:1 ratio, 216 patients. It's quite a large study for patients who have venous leg ulcers. There's 3 segments of the study, if you will, the daily treatment up to 8 applications over 2 weeks, followed by 10 weeks of very best standard wound management, and this is critical for this drug to be fairly assessed over time. A component of active wound closure either allowing the investigator to apply either a cellular tissue product or an autograft. Now this is the way we practice in clinic today. So it mimics real-world practice. This allows us to understand complete wound closure, which is a secondary endpoint. And then of course, there's a durability study, which is to most clinical trials, right? We're collecting all the safety data you would expect, and we have very good collaborations with 3 of the very best wound care companies that will provide us the necessary equipment and dressings to allow this drug to have the best chance for success. Next slide, please. So with that said, Phase III is, as you can see by this slide, it's kind of is busy, but it's designed based on a successful Phase II that Dr. Snyder mentioned. Both trials have up to 2 weeks of daily treatments during which the endpoint of complete debridement will be measured. This will be followed then by weekly visits to measure the endpoint of complete wound closure. So while the weekly visit period in Phase II was 12, the weekly visit in Phase III is plus 2, which equals 14. The weekly visit has been reduced in Phase III. And this is critically important because this will enhance the difference between EscharEx and placebo in the incidence of wound closure and it will make it much harder for the placebo to close, unfortunately, the patients in the same time frame. Now this also mimics clinical practice, and 12 weeks is a much better timeline, total clinical trial. Anyway, this is a clinical endpoint timeline that really matters. Other enhancements to the Phase III trial are obviously, the larger sample size as well as the standardized wound dressings by these 3 companies that I mentioned that will help us reduce the variability in treatment along the course of this trial. And probably even more importantly is the protocol this time mandates active wound closure with either a cellular tissue product or an autograft after the wound bed is prepared, Dr. Snyder mentioned what that meant, means the investigator will say, "This wound is completely prepared, debrided, granulated and we're ready to go on to the next phase," and they will be free to do that, applying a cellular tissue product or an autograft, which is key to wound closure. Next slide, please. So we anticipate that the first primary endpoint, which is, of course, complete debridement will be replicated from the Phase II trial. And this was mentioned before, it's quite extraordinary, 63% versus 30%. Let's look at the next slide. Let's look at the second co-primary endpoint, what's kind of different or special about that. Well, the second co-primary endpoint is looking at the incidence of complete wound closure at day 84, which is 12 weeks. Now wound closure, keep in mind, is the outcome of 2 very important steps: A, complete wound bed preparation, which we know that EscharEx can do based on previous work that we've done. And then active wound closure. So this trial allows this, as mentioned before. So based on the Phase II trial, and this was explained by Dr. Snyder earlier, is the median time to achieve wound bed prep was 11 days in the earlier Phase II versus 85 days for the placebo. So while 50% of the EscharEx arm will reach wound bed preparation during the 2 weeks of their daily visits, during that time only 25% of the placebo will get to the same point. Now what does that mean? It means that by the end -- that means that by the end of the daily visits, 50% of the EscharEx patients could initiate wound closure, while only 25% of the placebo will be able to do the same thing. So in fact, it will take all the way to day 85, which is the first day of the active period of the trial, the trial will be over, essentially, for 50% of the placebo patients to achieve wound bed preparation. Now this gives, we believe, EscharEx, and you can see this for yourself, a really significant head start. In fact, it gives us a 74-days head start. So we also know that based on the literature and autograft once placed early in this clinical trial can close the patient's wounds as soon as 2 weeks. And a cellular tissue product can close a wound within 6 weeks or sooner depending on, of course, the patient. Next slide, please. So here's to say that we've included additional notable factors that will help contribute to a high potential of success. We understand that a leap of faith is not a success strategy. And so we are basing this on evidence, on previous work that's been done in our clinical trials and the evidence of today in this field of practice. So we've derisked, we have the same API, we have a proven study design, with the improvements I've mentioned based on the Phase II, shorter trial period that improves our likelihood of wound bed preparation with leads, then, of course, to closure. It's a favorable protocol in that we have a mandatory active wound closure after the wound bed prep phase, which takes this -- the patients on to closure, as we mentioned, sooner. We've added an interim assessment for a sample size adjustment if needed, and we've standardized clinical practice, which is critical to reduce variability and enhance the consistency of the care that these patients need during the course of this trial. Thank you very much for your time. And now I want to pass it off to my esteemed colleague, Mr. Barry Wolfenson.

Thanks, Dr. Driver. Hi, I'm Barry Wolfenson. I'm the Executive Vice President of Strategy and Corporate Development here at MediWound. I've been in the advanced wound care industry for the better part of 20 years. And today, what I'm going to talk to you about is the DFU and VLU market specific to debridement in the United States and the anticipated position that we expect for EscharEx to hold in that market. Next slide, please. And so we've heard a lot about venous leg ulcers in the context of the study and the clinical work that we've done. As you may know, we are preparing for a DFU study, a diabetic foot ulcer study. So these are the 2 ulcers that are going to be included in this analysis, a lot of similarities between these 2 ulcers. They're the most prevalent -- 2 of the most prevalent chronic ulcers. They both occur on the lower extremities. Some differences, though, in the sense that venous leg ulcers are known to be very large, shallow, with a good amount of pain. The underlying etiology has to do with chronic venous insufficiency. So these ulcers are born out of the fact that the body is not able to push the blood back up efficiently, blood will pool at the lower extremities, causing tissue to break down and these ulcers will form. Because it's this blood flow, that's an issue, one of the things that's specific to venous leg ulcer treatment that you'll hear about is it requires compression therapy, so pressure being put back on to the limb to help the blood flow go back up. There's about 1.5 million new cases of these wounds per year. Diabetic foot ulcers are a little different. They're smaller than venous leg ulcers, they're deeper. And because of peripheral neuropathy, pain is not that much of an issue. Whereas, venous leg ulcers require pressure, diabetic foot ulcers occur on the bottom of the foot or the lateral aspect of the foot. So any amount of pressure that's applied to them makes the situation even worse. So what you'll see with the unique part -- component of diabetic foot ulcer treatment is not compression therapy, but offloading devices where pressure is actually removed. There's about 2.2 million new cases of these annually. The other thing that really distinguishes diabetic foot ulcers though, is the downstream bad impact that it could have on the patient with regard to infection, hospitalization amputation. So these are really critical ulcers that need to be healed as soon as possible. Either way, similarity between both, and we'll get to the metrics in a couple of slides, both of these wounds, the vast majority of them require debridement as a critical first step for treatment. Next slide. And so we'll go through kind of how we put together this model. A couple of things to say in advance: This project and the analysis was done by Alira health care, they're a health care consulting and data analytics company. They've got a great amount of experience in the wound care field, have worked for the large companies and the small companies alike. They really know this market very, very well. They used a combination of qualitative and quantitative surveying with an end of around 120, so a pretty decent sample size for this sort of analysis. Basically, starting out at the top line with the number of wounds that occur each year for these 2 indications, diabetic foot ulcers and venous leg ulcers. And then how many of them require debridement, what percent of them require to debridement. Furthermore, what are the current -- taking a look at today, what are the current debridement techniques that are used and what percentage of time is their utilization done. And then the respondents were introduced to a target profile of EscharEx, a product that would come to the market that looks like EscharEx and has the benefits of EscharEx. And they were asked, how would you then change your debridement practice. So this leads to a conversion rate by -- an anticipated conversion rate to EscharEx. So that drives the volume side of the equation. There was a pricing analysis that was done that we'll talk about. And together, those drive the TAM, the total addressable market revenues and our peak sales revenues. Next slide. So again, this is a big market. You could see by 2028, roughly 4 million of these ulcers. This is that figure that I had just talked about, the percentage of them that require debridement. It's about 72%. And you could see from 2028 and looking out another 10 years or so, this is a steadily growing market. The aging population, obesity, diabetes. Sadly, all these things continue to grow. And so this will be a continually growing and large market. Next slide. From a pricing perspective, we basically took the average cost of SANTYL per wound episode as our baseline to look at. And we got to that number. You could see that it's $740. We got to that number in a couple of different ways. Alira did what we would refer to as a bottom-up analysis where they basically take Smith & Nephew, the marketer of SANTYL actually publishes a dosing calculator. So you could see how much SANTYL would be used per month per patient. So we took that number, the published clinical study data that shows how long it takes for wounds to heal of certain indications with SANTYL and then the average price per tube of SANTYL. And when you put that all together, you get this figure of $740, again, for the average total cost just SANTYL, just the drug, no additional cost having anything to do with the treatment of the ulcer. Separately, we bought some data from another vendor called SmartTrak, and we did more of a top-down analysis where we took the top line data of how many wounds there are, again, this percentage of how many of them require debridement. And then the total sales in a year of SANTYL. And that number worked out to something not very different than $740. It was around $723. So the $740, we feel good with. Based on conversations in this analysis and prior conversations that we've had with payers, we believe, again, from a baseline perspective that based on our Phase II data, if that holds true in Phase III and nothing else, that we could take a 15% price premium to the baseline of SANTYL, and it's not going to cause any heads to turn or concern about that. So $851 is the sort of base case pricing that we'll use in this analysis. It should be noted, this doesn't take into account any health economics data that we might generate, the additional claims that we might be able to get from Phase III. We are doing a much more advanced market access and pricing study in 2025 that will cover both Europe and the United States, and we'll be modeling out what happens if our health economics data comes back really strong, could we take a higher premium. But for this base case analysis, we're taking this 15% price premium, which leads to $851. Next slide. And so suffice it to say, and you'll be hearing more from Dr. Lantis in a couple of slides here with regard to SANTYL, how it performs, the relative effectiveness of EscharEx and how that's deemed by the -- how that's perceived by the market. But suffice it to say that when people are introduced to a product, a drug for enzymatic debridement that can work like EscharEx, meaning that it could -- it leads to complete the debridement within a matter of days as opposed to weeks, if not months, that across the board in any setting that you go to, regardless of the type of HCP that you talk to or even payer, they see this as a dramatic impact on the care for venous and diabetic foot ulcers. There's a lot of value associated with the speed to debridement that EscharEx offers. Next slide. So much so that when you look at currently the utilization of enzymatic debridement among the various debridement modalities, we estimate that enzymatic debridement accounts for around 18% of the market. What we believe, based on our research, is that after we launch, when we reach our peak that enzymatic debridement could jump as an overall utilization among all the modalities of debridement up to 30% and that EscharEx will control about 22% of the total market or around 75% of the enzymatic debridement market. Next slide. So now we have all of the components of the funnel and let's see how they all come together. As we said, come 2028 we anticipate that there will be around 4 million diabetic foot ulcers and venous leg ulcers. So the very top of the funnel. About 72% of those will undergo debridement, so that nets that down to around 3 million of those ulcer types. And when you take that 3 million and you multiply it by the $851 in sales, you get to a TAM, a total addressable market of around $2.5 billion. And then further, when you take the 22%, which we estimate to be our peak sales, that nets down to a number of $725 million, which is a large number. Just putting it into context for SANTYL at around $370-or-so million in sales, it's if not the largest, it's certainly one of the largest single brands in all of advanced wound care. And at $725 million, it's almost a certainty that this will be the single most, if not one of the single largest brand in wound care, it's a very large brand. I'll now hand it over to Dr. Lantis, who will talk not more so than just being a large brand, but the unique characteristics of the market that make it a very compelling opportunity.

Thank you very much, Barry. It's a pleasure to be here today with my good friends, Rob and Vickie. I've been involved in chronic wound care now for 24 years, I'm Chief of Surgery here at Mount Sinai West in Manhattan, New York City; Professor of Surgery; and have been working with MediWound for over 8 years in helping with the research protocols. And it's really a pleasure to be here with you today. Next. So Barry already presented this slide to you fundamentally. But I think one of the interesting things, as he alluded to, there are all these forms of debridement to go on, the current enzymatic debridement world is focused on a lot of other etiologies of disease than just the diabetic foot data and the venous leg ulcer data that Barry presented to you. One of the reasons that, that data, and I think for all of you who work in the wound care space and invest in that area and analyze that, understand that most studies are focused on these pretty well-defined chronic wounds. However, a large amount of enzymatic debridement is also placed on pressure injuries and on postoperative wounds and things that are pretty hard to get your head around. And even some of the data that Barry and I have discussed previously don't even include atypical wounds, which may represent up to about 25% of lower extremity wounds. So there's a whole other market that an effective product will have a growth to a market. So expanding the market as Barry alluded to, I think, is a very real entity once there is a more effective enzymatic. Right now, surgical debridement in the hospital setting is something that is done for pressure injuries and such but is not really a desired effect. So there's actually a clinical desire for a product such as this that would be effective in the inpatient and in the long-term care setting. And with our aging population and worsening chronicity of disease, I think this is very clear. Next. So as has already been discussed, and quite frankly, I've been very involved with SANTYL's research and some of the things that Barry has alluded to, certainly is quite true. To keep in mind that SANTYL is almost a 60-year old product as well. And really, the one product that's out there being used. It has a single target of action. It is a slow debrider. There are many algorithms of care that I know Dr. Snyder and Dr. Driver use, where we will use the product to get us to a point, as Dr. Driver alluded to, a point that we might be able to use a closure technique, a product or a skin graft, et cetera. And that usually does take 4 to 8 weeks with SANTYL. You get there, but you get there slowly. So the idea that you could move to something where you had basically 6 episodes of care, and you had again, as Dr. Snyder alluded to, a sort of a triple threat, a reduction in bacteria, a promotion of granulation and adequate debridement is -- will be a game changer, not just for the therapies that Barry -- or the disease processes that Barry spoke about, but for all these other etiologies of lower extremity disease. I mean, again, the venous leg ulcer and diabetic foot ulcer, depending on how you look at it, it certainly probably only represents about 25% of the chronic wounds that are seen in the United States and the world. So a better therapy that can be used across various etiologies is going to be truly a market-changing event. And there is a significant superiority obviously, in the early -- in all of our Phase II trials and in our personal experience for those of us who have been involved in the trials. Next. So again, there are -- there have been a variety of trials taking a look at SANTYL collagenase, various etiologies of disease, but the biggest cohort has actually been a group of diabetic foot ulcers, but other chronic leg ulcers and venous leg ulcers. One of the interesting things is collagenase is quite specific and it may not even be all that effective in venous leg ulcers because it really is only looking at collagen whereas bromelain has multiple levels that it can cleave and open up. So it's probably a better agent across all etiologies. But I think this paper and other papers that have been similar to it have questioned whether -- how effective collagenase is in a variety of wounds outside of the diabetic foot ulcer. Next. So I think this is -- I think everybody gets a Snicker in the company when we look at this. But at the moment, the alternatives on the market, and this happens all the time and to the clinicians on this call, Vickie and Robert, it's quite often that our office gets a phone call, and it says, "Okay, I'm having problems getting SANTYL, what else can I use?" And you're kind of like, well, there are other things to use, but there are no other approved drugs for debridement. And of course, patients find that to be completely mind-numbing to them. They're like, what do you mean there's nothing else that has an effect like this? And there are some other agents that are not through the pharmaceuticals. But at the moment, there is no alternative to this single agent that is available in the U.S. and is selling, the $350 million worth of product a year. So right now, it is a market in need of comparator products definitely. Next. So why do people use SANTYL if it's not that great? Well, one is there are a lot of patients who really won't tolerate sharp debridement. And sharp debridement is not a good option for them due to pain and it's one of the reasons, quite frankly, that MediWound started with venous leg ulcers as a target, not diabetic foot ulcers. Most companies go right after diabetic foot ulcers, but venous leg ulcers made a lot more sense because they should be debrided, but they often aren't. People in this day and age, there are more and more patients who are on anticoagulation. So bleeding is an issue, possibly infection. Other things can be proximity to sensitive structures such as arteries, et cetera. You also have to have certain licensure to be able to sharply debride. And that's not available in all settings such as the home care setting or the skilled nursing care facility. And poor clinical settings, just it's not the right environment, et cetera. So SANTYL does work slowly in these environments, and it is effective, but it does take a long time. And even the studies show that with endpoints out at 6 to 8 weeks. In addition, of course, and I think most of us really don't want to practice in a risk-reduction type mindset, but there is the idea that if you're not -- if you see a wound like eschar on a heel, a dried area on a sacrum or the back of a person, and the idea is, could you put on something like Betadine, which is very low cost, but has really no clinical efficacy versus putting on SANTYL, which has been shown to have some clinical efficacy in these settings, you'll choose SANTYL because you want, as a health care provider, to do something active. And in certainly, the U.S. medical legal system, the idea that you're doing something active to help the patient is part of your role. Next. So how can EscharEx disrupt the market? Well, right off the bat, I think the thing is if you can get a faster result with a well-prepared wound because even -- now you have to keep in mind that sharp debridement doesn't really do this. Sharp debridement works very quickly, but that does not mean that wound has a good granular base. So this balance of being able to remove the chronically bad tissue and bring in good tissue is really unique to EscharEx. I think certainly, in DFUs, this is crucial. I think this is quite frankly, in my world, more crucial for a whole host of other wounds. But I think the idea that you can get a good result quickly in any type of wound, whether that's a postoperative wound, a pressure injury and an atypical wound, which are a huge portion of the market, this rapid debridement with a reduction or no increase in pain and decreased bacterial burden, as Dr. Snyder alluded to, is really going to make people take notice of this product. The ability to actually, facilitate wound closure or as Vickie alluded to, getting the wound ready for closure with a skin graft or an off-the-shelf type item is going to also facilitate that closure speed distinctively. The idea that you can get rid of bacteria at the same time, which is an issue we all deal with is going to -- and we look forward to. Quite frankly, SANTYL at one point in time, had some powdered antimicrobials that it could be mixed with that helped with some antimicrobial activity. And those don't exist anymore. So we really don't have an agent right now that will do debridement and bacterial care at the same time. Then the reimbursement policy. I mean this is going to -- we'd really like to get wounds closed sooner. In the long term, there's a lot of conversation that in general, there will be -- episodic care will go away and the outcomes-based care will matter. So you get paid for closing a wound, which, of course, makes a lot of sense to the lay public. You shouldn't be paid for every debridement, you should be paid for getting the wound closed as soon as possible. And that's theoretically something that CMS and other payers want to move towards slowly but shortly. Next.

Okay. Thank you, Dr. Lantis, and thank you, everyone, for this excellent, focused and insightful presentations. Next slide, please. Maybe I would like to reiterate the 4 key takeaways. The Phase II data show robustness and consistency. Our Phase III program is derisked and designed for success. The diabetic foot ulcer and venous leg ulcer debridement represent an enormous market. And lastly, EscharEx represents an incredible and unique commercial opportunity. Next slide, please. So before we open the floor for discussions and Q&A, I'd like briefly to outline EscharEx broader development roadmap. So we have 2 critical milestones ahead. The first is set for mid-2026, when we anticipate interim analysis results. The second is by the year end of 2026 when we conclude this study. Beyond the upcoming Phase III study for venous leg ulcers, our immediate plans over the next 12 to 18 months include a head-to-head Phase II study against collagenase and a PK study and also a human factor study. These are small trials. Additionally, we plan to expand EscharEx indications to include treatment of diabetic foot ulcers with advanced clinical trial for this indication is already scheduled for 2026. Next slide, please. Okay. That concludes our presentation, and we would like now to open the floor for your questions.

[Operator Instructions] So our first question comes from Josh Jennings at Cowen.

I'd love to just start with maybe with Dr. Lantis and the great download on the precedent data for SANTYL. I guess, first, what percentage of cases do you -- does your center use SANTYL in, in terms of on the DFU and VLU side? I think you may have said roughly 25% of cases, SANTYL may be appropriate for. I'm not sure if I heard that correctly. And then any thoughts on the pricing that MediWound has put forward today, 15% premium to like an average dosing price for the SANTYL product.

Yes. So the question in regards to utilization, we use in our overall patient population that we see, we probably use about 12% of patients, so that's we'd say -- say, 100 patients a week, 12% to 15% of patients get SANTYL with a lot of those not being the 2 you heard about, right, the diabetic foot ulcer and venous leg ulcer. So a lot of these are the hist wounds, pressure injuries, nursing home patients, et cetera and that's ongoing. And I'd say most of our patients are getting more than -- are spending more than that $750 range because they're getting more -- larger wounds, bigger tubes. Barry didn't talk about the dosing size, right? But the dosing size of the tubes matters to the cost and the wound side, so the larger wounds cost more. And so we use probably over $1,200 per patient. And that issue is the 15% premium I think is going to be very easily justified because of the rapidity of what you're going to see. So right now, that's spread out over their pharmaceutical coverage over that period of time. But in this setting, you're going to see patients who get significantly better. And it's really going to change the algorithm of care, and I think Vickie alluded to this because even in our Phase II trial, we didn't really -- as clinicians, we didn't really get how good this was going to work. So we're kind of surprised. We literally were like, "Oh, the wound is ready for closure, but we're not ready to do that." So that's going to be some direct -- it's not going to be immediate adoption, but I think the 15% premium is very easy to justify when -- the rapidity of care. And you got to remember these applications, a lot of times are being put on by a nurse. They might be a person who has to go home and put it on their patient. They're going to have a caregiver they're going to be coming to. So there's an added cost for every time material can be applied. Most of these patients are not applying the agent themselves. Some can, definitely. But when you add in that added cost, you take that away, you take away that caregiver cost, the 15% is, I think, going to be very easily justifiable.

Excellent. Maybe the follow-up would be just where do you think that 15% utilization rate of -- for SANTYL goes with EscharEx, assuming that the Phase III study results kind of mirror the Phase II outcomes? And just a follow-up there, sorry to tack another one in here, is just thinking about the Phase III design, the lack of SANTYL being included in the standard of care arm or the control group. But having this head-to-head study that's being executed, how should we be thinking about the clinical community's kind of ability to execute a cross-trial comparison while using a smaller head-to-head study against SANTYL in terms of driving the utilization rate that you may cite here in this answer.

It's a great question. What we're going to see -- for me, you're going to see a lot more utilization of enzymatic debridement in both atypical wounds and in -- actually in venous leg ulcers because quite frankly, collagenase doesn't work in my hands that well in venous leg ulcers compared to bromelain. So we're -- I would say we'd see probably about a 7% increase. So I think the 15% going to about 22% utilization is going to be notable. The other thing that we haven't talked about, and I'm just throwing it out there, is we're going to start pushing -- we would be pushing for using this product in the hospital setting right now where we know that in the hospital setting, if you have a product that takes 8 weeks to work and the patient is only in the hospital for 5 or 6 days, for example, and has a pressure injury, you don't bother with SANTYL on that pressure injury in the hospital because it's not cost effective. You're going to need 6 more weeks later. So why bring it into a formulary. But with a product that can work in the hospital, so there's going to be a big uptick in certainly like my center using it in Midtown Manhattan. That being said, to your -- to the other question, I think that the -- so the Phase II trial that Dr. Driver and Dr. Snyder both alluded to, that actually did allow for SANTYL in the control arm that could be used. I think that it's going to be a cleaner definition. I think that the head-to-head study will be helpful. But so many people -- again, you have a product where most clinicians have a good idea of how SANTYL works. Like I know how it works. So when you come to me and say, "Well, there's an enzymatic debrider that gets things ready in 6 applications, what do you think about this versus SANTYL?" I have an automatic comparison. I already know how it works in my hands. I don't need a study to say these were like patients. So I think there's going to be pretty quick adoption because there's actually been a demand. And I'm going to throw this in real historically. But 20 years ago, there were a couple of products that were papain-urea based, and most of us who have been around for 20 years, remember them. And they were a bit more effective, and that went away for a whole host of reasons. But for 20 years, clinicians have been saying, "I wish I had a more effective enzymatic debrider. I like the idea. I wish I had a better one." And this is going to give you that right off the bat. So I don't think waiting for the head-to-head is going to be necessary to up-ramp sales and market adoption, I think, it will help and will help with P&T committees.

Great. I'm sorry to sneak one more in here, but I have to do it. Dr. Driver, thanks for your download of the Phase III trial design and maybe this will be for Ofer as well. But just wanted to make sure we were clear on the interim analysis. I mean is there a potential for safety and efficacy assessment to drive a cessation of the study and analysis? Or is that interim look really just to ensure that the enrollment number is adequate or maybe a combination of both?

So maybe I will start, Dr. Driver, and I will show another slide that we didn't plan to show in this session. So -- but it directly answers your question. So we are set to initiate the enrollment imminently, as we said. We guided and we did that. The IND was submitted already. We -- as shown here, the interim assessment is planned for mid-2026, with 2 possible outcomes. The first one is the trial is complete. The second one, we need -- additional patients will be needed to enroll because we need to maintain the 90% probability of success in the study. So these are the only 2 outcomes. The study is finished enrollment because it will be after 216 patients, or we'll increase it maximum to 350 patients. So I wouldn't expect -- if everything goes well, we anticipate completing the trial by late 2026. Dr. Driver, do you have anything to add to that?

No, I think you answered that question completely. Thank you.

So our next question comes from Frank Brisebois from Oppenheimer.

So that interim question was very interesting. I just wanted to kind of see here in terms of a catalyst. So can you just touch a little bit more on these co-primary endpoints and what do you think you need on the regulatory side to deem this successful and move forward? Do you need both co-primaries? Do you need a trend on the secondaries? Just any expectations around these endpoints would be helpful.

So as Vickie mentioned in her -- do you want to answer it, Vickie -- Dr. Driver?

Yes, yes, yes. So that's a really good question. So what do we need? So from a regulatory perspective, certainly complete debridement, hands down, we have to be good, fast and cheap, right? This has to happen quickly as we expect, within the 2-week period so that we can get to complete closure. But we need a trend for complete closure. And the reason we need a trend is that, as you know, primarily when you're looking at the primary endpoint, which is what this drug does, debride, and complete closure is really from an FDA perspective, a look at making sure that you don't backstage that wound. In other words, it doesn't get worse over time. They would be -- they will be very -- they will accept if we -- if it's unequivocal, right? On the other hand, from a clinical perspective, for clinicians to adopt it, they're going to want to see that there's a trend, right? We're, of course, hoping that there's more than a trend and that we can -- and we believe strongly that we can based on the fact that we have daily applications in our prior studies, it shows that really, it's about 5 to 8 days that it takes us to achieve that first important step, wound bed preparation, to then move to what we would do in clinical practice, which would -- to do something with an advanced product, and we've chosen 2 options that are everyday clinical practices to get it to wound closure. Does that answer your question, Frank?

Yes, that's super helpful. And then maybe I was just -- it seems like -- I was interested in the post hoc for the SANTYL versus EscharEx, but then from the comments from the KOLs here, it seems like it's pretty clear. People know how SANTYL works. So we kind of -- we know what it is, something quicker would be great. So I guess my question is, can you just explain a little bit more about the immediate adoption that might be a little slow where -- sorry, I think you mentioned the closure maybe is ready so fast that you wouldn't know what to do with it. Just a little bit about the initial adoption of the product.

Ofer, do you want me to...

Yes.

Yes, sure. So this is another great question because this brings it to clinical reality. How is it going to be adopted, right? We're going to need to do a fair amount of education because to your point, that we have not had this before. This is brand new. And to Dr. Lantis' point, in the past, we know we can't haul all these patients to the operating room and so this has been the problem we've had. So now we have something brand new. We've not had anything like this before. So we're going to have to do a fair amount of education, helping clinicians understand that they can depend on this to work pretty quickly and be prepared for that to happen. That's where the education is going to happen because we've been waiting weeks or months to do something next. Now we're going to actually be able to do that job much faster. Remember, these patients -- we heal a wound for them to get another one. And so patients are going to certainly be ready for this product because they've been clamoring for something. My God, can you imagine what it's like to be a patient and to be -- face a scalpel week to week to week to week and not have anything other as an option. It's terrible to dilemma for them.

I have one other thing to add. The quicker we get the wound prepared, the quicker we can start using some type of advanced product like EPIFIX or any other cellular tissue-based therapy or a split thickness skin graft. There's an old expression, time is tissue and the longer you wait, the less likely these products will work. So we're in a situation now with EscharEx where we can move very, very quickly through this paradigm and through this continuum of wound healing so that we have this beefy red granulation tissue, and we can begin very quickly to transition to some type of advanced therapy or a split thickness skin graft. So yes, there will be an educational dynamic, but I think there will be a very, very quick acceptance of this product and to Dr. Driver's point, and I had made it earlier as well, this is really a significant unmet medical need in the marketplace now. And I think that this will fill that gap.

Our next question comes from RK at H.C. Wainwright.