Good morning, everyone. Welcome to our KOL event highlighting EscharEx. My name is Ofer Gonen. I'm the new CEO at MediWound. I'm really excited to be with all of you today. Of course, I want to take this opportunity to thank our distinguished panel for being with us today as well. I see here many familiar faces, but for those who do not know me, let me introduce myself. Although I'm the CEO of MediWound just in the last couple of weeks, I've been part of the company for more than 10 years. I saw the company in many stages of its life. Today, I'm more excited than ever about the things that are going to happen in the future. I have 20 years of experience of leading global life sciences companies. My recent position was the CEO of a company called Clal Biotechnology Industries, which is the largest investment company in Israel in life sciences. My experience includes founding companies, investing in companies, bringing companies public to Nasdaq, leading all kind of business collaborations, licensing deals, and M&A transactions. I bring all this experience with me to MediWound, and I hope will make it a success. One personal thing to know about me, in my spare time, I'm a passionate chess player. When people ask me why I decided to lead MediWound, my answer is always, it's kind of a chess analogy. I'm saying just like in a chess game, MediWound has everything it needs in order to win. We have a clear strategy. We have a strong board member that just came here late. We have a clear strategy. We have all the pieces in place, and we just need to make the right moves in order to win. By the way, our winning piece is EscharEx, and you will hear about it soon. Okay. Now let's review the agenda for today. Today, we are going to discuss the EscharEx opportunity. We are going to share with you all clinical and commercial data that will enable you to better understand the promise of EscharEx and what it brings to the market. We will begin with a presentation of our chief clinical director, Dr. Snyder. It will be followed by presentations from our esteemed KOL, Dr. Lantis, Dr. Dove, and Mr. Feng. We will hear about the debridement practice in the United States. We will discuss some data from our phase II studies. We will learn about experience that is gained from treating patients. Dr. Dove will share it with us. Then we'll get some insights from market research conducted by a third party. I will then conclude with MediWound's corporate update, and I will say a few words about the future. I think it will be interesting. The Q&A session will be in the end, and we will take questions both from the audience here, and we will take it from the people who listen to the webcast. I think it is going to be a very interesting day. I hope you will enjoy. Dr. Lantis, the floor is yours. Okay. Dr. Snyder. We look alike. Yeah. Yeah. Okay. Good morning, everyone. A lot of familiar faces in the audience here, so, I feel very comfortable. I think we need to start first and foremost with the premise of debridement. Why is debridement important, and what is the unmet medical need in this space? I think understanding those concepts will lead to further discussion. It really all begins with debridement as a first step. It's really the centerpiece. It's the pivotal element that is necessary for good wound healing. Of course, promoting epithelialization of chronic wounds has been applied as a priority. Now, when we look at wounds, and we think in terms of how they're treated, we need algorithms. Very often, we use what we call the wound bed preparation model. It's a very holistic way of looking at things and of course we want to treat the whole patient, not just the hole in the foot or the leg. When we get down to the wound itself, there's a very easy acronym to remember, and that's DIME, D-I-M-E, debridement, control of infection/inflammation, moisture balance and imbalance, and wound edge preparation. The primary goal of debridement is really to remove devitalized tissue from the wound bed to promote wound healing. When you don't do that, the wound remains in a chronic state of inflammation. Debridement is important not only to stimulate wound healing, but also to remove bacteria, biofilm, and senescent cells. Senescent cells, of course, are not dead. They're just not active, and we have to do whatever we can to stimulate that to occur. Of course, chronic wounds that are not debrided actually create a Petri dish for bacteria to grow and all those elements that create a toxic environment in the wound. It's very, very important not only to promote wound healing, but also to prevent infection. When you look at the purpose of debridement, the underlying pathologic abnormalities in chronic wounds cause a continual build-up of non-viable tissue. The goal is to really remove that non-viable tissue. We need a balance between removing that necrotic tissue and removing that tissue which is healthy and appropriate and necessary for wound healing. We have to kind of look beneath the surface. You just can't look at the wound. You have to look at the biochemistry of the wound, and actually, we're looking at molecules. Of course, there has to be a balance between production and degradation. This is kind of a simplistic view of a very complex dynamic. If you're looking at an acute wound, you have a very predictable, very orderly, very well-orchestrated environment. When you have a chronic wound, you have an imbalance in that environment, so the wound fails to heal. A chronic wound, the balance is lost, and degradation plays a much greater role. These are some of the reasons why it's important to debride. First and foremost, we want to remove necrotic tissue because without doing that, the wound will not be able to heal because cells in the wound edge will not be able to proliferate and cover the wound. Of course, we want to remove senescent cells. We want to remove the non-migratory hyperproliferative wound edge. What does that mean? Well, basically, there are cells in the edges of the wound called keratinocytes, and those keratinocytes have to move across the wound in order to re-epithelialize it. When that doesn't occur, the wound fails to heal. This thick, hyperproliferative wound edge, therefore, has to be removed. We want to control excessive bacterial burden. Why? Because when you have high bacterial loads, that wound is stuck in the inflammatory phase of wound healing, and the wound fails to respond. It may allow the improved availability of growth factors. These are cytokines. They create chemotaxis and proliferation and kind of signal other cells and substrates to come to the wound to facilitate healing. We want to also evaluate abscesses and tunnels. When you don't debride a wound, very often you don't see those tunnels. You don't see the abscesses, so it's important to get rid of that tissue. Of course, we also, at the end of the day, want to manage the pathology. How significant is this? Well, every wound is contaminated with bacteria. That's just nature. When you have a contaminated wound or you have a colonized wound, we're really not that concerned. Left alone, that colonization becomes what we used to call critical colonization; now, we call occult infection. That occult infection can very, very easily spread to local infection, and that local infection certainly can spread to systemic infection, leading to septicemia. Patients who develop septicemia certainly are in jeopardy of limb loss and death, particularly in patients who are immunocompromised, like those with diabetes. Debridement very often is done or almost always done on an outpatient basis. It's done in doctor's offices. It can also be done at home. The mainstay of debridement is sharp debridement, the utilization of a 15 or a 10 blade. Now, there are some very, very positive things to this. A, it's fast and effective, but you need a specialist to do it, and very often that individual is not available. This can cause pain. It requires anesthesia. We have a lot more patients now who are on anticoagulants, and bleeding becomes an issue as well. In many, many cases, sharp debridement is not appropriate, and we're relegated to using enzymatic debridement or what we call autolytic debridement. Autolytic debridement basically is stimulating the body's own enzymes to debride the wound. This is usually done by an untrained healthcare provider or a family member or the patient himself or herself. It's used in conjunction with sharp debridement, that's one element of this, and it can be a negative. It just about anyone can apply it. We can use it in individuals who have underlying pathologies that would preclude us from doing sharp debridement, like peripheral arterial disease, and it will allow us to use it in wounds that are painful and moves this along to a point where we can use other advanced therapies. Not all wounds are appropriate. You need many applications in order for debridement to actually occur, and you may still need sharp debridement at the end of the day. This is the unmet medical need. You don't necessarily have to use a blade to debride a wound, and this is what the need is. We want a rapid and effective debriding agent on an outpatient basis that can be done without the need for sharp debridement. If you look at the unmet need, I mean, this is a pretty significant statistic. A rough prevalence rate of chronic non-healing wounds in developed countries is 1%-2%. Pretty substantial. There are 36 million diabetics in the United States. 25% of them will develop wounds in their lifetimes. There are 200,000 amputations performed in the United States, non-traumatic amputations, and most of them are done on patients with diabetes. Routine care of non-healing chronic wounds starts with debridement, a very, very necessary element. Sharp is the dominant debridement tool, but we are looking for a situation where we don't need that sharp instrument to create what we need, that balance that is required. There is a clear unmet need for an effective and easy-to-use non-sharp debridement product to debride wounds appropriately without the use of a blade. We now have EscharEx. EscharEx is a new biologic, very interesting, very important in my view. It's developed for debridement of non-viable tissue in hard to heal wounds, particularly in diabetic foot ulcers and venous leg ulcers. Studied extensively, used on many patients. EscharEx active pharmaceutical ingredient is a complex and concentrated mixture of proteolytic enzymes. The main ingredient is bromelain, and this will become very, very important in a lecture we'll give in just a little while. It comes from the stem of a pineapple plant. Pineapples have been around forever. This has been hidden in plain sight for a very, very long time, and the mechanism of action of the product is mediated by proteolytic activity of enzymes that allow debridement of non-viable tissue without the need for a blade. Any questions? A t the end. At the end. Well, I had 43 seconds, so I figured I would use my 43 seconds. Okay. At this point, I'd like to introduce my colleague and good friend, Dr. John Lantis. Thank you, Robert. You want to see it bigger? Yeah, bigger. Like this? You can also do it now. I don't think that there is a mouse here. Okay. Can't catch it. Okay, do we really need to see it? Here like this. Just a second. I'm also the IT person here. Okay. You can tell a guy who played chess would definitely be the IT guy, too. Be good at both. You know, this EscharEx product that Rob brought up is very interesting, and I'm gonna make a little editorial comment on his comments because sharp debridement is something. I mean, I'm a general and vascular surgeon. It's something we all do, but sharp debridement tends to either be too little or too much. The thing that happens with autolytic debridement, but definitely with enzymatic debridement, is our goal is to get the debridement just right. I will make some editorial comments in regards to the nature of some of the outcomes from this study. All studies that we present to you are gonna be a little bit difficult because they're, you know, modulated by the FDA, and of course, the FDA would like to have a yes or no answer. Is it debrided? Is it not debrided? Is it open? Is it closed? That's what they're looking for, although that's changing slowly. With that in mind, one of the things that I'll allude to as we get a little bit further along is that, EscharEx so far in our hands, you know, debrides a little bit differently. You get a wound that's looking better, acting better, and behaving quicker, which is all very hard things to study. As a principal investigator for this study, I've seen this, and it's very interesting. We've already talked about the mechanism of action. This is a debriding agent that debrides all the material in the wound, fundamentally. That's the big difference from what's commercially available in the U.S. right now. What's commercially available to us at the moment is really a collagenase, a product that debrides just the collagen, which is not all of the debris in the wound. It works slowly. It's effective in a slow fashion, but not as effective as we want. The clinicians about 20 years ago, there were some more caustic agents that were available. Most clinicians of Rob's and my generation, and certainly we kind of say, well, there used to be products that worked pretty well, better than what we have now, which is sort of an odd situation to be in. There's a real demand or, you know, a desire for this. EscharEx is obviously a cousin of NexoBrid, which has undergone effective trials in the burn market. We kind of have a sense of how this material works. I'm gonna talk to you first about a prospective study that I was not involved with that really looks at a group of patients who were treated with EscharEx. Now, EscharEx comes in, you know, it's been modulated to continue to be more palatable or more usable in the outpatient market and kinda coming from NexoBrid, a burn product where, and this is true of other products in the market. People say, "Oh, it works in burns." I'm like, "Well, that's a patient who's intubated in the ICU and has 24-hour nursing care and has doctors walking around all day, and that's not the outpatient wound care environment. It can't work in this population." The company's been working hard and has done a great job of taking a product that was, you know, in ICU, put it on for four hours, take it off, to now a product, put it on, leave it on for a while, let the patient go home, let them come back. That's kind of the story I'm gonna tell you for a moment. This first study took a look, a mix of patients, as you would expect, chronic venous leg ulcers, chronic diabetic foot ulcers, and then traumatic and postoperative wounds. Remember that about 25% of the wounds in the world are considered to be postoperative wounds. They're a very significant population of wounds that people don't think about, but this would be your aunt who has knee surgery, and then the superficial wound breaks down. The knee itself is okay, but the wound's a problem. She goes to a wound specialist. The orthopedic surgeon's totally happy with how the joint's working, but the wound needs to heal. Postoperative wound. Happens all the time. We just don't pay a lot of attention to them. In this particular group, this was a stronger formulation, if you will, of the EscharEx, 5%. This was up to 10 applications that went on for four hours, and then the stage two portion was a modification to this, which was really a 2.5% product that went on to eight applications. Fundamentally, eight applications over the course of a 2-week period, put on 24 hours, a 3-week period, in this case, at 3 x a week, really looked at the incidence of complete debridement and also at the safety. 23 diabetic lower extremity wounds, 24 VLUs, and 26 post-traumatic wounds. The study, you know, was not particularly different between any of the groups. The ages, the genders were all, you know, fundamentally normal. In general, there was a little bit of difference in gender. What happens at the end is that the wounds that are treated with the active product are really well debrided. 55% are adequately debrided versus 30% of the gel vehicle. The time to debridement was significantly different. Most of the patients who got good debridement were actually done in a week of treatment, within seven days. That's gonna be an ongoing theme. It's not only faster or better, but it's better at a faster time point, too. The incidence of complete debridement, as you can see, was significant in the VLUs and DFUs in review, and the safety was very good. Venous leg ulcers and diabetic foot ulcers, if the study drug was at 2.5% versus the gel vehicle up to eight applications, the AEs, the adverse events as reported, were not particularly significant, and the treatment and related problems were minimal at best. In summary, the patients treated with EscharEx demonstrated significantly higher incidence of complete debridement compared to patients treated with a gel vehicle alone, and the EscharEx was safe and effective. This started to give us a sense about what we could do with dosing for a particular population. Now, what you can see here is a wound that's debrided on the left-hand side, moving from top to bottom. For a second EscharEx treatment, you can see it's already looking very good. The third, which is post actually the fourth debridement or third picture, that's looking excellent. Then one week post-debridement, you can see this wound go on to diminish in size. Now, in the U.S., this might be a wound that you would stop actually in real clinical practice. You may stop at that one week post-debridement and use a skin substitute to help close. That's not the way these studies are designed, but that's another endpoint that would occur to the U.S. market. You see this, and you say, "Gee, now it's ready for closure. I can do something else." That's very attractive to us clinicians and to the patient. Second-generation EscharEx starts to become this sort of less potent but very effective product that has very limited side effects, and you can put on the patient on a daily basis and change a dressing in the office. The phase II, which first looked at venous leg ulcers. There was a lot of conversation about this with people like Robert, myself, and the company, et cetera. Part of this is in the US, there are a huge number of diabetic foot ulcer trials going on all the time. One population that's not looked at well is the venous leg ulcer population. They're also hard to debride, they have a lot of pain, and no one debrides them well, even the clinicians. I mean, we talk about sharp debridement, but the number of patients with venous leg ulcers who all benefit from sharp debridement but don't get it because it hurts too much, we have this big population that we're really in need. We said, "Let's put these in the trial." This was a three to three to two ratio trial with the active agent versus gel versus a nonsurgical arm as well. The breakdown looks like this. 196 patients enrolled. You can see at the top, 118 meet the inclusion criteria. It ends up with 120 randomized, 46 get into the EscharEx, 43 in gel. Since this was 221, a 3 3 2 model, the control group was 31. Busy slides, but what this comes down to the age, the weight, the height, they all are not statistically different between the various groups. Slightly more males, which is true in most wound care studies. The demographics skew a little bit towards Caucasian, in part because of multinational study, different sites or different locations, so probably not completely representative of our U.S. patient mix. The wound ages matter because older wounds do worse in general. Wound size matters, and I'll talk to you in a moment about how the trial did with all of that. The primary endpoints here for this trial, 63% of the patients had really complete debridement with EscharEx, 30% only with the gel vehicle. Now, the big difference here, if you look down, that 29 of the 46 patients treated with EscharEx, they got this done really within a two-week period. Fundamentally, the other group had a longer period of time that took them much longer, so they didn't debride as well or as quickly. Thank you. Also given that, you can see that the age differences are not statistically significant, the gender differences and the baseline pain. All these patients start with the same. They're just well-matched, is what this slide is saying. There was not any statistical anomaly. We didn't start with patients who were younger, better, et cetera, who got the active agent. When you start to look at the wound age, though, this starts to matter. You take a look over in the wound age of wounds greater than 28 weeks. Was there a difference between the groups there? You can see that in general, percentage-wise, it actually turns out that there were more old wounds, significantly more old wounds, in the EscharEx group just by randomization. That was not planned, but it worked out that way. If you take a look at the size of the wounds, there's not, you know, there's not a huge difference there. There's a slight difference in how different sites behave and how the various products behave, but not statistically significant whatsoever. Again, whether this was treated in the U.S. or outside, no statistical difference, and this is not true of a lot of other trials that I'm involved with. For example, like stem cell trials, they tend to do very differently outside the U.S. than inside the U.S., and that has a little bit to do with access to care. Regardless of what anybody says, we have much better access to care than a lot of other places do. Not Israel, probably, but otherwise. The improvement over standard of care, you can see on the left-hand side here, is very significant. What's really significant is the steepness of that curve, not just the overall number, but the actual improvement. The improvement over sort of best practices at the moment, not the gel vehicle, but best practices, would be, you know, very quick. This is what we saw in our own clinical practice. The patients, we actually, and I can say this, not that we're completely unblinded to our own data as of yet, but we had nobody who actually made it to the whole eight treatments over a two-week period. Everybody was debrided earlier than that. People got debrided very quickly, and that's what you see on your right-hand side as you look at it, I guess. Is that you'll see that very sharp uptake right here, and then it tapering off, which you expect because everybody's already been effectively debrided at a very early period. We were very pleased with that. It also works quickly and effectively. Another busy slide here, but this starts to become really important, and this is the one that's hard to get at. When Rob was talking about cutting away things with sharp, you know, debridement, I love sharp debridement. It works well, but I can get down to a healthy bleeding base, but that's not a granulating base. That's not usually something you can skin graft. It's not something you can use a cellular tissue-based therapy on. What we saw was these patients, as they were getting debrided, and we kind of call this active maintenance debridement or something of that nature, as we're getting them debrided, they're actually granulating very quickly at the same time. That first picture I showed you of the foot was evidence of that. You got rid of the bad stuff, and the good stuff there is, you know, fast coming behind it. This was a very interesting thing to see. You can see the gel vehicle, if you take a look across to the middle slide here and portion of the slide here, not nearly as effective in getting granulation tissue. The raw scores are below this, and then the estimated time to achieve complete debridement is, you know, striking, very striking. At nine days versus 63 days. You know, a very quick and effective debridement with granulation tissue forming at the same time. Again, no—if anything, wound closure would be much quicker. This shows that there's no difference, that this adequate debridement didn't slow down wound closure. In my estimate, this would usually be something that really will speed up wound closure dramatically because also what's gonna happen in the U.S. market once this is available is people will go on to use closure products much sooner and have the ability to close wounds much quicker, whether that's autogenous skin grafts or other closure therapies. We also anecdotally noted that a lot of our patients just went on to close very quickly, surprisingly quickly. Obviously, the patients were very happy about that. I mean, I've had patients who've come back since, had reoccurrences, and have just said, "Don't you have that trial again? Isn't that going?" I mean, people are even asking for it, and it's not even really available yet. There we have it. In closing, the safety, you know, was very effective. We really didn't have any problems. We initially had concerns about burning and peri-wound maceration and all these other things. We came up with some techniques to take care of that, which were not difficult. They're very traditional techniques that are familiar to wound and ostomy care nurses. This is a patient from our own group. You can see that this would be a very difficult wound to debride, like what's good, what's bad. Before is on the top left for you, then first treatment, second treatment, third treatment. You can see how pink and beefy red that looks at this point in time. Five days, two weeks, and 12 weeks, fundamentally closed. This was a person who'd had the ulcer for you know, for a year already. Was recalcitrant to other debridement techniques. In summary, you can see that there's very significant difference in the things that matter to the FDA, the rate of debridement and closure, things that are harder to get your head around as far as the FDA view of closure, with secondary products and granulation tissue, and the safety was very effective. We were very pleased with how the trial ran, and we're looking forward to proceeding with the next one. Now, I have Robert to come back up and talk about the potential action of this product on biofilm, which is also super interesting. John, I'm always impressed that you can get through that much material in 10 minutes. That was really something else. We're going to look at the ChronEx clinical trial. This is near and dear to my heart. It was something that I played a large role in. I'm going to kind of make the case for the fact that this product really represents a triple threat for healing wounds that are recalcitrant to other therapies. Our objectives are pretty straightforward. We're going to learn about the ongoing clinical trial, first and foremost, review some interim analysis, talk about managing biofilm, what it is, why it's significant, why it's important, why it's become such a hot-button issue for us. We're going to review Bromelain and its effect on biofilm, and also describe why this product could be a triple threat. What's the problem? Well, microbiologic infections really are the most challenging and the major reason why people have wounds that don't heal. This is very, very typically seen in patients who have biofilm, and biofilm is notoriously recalcitrant to any therapy that we throw at it. It's not only a problem that we see in wounds, it's a problem that we see in other diseases. You see it in cystic fibrosis. We think we see it in Crohn's disease as well. Again, tolerance to traditional antibiotics is really a problem. Infection really complicates wound treatment. Why? Because when you have high levels of bacteria, you have an inflammatory phase of wound healing, which is very, very hard to get out of. You damage tissue, reduce the wound tensile strength, and of course, this undesirable inflammatory response. Controlling and preventing infection certainly will aid in allowing us to heal these wounds. We talk about biofilm. Just briefly, what is it? It's basically a colony of virulent bacteria that are sitting in this polysaccharide Glycocalyx, this matrix, this tube, if you will. The bacteria are a little sliver right in the center, and you have this very thick tube that's surrounding it, and you also have metallic bonding, and that metallic bonding again forms this resistance. Anything that you try to attack it with can't get in through that Glycocalyx until now. The Glycocalyx really protects the bacteria from antibiotics and accounts for persistent infection. Now, when you look at biofilm and you think about how significant it is, this slide says 90% bacteria exist in biofilms. It's likely closer to 100% exist in biofilm. We do see planktonic bacteria, which of course are kind of free-floating. They're sitting on the surface. That planktonic bacteria will seed to form biofilm. Again, all very problematic, and when you have a biofilm, it can be 1,000 x more resistant to anything that we throw at it. It's a very significant problem, particularly in those wounds that are recalcitrant to other therapies. Biofilms don't play fair. They're difficult to culture. They're tolerant to biocides. They're tolerant to antibiotics. They're capable of regenerating. They talk to one another through quorum sensing, and they can live in the most horrendous situations and the harshest of environments. Again, very, very difficult to handle and very difficult to treat. This study comes along by Nancy Millenbaugh, out of San Antonio, looking at a Staphylococcus aureus biofilm, which looks very similar to what we see in nature. Staphylococcus aureus is the most common organism that we see in chronic wounds, and the anti-biofilm activity of four enzymes was reviewed, and one of those was Bromelain. They found that Bromelain reduced biofilm mass by 98%. This basically was looked at with electron microscopy, and it was confirmed. It basically showed and indicated that enzymes such as Bromelain may have an effective means of eradicating biofilm but could also be a very promising strategy for these multidrug-resistant organisms. I love this study, I have to tell you. I don't love many studies. I love this study. I feel that it's so important, and I'm really glad we can share it today. It was a prospective study performed to evaluate not only debridement but also the pharmacology and what it is doing to bacteria and biofilm. It was basically a single-arm study. It was open label, 12 patients. It was a very small study, you know, we have some ways to go. Three sites in the U.S. Duration was up to eight applications and then a 2-week follow-up. What we did was we did a 3 mm punch biopsy before treatment. We looked at wound fluid before treatment, and then after debridement, we repeated it so that we had a way to compare. What we were looking at was safety and efficacy, first and foremost, but we also wanted to see reduction of biofilm, reduction of bacterial load, and we also wanted to follow the biomarkers to see whether or not we were actually getting a transition from a chronic wound to an acute wound. How do we look at the bacteria? Well, we use a device called MolecuLight. Not too much time to go into the dynamics of this, but basically what it does is it fluoresces bacteria, and it converts it to pixels. Basically, you have two types. You have red fluorescence, and you have cyan fluorescence. Most are red fluorescence, and most are likely Staphylococcus aureus, and most bacteria will fluoresce red. This actually was a case of Dr. Dove's. I'm very, very happy that she's allowing me to share it with you. We looked at the bacterial load here because what the MolecuLight device does is two things. Number one, it shows us the amount of bacteria, but it also shows us where that bacteria is, so that when we take our biopsy, we know that we're taking it in an area that is full of bacteria. If you kind of look at what this looked like before, and you look at the number here, this was very substantial. Look at it post-treatment. It went down to almost zero. Now, when we looked at biofilm reduction, obviously we were looking at these biopsies, and the biopsies again were done based on what we saw with the MolecuLight device. The sections were stained and examined with laser microscopy. What they did was they created in a lab the scale, zero being no microorganisms and five being the worst, this thick, you know, mass of biofilm bacteria. Take a look at this. This is pretreatment. We had the highest biofilm score of five, and then post-treatment, the biofilm score went to one, which was really insignificant. We had a very significant result leading to the possibility that biofilm would not be a problem in healing this patient. In summary, we looked at clinical performance. 70% of patients achieved complete debridement during this treatment period. On average, complete debridement was about four applications of EscharEx. Just think about that because the product that is currently in the space is weeks of treatment. Significant debridement of wounds during the treatment period was about 85%. Significant decrease in wound size at this point, at the end of two weeks, was 35%, and it was very safe and well-tolerated. What was really important to me looking at this study was what happened to the biofilm. You saw a dramatic drop in biofilm bacteria, dramatic reduction to single organisms in many, many cases. Seven patients had positive red fluorescence. At baseline, it was about two, and it went below one. Of course, we're looking still at biomarker analysis. We have not yet gotten those results, but hopefully, we'll be able to share them very soon. Why do I say this is a triple threat? Well, first and foremost, we know that it's very effective against debridement without the need for a blade. Number two, bromelain could disrupt biofilm bacteria. Number three, Bromelain could have a dramatic decrease in planktonic bacteria, which all adds up to a healing wound. I actually did this with a minute to spare. I'm now going to turn it over to my friend and colleague, Dr. Dove. After you. Oh, thank you. Good morning, everyone. I was invited to speak today because I was one of the principal investigators in the phase II trial, and I'm gonna review some of the slides. Before I go into the photos, I would like to just kind of go over some of the points in the trial. Patients could have a maximum of eight applications of the IP. As Dr. Snyder stated, we did pre and post IP application biopsies, and we also used molecular imaging. Here we go with our first patient. This is a venous leg ulcer. I think that Dr. Lantis has said something really important, that these are difficult wounds to debride. This patient here has a left medial malleolus ulcer, and the lighting is a little bit bad, but if you look at the pre-debridement versus post-debridement, this patient only needed six treatments. They could have a maximum of eight treatments in all. That's quite a deep wound that we have here. It's hard to see here, but it's sloughy. It's hard to distinguish between the good tissue and the bad tissue visually with, you know, just the naked eye. It's also very deep and punched out. You see that it's macerated. It's maybe about three millimeters away from the underlying bone. Again, very, very difficult and very painful. These patients are very resistant to debridement. Even though they need it's in their best interest, you know, it's a bit, can be a bit of an argument on the clinical side. When we look at the post-debridement photos here, you'll see that, yes, he has a little bit of peri-ulcer dermatitis, macerated. It's a little bit denuded. If you look at the hue of the granulation tissue, this is faded and dusky. Here it's very robust and vibrant. Instead of this yellow slough, you see that there is healthy fatty tissue there, and you've lost some of the depth. Although the wound is not healed, this patient can then proceed to go on to have some type of cellular therapy. This is quite an active patient. He works full-time as a counselor. He also is a gentleman farmer. The fact that we could do this in just six short treatments without the product, it would be much, much longer and very complicated to treat him really because of the pain that the patient was experiencing. Quite a big difference in a very short amount of time. Some of the patients who had more treatments, they did have short drug holidays if they had excessive pain. This patient went straight through, with the exception of a drug holiday for the weekend. We didn't leave it on throughout the weekend. Now, if you look at the pre- and post-treatment MolecuLight images, you'll see a lot of fluorescing in the outer areas of the ulceration. You look post-treatment, it's completely resolved. We see that the biofilm, as per the MolecuLight, has been resolved, the biofilm. If we look at the biofilm score, which again was garnered via the biopsy, he didn't really have much of a change. In terms of the MolecuLight and the overall appearance of an ulcer, quite a significant change and improvement. We'll go on to patient number two, who was also a venous leg ulcer, and I think that she had quite a remarkable difference. When she initially came in for the trial, you may think, "Okay, that wound doesn't look too bad." In truth, it's just a stagnated wound. You see these rolled hyperkeratotic borders, a lot of necrotic tissue. She's got some dusty, non-vibrant granulation tissue with a lot of fat, fatty tissue in there. Her wound, again, was exquisitely painful. This is a patient who will not let me do a bedside debridement in the office. This is a patient that typically I may have to take to the OR and do something under anesthesia. But because this patient needs serial debridement, that's costly and very hard to do. When we look at the post-treatment, she only needed two treatments in total. This is a healthy, vibrant wound. This looks like an acute wound. This is an old chronic wound, but when you look here, you see really robust tissue. The wound is nearly not as deep as it was before, and even the borders no longer have that rolled edge to them. The wound looks like this is maybe a few weeks to a month old, whereas this is something that's long and stagnated. They all had compression in the study, but she also had markedly less inflammation and edema to the area. She did very well after two treatments. When we look at the MolecuLight imaging, you see the wound bed. You can see the. Oh, I'm sorry. Sorry. Sorry. Sorry. Yeah. I didn't get up at 5:00 A.M. this morning. Yeah. It's on Vegas time. I'm sorry about that. I'll wake everybody up. When you look at the... Just please turn the volume down. Sorry about that. I apologize. Again, when we look at the pre-debridement, you see that it's fluorescing. This is more of like a white-green color. Post-treatment, it's consistent with the clinical photos where this biofilm is completely gone. Her biofilm score, again, this was garnered with the pre and post biopsy. You see that she went from a two to a one. She did very, very well with the study, and she was quite happy. For her wound, we actually went on to put a cellular product on it when she was finished with the study, after she finished her follow-up, 2-week follow-up period. Now when we look at this patient, Dr. Snyder showed this patient briefly. This was actually one of my favorite patients in the study. When we look at his wound, he came into my office with this wound. This guy was working full part-times as in a pizza shop. He came in. I said, "You know, really, I need to take you to the OR and debride this." He was quite resistant to that, and I offered him the option of participating in a trial. He agreed to it because he did not wanna take any time off from work. When you look here, this necrotic patch right there, that was quite deep. It was almost to the level of his tendon into the bone. You see after five treatments, the depth is gone. This wound went on to heal maybe two weeks after his post-treatment. There was no exposed or palpable bone. This looks like a new acute wound. This does not look like this chronic wound. You can see that in terms of pre and post, it's a very dramatic difference, less edema. He's got no hyperkeratotic borders and fresh granulation tissue. That's not something that I typically see with sharp debridement. You know, I've been a clinician for 20 years, but when you're debriding, as Dr. Lantis said, there is an art to it, but I would have been very aggressive in terms of debriding this, and I probably would have debrided it to the level of the bone because we can't see with the naked eye. It's hard to separate the non-viable versus viable tissue. A lot of times we tend to be overly aggressive. This is a wound that went on to heal on its own after just five treatments. You see the MolecuLight imaging pre-treatment. You can see very clearly this is what we use to take our pre-treatment biopsies. You see post-treatment, again, after the few treatments he had, it's completely gone. He had the most marked difference in his biofilm score. He went from a five to a one, so really remarkable and very, very short treatment course. This is our next patient. This is a venous leg ulcer. Now, the ulcer itself, it looks small, somewhat unremarkable, but I find clinically, anecdotally, that sometimes these can be the most difficult patients, especially if you look at the peri-ulcer area. He's got this heavily scarred, fibrotic, inelastic tissue, rolled borders. You look, again, a little bit of granulation tissue mixed in a lot with the slough. Very superficial, but again, these wounds can linger on and on because of the age of it and the peri-ulcer condition and also the comorbidities of the patient. Now, when we look at after just two treatments, it's a completely different wound. Less edema. You see that it's very superficial. There's no hyperkeratotic tissue. Centrally, you can even see an island of epithelium. This is a wound that after the study, he went on to heal without any other advanced products, healed very quickly. Really remarkable improvement on him. When we look at the MolecuLight imaging, he lit up like a Christmas tree, very bright. You see post-treatment, there is some fluorescence, but minimal in comparison to his pre-treatment. His biofilm score went from a three to a zero, so he had no biofilm left after his treatment. Here is another. This one may be difficult to see. This is a very active patient who takes care of her granddaughter and a very sick husband. Quite a busy lady who has recurrent ulcers. We know that these are frequent flyer patients, so to speak. This is her ulcer pre-treatment, and she again only needed two treatments. It's deep, not as deep as the initial, the first patient I showed you, but shaggy borders. Again, she's got very inelastic, thick tissue. She's had many, many ulcers over the years, and she comes in. Typically, this is a patient that we'd attempt bedside debridement, sharp debridement. Again, very, very, very painful ulcerations. She enrolled in the study. She did very well. You see this very shallow ulcer. You see reduced edema, reduced inflammation. Again, it's red, vibrant granulation tissue. She went on to heal without any advanced modalities as well. Now when we look at her MolecuLight treatment, or MolecuLight image, the one flaw with that device is it doesn't fluoresce on darker skin, so this doesn't have as much weight for her because she's highly melanated. We can look at the biofilm, and we can see that there was indeed a reduction from two to one. Again, to reiterate, she went on to heal without any advanced modalities. There was no wound vac, no cellular therapy that was needed. Thank you for your time, and now we'll go on to Mr. Feng. There you go. Hi, good morning, everybody. As Dr. Dove mentioned, my name is Kevin Feng. I work at Oliver Wyman, a consulting firm that has been supporting MediWound's market research efforts. Our practice has been supporting the MediWound team for a number of years now in understanding the market potential for EscharEx, and I'm excited to share some of those insights with you today. Our work with MediWound has spanned multiple rounds of research dating back to 2015 in an effort to be very comprehensive and really continuously evaluate EscharEx based on both the latest clinical development plan and the latest data available. Today, I'll be spending most of our time sharing the insights from our latest round of research, which really focused on understanding how physicians perceive the recent phase II results and what that means for the EscharEx opportunity looking forward. Before we get to that, I'll first provide some background on the wound care market overall. Treatment of chronic wounds in the U.S. can often be very heterogeneous. There are a lot of differences by sites of care, by different treaters and specialties. That said, most chronic wounds in the U.S. are treated on an outpatient basis with follow-up visits generally 1x-3x per week. Similarly, while debridement is part of the standard of care in wound management, there are a lot of factors that go into choosing the specific method of debridement. You know, wound characteristics, efficacy, patient considerations. These are all top influencers of whether a wound undergoes debridement and the preferred method for debridement. Based on our epidemiology research, there are about one million patients with VLUs and about just over one million patients with DFUs in the U.S. annually eligible for debridement. Most of those patients will undergo debridement with our estimates of about 55% of VLUs and about 70% of DFUs undergoing debridement. The approach to debridement is also often driven by site of care. Almost all wounds at a wound care clinic will undergo debridement, whereas those seen in nursing homes or home health settings, fewer of them often require debridement because many can be caught earlier and managed early by nurses and won't require debridement given that early intervention. The choice of debridement method also differs by site of care as well. Sharp is generally considered the first-line standard of care within wound care clinics, either alone or in combination with other modalities. In some specialty practices like dermatology, you might see more of a split between sharp versus non-sharp methods, and then often in nursing homes or home health settings, those clinicians really rely on non-sharp methods, including both autolytic and enzymatic debridement. When it comes to enzymatic debridement in particular, current use is often limited due to a perception of low efficacy and high cost. In particular, a lot of physicians consistently report, as our other speakers has alluded to, a very slow speed of debridement with current enzymatic agents, often taking on the scale of weeks to months. Even those physicians who do tend to rely on enzymatic debridement note that this is a very slow process, that leads to very extended use of current products. High cost is also cited as a concern because the high cost of current products isn't really appropriately relative to the limited efficacy and the slow speed of debridement that we see with currently available products. Because of that, there's a pretty significant need for a more efficacious topical debridement agent, something that demonstrates more rapid time debridement over a shorter period of time, fewer applications, particularly in situations where sharp can't be used. This is seen as, you know, a gap in the market that was left by the recall of Papain products that Dr. Lantis alluded to. These were enzymatic agents available prior to recall by the FDA due to safety concerns. Before they were recalled, they were perceived as much more efficacious, and physicians reported using much more enzymatic agents before that, relative to what's used today, given that it had better efficacy compared to what you can achieve now with enzymatic agents. Now, moving to the perception of EscharEx based on the latest data among our physicians, and thinking about efficacy first, our physicians were very consistently enthusiastic about the efficacy profile. All of them immediately note the significantly faster speed of debridement based on the clinical endpoints, demonstrated by the incidence of debridement, the time to a number of applications needed for debridement. In addition to that, a lot of them appreciate the pharmacology data as well. Many of them noted that, you know, biofilm pharmacology data is becoming more important and emerging in the wound healing field. The biofilm reduction really demonstrates and supports what's already demonstrated by the clinical endpoints. The efficacy package overall really demonstrates a very clear benefit over current enzymatic debridement options today. On top of that stellar efficacy profile, very positive feedback on safety and dosing as well. Our physicians noted very minimal safety concerns with EscharEx, and that's a high bar to beat because currently available enzymatic agents, while they are subpar on efficacy with limited and slow speed of debridement, they are considered very safe, and they're used because they, you know, they won't cause any harm. Physicians feel very safe using them. It's a high bar to match, and EscharEx has matched that profile with very minimal safety concerns. And then very positive feedback on the dosing protocol as well on, you know, about five daily applications for the entire dosing protocol. Again, it's a testament to how well EscharEx is working and how much of an improvement it is compared to currently available options. Given such strong data from EscharEx, our physicians all anticipated that EscharEx would draw share from essentially all debridement methods on the market today across the board. That includes the current enzymatic use segment, where EscharEx would be expected to take the lion's share of the market, given significantly better data and efficacy profile. It also includes replacing some autolytic use. Really interestingly enough, it also includes potential to replace sharp debridement in some instances as the first line standard of care choice. Because of such a strong efficacy profile, many of our HCP thought this could compete with sharp debridement as a first line choice. That ultimately leads to many of our physicians anticipating a very significant expansion of the enzymatic use market compared to how it's being used today, given a much better efficacy and total clinical profile. Wrapping this up with market opportunity. Of course, anticipated enzymatic expansion results in significant upside when we look at the market opportunity for EscharEx in the U.S. Our estimate for the total addressable market across both VLUs and DFUs for EscharEx is about $2 billion in the U.S. That's based on the epidemiology estimates I shared earlier, over 2 million VLUs and DFUs annually, eligible for debridement per year, and about 55%-70% of those receive debridement based on our estimates. Given the strong profile, our market research and physician feedback suggests that EscharEx has the potential to capture about 30% of that market. That 30% market share estimate is based on combination of two assumptions. Given the significant expansion of the enzymatic market expected, we assume about 43% of wounds could be debrided by enzymatic methods, either alone or in combination with sharp. That's an increase from how it's used today in about 20% of patients. Within the enzymatic debridement segment, we assume that EscharEx would attain about 70% peak market share as the dominant product in the enzymatic market, given the superiority in data. All of this really points to a very meaningful market opportunity for EscharEx, again, given such strong phase II data. With that's all I have to share today. I'll pass it back to Ofer. Okay. Again, thank you all for joining us this morning, and I hope after listening to our STEM panel, you have gained a deeper understanding of why we're so excited for EscharEx. Let me give you a kind of a summary why we think we have a winner here. Let's go to the first row. The need is real. I think you are all convinced that the need is real. As you saw earlier, EscharEx is rapid, effective, non-surgical debriding agent, exactly what patients and physicians are looking for. Now look at the risk profile of the development, which is a very important element. The risk is minimal, not only because of the effectiveness of EscharEx. It is based on the fact that EscharEx is with the same API as NexoBrid. NexoBrid is our drug for treating severe burns. NexoBrid is already a commercial product. It has a marketing approval in 41 countries, and there are more than 10,000 patients that were already treated with this drug. We think that the risk profile of the development is relatively limited. Most importantly, EscharEx is superior to the non-surgical standard of care in all the relevant parameters that we are looking at. If we recap what we heard from the KOLs, we see that we have a better efficacy. Better efficacy means incidence of complete debridement. We are more rapid, which is better in the number of less applications and much better with the time to achieve debridement. Additionally, we have a shorter time to complete closure. I don't remember the numbers by heart, but we have significantly less numbers of days to close a wound. Additionally, we have a very strong effect on the biofilm and on bacterial burden. This is further demonstrate our superiority over the other modalities. Following what you heard about the EscharEx today, we decided that we cannot be more excited to continue and develop it globally. Globally for VLUs and DFUs. The development cost of additional territories is marginal. Therefore, we develop it for the United States, but we will go for other markets, which we believe will also accelerate the time to market for approvals. As you can imagine, we are also exploring potential partnerships, and we have significant interest and inbound approaches from the biggest strategic players in the market. None of them can remain indifferent to our capabilities in debriding wounds. As far as we know, most of them are interested in finding an effective debriding agent. Based on all we discussed, it is anticipated that EscharEx withdraw market share from all the relevant debriding agents, not only from the enzymatic ones. We are also aiming for sharp, and therefore, it implies a 30% market share for a $2 billion market. We're excited. From that, here I'm going to summarize and tell you what you should be expecting from us, from MediWound going forward. After what you heard today, EscharEx is definitely our main focus. We're looking for the best strategy to accelerate the time to market because we know that we have a game changer. We have several options. We can develop it on our own, but we can potentially collaborate with a strategic player. But no matter the pathway, we are moving forward as we understand that we have a billion-dollar opportunity. As for NexoBrid, we remain on track with our timeline for a mid-year resubmission, and we will announce the filing when it has been accepted by the FDA. We continue to collaborate with BARDA and with the Department of Defense, and we are very pleased with the collaboration and about to complete BARDA's procurement for emergency stockpile. In addition, I can say that we are encouraged with Vericel's pre-marketing or pre-launch activities. Another thing about MediWound, if you look at Europe, we have a continued growth in Europe, and we are planning to submit a pediatric label by the end of the year. It is supposed to increase our market quite significantly. In the rest of the world, we anticipate additional market approvals towards the year-end, and some of them are in major territories, such as in Japan, which is considered a very big market, and in India. Lastly, let's speak about MW005. It's our non-melanoma skin cancer drug candidate. The data that we just announced in our press release yesterday looks very promising. The market today is definitely ready for an effective topical solution for BCC. The MW005 provides for us another opportunity for MediWound, and we leverage the enzymatic debridement for additional markets. We are now evaluating all kind of strategic options that the company have around this specific product. Now I will open the floor for all kind of questions, Q&A. We are ready. For those on the webcast, please submit your questions via email at questions@lifesciadvisors.com. Hi. Thanks to the MediWound team for hosting today, and the physicians for joining, and then Kevin as well for the market data. Wanted to just ask about the phase II data, and just the Santyl group. I know it's a small group within the standard of care arm. Just anything you can share about the performance of that group. I think it was less than 10 patients, so not really powered. On top of that, just for the physicians, just thinking about the data that's or the literature supporting Santyl and just how should we be thinking about that cross-trial comparison, this phase II data versus what we know about Santyl's efficacy. I think the one thing that we don't know about, you know, Santyl versus, you know, the EscharEx product is more probably has to do with mechanism of action, et cetera. There is some data in the Santyl history that shows that some of the collagen split products is broken down by Santyl actually had some pro-growth function. You know, just the efficacy of debridement is a you know, potentially a totally different question. I think some of the Santyl usage, honestly, at the moment, when you just look at market share, is a lot of people will actually use Santyl till closure. You get over. Fundamentally from labeling, you get over-prescription of Santyl, you would say, but people feel comfortable letting wounds go on. They can't market it that way, but it gets used that way. This product is probably different than that. I think, on the other hand, one thing that wasn't commented on, most likely EscharEx, in its efficacy profile, once you use it on things that, you know, on label, if you will actually grow the market for debridement in areas like pressure ulcers and things that aren't well-studied. I think that our standard of care arm behaved. In this day and age, it's hard to have a standard of care arm, is what it comes down to, because we got advanced products. You're kind of randomizing some. This is a problem with all trials. The FDA is sort of saying, "Well, we want a standard of care arm." You say, "Well, I already have better than standard of care." Limiting that's gonna continue to be a problem. We're not completely unblinded to our data yet, but the standard of care arm did not behave, I mean, it's small, but it did not behave very differently. I think the more important arm is the gel arm, honestly, 'cause then you, we, I think you've all been involved with products where the gel actually did something, you know? I think this was a very noticeable, like who got what. I mean, it's hard to be blind. We are blinded to it, but you were kinda, I know what's working and what's not. Understood. If I may add, when we spoke with the physicians after the study and no one was surprised on the behavior of the non-surgical standard of care arm, it is very consistent with what they see in their clinic. Excellent. Just for the physicians, you know, just assuming crystal ball question, but assuming phase II data was good enough in a hypothetical scenario to get approval for EscharEx, can you just talk about how your expected utilization of the product in your practices? Oh, yes. In my practice, after being in two of these different studies with this product, it probably will become a first line, just because when you're considering the patient's acceptance of what treatment they would like, they want something fast, and they want something a little bit less painful. In particular, for the venous leg ulcer patients, those are very, very painful, excruciating. If you can offer them something faster to get them healed or get them to debride quicker, that's what they're gonna opt for. I think eventually it will be first choice for patients and for the providers as well. Something, something else to keep in mind. Patients are getting older, and they're getting sicker, but they're living longer because we have treatments for them. You know, when I started practicing, we didn't see diabetic patients that were over the age of 60 because they died. Now we see patients in their 90s that have had diabetes for 60 years. You have many, many patients that are not candidates for sharp debridement. I wanted Dr. Lantis to comment on this as well. It was a question I had for him. There are many reasons why sharp debridement is not a good alternative. This product really will replace that, and that's really the key. I think for me, who you know treats all types of wounds, I think it'll be a growth of the use of an enzymatic debridement, if you will, for certain areas that we don't really use it in, or we only kind of experiment with it at the moment. One would be for the ischemic ulcers that are not revascularizable, which is you know a small percentage at this point, but still some grouping. People have gangrene, dry gangrene, who we are taught not to debride sharply 'cause if we cut through it'll turn black. But I think there's an opportunity. Some of those people have marginal healing, and that's an area of growth, and that's still probably you know a quarter of a million patients in the U.S. Definitely the pressure ulcer world. This is a place that a lot of folks right now some are getting, you know, the collagenase at the moment, but a lot of times people don't think it's that efficacious, so they don't do it. It also goes on, has a cost, and goes on for a very long time. I think definitely using this on ischial and sacral pressure wounds will be a growth area and would be a place where I might say paint it with Betadine now. I would try this because the nice portion about this, I think the other thing you have to keep in mind is this, for a surgeon, actually almost seems surgical because you're doing this in a short timeframe. You know, again, you're getting this done, and the way the trial's set up is actually good. You know, you're gonna get results. You expect results in two weeks. If you don't have them, you go on to the next thing. A lot of surgeons, that's one reason they don't use enzymes, is they think, well, three months, why am I gonna do that? I think there'll definitely be an expansion of usage, and definitely VLUs. The other category is also the atypical wounds. There's a very large percentage, and a lot of them get treated as VLUs, so the market research is always hard on this one. I think Kevin and I talked about this a little bit. Is that the folks who have lower extremity ulcers, who have rheumatoid arthritis, lupus, things like that, they don't get debrided 'cause they hurt way too much. Therefore, they do terribly. Those patients would also. I think this is gonna be an additive. It would take some portion of the market, but actually I think it will grow the market. I have one last comment. My colleague and I last night had a kind of a sidebar conversation about the impact of COVID and the fact that patients are not as readily available to go to doctor's offices. A lot of it is being done remotely through telemedicine. These patients are not coming in for sharp debridement. Right now we don't really have, in my opinion, a really effective therapy for use at home that isn't a very long process. What I envision is that this product can be used at home. The patient is debrided in a reasonably very short period of time and then can come in for a definitive procedure or an application of a cell or tissue-based therapy. That's another aspect. I mean, medicine is changing, and I think this should be part of that dynamic. Great. One last question, [inaudible], and just on the next step in the clinical development program for EscharEx and just for the MediWound team, just your, I guess, ideal scenario in terms of how a phase II trial, what it would look like. I mean, would it mirror the phase II design? Would you include some of the biofilm burden, bacteria burden, infection control measures as a secondary endpoint? Would you expand the sample arm to have more better head-to-head comparison to drive uptake in that enzymatic debridement segment of the market? Any just color in terms of what you view as the ideal trial design going forward for the phase III program would be great to hear. Thanks. It's a very good question. As we communicated, we are going to go to the FDA next quarter and discuss with them how the pivotal study look like. What we can say at this stage is that the phase II was so robust, and we saw everything that we wanted to see in the phase II. We think that we have a clear pathway with a single phase III trial. If it is not the case, we might need to do two phase III studies, but then we will split it to DFUs and VLUs. Having said that, we saw in the phase II study was so robust, so we don't think that we need to change dramatically the way how the phase III will look like. Therefore, it's again another for us it's a kind of less risk because we know how the data will look like. Hi, everybody. A.J. Simon with Cowen. I'm on Josh's team as well. I had a question. The clinical data is very impressive. Congratulations on that. Thank you. Curious, do you guys have a plan to demonstrate a reduction in cost for healthcare facilities to possibly justify the price point in the future? As for the price cost, as Kevin said, in the market analysis, we took the Santyl cost and/or the nonsurgical center of care cost. I'm sorry. We definitely consider increasing substantially the market because, as far as we understand the situation, we set a new bar of efficacy. Suddenly, there is a product that work, but we will need to work about it, to work at it, and we will give you, and we'll communicate our strategy later on. Hi, this is RK from H.C. Wainwright. Thanks, Ofer and Sharon for holding this analyst day and the panel for educating us on EscharEx. When you're thinking about EscharEx and the usage of EscharEx, what other factors do you consider outside of the wound age itself, you know, which you talked about in your analysis, becomes a factor for complete debridement and also wound closure? Well, I can answer first, and then the panel can certainly weigh in. The older a wound is, the more difficult it is to treat and the more difficult it is to close. That's particularly true in venous leg ulcer patients. Clearly there's an unmet need there that I think this will fill. I also think it's going to have a significant, I mentioned this earlier, significant relevance to those patients who are not candidates for any other type of sharp debridement. We're seeing more and more of those patients. I think John can probably elucidate further in the vascular patient, particularly, who has a wound where the patient has some marginal circulation, you know, where we don't want to, you know, do a significant amount of sharp debridement because obviously that could be deleterious. This could be a very formidable alternative for that. John, do you wanna weigh in on that? Well, I think the parameters really that to your question, you know, almost every wound, if you looked at actually those wonderful slides, the first two slides that Kevin put up. Theoretically, you treat the underlying condition of the patient as best you can and take that into consideration, and then you treat the underlying cause of the wound, which may or may not be related or etcetera. The thing that happens is your next step, your first step for really all wounds, as we're taught, and we think we have the data to show it, despite of debate, is that debridement is probably number one. The thing that happens after you debride a wound, also if you standardly sharply debride a wound, and we've shown all types of groups have shown this, our group's shown it, bacteria come back, and they come back usually within a week. They probably come back sooner. We kind of debride sharply, then we use something to decrease the bacterial burden, then we debride again, and then we decrease the bacterial burden, then we debride again. That often goes on for four weeks, six weeks before we close the wound. The thing is that if you actually look at the data, you know, Kevin showed some nice data, but it looks like about 25% of venous leg ulcers really get debrided at all. Probably about 80% of diabetic foot ulcers and atypical wounds don't get debrided 'cause they hurt too much. The issue is the possibility here is that you have a product that will debride the wound and reduce bacterial burden, which is part of our teaching, but we don't follow it because of all the other issues. I actually think it's, like, to flip your question, there's all these reasons we don't debride, and there's all these reasons that are usually economic, that we don't use an agent that kills bacteria. Probably the best one that's on the market in the U.S. actually has very poor coverage, so we just don't use it. We kinda skip. You know, it's almost as if you had. When we look at wounds, I always say this, it's almost as if a lot of the times we have a breast cancer patient, for example, and we say, "Well, we'll do a mammogram, but we, you know, we'll only do a biopsy if, you know, if the patient's okay with it, and then we'll only treat them with chemo if they can afford." Well, we wouldn't do that, but then we do that with wounds. The hope would be that EscharEx would have our algorithms be more routinely followed. Like, we would just be able to do this for every wound, you know. There'd be very few reasons not to in this case. There, that's the big difference is we know what we're meant to do, but we don't do it for all these other patient reasons, and this product allows us to overcome those patient reasons. Dr. Dove, do you want to? Yes. I would like to add one caveat also is in terms of diabetic foot ulcers. Depending on the location and the age of the wound, there can be a sense of urgency. You know, if you have ulcers in certain locations that are very close to the bone, that there's a higher chance for osteomyelitis, which is a next step, is gonna be an amputation. When you have those patients that you know time is really a factor, you are gonna step up your protocols and be sure to incorporate debridement regularly and earlier, a little bit more diligently than you may in an ulcer that, you know, a venous leg ulcer that you have a little bit of time. Thanks for that. Your study and Dr. Dove, in your first patient, we did not see much of a change in the biofilm even though that patient had like six applications. Yeah. Whereas the second patient that you talked about had only two applications, but there was a change in biofilm. What do you think is happening there between them? Well, you know, if you look at some of the literature for biofilms, we do know that biofilms, as soon as you debride, they form again very quickly, and they get more and more sophisticated. I would just think it has to do with the biofilm itself rebuilding very quickly. You know, how sophisticated is that biofilm, which is why we need to debride regularly because that is atypical. Also, there's not a lot of research in terms of biofilm. That's a very sort of a newer concept that is catching on in the world of wound care. 20 years ago, when I started, there was minimal discussion about biofilm as it pertains to lower extremity wounds, and now we're kind of at the dawn of a new age in terms of looking at biofilms. One thing I would add, when we evaluated the biofilm, we evaluated it with a biopsy based on what the MolecuLight device was telling us. Again, it's one area. Yeah. We don't really know what's going on in the rest of the wound. In that one area, perhaps you may not have seen the result that you expected. Also, some will have a very low level of biofilm. I believe that first case started with a two or started with a one and stayed at a one. A one is not something that is necessarily virulent or pathogenic. I don't know how meaningful that is, but again, in studying it, we didn't excise the wound and look at all of it. We just looked at one area. That could be an explanation. Does it depend on what type of bacteria is in the wound that- Yeah, definitely. Affects the biofilm. Just like Dr. Snyder said, not all biofilm is pathogenic. Most biofilm in nature, biofilm is everywhere, but it depends on that the patient, the host. If you look again at the literature, you're looking at the biofilm, and it's what's that host response to that particular type of bacteria. If you look at patient to patient, each biofilm is gonna be unique, and each biofilm's gonna have a unique interaction with that patient's physiology. It's a complex question. That host response is critical. One last question from me is MolecuLight data accepted by the FDA or is this standardized, and how does it correlate with the biofilm score itself? As far as I know, what they're doing is they're working towards developing a model as to which diagnostics would be appropriate to be used in studies. I don't know how far they've gotten actually with the FDA. Yeah, no, it's not. Just to comment on the biofilm in general, I mean, there's a lot of debate in the wound care world whether that matters a lot or not, to be very honest. It's nice to know that there's less, you know. I think the reality is, if I was looking at this externally as a non-clinician, I would really look at the closure rates and the preparation for closure. 'Cause again, that's one of the things we've had a lot of conversations with both the company and with the FDA. You know, in general, a lot of these wounds on day five now could get a you know a already FDA-cleared or a predetermined skin substitute or skin you know they could get that quickly, much quicker than usual. That's not really what the FDA wanted to see. In clinical practice, that will probably be what happens. I think what it will come down to is really that the beefy red granulation tissue, the healthy tissue, the stuff that you know you can heal, which as I said when I was alluding to the data, it's awfully hard to tease that portion out. But that closure data, and again, you gotta remember that the closure data here, this was shown to be not you know a non-inferiority. I mean, it was just a non-inferiority. You didn't wanna show that we're debriding the heck out of the wound, and it doesn't close. It's not designed to. The study wasn't powered to show closure. It's to show debridement. I think the biofilm stuff is really cool. It's very interesting. It's good talking points, honestly. The closure data is gonna be, and I think that might be one of the things we're gonna work with the FDA again to try to get them to accept, you know, do something towards the closure end of it, which they're very interested in. It's still very hard to get a debriding. I mean, they even said this. The FDA says, "What? Well, why does debridement matter?" We spent a lot of time with them. Yeah, FDA, it's important to mention, the FDA agreed that the primary endpoint of our studies. Yes. Will be debridement, and they accepted it as the, as the primary endpoint. This is very important because this is exactly what our study does. We show that we closed it in, it's not, it was not significant, but we closed it in a much less time, definitely relatively to the standard of care, but also, if we compare it to the gel vehicle. Yeah. So- Just to very quickly, I mean, our cohort at our place, I mean, my research fellow was like, "These are closed." You know, we'd be like, "Well, we're gonna take them out, you know, not take them out of the trial, but we're done with applications." You know what I mean? Like, day four, we're done. They'd be like, "Oh yeah, they're closed." We definitely saw closure at a very, you know, at a higher rate than we expected. You know, there's also very good data that shows obviously that particularly in diabetic patients, the longer a wound stays open, the more likely it will become infected. In diabetic patients, certainly that could very, very easily cause that patient to succumb to an amputation. If we can get that wound to be debrided very, very quickly, then we can transition to something else. There's also some very good data that shows that standard of care alone, particularly in diabetic patients, is really not that effective at 12 and 20 weeks. Very often, we do need an advanced product, but if you don't debride the wound thoroughly, it just acts as a good medium to feed the bacteria and the enzymes that are sitting in the wound rather than actually being effective. Zentais. I'm Peter Hellman. I'm a journalist, so I'm not from the medical world. The first thing that caught my eye about MediWound, 'cause I'm a journalist maybe, was the idea of a pineapple stem. I thought, "This is great. Pineapple stems?" My question is there anything to stop other entities from grabbing a plane down to Costa Rica, buying a busload of pineapples, and in effect, becoming competitors for MediWound? I mean, there are a lot of pineapples out there. Well, it's not that you're taking the pineapple stem, and you apply it on the wound. There is a very complicated process which is patented. There were many trials, many attempts in the past just to try to take a simple bromelain that didn't go through our process and apply it on wounds and burns, and you see no significant activity. We are not worried about it. Are there other fruits or products that have the similar Bromelain enzyme in them? No. Hi. This is Nathan Weinstein from Aegis Capital. Thank you, Ofer and the MediWound team and also the KOLs for the information. A wonderful presentation. Two questions from me. One, in clinical practice, what types of medicines do you see your patients on? A lot of those photos were quite shocking. I mean, are they on different types of pain remediation medicines? The second question is, the at-home potential. That's the first I've actually heard of that concept. Very intriguing. Could you share a little more about what that might look like down the line? Well, it's funny, we kept the real gross pictures out of the presentation. The ones that you saw were the mild ones. I'm gonna let Dr. Dove answer that question. In terms of these patients with the chronic venous leg ulcers, really just over-the-counter non-steroidal anti-inflammatories, just because of the nature of pain management nowadays. They have to learn to live with it, and we try to be gentle. Patients did very well with that. In terms of what I have at my disposal, you know, without having this product, really Santyl, Versajet, and sharp debridement, that's what we do nowadays in our clinical practice. Thank you. The second question was the potential for at-home use or at-home applications. That's the goal. It's outpatient settings. It's done at home, and this is when Dr. Snyder said that during these days that people do not want to go to the clinic, EscharEx is ideal because you can apply it to yourself at home. Because of time, I apologize. We have one more question from the web, from Ryan Zimmerman of BTIG. He wants. He asks, "Can you speak about the commercialization strategy? About the commercial of EscharEx? Yes. Okay. As I said earlier, we have a kind of many inbound approaches from most of the strategic players in the market. We are considering all kind of alternatives. We know that we have a blockbuster in our hands, so therefore we are pushing forward to have it approved as soon as we can. But when we have an update about it, I'll let everyone know. Okay, thank you all for coming. We enjoy this morning.