MediWound Ltd. (MDWD) Earnings Call Transcript & Summary

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 couple of -- the last couple of weeks, I've been part of the company for more than 10 years. I saw the company in many, many, many stages of its life. But 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 Cloud 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 we'll make it a success. One person has thing to know about me in my spare time, I'm a passionate Chess player. So when people ask me why I decided to leave MediWound, my answer is always taken a kind of a chess analogy. I'm saying just like in a chess game, MediWound has everything its 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. And by the way, our winning piece is EscharEx and you will hear about it soon. Okay. So 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 promising of EscharEx and what it brings to the market. We will begin with the presentation of our Chief Clinical Director Dr. Snyder, and 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. and 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 like. Okay. So good morning, everyone. A lot of familiar faces in the audience here. So I feel we're first comfortable. I think we need to start and foremost with the premise of why it's been important. And what is the unmet medical need in the space? I think understanding those concepts will lead to further discussion. So it really all begins with debridement as a first step. It's really the center piece. It's the pivotal element that is necessary for good wound healing. And 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 and very often, we use what we call the wound bed preparation model. It's a very holistic a 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, it'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. So 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. So 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. And 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. So it's very, very important, not only to promote wound healing but also to prevent infection. So when you look at the purpose of debridement, the underlying pathologic abnormalities in chronic wounds cause a continual buildup of nonviable tissue. So the goal is to really remove that nonviable tissue, but we need a balance between removing that necrotic tissue and removing that tissue, which is healthy and appropriate and necessary for wound healing. So 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. And of course, there has to be a balance between production and degradation. And this is kind of a simplistic view of a very complex dynamic. But 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. So a chronic wound, the balance is lost, the degradation plays a much greater role. So 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. ] And 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 that 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 abscess and tunnels. When you don't debride the wound, very often, you don't see those tunnels. You don't see the absences. So it's important to get rid of that tissue. And of course, we also, at the end of the day, want to manage the pathology. So how significant is this? Well, every wound is contaminated with bacteria. That's just nature. So when you have a contaminated wound or you have a colonized wound, we're really not that concerned. But left alone that colonization becomes what we used to call critical colonization, now we call a cult infection. That a cult 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 the limb loss and death, particularly in patients who remain compromise like those with diabetes. So debridement very often is done or almost always done on an outpatient basis. It's done in doctors' offices. It can also be done at home. The mainstay of debridement is sharp debridement, 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, requires anesthesia. We have a lot more patients now who are on anticoagulants and bleeding becomes an issue as well. So 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. But this is usually done by an untrained health care provider or a family member or the patient himself or herself. So it's used in conjunction with sharp debridement. So that's 1 element of this, and it can be a negative. 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. But 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. So this is the unmet medical need. You don't necessarily have to use a blade to debride the 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. So 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% to 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, nontraumatic amputations, and most of them are done on patients with diabetes. Routine care of non-healing chronic wound 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. So 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. So we now have EscharEx. EscharEx is a new biologic, very interesting, very important, in my view. It's developed for debridement of nonviable tissue in hard to heal wounds, particularly in diabetic foot ulcers and venous leg ulcer studied extensively used on many patients. EscharEx active pharmaceutical ingredient is a complex and contracted a mixture of proteolytic enzymes. The main ingredient is bromelain, and this will become very, very important and [indiscernible] will give in just a little while. It comes from the stem of a pineapple plant. Pineapples have been around forever. So 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 allowed debridement of nonviable tissue without the need for a blade. So -- any questions? At the end. Well, I had 43 seconds. So I figured I would use my 43 seconds. Okay. So at this point, I'd like to introduce my colleague and good friend, Dr. John Lantis.

Thank you, Robert. Let's go. You tell a guy, who play would definitely be the IT guy, too. We could have both. So this EscharEx product that Rob brought up is very interesting. And I'm going to 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. And the thing that happens with autolytic debridement, but definitely with enzymatic debridement is our goal is to get the debridement just right. And I will make some editorial comments in regards to the nature of some of the outcomes from this study. And it's difficult, all studies that we present to you are going to be a little bit difficult because they're modulated by the FDA. And of course, the FDA would like to have a yes or no answer. So is it debrided, is it not debrided? Is it opened? Is it closed? And that's what they're looking for, although that's changing slowly. But with that in mind, 1 of the things that I'll allude to as we get a little bit further along, is that EscharEx so far in our hands, 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. But as a principal investigator for this study, I've seen this, and it's very interesting. So 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 a big difference from what's commercially available in the U.S. right now and was commercially available to us. At the moment, it's really a collagenase product that debride 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. And the clinicians, all about 20 years ago, there were some more caustic agents that were available. So most clinicians of Rob is my generation, and certainly know products we use -- 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. And so there's a real demand or desire for this. EscharEx is obviously a cousin of NexoBrid, which has undergone effective trials in the burn market. So we kind of have a sense of how this material works. I'm going to talk to you first about a prospective study that I was not involved with that really looks at a group of patients were treated with EscharEx. Now EscharEx comes in -- it's been modulated to continue to be more palatable or more usable in the outpatient market and kind of coming from NexoBrid, a burn product where -- and this is true of other products in the market. People say, oh, it works in burns. And I'm like, well, that's a patient who's [indiscernible] 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. So the company has been working hard and has done a great job of taking a product that was in ICU, put it on for 4 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. And that's kind of the story I'm going to tell you for a moment. And so -- this first study took a look at mix of patients, as you would expect, chronic venous leg ulcers, chronic diabetic foot ulcers and then traumatic and postoperative wounds. And remember that about 25% of the wounds in the world are considered to be postoperative wounds. So they are a very significant population of wounds that we don't -- 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 is a problem. She goes to a wound specialist, the orthopedic surgeons totally happy without the joints working, but the wound needs to heal, postoperative wound happens all the time. We just don't pay a lot of attention to them. So 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 4 hours. And then the Stage 2 portion was a modification to this, which was really a 2.5% product that went on to 8 applications. So fundamentally, 8 applications over the course of a 2-week period, put on 24 hours or a 3-week period in this case at 3 times a week. I really looked at the incidence of complete debridement and also at the safety. 23 diabetic low extremity wounds 24 VLUs and 26 post traumatic wounds. The study was not particularly different between any of the groups, the ages, the genders were all fundamentally normal. In general, there is a little bit of difference in gender. And what happens at the end is that the wounds that are treated with the active product are really well debrided. 55% are adequately to debrided versus 30% of the gel vehicle. And the time to debridement was significantly different, right? So most of the patients who got good debridement were actually done in a week of treatment within 7 days. So that's -- and that's going to 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 the 8 applications. The AEs were -- the adverse events as reported were not particularly significant and the treatment and related problems were minimal at best. So in summary, the patients treated with EscharEx demonstrated a significantly higher incidence of complete debridement compared to patients treated with the Gel Vehicle alone and the EscharEx was safe and effective. So this started to give us a sense about what we could do with dosing for a particular population. Now what you could 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 and which is actually the fourth debridement or third picture, that's looking excellent. And then 1 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 1 week post-debridement and use a skin substitute to help close. So 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, and that's very attractive to us clinicians and to the patient. So the 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 dressing in the office. And the Phase II was first looked at venous leg ulcers. So there was a lot of conversation about this with people like Robert, myself and the company, et cetera. And part of this is in the U.S., there is -- there are a huge number of diabetic foot ulcer trials going on all the time. So 1 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 1 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 this big population that we're really in need. So let's put these in the trial. So this was a 3 to 3 to 2 ratio trial with the active agent versus gel versus a nonsurgical arm as well. And 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 and since this was a [ 2:2:1 ] -- sorry, [ 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 a multinational study different sites or different locations. So probably not completely remonstrative 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 about in a moment about how the trial did with all of that. So 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 is if you look down that 29 of the 46 patients treated with EscharEx, they all -- they had this done really within a 2-week period. And 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. Also given that -- you can see that the age differences are not statistically significant, the gender differences and the baseline pain. So all these patients start with the same, they're just well matched as 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. So you take a look over in the wound age of wounds greater than 28 weeks was there a difference between the groups there. And you can see that in general, percentage-wise, it actually turns out that there were -- it worked 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. And if you take a look at the size of the wounds, 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. So 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. And regardless of what anybody says, we have much better access to care than a lot of other places do not [ as real ] problem, but otherwise. The improvement over standard of care, you can see on the left-hand side here is very significant. But what's really significant is the steepness of that curve, not just the overall number, but the actual improvement. So the improvement over sort of best practices at the moment, not the Gel Vehicle, but best practices would be very quick. And this is what we saw in our own clinical practice. So the patients -- we actually -- and I can say this, not that we're completely unblinded to our own data as yet -- but we had nobody who actually made it to the whole 8 treatments over a 2-week period. Everybody was debrided earlier than that. So 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 tapering off what you expect because everybody has already been effectively debrided at a very early period. So we are very pleased with that. So it also works quickly and effectively. Another busy slide here, but this starts to become really important. And this is the 1 that's hard to get at. And when Rob was talking about cutting away things with sharp debridement, I love sharp debridement, it works well. But I can get down to a healthy bleeding base, but that's not a granular base. That's not usually something you can skin graft. It's not something you can use a cellular tissue-based therapy on. And what we saw was that 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. And that first picture I showed you of the foot was an evidence of that. You got rid of the bad stuff and the good stuff there is fast coming behind it, and 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 a 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 striking -- very striking at 9 days versus 63 days. So 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 going to 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. And we're -- 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? So I mean people are even asking for it, and it's not even really available yet. So there we have it. So in closing, the safety was very effective. We really didn't have any problems. We initially had concerns about burning and periwound 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. And before is on the top left for you than first treatment, second treatment, third treatment. You can see how pink and beefy red that looks at this point in time, 5 days, 2 weeks and 12 weeks fundamentally closed, but this was a person who had the ulcer for a year already. So -- and was recalcitrant to other debridement techniques. So in summary, you can see that there's a very significant difference in the things that are -- that matter to the FDA, the rate of debridement closure. Things that are harder to get your head around as far as the FDA of closure with secondary products and granulation tissue and the safety was very effective. So 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. So we're going to look at the PharmEx clinical trial. This is near and dear to my heart. It was something that I played a large role in. And 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. So 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. So 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. And 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. And again, tolerance to traditional antibiotics is really a problem. So 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 damaged tissue, reduce the wound tensile strength and of course, this undesirable inflammatory response. So controlling and preventing infections certainly will aid in allowing us to heal these wounds. So 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. So the bacteria are a little sliver right in the center, and you have this very thick tube that's surrounding it. You also have metallic bonding and the metallic bonding, again, forms this resistance. So anything that you try to attack it with can't get in through that glycocalyx until now. So 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 exists 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. But that planktonic bacteria will see to form biofilm. So again, all very problematic. And when you have a biofilm, it can be 1,000x more resistant to anything that we throw at it. So it's a very significant problem, particularly in those wounds that are recalcitrant to other therapies. So biofilms don't play fair. They're difficult to culture, they're tolerant to [ biosite, ] they're tolerant to antibiotics. They're capable of regenerating, they talk to 1 another through quorum sensing and they can live in the most horrendous situation, so harshest of environments. So again, very, very difficult to handle and very difficult to treat. So this study comes along by Nancy J. Millenbaugh out of San Antonio, looking at a staph aureus biofilm, which looks very similar to what we see in nature, staph aureus is the most common organism that we see in chronic wounds. And the anti-biofilm activity of 4 enzymes was reviewed. And 1 of those was bromelain, and they found their bromelain reduced biofilm mass by 98%. So this basically was looked at with electron microscopy and it was confirmed. So it basically showed and indicated that enzymes such as bromelain may have an effective means of eradicating biofilm, but it could also be a very promising strategy for these multidrug-resistant organisms. So 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. So it was a prospective study performed to evaluate not only debridement but also the pharmacology and what it is doing to bacteria and biofilm. So it was basically a single-arm study. It was open label, 12 patients. It was a very small study. We have some ways to go 3 sites in the U.S. duration was up to 8 applications and then a 2-week follow. What we did was we did a 3-millimeter 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're looking at with 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. So how do we look at the bacteria? Well, we use a device called MolecuLight to -- not too much time to go into the dynamics of this, but basically what it does is it fluoresces bacteria. It converts it to pixels. And basically, you have 2 types. You have red fluorescence and you have cyan fluorescence. Most are red fluorescence and most are likely staph aureus. And most bacteria will fluoresce red. So this actually was a case of [ Dr. Dove's ]. I'm very, very happy that she's allowing me to share it with you. So we looked at the bacteria load here because what the MolecuLight device does is 2 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 in an area that is full of bacteria. So if you kind of look at what this looked like before and you look at the number here, this was very substantial, but look at it post-treatment. It went down to almost 0. 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 MolecuLight device. The sections were stained and examined with laser microscopy. And what they did was they created in a lab, the scale, 0 being no microorganisms and 5 being the worst. This thick mass of biofilm bacteria. So take a look at this. This is pre-treatment we had the highest biofilm score of 5. And then post-treatment, the biofilm score went to 1, which was really insignificant. So we had a very significant result leading to the possibility that biofilm would not be a problem in healing this patient. So in summary, when we looked at clinical performance, 70% of patients achieved complete debridement during this treatment period. On average, complete debridement was about 4 applications of EscharEx, 4, 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 2 weeks was 35%, and it was very safe and well tolerated. But 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. 7 patients had positive red fluorescence at baseline, it was about 2, and it went below 1. And 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. So 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. And number three, bromelain could have a dramatic decrease in planktonic bacteria, which all adds up to a healing wound and I actually did this with a minute to spare. So I'm now going to turn it over to my friend and colleague, Dr. Dove.

Thank you. Good morning, everyone. So I was invited to speak today because I was 1 of the principal investigators in the Phase II trial. And I'm going to review some of the slides. So 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 8 applications of IP. And as Dr. Snyder stated, we did pre and post IP application biopsies, and we also use MolecuLight imaging. So here we go with our first patient. This is a venous leg ulcer. And I think that Dr. Lantis has said something really important that these are difficult wounds to debride. So this patient here has 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 6 treatments. They could have a maximum of 8 treatments in all. But that's quite a deep wound that we have here. And 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 just the naked eye. And it's also very deep and punched out. You see that it's macerated, it's maybe about 3 millimeters away from the underlying bone. So again, very, very difficult and very painful. And these patients are very resistant to debridement. Even though they need it, it's in their best interest, it can be a bit of an argument on the clinical side. So when you look at the post-debridement photos here, you'll see that yes, he has a little bit of periulcer dermatitis macerated, it's a little bit [ denuded ]. But if you look at the view of the granulation tissue, this is [indiscernible] and dusky. And here, it's very robust and vibrant. And instead of the scale of slough, you see that there is healthy fatty tissue there, and you've lost some of the depth. So although the wound is not healed, this patient can then proceed to go and to have some type of cellular therapy. And this is quite an active patient. He works full time as a counselor. He also is a gentleman farmer, so the fact that we could do this in just 6 short treatments without the product, it would be much, much longer and very complicated to treat them really because of the pain that the patient was experiencing but quite a big difference in a very short amount of time, that 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 the 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 [ fluorescent ] in the outer areas of the ulceration, you look post-treatment, it's completely resolved. So we see that the biofilm as per the MolecuLight has been resolved, the biofilm. And if we look at the biofilm score, which again was garnered via the biopsy, he didn't really have much of a change. But in terms of the MolecuLight and the overall appearance of an ulcer quite a significant change in improvements. We'll go on to patient #2, 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. But 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 fatty tissue in there. And 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 2 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 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 or a month old, whereas this is something that's long and stagnated. And they all had compression in the study, but she also had markedly less inflammation and edema to the area. So she did very well after 2 treatments. And when we look at the MolecuLight imaging, you see the wound bed, you can see there -- I'm sorry, sorry, sorry. I think it up at 5:00 this morning. It's the wake-up time. I'm sorry about that. I'll wake everybody up. So when you look at the -- just can you turn the volume down. Sorry about that. Okay. There we go. So I apologize. So again, when we look at the pre-debridement, you see that it's [ fluorescing ] -- this is more of like a white green color. And post-treatment, it's consistent with the clinical photos where the biofilm is completely gone. And her biofilm score, again, this was garnered with the pre- and post-biopsy. You see that she went from a 2 to 1. She did very, very well with the study, and she was quite happy. So 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 long-term -- or her follow-up, 2-week follow-up period. Now when we look at this patient, Dr. Snyder showed this patient briefly. This was actually 1 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 in a pizza shop. He came in, I said, 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. And he agreed to it because he did not want to take any time off from work. So when you look here, this is necrotic patch right there, that was quite deep. It was almost to the level of his tendon into the bone. But you see after 5 treatments, the depth is gone. This wound went on to heal maybe 2 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. And that's not something that I typically see with sharp debridement. 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 nonviable versus viable tissue. And a lot of times, we tend to be overly aggressive. So this is a wound that went on to heal on its own after just 5 treatments. And you see the MolecuLight imaging pre-treatment, you can see very clearly, this is what we used to take our pre-treatment biopsies. And you see post-treatment, again, after the few treatments he had, it's completely gone. And he had the most market difference in his biofilm score. He went from a 5 to 1. 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 and 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 2 treatments, it's a completely different wound. Less edema, you see that it's very superficial. There's no hyperkeratotic tissue. And centrally, you can even see an island of epithelium. And 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. And 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 as pre-treatment. And his biofilm score went from a 3 to 0. So he had no biofilm left after his treatment. And here is another. This 1 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 flier patients, so to speak. This is her ulcer pre-treatment, and she again only needed 2 treatments. It's deep, not as deep as the initial or the first patient I showed you with shaggy borders. And again, she's got very inelastic thick tissue. She's had many, many ulcers over the years. And she comes and typically, this is a patient that we'd attempt bedside debridement, sharp debridement and again, very, very, very painful ulcerations. She enrolled in the study. She did very well. And you see this very shallow ulcer, you see reduced edema, reduced inflammation. And again, it's red, vibrant granulation tissue. And she went on to heal without any advanced modalities as well. Now when we look at her MolecuLight treatment, I look at MolecuLight image, the 1 flaw of 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 ] but we can look at the biofilm and we can see that there was indeed a reduction from 2 to 1. And again, to reiterate, she went on to heal without any advanced modalities. There was no wound vac, no cellular therapy that was needed. So thank you for your time. And now we'll go on to Mr. Feng.

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 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. But 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 1 to 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, 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 1 million patients with VLUs and about 1 million patients -- just over 1 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. And the approach to debridement is also often driven by site of care. Almost all wounds at wound [ seen ] and wound care clinic will undergo debridement whereas those seen in nursing homes or home health settings, a fewer of them often required 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 while 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 turbine 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 and that leads to a very extended use of current products and high cost is also site as a concern because of the high cost of current products isn't really relative -- appropriately relative to the limited efficacy and the slow speed of debridement that we see with currently available products. And that -- 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. And this is seen as a gap in the market that was left by the recall of [indiscernible] products that Dr. Lantis alluded to, these were enzymatic agents available prior to recall by the FDA due to safety concerns. But before they're recalled, they are perceived as much more efficacious and physicians for producing 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 a significantly faster speed of debridement based on the clinical end points demonstrated by the incidence of debridement, the time to and number of applications needed for debridement. And in addition to that, a lot of them appreciate the pharmacology data as well. Many of them noted that biofilm pharmacology data is becoming more important and emerging in the wound healing field. And so the biofilm reduction really demonstrates and supports what's already demonstrated by the clinical endpoints. So 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 won't cause any harm. And so if it's [indiscernible] feel very safe using them. And so 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 about 5 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. So 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 expected to take the lion's share of the market given significant better data and efficacy profile. It also includes replacing some autolytic use. And 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 HEP thought this could compete with sharp debridement as a first-line choice. And 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. And so wrapping this up with market opportunity. Of course, the enzymatic -- 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% to 70% of those received debridement based on our estimates. And then 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 a combination of 2 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, it's an increase from how it's used today in about 20% of patients. And then within the enzymatic share 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. And so all of this really points to a very meaningful market opportunity for EscharEx, again, given such strong Phase II data. And with that, that's all I have to share today. I'll pass it back to Ofer.

Okay. So again, thank you all for joining us this morning, and I hope after listening to our esteemed panel. You have -- you gained a deeper understanding of why we're so excited from EscharEx. Let me give you a kind of a summary why we think we have a winner here. So 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's rapid, effective nonsurgical 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 because of the effect -- not only because of the effectiveness of EscharEx, it is based on the fact that EscharEx is in the same -- with the same API as NexoBrid. NexoBrid is our drug for treating severe burns. And NexoBrid is already a commercial product, marketing -- it has a marketing approval in 41 countries, and there are more than 10,000 patients that were already treated with this drug. So we think that the risk profile of the development is relatively limited. But most importantly, EscharEx is superior to the nonsurgical standard of care in all the relevant parameters that we are looking at. If you -- if we recap what we heard from the KOLs, we see that we have a better efficacy, better efficacy means incident 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. And additionally, we have shorter time to complete closure. I don't remember the numbers by heart, but we have a very low -- very less -- significantly less numbers of days to close a wound. Additionally, we have a very strong effect on the biofilm and on bacterial burden. So 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. So therefore, we develop it for the United States, but we will go for other markets which we believe that 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 wound. And as far as we know, and most of them are interested in finding an effective debriding agent. Lastly, based on all we discussed, it is anticipated that EscharEx will draw -- will draw market share from all the relevant riding 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, and 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. So 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 $1 billion opportunity. As for NexoBrid, we remain on track with our time line for a midyear 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 from 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 prelaunch activities. Another thing about MediWound, if you look at Europe, we have a continued growth in Europe, and we are planning to submit the pediatric label by the end of the year, and it will -- 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 005, 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. And the 005 provides for us another opportunity for MediWound and will leverage the enzymatic debridement for additional markets. And we are now evaluating all kinds of strategic options that the company have around this specific product. So now I will open the floor for all kind of questions, Q&A. We're ready.

For those on the webcast, please submit your questions via e-mail questions at lifesciadvisors.com.

Thanks to the MediWound team for hosting to [indiscernible] physicians for joining. I mean Kevin as well for the market data. I wanted to just ask about the Phase II data. And just to [ SANTYL ], 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. But on top of that, just for the physicians. Just thinking about the data that -- 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?

So the -- I think the -- the 1 thing that we don't know about SANTYL versus the EscharEx product is more probably has to do with the 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 have some pro-growth function. And just the efficacy of debridement is 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 to closure. So 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, this product will -- the 1 thing that wasn't comment on most likely EscharEx in its efficacy profile once you use it on things on label, if you will. We'll actually grow the market for debridement in areas like pressure ulcers and things that aren't well studied. So 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. So you're kind of randomizing some -- and this is a problem with all trials. The FDA is sort of saying, well, we want a standard of care arm. And you say, well, I already have better than standard of care. So limiting that's going to be -- continue to be a problem. And we're not completely unblinded to our data yet, but the standard of care arm did not behave I mean, it's small, but not behave very differently. I think the more important arm is the gel, honestly, because then I think we've all been involved with products where the gel actually did something. So I think this is a very -- is very noticeable like who got what. I mean it's hard to be -- we are blinded to it, but you're going to -- I know what's working, what's not, so.

If I may add, when we spoke with the physicians after the study and no 1 was surprised on the behavior of the nonsurgical standard of care arm. It is very consistent with what they see in their clinic.

Excellent. And then just for the physicians, just assuming crystal ball question, I was 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?

Dr. Dove?

Yes. So in my practice, after me in 2 of these different studies with this product, it probably will become a first line just because when you're considering the patients' 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. So if you can offer them something faster to get them healed or get them debrided quicker, that's what they're going to opt for. So I think eventually, it will be first choice for patients and for the providers as well.

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. 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. So 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 have for him. There are many reasons why sharp debridement is not a good alternative. So this product really will replace that. And that's really the key.

I think for me, who treats all types of wounds. I think it will 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 a small percentage at this point, but still some grouping people have gangrene, dry gangrene, who are taught not to debride sharply because if we cut through it, it will turn black. But I think there's an opportunity and some of those people have marginal healing. And that's an area of growth, and that's still probably 0.25 million patients in the U.S. Definitely, the pressure ulcer world. This is a place that a lot of folks who right now some are getting the collagenase at the moment. But a lot of times, people don't think it's that efficacious, so they don't do it. And it also goes on has a cost and goes on for a very long time. So I think definitely using this on ischial and sacral pressure wounds will be a growth area and would be a place that I would -- where I might say painting with Betadine now. I would try this for -- because the nice portion about this, I think the other thing you have to keep in mind is this for a surgeon actually almost seem surgical because you're doing this in a short time frame. Again, you're getting this done and the way the trial setup is actually good. You're going to get results, you expect results at 2 weeks. If you don't have them, you go on to the next thing. And a lot of surgeons, that's 1 reason they don't use enzymes as they think, well, 3 months. So why am I going to do that? So I think there will definitely be an expansion of usage and definitely VLUs. And the other category is also the atypical wounds. There is a very large percentage. And a lot of them get treated as VLU. So the market research is always hard on this one. I think Kevin and I have talked about this a little bit. But is that the folks who have lower extremity ulcers, who have rheumatoid arthritis, lupus, things like that. They don't get debrided because they hurt way too much. And this would give -- and therefore, they do terribly and those patients were also. So I think this is going to be an additive -- it will take some portion of the market, but actually, I think we'll grow the market.

I have 1 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 doctors' offices. So a lot of it is being done remotely through telemedicine. And so these patients are not coming in for sharp debridement. And 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. So 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, sneak 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 III 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 SANTYL arm to have 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 for the Phase III program would be great to hear.

So 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. So 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 2 Phase III studies but then we will split it to DFUs and VLUs. Having said that, we saw in the -- 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. And therefore, it's again another -- for us, it's a kind of less risk because we know how the data will look like.

[ Ajay Soman ] with Cowen. I'm on Josh's team as well. So I had a question, the clinical data is very impressive. Congratulations on that. Curious, do you guys have a plan to demonstrate a reduction in cost for health care facilities to possibly justify the price point in the future?

As for the price cost, we -- as Kevin said, in the market analysis, we took the SANTYL cost and or the nonsurgical standard of care cost, I'm sorry. But we definitely consider increasing substantially the market because we -- as far as we understand, the situation we set a new bar of efficacy. Certainly, there is a product that works, 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.

This is RK from H.C. Wainwright. Thanks, Ofer and [ Snyder ] for holding this Analyst Day and the panel for educating us on EscharEx. So when you're thinking about EscharEx and the usage of EscharEx, what other factors do you consider outside of the wound age itself, which you talked about in your analysis becomes a factor for complete debridement and also wound closure?

So -- well, I can answer first and then the panel can certainly weigh in. The older wound is, the more difficult it is to treat and the more difficult it is to close, and that's particularly true in venous leg ulcer patients. So clearly, there's an unmet need there that I think this will fill. But 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. And 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. We don't want to do a significant amount of sharp debridement because, obviously, that could be deleterious. So this could be a very, very formidable alternative for that. John, do you want to add on that?

Well, I think the parameters really to your question, almost every wound, if you looked at actually, there was wonderful slides, the first 2 slides that Kevin put up, but theoretically, you treat the underlying condition of the patient as best you can and take that in consideration, and then you treat the underlying cause of the wound, which may or may not be related or et cetera. But the thing that happens is your next step, your first step for really all wounds as we're taught. And we think we had the data to show at this slide of debate, but is the debridement is probably number one. And 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 us our group has shown it, bacteria come back and they come back usually within a week they probably come back sooner. But -- so we kind of debride sharply then we use something to decrease the bacterial burden than we debride again and then we increase the bacterial burden than we debride again and that often goes on for 4 weeks, 6 weeks before we close the wound. The thing is that in -- if you actually look at the data and Kevin showed some nice data, but it looks like about 25% of venous leg ulcers really get debrided at all and probably about 80% of diabetic foot ulcers and no atypical wounds get debrided because they hurt too much. So 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. So I actually think it's I'd 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. The best 1 that's on the market in the U.S. actually has very poor coverage. So we just don't use it. So we kind of skip -- 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, we said, well, we'll do a mammogram, but we'll only do a biopsy if the patient is 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 women. So 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. There will be very few reasons not to in this case. So that's the big difference. 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 1 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 because 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 the next step is going to be an amputation. So when you have those patients that you know time is really a factor you are going to step up your protocols and be sure to incorporate debridement regularly and earlier, a little bit more diligently [indiscernible] and also that venous leg ulcer that you have a little bit of time.

And then talking with your [indiscernible] in your first patient, we did not see much of a change in the biofilm, even though that patient had like 6 applications. But the second patient that you talked about had only 2 applications, but there was a change in biofilm. So what's -- I mean what's the -- what do you think is happening there?

Well, 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. So I would just think it has to do with biofilm itself rebuilding very quickly, how sophisticated is that biofilm, which is why we need to debride regularly because that is atypical, but also, there's not a lot of research in terms of biofilm. That's very -- sort of a newer concept that is catching on in a 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. But again, it's 1 area. So we don't really know what's going on in the rest of the wound. So in that 1 area, perhaps you may not have seen the result that you expected. Also, some will have a very low level of biofilm. So I believe that first case started with a with the 2 or started with 1 and stayed at 1. 1 is not something that is necessarily virulent or pathogenic. So 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 1 area. So that could be an explanation.

And also, does it depend on what type of bacteria is in the wound?

Yes, definitely. 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. And if you look again at the literature and you're looking at the biofilm and it's what's that host response to that particular type of bacteria. So if you look at patient to patient, each biofilm is going to be unique and each biofilm is going to have a unique interaction with that patient's physiology. So it's a complex question.

That host response is critical.

And 1 last question from me is MolecuLight data accepted by the FDA or is this standardized and how does it correlate with the biofilms or...

So 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.

No, it's not. And just a 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 is -- it's nice to know that there's less. I think the reality is as looking at this externally as a non-clinician. I would really look at the closure rates and the preparation for closure. Because again, that's 1 of the things we've had a lot of conversations with both the company and with the FDA. In general, a lot of these wounds on day 5, now could get already FDA-cleared or predetermined skin substitute or skin, they could get that quickly, much quicker than usual. But that's not really what the FDA wanted to see. In clinical practice, that will probably be what happens. So 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 and when I was alluding to the data, it's awfully hard to tease that portion out. But that closure date -- and again, you got to remember that the closure data here, this was shown to be not a non-superiority, I mean it was just a non-inferiority, we don't want to show that we're debriding the heck out of the wound, and it doesn't close. So it's not designed -- the study wasn't powered to show closure, it's to show debridement. So I think the biofilm stuff is really cool. It's very interesting. It's good talking points, honestly, but the closure date is going to be -- and I think that might be 1 of the things we're going to work with the FDA again to try to get them to do something towards the closure end of it, which they're very interested in, but it's still very hard to get it debrided. I mean, they even said this -- the FDA says well, why does debridement matter. So we spend a lot of time with.

Yes. But the FDA, it's important to mention the FDA agreed that the primary endpoint of our studies will be debridement and they accepted it as the as the primary endpoint, and this is very important because this is exactly what that study does. And we showed that we closed it it's not -- it was not significant, but we closed in much less time definitely relatively to the standard of care, but also if you compare it to the Gel Vehicle.

And just very -- I mean our cohort in our place, we could -- I mean my research fellow was like these are closed. We get -- we'd be like, well, we're going to take -- we're not taking them out of the trial, but we're done with applications. You like day 4, we're done. So we definitely saw closure at a very -- at a higher rate.

There's also a very good data that shows, obviously, particularly in diabetic patients, the longer wound stays open, the more likely it will become infected. And in diabetic patients, certainly, that could very, very easily cause that patient to succumb to an amputation. So 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 take in diabetic patients is really not that effective at 12 and 20 weeks. So very often, we do need an advanced product, but if you don't debride the wound thoroughly, it just acts as a good media to feed the bacteria and the enzyme that is sitting in the wound rather than actually being [indiscernible].

I'm Peter Helman, I'm a journalist -- so from the medical world. The first thing that caught my eye about MediWound because journals maybe was the idea of a pineapple stems, I thought this is crazy pineapple stems. So my question is, is there anything to stop other entities from revenue playing down to Costa Rica in busload of pineapples and in effect, becoming competitors for MediWound. I mean, there are a lot of pineapples out there, so.

Well, it's not that you are taking the pineapple stem and you apply it on the wound. There is a very complicated process, which is patented. There were many trials -- that 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. So we are not worried about it.

And are there other fruits or products that have the similar [indiscernible]?

No.

This is Nathan Weinstein from Aegis Capital. Thank you all for the MediWound team and also the KOLs for the information, a wonderful presentation. Two questions from me. 1 in clinical practice, what types of medicines do you see your patients on? And a lot of those photos were quite shocking. I mean, are they different types of pain remediation medicines. And then the second question is the at-home potential. That's the first I've actually heard of that concept. I'm 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 ghost pictures out of the presentation. So the ones that you saw were the mild ones. I'm going to let Dr. Dove answer that question.

So in terms of these patients with the chronic venous leg ulcers, really just over-the-counter nonsteroidal 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. And patients did very well with that. But in terms of what I have at my disposal without having this product, really SANTYL, [ VERSAJET ] and sharp debridement, that's what we do nowadays in our clinical practice.

And then 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.

And because of time, I apologize. We have 1 more question from the web from Ryan Zimmerman of BTIG. He wants -- he asks, can you speak about the commercialization strategy?

About the [ commercialization ] of EscharEx. Okay. So as I said earlier, we are in a -- we have a kind of many inbound approaches from all the -- most of the strategic players in the market. We are considering all kinds 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. So thank you all for coming. We enjoy this morning. And let's be in touch in the next quarter.

Thank you, everybody.