MediWound Ltd. (MDWD) Earnings Call Transcript & Summary

Good day, and welcome, everyone, to the MediWound Analyst Day, which will feature presentations by esteemed key opinion leaders, Dr. Robert Kirsner, Dr. Adam Singer, Dr. Robert Snyder and Ilina Sen, who will speak today about the wound debridement market and opportunity. All of our speakers and members of the management team will be available for a Q&A session following the formal presentations. Let me remind everyone that during the event, speakers may make forward-looking statements. Forward-looking statements are subject to numerous risks and uncertainties as described in the company's 10-K and within other filings. Also, I would like to note that this call is being recorded on the day of today's event, March 30, 2021. Now I would like to turn the call over to Sharon Malka, Chief Executive Officer of MediWound, who will begin today's event with an overview of the company. Sharon?

Thank you, Sara, and welcome, everyone, to our event today. We are very pleased to have such a tremendous group of physicians and experts speak today. We are very excited about the opportunity for EscharEx. And hopefully, at the end of this day, you will share our enthusiasm. Let me begin with a quick overview of our company. MediWound is a fully integrated biopharmaceutical company focused on next-generation biotherapeutic solutions for tissue repair and regeneration with a diversified and differentiated product portfolio. Our balanced portfolio comprised of commercial product and promising product candidates, all based on the same active ingredients, a complex of proteins and Enzymes and enriching bromelain derived from the pineapple stem. Our first commercial product, NexoBrid, is a biological orphan drug indicated for eschar removal of severe burns. NexoBrid is commercially available in Europe and other international markets, and the BLA is under review of the FDA while an expanded access program is up and running, enabling U.S. burn centers to treat severe burnt patients with NexoBrid. We have a strategic collaboration with BARDA for funding and support of the development and approval of NexoBrid in the U.S. as well as for the procurement of NexoBrid for U.S. emergency stockpile. In addition, we have signed a commercial collaboration with Vericel for North American market. EscharEx is our next-generation bioactive debridement agent under development for chronic wounds. We are truly excited about the opportunity and believe EscharEx can be a key generator of value creation as we advance its development program. We are currently conducting a U.S. Phase II adaptive design study and completed preparations for the initiation of a pharmacology study, those we'll further discuss later today. Our third product candidate, 005, is a biological drug product candidate based on the same active ingredients for topical self-administration for the treatment of non-melanoma skin cancers. Non-melanoma skin cancers, including basal cell carcinoma are, by far, the most common of all types of cancer and represent a significant potential market opportunity. This new program represents a strategic goal to leverage our enzymatic platform technology to develop innovative solution for unmet medical needs. Before I turn the call over to Dr. Kirsner for the first presentation, let me first quickly provide an overview of our agenda for the day. We will begin with a presentation from Dr. Kirsner, who will review the current U.S. chronic wound debridement practices. llina Sen from Huron Consulting Group will follow with an overview of the U.S. debridement market landscape and market opportunity. Dr. Singer will share data from a study assessing the debridement efficacy of EscharEx in a posing model and compare it with the current commercial enzymatic debridement agent. And finally, Dr. Snyder will provide an overview of EscharEx pharmacology study and its opportunity in reducing biofilm burden and inflammation. Following the formal presentations, we will have an expert panel where all of our speakers today will be available for a round table Q&A session. We have a very full day, indeed, so without further delay, let me introduce our first speaker, Dr. Robert Kirsner from University of Miami. We are honored to have him here today to speak on the current practice of chronic wound debridement. Dr. Kirsner, please go ahead.

Thank you very much. It's a great pleasure to be part of this meeting today, and I'm going to focus on the Chronic Wound market to give you a little bit of an overview and then 15 minutes really drilled down a little bit on debridement practices. And of course, anything I don't cover, we have a great Q&A session at the end that I can -- we can answer. So by way of background, I'd like to tell you a little bit about myself. I'm a dermatologist by training, and I've also did a clinical and research fellowship in wound healing as part of my training. For the past 25 years, I've directed the largest wound healing meeting in the United States called the Symposium for Advanced Wound Care. Currently, there is both the spring meeting and a fall meeting, and it attracts approximately 7 -- those 2 meetings attract approximately 7,000 participants each year. Every 4 years, there's a world meeting called the World Union of Wound Healing Societies Meeting, and I'm currently on the International Steering Committee for the meeting that will be held in Abu Dhabi in 2022. And my home institution, University of Miami, we're renowned for our wound healing clinical care and research program. It's the largest research program in wound healing, irregardless of specialty in the United States. We have 15 PIs who work on various aspects of wound healing from the lab to the clinic and then back to the lab. And I've been involved in, obviously, both education, but also in organizational wound healing. And I've advised many companies, including some of the very large service companies that deliver care in wound centers throughout the United States. I've headed their advisory committees. And I've been involved in many, many different efforts led major randomized controlled trials that were published in very high-profile peer-reviewed journals. I've been involved with broad clinical activities and humanitarian efforts as well. For example, after the earthquake in Haiti, we arranged a wound healing effort that sent 400 wound healers to Haiti to help with the crisis that was there. So that's a little bit by way of background as I launch into the clinical problem that we're going to be facing today. And that's chronic wounds. And I'm going to use these 2 wounds as an example, the diabetic foot ulcer and then the first focus of MediWound, which is in chronic wound market is the venous leg ulcer, and these are wounds that are very, very important. The reason why they're important is that they have a very high prevalence. They're very, very costly in terms of patient cost and economic costs. And they have a lot of complications that if you do not deal with these wounds early and efficiently, all of those costs begin to rise. So while the cost that we currently exist may be high and even -- but the part of that cost is because we don't deal with these wounds very efficiently. And there's opportunities to create a win-win-win situation for society that the patients can win, the health providers can win and the payers can win as well by giving better care earlier in the treatment course. So let me dive a little bit deeper into this high prevalence, high cost and high complications related to these common chronic wounds as an example. So just to give you some data -- and the data keeps emerging. So any data I will give you, I will tell you that really underestimates the problem because this problem is a growing epidemic. And it's estimated in 2009 in a publication by [indiscernible] and others, including myself, that chronic wounds affect upwards of 6 million Americans each year, given the increase in the elderly population in the United States, the increase in diabetes, the increase in comorbidities, that number has risen over the past 12 years since this publication. And conservative estimates suggest that in direct costs alone, the costs are over $40 billion annually, and that does not include the cost of complications of these conditions. So it's a very prevalent, very widespread disease with high cost of direct care for patients. And these are important diseases. I'm going to show some examples of diabetic foot ulcers and venous leg ulcers. There's even more data for pressure ulcers, which I -- because of the time I'm not going to touch upon. But the most important, obviously, complication is mortality. And what we've learned over the last 10 or 15 years is that if you have a foot ulcer and you have diabetes, that your 5-year mortality rate is higher than many cancers. Here in the graph, the red line, it shows that a typical diabetic neuropathic foot ulcer. And if someone has that, they have a 45% 5-year mortality, which, as you can see, is higher than prostate, breast and Hodgkin's disease and similar to colon cancer. So this is under recognized and underappreciated impact of these ulcers. And there's opportunities. There are opportunities not only to help the patient's ulcers, but maybe impact these rates as well. With regard to venous ulcers. This publication is very interesting because it really highlighted how prevalent and how costly this disease is. This was a publication that looked at insurance databases for older patients, the Medicare insurance database and for younger patients, private insurance databases. And all of these wounds tend to increase with age. And you can see in the Medicare database, about 2.2% of the Medicare age populations as a venous leg ulcer. It's slightly lower in younger populations, but still 1 in 200 patients who are under the age of 65 and covered by private insurances have a venous leg ulcer. We used to say that we thought that there was about 0.5 million to 1 million Americans with venous leg ulcers, that was an underestimate. And this was published in -- this paper was published in 2014. So the number is even higher. But at that time, it was estimated that 2.2 million Americans have the venous leg ulcer each year in the United States, higher than we had estimated by 3x or 4x, and the number continues to rise. Interestingly, if you have 2 patients who are matched, those with a venous leg ulcers and those without, the patients with venous leg ulcers cost about $6,000 to $7,000 more. And if you take that $6,000 to $7,000 and then multiply it by that 2.2 million, the total incremental cost of caring for venous leg ulcers is close to $15 billion in direct cost of loan. Now there are indirect costs as well. And this is in just the patients who work in that private insurer population. There seems to be a 50% increase in work loss days if you have a venous leg ulcer. The average American takes about 2 weeks off for sick days each year, and patients with venous leg ulcers take about 3 weeks off each year. So there's an indirect cost that is not even included in that $15 billion incremental cost. Okay. Listen, [Technical Difficulty] talked about [Technical Difficulty] wounds. And we talked about the [Technical Difficulty] for venous leg ulcers and diabetic foot ulcers, and how standard of care and then adjuvant care fit together. But I wanted to highlight that on the standard of care for all of these wounds is the goal of debridement. That is a critical aspect, whether you have a venous leg ulcer, whether you have a diabetic foot ulcer, debridement is really a critical part of the standard of care. And it's -- and because of many factors, it's often underdone, and we'll talk more about this as the morning goes on. Now when you do debridement, there are lots of different things you try to accomplish. There's a lot of reasons to debride, and there's that circle that shows bacterial load and protease production and growth factors, all of those are conceptual reasons why one would debride so that the wound had an opportunity to heal, and that's why it's part of standard of care. Just to summarize this into kind of easy points. We debride to remove the necrotic tissue and to expose and stimulate functional and dividing migrating cells. So we try to get to the healthy cells. So those are the cells that really can heal, and we'll talk more about that. Bacteria often contaminates or colonizes, contaminates or infect chronic wounds. And by debriding, you both remove some of that bioburden, but also change the environment in which those bacterial cells may feel comfortable in living. And by changing that environment and reducing the bioburden, you also reduce inflammation, and this inflammation drives a highly proteolytic environment, which breaks down tissue further. And then obviously, all of those things are to get to an environment where wound healing can occur. Now we do -- we perform debridement in many different ways, and I'll talk about the types of debridement, but just to show you a pictorial of what -- this is an upper back actually of someone who has a -- not a venous leg ulcer or a diabetic foot ulcer, but it was so dramatic, this chronic eschar. And in this case, one of the ways we debride is we take a scalpel and we remove that in the chronic eschar. You can see I'm lifting it up over there. And if the goal was to remove that necrotic tissue, then what -- by doing this, I accomplished my goal of debriding. And without doing that, that wound would have been condemned to not healing. But there are other reasons and other rationale for debridement beyond just that very visual representation I'm showing in this picture right here. And one of those things that happen is at the cellular level, that when a wound is new and the wound is fresh, when the wound is acute, there is the cells that live in the wound. Those are the -- one of the cell types is called fibroblast. They proliferate and you could see that if you take cells from a young wound and put them in culture, they fill the culture dish and proliferate. But as the wound gets older, and if you fail to intervene early and fail to do the right things from the very beginning, then the cells become refractory and they don't proliferate, they don't expand. And you can see in that little picture with the chronic wounds. Those cells are much, much fewer. They're not completely filling the dish like in the acute wounds, and they're almost starving. They're stretching out and look abnormal. So debridement facilitates the health of the cells that participate in the healing process. And even beyond that factor, the cells that are early on in the wound process are much more responsive to the normal stimuli that make wounds heal. So here's an example of taking cells and then trying to stimulate them and the cells might be from the normal skin, they may be from wounds that are early in there, the process, and then there are wounds that are later on. And it's much more -- the cells from the skin scan or from early wounds are much more responsive to growth promoting factors like this platelet-derived growth factor you're seeing here. And debridement helps to reset and renormalize this process, taking a failing wound and converting it into a more responsive and healing wound. With all of that, things that are going on, is well and good, but what about what happens in real life? And this is some work that was done by one of these large wound healing groups that run wound centers throughout the United States. They looked at their database. And this was a huge database of over 300,000 wounds and over 150,000 patients at over 500 wound centers in the United States over a 4-year period, including those chronic wounds I talked about before, the venous leg ulcers and diabetic foot ulcers making nearly half of the wounds in this data set. And they looked at debridement across a group of different types of wounds. And there are lots of different types of wounds. They had very good -- generally good healing rates overall, and you could see the diabetic foot ulcer and the venous leg ulcer among these. But the take home message of this paper was that when debridement was performed -- using all different types of debridement. Debridement was performed, healing rates were better. That's the simple message. So if you debrided and you debrided more frequently, the healing rates were dramatic. So here, you have a huge data set, 300,000 wounds that are taking all those ideas and principles and showing them in real-life that debridement makes a clinical difference and improved outcomes for these patients. Now there are different types of debridement. There are a number of different tools in one toolkit. There's using a scalpel, which we call surgical debridement. There's using dressings that may -- be called mechanical debridement or autolytic debridement. There are use of maggots that we call biosurgical debridement. And then what we're going to focus on the rest of this session or a lot of this session is this enzymatic debridement to apply enzymes to liquefy the necrotic tissue. And all of these tools may have a place across the spectrum of caring for wounds, but there are different factors to consider when you're thinking about which one of these tools you might use. And based on these factors about what the difference in the different wound types, so not all wounds are homogeneous. How much pain is going to be associated with different types of debridement processes? How much bleeding is going to occur? And then the cost of doing it. For example, if you have to go to the operating room to perform it or there's a -- or billing costs associated with facility fees or physician fees. The settings you made, a patient who's in the hospital or in the outpatient wound center who may need a different type of debridement tool than if you're in a long-term care setting or you're older, you can't tolerate and go to the operating room. And then, of course, the convenience for both the physician and the patient. So this little chart showing cost on one arm and convenience on the other kind of stratifies where things might be higher versus low-cost and more convenient versus less convenient taking into account now the idea of the effectiveness of these different debridement options. So what you're going to hear about is that there's an opportunity -- there's a dramatic opportunity because debridement is part of the standard of care, and there's a need for rapid nonsurgical debridement for people that don't have necessarily a skill set that allows them to go to the operating room and have OR privileges. It's going to be perfect for a number of different settings this opportunity, especially those in skilled nursing facilities, for example. And not only do you prepare the wound to heal for -- with on its own. But if it needs help, if it needs that adjuvant therapy, there's an opportunity to rapidly prepare the wound for other therapies to work better. And this is going to be short, focused therapy that allows the patient to get on to that healing curve, get them healed quickly and avoid all the complications that are associated with non-healing wounds. So I'm going to stop here and just summarize what I told you is that debridement is the cornerstone of great wound care. It's critical debridement is performed across various wound types. There are many different options, and it's very important that selecting the type of debridement is paired with the right patient at the right time with the right physician in the right setting. And not only does it allow the wound to heal on its own, but even if a wound needs help and needs adjuvant therapies, debridement is still critical and part of the planning process when you move on to advanced therapies. So I want to stop here. I'll hand the slide and the presentation over to our next speaker and look forward to answering any questions in the Q&A session again. Thank you very much for your attention.

Thank you very much, Dr. Kirsner for providing your presentation. And now I would like to introduce our next speaker, llina Sen, from Huron Consulting Group who will provide an overview of the U.S. debridement market landscape and EscharEx market potential. llina, please go ahead.

Thank you, Sharon, and thanks, everyone. Excited to be here on behalf of the MediWound team. What we'll cover today is the findings from a number of exhaustive rounds of comprehensive research within the U.S. market. We'll share findings in terms of where the unmet needs today, the role of the different stakeholders. We'll review market sizing and also the expected positioning and market opportunity for EscharEx in the future market state. And just to recap quickly the magnitude of research that has been completed, we did run interviews, in-depth interviews, across stakeholders, both qualitative and also quantitative, a survey of 200 physicians. We've refreshed the research to reflect the latest findings just in 2020. And so all of that has built into the findings that we'll review here. We also did conduct a very in-depth market sizing analysis. While there's quite a bit of information available around the prevalence of chronic wounds, the incidence as it relates to the number of treatable cases in a given year that ladders up to the opportunity for EscharEx, that data is far more fragmented. So we did work with the team to develop a very nuanced and in-depth market sizing analysis, which then was the feeder into the market opportunity analysis that we'll review as part of today's overview. In terms of level setting around the chronic wound patient journey, some of this, Dr. Kirsner already reviewed, but wanted to recap for everyone that in the United States, for chronic wound patients, a majority of them are treated in the outpatient setting. From there, they're often triaged to an outpatient clinic, typically a wound care clinic, where patients are generally followed up 1x to 3x per week, and a majority also do receive some home care follow-up therapy. There are some DFU or leg ulcer clinics in the U.S., but a majority of patients are truly seen in the wound care setting, where a rotating panel of 4 to 5 different specialties are seeing the patient in that setting. In the home care setting or in the nursing home setting, long-term care setting, a majority of patients received some level of follow-up once every few days. And why this matters is, one, understanding how often patients are being seen, which physicians are seeing them to make sure that the protocols are in line with the current standard of care in the United States today. Moving on to the current Standard of Care, which, again, was already reviewed in quite a bit of Dr. Kirsner, but just to summarize here. In terms of the work-up for patients, there's a number of factors that are reviewed to determine the best choice of debridement method. It could be a range of factors from patient history, ruling out infection, looking at blood flow, assessing the need for debridement overall. And then from there, the choice of debridement method can be driven by a number of different considerations. The wound characteristics themselves, the depth, the severity, the size, the outcomes of each of the debridement methods, patient considerations, their ability, for example, to tolerate pain, the site of care and the skill of the practitioner. So for example, in a nursing home setting, you often have less access to a surgeon. So non-sharp modalities are used in those settings where enzymatic certainly plays an important role. Time and frequency of debridement to make sure that the protocol fits into the frequency with which patients are seen within that site of care. And then certainly, cost reimbursement financial incentives for the physician, all of those play a role. And ultimately, the most frequent method of debridement today is sharp treatment, which is alone. We also have autolytic or enzymatic in combination as an adjunct to sharp-used quite frequently. And then you also have mechanical surgical, jet lavage and other types of modalities that are used much less frequently. From a market sizing perspective, we wanted to focus here around incidents of VLUs and DFUs. You saw previously Dr. Kirsner reported 2.2 million prevalent cases of VLUs. We need to drill that down as we're thinking about market sizing and market opportunity to the incident lens. So understanding in a given year, how many patients are presenting with VLUs, DFUs, those reflect the treatable opportunity cases for EscharEx. And so for both VLUs and DFUs, it's close to -- it ranges close to 1 million cases per year. And this reflects for VLUs, for example, the incidence reflects also a recurrence rate. So this is not truly unique incident patients, but it reflects recurrent as well as does the DFU numbers. So again, the goal here and the intent is to size the total incident treatment eligible patients in a given year. And then within that, we then subsegment it by those that undergo debridement. And this was based on the 200 physician survey, the quantitative survey, that was previously run. So in the U.S., 55% of VLUs undergo debridement, 70% of DFUs -- there are certainly variability in these numbers and certainly upside in these numbers, but That this does reflect the consensus output coming out from the physician panel we surveyed in 2016. Okay. In terms of the debridement approaches, and we're focusing on VLUs specifically here. The specific use of debridement modalities, you'll see that sharp only is used in about 40% of the debride VLUs. The drivers of use of this are, certainly, it's fast, it's efficacious. And the treaters here are generally surgeons. So any site of care where you do have access to a surgeon, sharp only is the prime -- is a key modality that's used to debride patients. In terms of looking at enzymatic, whether it's enzymatic only or enzymatic as an adjunct to sharp, that reflects about using about 25% of VLU patients today. The drivers of use is certainly the fact that it can be applied in any setting. You do not need to have a surgeon, so it can be also used by non-skilled health care professionals. And it certainly makes sense for patients with fibrotic tissue that remained in the wound after sharp. And then other modalities that are less frequently used, autolytic, sharp and autolytic and other modalities. And really, it is the choice -- the site of care that drives the choice of debridement mortality. Okay. So then as we drill into the use of current enzymatic -- commercially available enzymatic modalities, there are some limitations in use of the class today, driven by what is currently available on the market. So again, the use overall is restricted to an adjunct to sharp or in select cases, it is used alone. The opinion of the efficacy of the current commercially available enzymatic products ranges low-to-moderate point of view from the most recent qualitative research we conducted. And really, it is -- the application is almost always frequently less than daily. So it's more possible for daily application and nursing homes or for patients that have caregivers -- or commercially available agent is generally only applied about every 2 to 3 days. Efficacy is viewed as modest. Time to debridement varies certainly based on wound, size, duration, with average use of this product for about 6 to 8 weeks total. One of the bigger drawbacks also is the noted cost of the class patients use about 6 to 8 tubes of the currently available modality for about a $2,000 AWP pricing. As we look at unmet needs, there's been consistent feedback across all of the research that we have conducted that there is significant need for a rapid-acting and safe enzymatic agent. Clinicians voice the need for this effective, safe and affordable, nonsurgical modality since sharp is not suitable for all sites of care, and it does require trained staff to perform. So certainly, very, very strong and consistent unmet need heard across all the research we conducted across stakeholders. There is a gap in the market for this type of enzymatic modality. And as we look at the pipeline, there is a fair bit in development for chronic wound healing, but not specific for debridement approaches. So there is a unique gap that EscharEx is filling in terms of addressing the unmet need, and also in looking at the pipeline and what's coming -- upcoming in development. We tested the latest EscharEx profile. And given the unmet need, the clinicians that we interviewed certainly welcomed it as another option for them to consider, especially for HCPs that rely on non-sharp modalities for debridement. So the eligible patient population is similar to the current enzymatic modality. Patients see net sites of care that are not conducive for sharp. It can be used as an adjunct to sharp in wound care clinic settings. It can be used for patients who are not suitable for sharp, so thinking about patients that are sensitive to pain, have anxiety about sharp or have arterial disease. Patients with removable compression to enable the more frequent application. The feedback was most favorable in specialties with lower sharp use. So certainly, nurses, dermatologists. For sharp treaters, they would want to see head-to-head data or at least be able to compare the efficacy against the current enzymatic standard of care approach. And superiority data is seen as clinically meaningful to drive favorable adoption of EscharEx in the market. Daily dosing is something that needs to be -- it was noted as possibly challenging, but not necessarily a disadvantage in comparison to the current Standard of Care. As we look at the overall market opportunity, we have built this up from an epidemiology-based assessment, where, again, starting from an incident patient pool of those eligible for debridement in a given year, you have about 2,000 incident patients across VLUs and DFUs. As we saw from the quant survey output, about 55% to 70% of those wounds are derided-based on VLU versus DFU. Currently about 20% -- 20% to 25% of patients are debrided today, but we do expect that to expand up to 32% based on research feedback, assuming the profile that we are assuming for EscharEx and demonstrating meaningful differentiation from the current Standard of Care, superiority against the current Standard of Care. And then in terms of preference share for EscharEx, 70% at peak based on that superiority profile. And in terms of price, we're assuming $1,500 in a base case scenario, assuming 5 applications on average at about $300 per application. So the market here, in summary, is $2 billion. So as we're thinking about the total addressable market for VLUs and DFUs, it is estimated to be $2 billion in the U.S. We estimate the potential market share to be in the 20% to 25% range of that. So reaching at peak about 2030, $500 million in sales for EscharEx. That summarizes the overall insights that we've -- we wanted to share in terms of the market research and the market sizing that has been conducted. I'll pass it back to Sharon and look forward to the Q&A.

Thank you very much, llina. Next, it is my pleasure to introduce Dr. Adam Singer from Stony Brook University who will review the data from a head-to-head study comparing EscharEx debridement efficacy to the current commercial enzymatic debriding agent. Dr. Singer, please go ahead.

Thank you. Good morning, and it's a pleasure to be here. I've been involved in both preclinical and clinical wound research for approximately 3 decades. And have received funding both from industry as well as the NIH, the Department of Defense and BARDA. And one of the areas that I've particularly been interested in is the development of new models, particularly in pigs for assessing various novel therapies for wound care. And today, I'll share with you the results from our study on the development of a porcine model for eschars and evaluation of a novel bromelain-based enzymatic debriding agent, which is, of course, EscharEx. So we know that there are lots of chronic wounds every year. And despite the fact that it's a major problem, there are very few novel therapies that have been introduced in the last few years. And part of the reason why novel therapies have been blunted is the fact that there's very few good animal models. And in many cases, of course, the regulatory agencies would like to see some evidence from animal models before approving products for use in humans. Now of all the animals, the pig is the most optimal, and that's because the skin, and you can see here a slide of human skin and pig skin at the top. The skin of the pig is most closely resembling that of humans, both from an anatomical and from a physiological standpoint. However, the problem is that pigs heal very well and very quickly. So it's been extremely challenging to develop models where you have delayed healing similar to chronic wounds. So for the purposes of this particular model, we used information that was available for many years with regards to doxorubicin. Now doxorubicin is an antineoplastic agent used for a variety of cancers. And one of the side effects that's been described is that if there's accidental extravasation into the soft tissues, it creates necrosis of the skin. And so that's why this particular agent was chosen for the development of the model. So the objective of this particular study was not only to develop a porcine eschar model by injecting the doxorubicin into the skin, but also specifically to assess the efficacy of this EscharEx in this model. And then finally, to compare the efficacy of the EscharEx with a commercially available enzymatic debridement agent, collagenase. So what we did is we created full-thickness excisional wounds with a sharp scalpel, and this was created on 3 pigs. It was created on the backs of the pigs And then the edges of the wounds that were created were injected with various concentrations and volumes of the doxorubicin. After creating the wounds and injecting them, we covered the wounds with a petrolatum gauze for about 9 days and then covered it with a non permeable layer of paraffin a few days and then finally dry gauze. And then monitor the wounds for a period of up to 46 days to see the development of an eschar. So these are the 3 experimental animals. You can see, we created 8 wounds on each of the animals and then we treated them with a variety of different concentrations and volumes of doxorubicin with several wounds used as the control that were not treated. So here we see a typical wound that was created on the left side. In A, we see a full-thickness excisional wounds 10 days after creating the wound, in which time it was covered by an inclusive dressing. And what you see here is you see some redness in the tissue surrounding the wound. And then by day 18, what you're seeing here is 2 distinct areas. You have a surrounding area at the edges where they look black and dry or necrotic or dead. And then in the center, you're beginning to see sluff and exudate, which is a proteinaceous debris, which is more typical of human wounds and chronic wounds. So here we see representative wounds with varying concentrations in volumes of doxorubicin that were injected. And what we see in general is that with increasing volumes and concentrations, the necrotic tissue, both at the wound periphery is more homogeneous as well as in the center. And again, if we look down here at this bottom wounded, F, where we injected it with 0.75 milligram per CC concentration and 4.8 milliliters. Again, you could see 2 distinct areas: a central area, which is very much like the chronic ulcers that we see in humans where you have this yellow sluff, exudate debris, whereas in the periphery, you have necrotic tissue. And of course, what we're going to focus on is the center, which is the wound that looks more like chronic wounds, whereas the periphery, this necrotic tissue is somewhat dissimilar for most of the wounds, but it's important because it helps to create this chronic wound and prevent it from healing, which normally occurs in pigs. Now here, we have some representative histomicrographs, so we took biopsies, both from the center of the wound in B and from the periphery. So in the periphery, what you see here at the top is this necrotic tissue, it's like a pancake, where all the cells, you can't even make out the epidermis and dermis, it's flattened. It's mummified necrotic tissue. And below that, you see this granulation tissue. Now the center of the wound, which is more like the wounds and humans, you can see a proteinaceous exudate here with very few cells. Obviously, there's no epidermis and dermis because that was removed. And then below that, in the deeper structures, you can see this deep granulation tissue. So it's this tissue with the 2 stars that really is more similar to the human ulcers that will be the focus of the rest of the study. So after we were able to validate our model and find the optimal conditions for creating these eschars, we created additional wounds on another set of animals. And then what we did is we randomized them to treatment with up to 16 daily applications of various concentrations of the EscharEx from 0.1% to 5% or the commercially available collagenase debridement agents. Of course, as you will know, EscharEx is a concentrator proteolytic enzymes-enriched in bm, which is derived from the pineapple stems. So this is a schematic of the study design, just to remind you. So we created the wounds on day 0 by excising tissue. Then we injected it twice, both at day 1 and day 6, with the doxorubicin to create the necrosis. We applied dry gauze for the next 11 days. And then on day 17, we started daily applications of topical agent every day for up to 16 applications. If the wounds required more than 16 applications, this was considered a failure, and the study was terminated. So what we see here on the right is representative wounds before and after 10 applications. So if we go from A and go down the column, you can see here, this is the wound with the typical necrotic sluff in the center, and we see more of the necrosis on the periphery. And you can see with increasing concentrations of EscharEx before application and after application and then the collagen as at the bottom. Let's look here at J. This is a wound that was treated. And after 10 applications, you can see it's completely debrided. It's very clean. But interestingly, not only is the ulcer wound bed now completely clean and ready for healing, whether it be spontaneous or grafting, but also the periphery, which really was not the subject of our study. But even the necrotic mummified tissue in the periphery was completely debrided with the various concentrations of the EscharEx. In contrast, here at the bottom, we see before and after the applications, there is very little debridement. Not only is there sluff remaining at the center, which is typical of the chronic wounds in humans, but we also see no debridement of the tissue in the periphery. And here, we kind of see this dose response curve on here on the left, we're looking at the median number of applications that are required to achieve more than 95% removal of the central eschar. You can see with all of the concentrations of EscharEx, generally between 4 and 5 applications are all that required, whereas the collagenase here, the reason why it says it's 16 is because that's where we ended it. But if you look at the percentage of wounds that are debrided over time, you can see all of the EscharEx are completely debrided by the end of the study period whereas with the collagenase, we're not even seeing the beginning of debridement until day 10. And by the end, not all the wounds are completed debrided. So this clearly shows the efficacy of all of the concentrations of EscharEx, and we did see a general dose response curve with the EscharEx. So if we summarize this particular study, we see a central eschar as seen in human chronic [indiscernible] wounds, which is consistently formed in the pigs by intradermal injection of doxorubicin. We see that the EscharEx is more effective than the commercial collagenase debridement agent in debriding eschars. And we also wanted to present results from another model of a contaminated ischemic model where we evaluate EscharEx, and the results are consistent, both in the current model and in the previous one. And just briefly, the previous model, what we did is we created an ischemic wound by inserting these O-Rings below and above the skin. And then by screwing on these nuts, we were able to compress the skin, sandwiching it between the 2 different rings, which created ischemia and necrosis in the center, you could see it here. And then we basically excised the product tissue and then we contaminated it with staph aureus, which then created this chronic sluff. And what we see here is we compare the EscharEx to the vehicle. And you can see over time, after about a week, all of the EscharEx-treated wounds were adequately debrided, whereas with the vehicle, none of the wounds were debrided. So this is just more confirmation of the efficacy of the EscharEx in more than one animal model. Now of course, there are several limitations to this study. Obviously, the sample size was relatively small. And although pigs are the best model for humans, certainly, they're not identical, and follow-up was relatively short. So to summarize, in this model, we described a model for creating eschars, which are similar to the chronic wounds and humans. We show that the EscharEx was significantly more effective than the commercially available collagenase in removing eschars. And therefore, we believe that this data supports the ongoing clinical trials of EscharEx. Thank you very much.

Thank you very much, Dr. Singer, for this presentation. Now it is my pleasure to introduce our last speaker today, our Medical Director, Dr. Robert Snyder from Barry University, who will provide an overview of EscharEx opportunity in reducing biofilm and inflammation burdens. Dr. Snyder, please go ahead.

Thank you very much. It's my pleasure to be here this morning. I'm going to look at EscharEx, and I'm going to call it a triple threat in managing biofilm and bioburden. Next slide, please. Just a little bit about myself. I'm Chief Medical Director for MediWound. I've been in the wound care space for over 30 years. My practice has been limited to wound management and limb preservation during that time. I'm Interim Dean and Professor and Director of Clinical Research at Barry University School of Podiatric Medicine. I've been principal or lead investigator on more than 65 randomized controlled trials. I published more than 165 peer-reviewed and trade journal articles on wound management and related topics. I've lectured nationally and internationally on wound management, and I've also been the President of past -- or I have been the past President of 2 major wound healing societies. Next slide, please. So the objectives of my talk are pretty straightforward. First and foremost, we're going to discuss an overview of managing biofilm and bioburden in chronic wounds. We're going to look and review bromelin and what its potential effect is on biofilm. We're going to learn about a new pharmacologic study regarding EscharEx and this topic. And we're going to describe why EscharEx may be what I like to call the triple threat to treating chronic wounds. Next, please. So I'm going to start by looking at 2 quotes, just to outline and define the problem. Microbiologic infections are the single most important cause of chronic non-healing wounds. Chronic wound infection typically forms biofilm, which notoriously recalcitrant to conventional antibiotic therapy. Bacterial biofilms are an ever-growing concern for public health, featuring both inherited genetic resistance and a conferred innate tolerance to traditional antibiotic therapies. And we not only see this in chronic wounds, but we also see it in other diseases like cystic fibrosis and Crohn's disease. Next slide, please. So infection really complicates wounds and also impedes healing. Obviously, when you look at the wound healing continuum, you look at the type of bacteria that we see, starting with contamination going all the way up to infection. Obviously, every wound has bacteria. But when the bacterial burden reaches 10 to the fifth colony-forming units or greater, wound healing is delayed. Additionally, bacteria in and of itself will release its own enzymes, endotoxins and exotoxins. And of course, this can have a deleterious effect on the extracellular matrix, basically destroying the infrastructure of the wound. So when you talk about impeding healing, certainly, bacterial bioburden will damage tissue, it will reduce wound potential strength, it will induce an undesirable inflammatory response. Every single time, the wound tries to move into the proliferative phase of wound healing, it's stuck in the inflammatory phase due to this infective process. So thus, controlling or preventing infection is truly an essential part of the wound healing process in order for that wound to progress normally. Next, please. So let's turn our attention to biofilm. What is a biofilm. Well, Biofilm is really a community, a heterogeneous community of bacteria and fungi that are kind of living together, and they basically communicate with one another through their genetic material. You see a very thin layer of this heterogeneous bacteria surrounded by this thick glycocalyx or this thick tube or matrix. These microbes secrete a protective matrix called EPS made from polymers, including proteins, glycoproteins, polysaccharides and DNA. You also have metallic bonds, no metallic ions bind polymers with the EPS together. So this forms a very resistant barrier. And it makes it very, very difficult for anything to penetrate it. Currently, the only thing we have available to treat biofilm is sharp debridement. But unfortunately, I cannot do sharp debridement in practicality every single day. So what tends to happen is, even though we may start to treat biofilm, that biofilm will recur in a mature form within 72 hours. Imagine if we had a product or a therapy that we could utilize as maintenance so that this biofilm could be addressed on an ongoing basis. Because this glycocalyx truly protects the bacteria from antibiotics and accounts for persistence of infection. So obviously, we want to be able to counteract that. Next, please. So how prevalent is biofilm in wounds. Well, we have 2 basic types of bacteria. We have what's called planktonic bacteria or free-floating bacteria, but this only really accounts for about 10% of the bacterial burden that we see in chronic wounds. 90% of bacteria, we feel exist in biofilm. In fact, some of the current literature states that perhaps even 100% of bacteria exist in a biofilm. So if wounds are not healing, very, very often if we're doing all the right things in the wound is still recalcitrant, the biofilms are usually the culprits. Bacteria protected by this biofilm EPS can certainly be a 1,000x more tolerant to antibiotics than planktonic bacteria. Next, please. So biofilms don't play fair. They're very difficult to culture. We have to use polymerase chain reaction in order to really get a true sense of whether or not biofilm even exists. It's very tolerant to biocides. They're tolerant to antibiotics. They're capable to regenerating what's really significant and very important is the biofilm phenotype is highly adaptive. So it survives even in the harshest environments. Next, please. So one of the benefits of bromelin. This was a very interesting study done out of San Antonio Department of Naval Research. And what they did is they looked at a staph aureus biofilm model. There are many different types of models, some used pseudomonas, other staph aureus. This really mimicked wound-like conditions. The anti-biofilm activity of 4 enzyme compounds were reviewed. And bromelin, of course, which is the main compound for EscharEx reduced biofilm mass by 98%. Scanning electron microscopy confirmed detachment of the biofilm EPS in bacteria from growth surfaces. Overall, the results actually indicated that the enzymes such as bromelin actually may be very effective as a means of eradicating biofilms and also could be a promising strategy to improve treatment from multidrug-resistant bacterial infections. Next, please. So the next logical step was to see what this did in vivo. So we're now conducting a clinical pharmacologic study. It's a prospective study performed to evaluate clinical performance and pharmacological effect of EscharEx, the debridement of lower leg ulcers, venous leg ulcers and diabetic foot ulcers. It's considered a clinical Phase II trial. As far as protocol design, we're going to look at the pharmacologic effect in patients with these 2 alterative conditions. It's a single-arm open-label study. We're going to look at about 15 patients at 2 or 3 sites in the United States. We'll be able to use the product of the 8 treatment applications, and then we'll have a 2-week follow-up. What's really important here is we're going to be looking at biofilm, and we're going to be looking at biomarkers as well as planktonic bacteria. So we're going to do this by punch biopsies before we treat and after we treat, looking at wound fluid before and after and also evaluating with fluorescence utilizing the MolecuLight technology. Data collection, we're going to be looking at incidents and time to complete debridement. We're going to log carefully biofilm biomarkers, like cytokines and matrix metalloproteases as examples. We're also going to look at planktonic bacteria as well. Obviously, we're going to be very, very mindful of safety, both systemic and local. We're going to be looking at adverse events, if they occur. And we're going to be followed with laboratory data. The time line, the study was initiated very recently. And of course, the expected time frame is going to be in the first quarter. I'm pleased to report that everything has been completed. We now have IRB approval, and we're ready to begin this trial in earnest. And the expectation is that we're going to be able to have several publications coming out of this very important study. And of course, those individuals that are going to be involved in the research will play a very important role in these manuscripts. Next, please. So I get back to the EscharEx as a triple threat. So let's talk about why. First and foremost, it's -- you may have very efficient wound debridement, and this would allow the conversion of chronic wound into one that's acute. Bromelin could disrupt biofilm bacteria in vivo. And bromelin certainly could decrease planktonic bacteria. So thank you very much for your time, and I look forward to answering your questions during the Q&A.

Thank you very much, Dr. Snyder. Now before we open the call for a Q&A session. Let me take a moment to review our current strategy regarding EscharEx development program and provide a brief corporate update. EscharEx is a topical enzymatic agent under development designed for outpatient setting in line with the current equipment workflows and reimbursement programs, addressing both the medical and commercial need as described in detail by Dr. Kirsner and llina Sen. EscharEx is designed to be an easy to use product for topical once-a-day application demonstrated high potency. It effectively debride severe wounds within less than a week. We continue to actively recruit patients in our U.S. Phase II adaptive design study for the treatment of venous leg ulcers. The study is designed to assess the safety and efficacy of EscharEx compared to gel vehicle as well as head-to-head with the current nonsurgical Standard of Care in the U.S. The study with an all 120 patients with values in the U.S. and includes a predefined interim assessment after 80 patients will complete treatment. This interim assessment is for futility analysis followed by sample size analysis, enabling to adjust the study sample size based on the interim assessment. The primary endpoint of this study, as agreed with the FDA, will be incidence of complete debridement clinically assessed and compared with the gel vehicle. This is the same primary endpoint of our prior successful Phase II study with EscharEx and the same like we used in the NexoBrid development plan. This endpoint is in line with the intended indication of EscharEx, debridement of chronic and hard to heal wounds. We also agreed with the FDA that wound closure would be assessed as a safety measurement to demonstrate that there is no deleterious effect on wound healing. Secondary endpoints will include time to complete debridement, pain reduction, wound reduction, wound area reaction and quality of life. The company reiterates its expectation for an interim assessment around midyear 2021, and anticipates completing patient enrollment by year-end 2021. We believe that this study design enables to demonstrate efficacy, safety and clinical benefits over both placebo and Standard of Care as required by the FDA as well as other stakeholders, such as payers, patients and health care professionals. The study design or the design of this study is based on our recent in vivo study, assessing the efficacy of EscharEx in debriding how to heal wounds as presented by Dr. Singer, as well as our previous successful Phase II study conducted in Israel and Europe. In this Phase II study, EscharEx had significantly higher incidents of complete debridement after up to 10 daily applications and debridement was achieved earlier. The safety profile was comparable and no deleterious effect on wound healing was observed. We also conducted a post hoc analysis with only VLUs and DFUs, and the effect was even greater. As a matter of fact, in more than 90% of the successful patients, debridement occurred after 4 to 5 applications on average. As mentioned by Dr. Snyder, I am pleased to report that our pharmacology study with EscharEx is ready to enroll patients following IRB approvals, and we will commence as planned in the coming weeks. As was presented by Dr. Snyder, we are looking to explore EscharEx potential clinical benefits associated with chronic wounds management. The study is an open-label single-arm study assessing the pharmacological effect of EscharEx in up to 15 patients with both VLUs and DFUs. The study will provide us with a better understanding of what is happening in the wound bed during and after the debridement with EscharEx, and more specifically, it will enable to assess the effect on reduction in bioburden, reduction in inflammation and initiation of healing process. We expect data from this study in the second half of 2021. Based on the data shown today, we believe EscharEx has the potential to become a game changer in this sizable market. EscharEx can have a meaningful impact on chronic wound management, offering significant benefits for patients, health care professionals and payers. As described in details by llina Sen, the U.S. targeted addressable market for EscharEx is estimated at about $2 billion, and we believe that depending on efficacy superiority and cost effectiveness, EscharEx cannot only replace the current enzymatic product but also expand the current enzymatic use across all sites of care. EscharEx's primary target site of care will be site of care, not suitable for sharp procedures following by other sites of care, while pricing and reimbursement will be under the current coverage code for nonsurgical debridement. Moving to NexoBrid. We are pleased with our strong revenue growth of NexoBrid, aided by our strategic partnership with BARDA, our revenue growth in Europe and our continued expansion globally through distribution agreements with partners who are leaders in each of their countries. We completed the patient enrollment stage in the NexoBrid pediatric study and expecting top line data, including the 12 months follow-up results in the second half of 2021. In NEXT, our expanded access program, we continue to enroll burn patients, adding the pediatric population to this program. We continue to work together with BARDA, Vericel and the FDA during the regulatory review process as our U.S. commercial partner for NexoBrid, Vericel, is actively preparing for commercial launch. Lastly, we are excited with our new product candidate 005 for the treatment of non-melanoma skin cancer. We are advancing the initiation of a Phase I/II open-label randomized clinical study for 005 in basal cell carcinoma, designed to evaluate safety and tolerability using different schedules of administration as well as to provide a preliminary evaluation of its efficacy as measured by a percentage of target lesion with complete histological clearance. In parallel, an investigator-initiated Phase II trial is being initiating at Soroka Medical Center in Israel, designed to evaluate the safety and efficacy of 005 in removing non-melanoma skin cancer and pre-cancerous lesions in up to 50 patients. As you can see, we have several tremendous opportunities and near-term catalysts before us in all 3 programs, and we look continuing to executing on our strategy and bringing new therapies to market. With that, I have concluded with the corporate update and it is now my pleasure to open up the call for your questions. Operator?

[Operator Instructions]

So our first question from Josh Jennings from Cowen is as follows: What accounts for today's demand for autolytic debridement when enzymatic debridement has been available for years as a more effective alternative? Do you expect EscharEx to attract demand as an alternative to autolytic debridement? And what drives the migration that's specific to EscharEx? Now I would like to turn the call first to Dr. Kirsner, please.

Thank you. That's a great question. There's no doubt that there is a market for enzymatic debridement out there, and there have been successes, commercial successes with the enzymatic debridement. But several things suggest that there are greater opportunities. One is that the benefits of the current products in enzymatic debridement are limited. And I think with better, faster and more complete debridement with a novel enzymatic debriding agent, I think there's opportunities to capture both the enzymatic debriding market and to convert people who -- patients and providers who are currently using other forms of debridement, such as autolytic agreement to the use of EscharEx therapy. So I think there's opportunities across the spectrum of types of debridement to grow the use of EscharEx.

Thank you very much, Dr. Kirsner. And our next question is from Kevin DeGeeter from Oppenheimer. Can you please comment on the use of debridement method for sensitive areas such as face, hands or difficult to heal sites, such as joint, to use different methods depending on the size of the debridement? And again, I will turn this specific question to you, Dr. Kirsner.

Yes. The decision -- thank you for that question. The decision to choose a certain debridement type is complex, and we touched on some of these talks about the various complexities. So it's really a combination of lots of different things. Certainly, the provider skill is a very important part of it. If someone is not comfortable using one type or another type, that's going to be an important decision maker. The second is access to certain the technologies that one might want to use. Within that complexity is location of the wound. And certainly, there are opportunities to -- within different specific areas that you may choose an enzymatic versus a surgical debridement opportunity. But I do want to point out that debridement is going to be essential in many, many, many, if not most, wound situations. So if you have -- if you're a provider that doesn't like to do surgical debridement and you don't have other opportunities to choose a good debriding agent. By having novel and better debriding options, you're going to convert somebody, a provider, into someone who doesn't use debridement and to those that do use debridement, and patients will benefit from that shift of care. So I think that -- and you could have -- and certainly the face or the hands, you may have certain reluctant debriders, and if you could use a cream or ointment as opposed to taking a scaffold to someone's face, that may be preferable, especially if you don't have all the confidence in the world on your skill set.

Thank you very much. The next question is from Ryan Zimmerman from BTIG. And it's directed for llina Sen Huron Group. From the Huron data suggesting surgeons want to see a head-to-head data. Is this for a head-to-head against the collagenous product or sharp debridement? llina, please.

Sure. Go ahead. It's a good question. The feedback that we received is that they would -- for people who -- for practitioners who use enzymatic or sharp modalities in order to better understand how effective EscharEx is, they would like to see data that compares as against the current commercially available enzymatic products. So they recognize that the endpoints might be different in terms of the study that was previously run versus the current study design for MediWound. But they would ideally like to see the comparison against the commercially available enzymatic modality.

Thank you very much. Our next question is from RK from H.C. Is there a time period within a wound progression when you need to use the debridement? And what type of debridement is successful? I would like to turn this call to Dr. Snyder. Dr. Snyder, please.

Thank you for that question. To Dr. Kirsner's point, debridement is almost always a sine qua non, unless there's some contraindication, what would that be? Let's say you had a diabetic patient who had an ischemic limb or someone who just refused debridement, a patient who just did not want debridement. So debridement is the kind of the centerpiece, as Dr. Kirsner aptly pointed out. As far as what modality to pick? Again, a lot of it is based on the patient at the center of the equation. Does the patient want sharp debridement? Is the patient amenable to this? What is the skill set of the individual who's performing it? Do they feel comfortable doing it? Is the patient homebound? If the patient is homebound and is perhaps seen by a home health nurse, more often than they see a doctor, enzymatic debridement may be a very, very important choice. Pain could be another factor. Individuals are very concerned with sharp debridement, about experiencing pain during that procedure. So utilizing enzymatic agreement, as an example, could be a very, very good alternative. So I hope that answers your question. Again, just to reiterate, irrespective of which debridement modality you use, debridement is the centerpiece of the equation.

Thank you very much, Dr. Snyder. Our next question is from Ryan Zimmerman from BTIG. And the question is as follow: can you elaborate on what is meant by complete deployment of nonviable tissue? What is deciding that? And is there any scale that is used to make the decision or it is subjective to the physician? Thank you. Before I hand the call, I will reiterate what I already mentioned in the description of the ongoing Phase II study, that complete debridement is clinically assessed. Now I'd like to turn this call to Dr. Adam Singer as a practitioner, followed by other practitioner. Please, Dr. Singer.

Yes. Thank you. Unfortunately, there are not a lot of well-validated methods for some of the aspects of monitoring wound healing. And tissue biopsy, of course, is considered the gold standard. Unfortunately, performing biopsies on wounds, especially hard to heal wounds is very challenging. Certainly, we're looking forward to the studies on the pharmacological aspects of EscharEx. And so therefore, the assessment today is based on a clinical assessment. And I think that, in many cases, it's very dramatic, like some of the images that we saw in the other presentations where the sluff is a yellowish, greenish tissue as opposed to a viable tissue, which is more a bright red, shiny, moist appearance. So it's generally fairly apparent even to the patients. And we've treated several patients as part of this clinical trial. And several of the patients themselves are very -- it's a very dramatic change between the un-debrided and debrided appearance.

Thank you very much, Adam. Our next question is from Kevin DeGeeter from Oppenheimer. For chronic wounds, for which there is a need for a repeat debridement, do you tend to use the same debridement modality for subsequent procedure? Or are there any benefits for applying other modalities? And I will turn this call to Dr. Kirsner.

Yes. So typically, if someone's going to undergo a sharp or surgical debridement initially, they probably would have a different type of debridement consequently. Because oftentimes doing that initial debridement with the scalpel requires a lot of effort. It requires pain management, hemostasis and the proper setting. So oftentimes, for subsequent debridement, there may be a little bit of a step-down approach. So even in situations where someone might be a candidate for an initial sharp debridement, it's very possible that the subsequent debridement might include using enzymatic debridement or other debridement methods. So there's opportunities even if -- or to transition, which is another benefit of this product.

Thank you very much. Our next question is from [indiscernible] from [indiscernible] Partners. And the question is, will the interim Phase II adaptive design study have any efficacy data? And do you need to show superiority to enzymatic Standard of Care for approval? So I will take these questions. Our interim assessment is, as I said, for futility analysis, followed by sample size analysis just to provide us with the ability to increase sample size if required in order to meet the -- and the primary endpoint, and it's based on a primary endpoint. We will not look into the data during this interim assessment and data will be analyzed only by the end of this study. And regarding the primary endpoint, the primary endpoint of complete incidence of complete debridement is referring to the comparison between EscharEx and the gel vehicle arm. Now we'll go to the next question. And the next question is from RK from H.C. Can you please compare and contrast EscharEx against collagenous? And what would you be looking so in terms of efficacy that will make you comfortable to use for debridement? And because Dr. Singer was leading the comparator study, I will turn the call to Dr. Singer, please.

I think it's quite surprising how relatively large a market the currently available collagenase product has because its efficacy is very minimal. It's applied because I think there's really no alternative, but it often takes weeks to see improvement with the current product. And I think that at least based on the animal studies as well as experienced from the clinical trials that have been started, there's a fairly dramatic difference between the debriding efficacy of the EscharEx and the collagenase. So I think that the primary endpoint that was selected, which is the time to complete debridement or the percentage of wounds that are completely debrided within the time frame is very applicable and the best way to compare that because the differences are quite large based on the animal studies and preliminary studies and will be apparent. So I think that the efficacy is relatively easy to measure when comparing it to the collagenase product that's currently available.

Thank you very much, Dr. Singer. Our next question is from Elad from Tao Pharmaceuticals. And the question is, what are the expected EscharEx adverse events? Is there a pain associated with the treatment and how it compares to the collagenous product? So before I turn this call to Dr. Snyder, I will share with you that from our prior Phase II study conducted with EscharEx, we have no reports of specific pain associated with the use of EscharEx compared to the gel vehicle. And to date, with our ongoing study, we do not -- a way of any reporting of our first event, including -- or specific adverse event, including pain associated with the product in any event. The protocol enable physicians to use any kind of local medication for treating this pain. And just to complete the response, I will turn the call to Dr. Snyder to share with -- from his experience, please, Dr. Snyder.

Thank you. So I wholeheartedly agree with your comment. I have not seen any patients experience any deleterious effects. There is very little, if any, complaint of pain. The product is well tolerated. And certainly, in my view, having used the alternative product in the marketplace for a number of years, particularly in the home health care arena, I don't see any significant difference as far as complaints, a pain or discomfort or any adverse effects that I can bring up at this point.

Thank you very much. Last question is from Nathan Weinstein from Aegis Capital. May you please discuss the strategy around building market awareness of EscharEx that will be crucial to a successful commercialization efforts? And to that end, I will reiterate our strategy, commercial strategy, which is basically targeting sites of care, which are not suitable for sharp as a primary sites of care, followed by other sites of care, leveraging their -- the potential superiority of EscharEx. And to that end, we are using the pricing and the market access already available for the nonsurgical debridement agent currently available in the market. And at this time, there are no further questions in the queue. And I would like to recap and have closing remarks. So first of all, thank you, everyone, for joining us today. We look continuing to executing on our strategy and bringing new therapies to market and to updating you, again, on our next earnings call. Thank you very much. And I would like to thank our expert panel. Thank you very much for joining us today.