Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Yehuda Leibler. Please go ahead. Good morning, everyone, and welcome to PolyPid's Investor Day. My name is Yehuda Leibler from Arx Investor Relations. With me on the call today, you have Dikla Czaczkes Akselbrad, Chief Executive Officer of PolyPid, Ori Warshavsky, Chief Operating Officer, U.S. of PolyPid, our guest, Dr. Warren Joseph, and joining us on the live Q&A will be Jonny Missulawin, Chief Financial Officer of PolyPid. Earlier this morning, PolyPid issued a press release outlining today's announcements. That release and the presentation you'll see today are available on the Investors section of PolyPid's website. The prepared remarks were recorded ahead of today's event, and the Q&A session you'll see at the end is live. Before we begin, I'd like to remind you that during today's event, management and our guest will make forward-looking statements within the meaning of the federal securities laws. For example, management is making forward-looking statements when it discusses the U.S. Food and Drug Administration's, or FDA's, review of the new drug application, or NDA, for D-PLEX100. That includes the priority review designation and the Prescription Drug User Fee Act, or PDUFA, goal date of November 28, 2026. Forward-looking statements also include possible label expansion beyond colorectal surgery, the FDA pre-approval inspection of the company's manufacturing facility, the potential approval of D-PLEX100, and the expected commercial launch of D-PLEX100 by Azurity Pharmaceuticals in the United States in 2027. They also include the company's exclusive commercialization partnership with Azurity for the United States and Canada. That covers the partnership's economic structure, potential milestone payments, tiered royalties, and transfer price, and the joint development activities, as well as label expansion programs contemplated under that agreement. The forward-looking statements on this call also cover potential reimbursement for D-PLEX100, including the New Technology Add-On Payment, or NTAP, status. Additional forward-looking statements include the European Medicines Agency's, or EMA's, review of the Marketing Authorisation Application, or MAA, for D-PLEX100, and the anticipated timing of that review. They also include the company's plans for commercialization of D-PLEX100 in Europe and other territories following the reversion of European rights from ADVANZ PHARMA, including potential partnerships. Forward-looking statements also include the design, development, planned regulatory pathway, and anticipated timing of the investigational new drug application and clinical trials of PD01B, as well as its potential benefits. Finally, they include the company's Kynatrix technology and other pipeline programs, including its long-acting metabolic program, and the company's growth strategy and expected milestones through 2030. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond the company's control. These include the risks described from time to time in the company's filings with the Securities and Exchange Commission. Accordingly, you should not place undue reliance on these statements. I encourage you to review the company's filings with the SEC, including its annual report on Form 20-F, filed on February 25, 2026. PolyPid disclaims any intention or obligation, except as required by law, to update or revise any forward-looking statements. PD01B is an investigational product candidate and has not been approved by the FDA or any other regulatory authority. Dr. Joseph's views are his own. This event contains time-sensitive information and speaks only as of today, October 28, 2026. With that, I'd like to turn the event over to Dikla Czaczkes Akselbrad, CEO of PolyPid. Dikla? Thank you, Yehuda, and good afternoon, everyone. It is great to be here. We are now exactly one month away from our PDUFA date, so it is obviously a very exciting and important time for PolyPid. This is also our first event since we signed our U.S. partnership, other than our quarterly call. For a long time, one of the questions I was asked more often by investors was: When are you going to sign a U.S. partnership, and what will that partnership look like? I think we can now say that this question has been fully answered. Today, I would like to move the discussion forward and focus on the next question. What will PolyPid look like in 2030? I will start with a very brief recap of where we are today, and then I will focus on three key growth levers that we believe can drive PolyPid through 2030. We will also introduce our next product candidate, PD01B, and its potential role in diabetic foot infection. Ori will take you through the program, and then we will hear from Dr. Warren Joseph, who will provide his perspective on the significant unmet need in diabetic foot infection. Let's start with where we are today, because the last six months have been a period of significant progress for the company. In July, we signed an exclusive licensing agreement with Azurity Pharma covering U.S. and Canada. Under the agreement, we received a $30 million upfront payment, and we are eligible for an additional over $290 million in development, regulatory, and sales milestones. We are also entitled to tiered royalties on net sales ranging from the mid-teens to mid-20s, and we have a prenegotiated transfer price for each vial that we will manufacture and supply to Azurity Pharma. Another important component of our agreement is label expansion. Azurity Pharma will fund the clinical development for label expansion. Since signing the agreement, our working relationship with Azurity has been excellent. Azurity is building out its sales force, national accounts, market access, and medical affairs team ahead of potential launch in 2027 with a hospital footprint that reaches more than 1,700 leading U.S. hospitals and academic centers. Our teams meet regularly across medical, regulatory, supply chain, and commercial functions, and we are working closely together to prepare for day one of launch. On the regulatory front, the NDA that we submitted earlier this year is under priority review with a target PDUFA date of November 28, 2026, and all scheduled FDA interactions on track and aligned with D-PLEX100's PDUFA goal date. In addition, an application for a New Technology Add-on Payment, or NTAP, was submitted to CMS in October this year, with a decision expected next August. If approved, NTAP would provide additional hospital reimbursement for D-PLEX100 in the inpatient setting. In Europe, we submitted our Marketing Authorization Application to the EMA in September, and it was validated at the end of that month. D-PLEX100 is now under formal review by the EMA. Earlier this month, we regained full European commercial right to D-PLEX100, which I will come back to in a moment. The bottom line of this, over the past six months, we told you what we would do, and we did it. So why hold this event now? From day one, we built PolyPid to be a platform company. D-PLEX100 was always meant to be our first product, not our only one. Our technology delivers a drug at high concentration over a controlled period of time, and the value of that goes well beyond colorectal surgery and well beyond surgical site infections. So why now? With D-PLEX100 approaching potential approval and with a commercial committed partner funding the U.S. launch and label expansion, we are now in a position to move forward on several front at once. D-PLEX100 has demonstrated what our technology can do. Now we are putting the platform to work. We think about value creation over the next several years through three key levers, spanning from near, mid, and long-term. First, maximize the potential of D-PLEX100 throughout our U.S. partnership, including label expansion beyond colorectal surgery. Second, bringing D-PLEX100 to additional territories, starting with Europe. Third, build a pipeline based on our technology platform, beginning with PD01B. Our base case is that D-PLEX100, subject to approval, will be approved for patient undergoing colorectal surgery with large incision. That is the patient population covered by our initial U.S. application. But surgical site infection isn't only a colorectal problem. It is a surgical problem, and it carries a significant burden, both clinical and economically, across many different surgeries. Our first step is to expand into broader abdominal surgery, including GI procedures and hysterectomies. This represent around 4 million surgeries each year in the U.S., with close to half of them being open procedures. We plan to initiate discussions with the FDA in the fourth quarter of this year. Beyond that, we see additional opportunities in soft tissue surgeries such as breast reconstruction and post weight loss body contouring. This is a fast-growing segment as more patient experience significant weight loss with GLP-1 therapies. These are also procedures involving very large incisions. Then there are opportunities in bone-related surgeries, including trauma and fracture fixation, as well as lumbar fusion. Importantly, under our agreement, Azurity funds the clinical development of the label expansion programs that we pursue together while PolyPid retain clinical and scientific role. This make label expansion one of the most capital-efficient growth opportunities available for us. The product is already developed and manufactured, and it is already in the hands of a commercial partner that is funding the clinical development work. The decision on which indication to prioritize will be made jointly with Azurity following potential approval, and we will update you as those plans take shape. Our second lever is geography. In the U.S., launch is expected in 2027, subject to approval. In Canada, we plan to submit a new drug submission in 2027. With the EMA validated and under EMA review and full European right now back with PolyPid, we control our European strategy. We are evaluating how to maximize the value of D-PLEX100 in Europe, including active partnership discussions. I would also say that having the U.S. partnerships gives us a strong template to what such a collaboration should look like, what are the key elements that needs to be agreed on, and we can leverage this into a European agreement. Our third lever, and the one we are focusing on today is the pipeline. Kynatrix allows us to do three things with a drug. First, improve its efficacy by achieving a high concentration exactly where it's needed. Second, extend the release of the molecule over time. Third, minimize systemic side effect and toxicity. We apply these capabilities across three therapeutic area. Surgical site infection, where D-PLEX100 sits, infection treatment, where PD01B sits, and metabolic disease, including obesity. Here is how that all comes together. One platform covering both prevention and treatment. D-PLEX100 in colorectal surgery with our PDUFA date on November 28, 2026, our MAA under review in Europe, and Canadian submission planned for 2027, followed by label expansion into additional surgeries. In infection treatment, we have PD01B, which is moving towards a pre-IND meeting and a first-in-human study. In metabolic disease, we have PD03A, our long-acting GLP-1 program, where early preclinical work is ongoing. It is encouraging to see how much interest there is across the industry in long-acting delivery for these drugs. Our nearest and most mature opportunity for a new product is in infection treatment. With that, I will hand over to Ori to introduce you to PD01B. Thank you, Dikla. Why did we choose this indication? There are over 40 million people with diagnosed or undiagnosed diabetes in the U.S., and close to a third of those will develop a diabetic foot ulcer at some point in their lifetime. We know that 50% of ulcers can be infected, and from literature, we see that 1.5 million to 1.6 million people live with diabetic foot infection every year. When we look at complications, in diabetes, the number one complication that leads to hospitalization is an infection. Looking at severe and moderate DFIs, up to 20% of those with diabetic foot infections will end up with some level of amputation, whether it is a toe or a foot, or maybe a larger part of the leg. The implications are huge in terms of time with the doctors, surgery time, surgeon time, and even downstream after an amputation, quality-of-life implications, and implication on caregivers and the patient itself. Why did we choose this indication? It is a big market with great unmet need. It is a space where both physicians and investors know very well. There have been attempts in the past to apply local antibiotic to treat the infections. I think more important, diabetic foot infection is a local problem. It is a problem of poor blood flow, and it is a problem that systemic antibiotic does not solve completely. Very similar to what we saw with SSI, where Kynatrix, applying locally, managed to impact infection rates. This is what we plan to do. Take Kynatrix, apply local high concentration for a long enough duration of time to close that gap in current infection treatment. What is PD01B? It is a hyperlocal, high-concentration doxycycline released in the diabetic foot wound for several weeks. The indication would be treatment of moderate to severe diabetic foot infection after wound debridement, and it will be developed under a new NDA under the 505(b)(2) pathway. Let us talk about what PD01B is and what it is not. What it is not, it is clear. It is not D-PLEX100. The two products have different goals, different indications. They will be prescribed by different physicians in different settings. While D-PLEX100 is designed for prevention of surgical site infections after colorectal surgery, PD01B is for treatment of moderate to severe diabetic foot infection. It will be prescribed by podiatrists and wound care specialists in the wound clinic, as opposed to surgeons applying D-PLEX100 in the operating room. The two products have different release profiles, and PD01B will have its own intellectual property portfolio. Just recently, we applied for a patent application for a new patent from PD01B. In terms of commercial rights, we own all the worldwide rights for PD01B, while Azurity maintains the rights for D-PLEX100 in the U.S. and Canada for surgical site infections. In short, we have a platform, Kynatrix, with two distinct products coming out of it. The fact that we do share the platform means that we are not starting the development of PD01B from zero. We can leverage a lot of the experience and the knowledge that was gained over the years to really hit the ground running. First, Kynatrix as a technology is a validated technology. It has been proven in a large phase III. Also, doxycycline, a broad-spectrum antibiotic, is well-known. It has been on the market for many years. It is well-characterized with a clear safety record. The formulation design is relying on what was done with D-PLEX100, as well as the CMC and manufacturing processes. We will be using the same manufacturing site that is used for D-PLEX100. That is not to say that there is no work to be done. There are adaptations that need to happen. Some of the methods, some of the testing need to be designed, but we are not starting from scratch. Even more specifically, in the preclinical work, over the years, we have generated a lot of information, preclinical safety information, toxicity information, microbiology information. All that work will serve as the base for the new development. Some of it will need to be adjusted. Some of that will need to be done based on the DFI indication, but we are not starting from zero. In terms of timeline, we are expecting to meet the FDA for pre-IND meeting in the second half of 2027, and also have a first-in-human trial also in the second half of 2027. With that, it is my pleasure to introduce Dr. Warren Joseph to talk about the clinical need in diabetic foot infection and the place in therapy of locally applied antibiotics. Back to Warren, please. If you do not mind just introducing yourself as you start your presentation. Thank you very much, Ori. I have to say I am very honored to have been invited by PolyPid to speak to you all today. Just to give you a little bit about my background, as Ori mentioned, my name is Warren Joseph. I am a podiatrist. Spent most of my career in the Philadelphia area, now based out of Arizona, but I have a little bit of an unusual background. I was the first podiatrist to have formal fellowship training in infectious diseases. I trained at Hahnemann University Hospital in Philadelphia in ID. After I finished my infectious disease fellowship, I joined the faculty of what is now the Temple University School of Podiatric Medicine, where for 15 years I taught a course on lower extremity infectious diseases, and I ran a diabetic ulcer clinic. This was before everybody and every hospital had wound clinics, and everybody was a wound specialist. We basically just treated diabetic foot ulcers. I left the university, oh, about 25 years ago. I have been on staff at a number of hospitals in the Philadelphia area, credentialed in both podiatry and infectious diseases. So my entire career has essentially been the in and outpatient treatment of patients with diabetic foot infections. Currently, I am an adjunct clinical professor at the Arizona College of Podiatric Medicine, Midwestern University in Glendale, Arizona, where I give lectures on infectious diseases, and I run a course on evidence-based medicine and research. Just about everything I say in any lecture I give, I try to make sure it is backed with research. Also, for the past 35 years, I have been editor-in-chief of the Journal of the American Podiatric Medical Association, which is the largest circulation peer-reviewed index in our profession. Again, it goes to my background in believing everything has to be evidence-based. I also will tell you that I was the first podiatrist, in fact, there are only two of us to this date, ever elected as a fellow of the Infectious Diseases Society of America. I was invited back in 2004 to sit on the IDSA Diabetic Foot Infection guidelines, and I have been an author of the original guidelines and the 2012 revision, which we are going to talk about somewhat in this lecture. Now, before I start, I do realize that we probably have quite a variety of levels of expertise in this particular audience. Some of you have a lot of biomedical experience, some of you may even be physicians, some not so much. I am going to try to thread the needle a little bit here to keep it interesting for those of you who already know a lot and not to bore people with too many technical terms for those of you who might not be as comfortable with it. You will have to let me know at the end or during the question and answer whether I was successful with that or not. What I am going to do is talk about topical antibiotics for the treatment of diabetic foot infections. The topics I am going to cover include what is the scope of the problem? What happens when the treatments we have up to this point do not work, something goes wrong? What are the theoretical advantages of topical antibiotics, and where might they find a place? There have been topicals that have been tried. What are they, and if they have been tried, how have they done and why have they failed? Then finally, we will end up with just a little bit of a discussion on where exactly does PD01B fit in. Let us start by, again, looking at the scope of the problem of diabetic foot infections. The International Diabetes Federation estimates that there are 589 million people in the world with diabetes, of which about 38.5 million are in the U.S. That is somewhere in the neighborhood of 10%-12% of the U.S. population has diabetes. That number is probably an underestimate because it is thought that about four in 10 people who have diabetes may not even realize they have it, and this is just going to keep growing. By 2050, so only about 24 years from now, the IDF estimates that that number is expected to reach 853 million people worldwide. Of those now 589 million people, one in three of those will eventually develop an ulceration on their foot somewhere in their lifetime. In North America, we have some of the highest rates of diabetic foot ulcerations in our 38.5 million patients with an estimate of about 13% having an active ulcer at any given time. It is a huge problem that affects a lot of people. It goes on, though, because once the patient has that diabetic ulceration, that hole in the foot, usually due to neuropathy or loss of feeling because the patient with diabetes has an inability to feel pain, 50%-60% of those ulcerations will become infected and require antibiotic treatment sometime during the course of the presence of that ulceration. In fact, diabetic foot infection is the single most common cause of hospitalization in patients with diabetes. It is not hyperglycemia, it is not renal issues, it is diabetic foot ulcer, diabetic foot infection. Those ulcerations that become infected are not just necessarily superficial infections. About 20% of them, one in five, will develop bone infection, osteomyelitis, and once you have osteomyelitis, there is a high risk of amputation. In fact, patients with diabetes are 25 times more likely to undergo amputation than people with any other condition. In fact, diabetes is the number one non-traumatic cause of amputation. A lot of these patients are getting amputated, and of those patients who are getting amputated, 85%, so essentially all of them, are preceded by a foot ulceration. This is what we have, the natural history of the disease. Diabetes leads to neuropathy or loss of feeling. Loss of feeling leads to that ulceration or that hole in the foot. That hole in the foot leads to infection. That infection can lead to bone infection or osteomyelitis, and all of that can lead to amputation. It used to be said that somewhere in the world, a limb is lost every 30 seconds. That is not said anymore. Now, every 20 seconds somewhere in the world, a limb is lost. That being said, there is hope. The widespread acceptance of the GLP-1 receptor agonists that are being used in diabetes have actually been shown in a number of observational cohort studies, in other words, studies just looking at large populations of people, to reduce the number of amputations. So better control of diabetes, loss of weight, maybe even better control of the neuropathy, leads to fewer amputations. But we are not there yet. That is the future, and hopefully that will keep growing. It will make my life a little more boring, but at least we know we are headed in the right direction. Now, I do admit I am going to have a couple of gory pictures. Nothing too bad for you. Some of you will enjoy these, some maybe not so much. But this shows you how rapidly a diabetic foot infection can progress. This is a one-page article that was published in the New England Journal of Medicine a number of years ago. What happened here is a 50-something-year-old male developed an infection on his foot, and you can see that picture on day one. He decided that instead of going to the emergency department and seeing his doctor, he was just going to sit home and take pictures of his foot over the next, 10 days or so. Every day he took a picture, and you can see from one day to the next how significantly that infection progressed until day 10, where you actually have dead tissue, gangrene there. He finally decided to go to the hospital, and fortunately, he was treated by some people who clearly knew what they were doing because you can see he saved his foot. But this is just such a clear example of why and how exactly these go bad, and how quickly they can go bad. Not only that, let us compare the complications of diabetic foot ulceration and amputation to cancer. This is an editorial that was written about 20 years ago in the International Wound Journal from some friends and colleagues of mine that looked at diabetes-related wound complications and how they compare to mortality with cancer. Most people do not think to compare those two. But what they did is they looked at the five-year mortality rates of patients presenting to their primary care physician for the first time with a diabetic foot ulceration compared to the five-year mortality rates for the most common cancers. What you see here is if you look at neuropathic ulcer, the five-year mortality is significantly higher from a diabetic foot ulcer than the five-year mortality for breast cancer, prostate cancer, and Hodgkin's lymphoma. If you move a little bit to the right there and you see that now you have an ulceration with peripheral arterial disease, the five-year mortality rate is even higher than colorectal cancer. Now, it is not the ulceration. It is not necessarily the infection that is killing the patient, but it is a marker for the deeper systemic issues. But this changes the way we need to think of this condition. If a patient's diagnosed with cancer, they will undergo chemo, radiation, surgery, everything known to man to take care of that cancer. But if a patient has a diabetic foot ulceration, some of them, we can't stop them from drinking their sugary soft drinks and their refined sugars to try to bring their glucose under control. This disease, this diabetic foot disease, will kill patients more readily and more commonly than most of the cancers everybody fears. I mentioned before that I'm a fellow of the Infectious Diseases Society of America, and back originally in 2004 and then in 2012, we published the first actual clinical practice guidelines for the diagnosis and treatment of diabetic foot infections. This is the face sheet from our 2012 guideline. In this guideline, we actually came up with a classification system for diabetic foot infections that's still in use today. Now, 2012, this guideline's a little bit outdated. It has been superseded by this document, which came out in 2023, and this is a joint guideline between the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot. You can see the website there, iwgdfguidelines.org. A lot of these guidelines are very similar. This joint guideline took a lot of what we did in 2012 and just expanded upon it. But one of the things that really did not change is the infection severity scale. Now, what we did in originally 2004 and then again in 2012 is we classified foot infections as to one of four types. These infections or these wounds were either non-infected, had a mild, a moderate, or a severe infection. Just using plain English. To me, that's a lot easier to remember than saying this is a grade 1 or a grade 4 ulceration. No one ever remembers that. But a non-infected, mild, moderate, or severe infection. What do each of these mean? Well, a non-infected ulceration is just that. It's a wound that has no clinical signs of infection. We diagnose infection looking for clinical signs and symptoms, redness, warmth, tenderness, or the presence of pus. If you have none of those, the wound is not infected. A mild infection has to have at least two of those signs, and you can see them listed here, swelling, erythema is redness, tenderness or pain, increased warmth or induration, which is hardness, and then purulent drainage, which basically just means pus. But that redness, that warmth, can't extend more than 2 centimeters. That's a mild infection. Our moderate and severe infections look exactly the same. They have basically two or more of these conditions, of these signs, the redness, swelling, pain, pus, but it extends more than 2 centimeters from the wound. The difference between our moderate and our severe infections is that the moderate infections, the patients are well. They're systemically well. The severe infections, these patients are septic. They are systemically sick. They have the signs of what we call systemic inflammatory response syndrome. So that's really the main difference between moderate and severe. Clinically, they're going to look very, very similar. So let's look at some pictures. This is a non-infected wound, and you can see it's clean. There's good, what we call granulation tissue, good beefy red tissue in the base of this wound. There's no redness or swelling around that wound. This is a clean, non-infected ulceration. Now, look in the left picture. This is under a big toe, a hallux. The ulcer looks pretty good. Again, you have good red granulation tissue, but if you look at the whole toe, look at the top of the toe, the so-called dorsum of the toe, you can see the entire toe is red. The entire toe is a little swollen. So we would consider this a mild infection. Moderate infection, here you see a wound. Again, the wound doesn't look too bad, but you'll see there's a little hole right where that probe is, and I actually took that probe and was able to go into that hole and stick this all the way up through the top of the foot. And what you see, if you now look at the top of the foot, is the entire forefoot is red and swollen, and you see that blister between those two middle toes there. That's a sign that this is at least a moderate, maybe a severe infection. How do we differentiate again? Well, this patient was not sick. They didn't have a temperature. They didn't have a high white blood count or any of the signs and symptoms of sepsis. On the other hand, this is a different situation. You can see here the wound on the bottom of the foot. It does not look as clean and healthy as those other wounds look. You can see off to the right, there's some pus dripping out of some further openings. This entire foot, ankle, and into the leg was red and swollen. This patient had elevated white blood count, white blood cell count, had a fever, chills, all of the signs and symptoms of sepsis. This is what we would call a severe infection. So what do the guidelines, either the IWGDF or originally our IDSA guidelines, say about topical antibiotics? I think it's worth reading. I've highlighted a couple of lines here, but I think it's worth reading this whole little paragraph. "Treatment with topical antimicrobial therapy has many theoretical advantages, particularly requiring only a small dose directly at the site of infection, thus potentially limiting issues of cost, adverse events, and antibiotic resistance." So there is at least a theoretical advantage to these topical antibiotics. The potential advantage of topical antibiotics over systemic antibiotics, and by systemic we mean antibiotics that are given by mouth orally or by IV, what we call parenteral therapy, intravenous therapy, is to deliver very high concentrations of an antibiotic at the site of infection that can't be used by giving an antibiotic that has to go through the entire system before it gets to the wound. And the other potential advantage of just treating the wound with high doses of antibiotics and not the whole system is limiting adverse reactions, limiting side effects of antibiotics. The most serious being what we call C. diff colitis or Clostridioides difficile colitis, which is a severe form of diarrhea and colitis that can actually be fatal. So what they say in the latest International Working Group, that 2023 document, about topical antibiotics doesn't look particularly promising. They say, "We suggest not using topical antibiotics in combination with systemic antibiotics for treating either soft tissue infections or osteomyelitis in patients with diabetes." Now, notice that they put after this, "conditional and low." That's what we call a GRADE. A GRADE is used to give a strength of recommendation and the amount of evidence on which they base that recommendation. You notice it says conditional here. According to the GRADE guidelines, a conditional recommendation means that there is a potential benefit to the intervention, topical antibiotics, but we just don't have enough evidence to support it yet. That's why it says low or low level of evidence. This was a conditional recommendation based on a low level of evidence, and they gave a rationale for this. They said there's insufficient evidence, just what I said, on whether adjunctive agents, topical antibiotics, meaningfully affect clinical outcome, and the safety of routinely using local antibiotics has not been clearly established. They say, "We suggest against the use of topical antibiotics. Future studies should apply learning from prior studies to ensure statistically robust and clinically universal randomized controlled trials." What this means is that we don't have the evidence now, but we certainly believe that there is potential that topical antibiotics are going to work, and we should therefore be doing randomized controlled trials. At the very end of the guideline, they put a list of controversial topics and things that they feel are areas of high interest. One of the areas listed of high interest is studying the effectiveness of topical antibiotics for diabetic foot infections. Let's now switch gears a little and talk specifically about topicals. What are the advantages of topicals? Well, it's already been talked about that they do achieve high local concentrations with limited systemic absorption. You're not getting the antibiotic going through the system and causing side effects, and that limits overall antibiotic exposure. This is what we call antimicrobial stewardship. That's a buzzword in pharmacy and infectious diseases that basically means we want to cut down the amount of antibiotics being used in the world in order to prevent the development of multi-drug resistant bacteria and to reduce the number of adverse events. Using topical antibiotics is a perfect fit for this huge area of antimicrobial stewardship. The benefit is there are essentially no disadvantages. The studies that have been done show that there's no danger to using topical antibiotics, and there is a lot of potential upside here. What are some of the rationales for using topical, some of the questions that need to be answered? Well, we know all wounds are colonized. That's why, again, they become infected. They start with bacteria just living on the surface. Many of these are colonized with multi-drug resistant organisms like methicillin-resistant Staphylococcus aureus, or MRSA. Let's look to maybe reduce the amount of MRSA that's on a wound. Could reduction in that colonization decrease the subsequent infection rate? Could reduction in colonization increase the healing rate? Again, this is looking at not only the treatment aspects of topical antibiotics, but the prevention aspects of topical antibiotics, because the only way to prevent that wound from getting infected, as I said before, is to heal it. What's been out there? What's been tried? Well, this is probably the most notorious, infamous, I could use a couple of different phrases, study or product that was looked at in the area of topical antibiotics, and this is pexiganan. Pexiganan is an antimicrobial peptide derived from the skin of the African clawed swamp frog. Fascinating story behind it, discovered by Dr. Michael Zasloff you see listed here. It had very broad-spectrum antibiotic activity, incredibly broad-spectrum antibiotic activity. They did this phase II study, and once again, you see Dr. Lipsky's name here, was a study that looked at the use of pexiganan versus ofloxacin, which at the time was an oral antibiotic that was being used, it's really not used anymore, for treating mildly infected diabetic foot ulcerations or diabetic foot infections. This was a multi-center, randomized, controlled, double-blind study. What they found is basically the combined data from the two trials demonstrated equivalent results. In other words, whether you use the topical pexiganan or the oral ofloxacin, the outcomes were the same. That's really promising. They furthermore came out to say that bacterial resistance to ofloxacin emerged in patients who received ofloxacin, but no significant resistance emerged on the patients who received pexiganan. Get back to antibiotic stewardship, preventing development of resistance, and that's what you see happening here. This was enough to allow them to go on to a phase III clinical trial. I was vice chair of this study. Dr. Lipsky was the chair of this study. It was the first ever placebo-controlled study for a diabetic foot ulcer infection, and it failed. It failed. You can see here we learned some lessons from this failure. We found that a trial of topical antibiotic therapy in treatment of mild diabetic foot infection is feasible and can be safely conducted. There were no adverse events because of the conduct of the study. We were able to get it through on multiple IRBs around the country. That was not a problem. It helped us gain more information about the natural history that I discussed about mild diabetic foot infections. Unfortunately, the topical treatment with pexiganan did not show statistically significant superiority over the vehicle in terms of either clinical or microbiological outcomes. In fact, just treating the wound, standardizing good wound care, did fairly well. The patients got better about 50% of the time. This study failed. Again, it opens the door for further well-done studies, and we know now that we can safely conduct this sort of study on topical antibiotics. To kind of wind up a little bit, let's look at what does the overall evidence show. This is a systematic review. Again, a review across all studies in the world literature. This is updated from that Cochrane review, which was 2017. This was just published a couple of months ago in Journal of Diabetes, a meta-analysis on local versus systemic antibiotics for diabetic foot infections, systematic review and meta-analysis. Their conclusions were the combination antibiotics or the combination of local plus systemic antibiotics improved healing rates. You got faster healing times. However, they did say that high quality, blinded randomized controlled trials are required. There's a need for this. There's an urgent want to get these good clinical trials. This is what we call forest plot. I teach reading forest plots in my course on evidence-based medicine. I'm not going to teach it to you other than to say, if you look at that big black vertical line that goes to the number 1, that is the line of no difference. If you have anything to the right of that line, that favors systemic antibiotics with local antibiotics. Over to the left of that line, favors just systemic antibiotics. You can see across all of the studies that were done in this field, every one of them does favor systemic with local antibiotics. Some of them just don't meet statistical significance. But it's there. The basis is there. We know that this combination is beneficial, and we know theoretically just using a topical could be the answer. To finish up, where does PD01B fit in? Well, they're not reinventing the wheel here. This is not using a new antimicrobial peptide like pexiganan or a new antibiotic that's never been approved. PolyPid is using doxycycline. Doxycycline is an excellent antibiotic. In fact, it's been my antibiotic of choice for the treatment of MRSA infections, methicillin-resistant S. aureus, for probably 20 plus years. It has a long track record. It's active against most of the organisms we find in diabetic foot, including Staphylococcus, I mentioned before, plus MRSA, and Streptococcus. These are the gram-positive organisms that cause most diabetic foot infections. Doxycycline has a unique property of being inherently anti-inflammatory. What that means is it helps cut down the redness, the swelling, all of those signs you get of infection. By cutting those down, it can actually improve wound healing. There have been studies on topically applied tetracyclines for wound healing, not just treatment of infection, actually wound healing. Clinical data supports claims that it helps heal wounds and decreases scarring. It is a drug, doxycycline. It's well-characterized with an established clinical safety profile. Again, PolyPid is not coming up with a new antibiotic and reinventing the wheel. It's a new delivery system. That new delivery system leads to elevated and prolonged local antibiotic levels with no systemic absorption. Getting back to antimicrobial stewardship, you don't want that antibiotic in the system causing resistance and causing adverse events. Because of that high level, you can get rid of the organisms on the surface of the wound and hopefully prevent the wound from becoming infected or, if the wound is already infected, hopefully treat that infection. This is ideal from an antimicrobial stewardship perspective, and with their prolonged delivery system, it makes it a lot easier for the patient and the clinician. They're not changing the dressing. In the pexiganan study, patients had to change the dressing twice a day. You know how much room that opens for complications? Here, you don't have that. It's a prolonged elution of antibiotic. They're not going to have to be fiddling around with the dressing and potentially causing complications. Quite frankly, if you look at their data from their studies on abdominal surgical site infections, to me, that portends a very good potential outcome in the treatment of diabetic foot infections. With that, I want to thank you very much for your attention. I know we're going to have a question and answer period at the end of the session. I'll be happy to answer any questions you may have. Thank you for your attention. Thank you, Dr. Joseph. Let me bring it all together. For D-PLEX100, we have a PDUFA a month from now with U.S. launch expected if approved in 2027, followed by NTAP decision in August 2027, and expected label discussion that are initiated later this year and will allow us to support potential approval in the following years. In Europe, MAA was submitted on September this year, and EMA decision is expected on the second half of 2027, with a potential European launch in early 2028. Canadian submission is expected for 2027 following NDA approval, and PD01B pre-IND meeting and first-in-human clinical studies are expected on the second half of 2027. With that, I will now turn the call over for your question. Thank you. As a reminder, to ask a question, you will need to press star 1 and 1 on your telephone and wait for your name to be announced. To restore your question, please press star 1 and 1 again. We will now take the first question from the line of Brandon Folkes from H.C. Wainwright. Please go ahead. Hi. Thanks for taking my questions and congrats on all the progress. So maybe just firstly, why do you think this product, PD01B, could have success where some of the other local antibiotics have failed? I know we touched on it a little bit, but just elaborate there. And within that, if you could just elaborate on the release profile, and what you believe the timeframe of that release profile needs to be to be successful. Then maybe secondly, how do we think about the standard of care in the control arm in a clinical trial moving forward here? Thank you. Thank you, Brandon, and good to see you here. Let's start. Since there were a couple of questions, I will get back to you to make sure we are answering each one of them. I will start with the first one, of why should the PD01B be successful where other products have failed. A couple of things here that I think are important. First, some of the programs that have failed, especially in phase III, were tested in mild infections. We are targeting where, and Dr. Joseph related to him his in comment, where good wound care alone has good effects. The real problem comes when we start to see moderate DFI and severe DFI, and we are targeting that area. That is one thing. The other is our unique formulation, and you asked about it in the sense of the release profile and the difference. We have shown with D-PLEX100 that our controlled long-acting approach of 30 days or weeks in the PD01B is very efficacious. We see it, by the way, also, when you look at the DFI and the patient journey, infection is not something that is cured or treated within matters of hours or days. It takes days to weeks to eradicate the bacteria. Our approach here is very applicable. The other thing is, and this is also looking at broadly on development other than localized, what we refer to as hyperlocalized approach. Being at the site of infection, avoiding some of the problems that are associated with DFI. For example, poor blood supply to the area and so on makes it stronger and much more appropriate for this indication. That is about both in terms of the length and why we think PD01B could be successful when other products have failed. Now, you were asking also on the standards of care and how we will be. The plan is to be on top of standards of care. Again, from the point of view that these products, we are going to be targeting patients with moderate to severe, so we will be on top of standards of care. Ori, you want to add something on that? Or maybe Dr. Joseph, you want to add something about the standards of care today? Yeah. Thank you. It is a great question. You bring up a lot of interesting points. As for the standard of care, I think you were asking what the control would be in this clinical trial, and I am sure that is yet to be negotiated with the agency. But I would almost guarantee that the agency would require a systemic antibiotic as the "standard of care" or the control arm here. I think it remains to be seen whether or not they are able to negotiate a combination of maybe a third arm or a combination of the 01B with systemic antibiotics or just by itself. But the control arm would probably be systemic antibiotics, which is the standard of care. Now, usually, we are looking at oral. Certainly, we have said in the guidelines that oral can be used for both mild, moderate, and even some severe. But for the severe infections, particularly by definition, where the patient is septic, that would probably have to be parenteral or systemic IV antibiotics. The other thing, you asked about why would this maybe be successful when the others aren't, and I touched on that a little in my talk, is because PolyPid's not reinventing the wheel here. When we were working with pexiganan, it was a brand-new compound. The whole idea of antimicrobial peptides, back then, the science was relatively new. It's developed quite a bit since then. But it was a totally different molecule where there was really no experience. There was some in vitro work, in other words, in a test tube work that had been done with it, and that phase II study against ofloxacin had been done. But it was a large compound. It didn't get into the wound very well. The patients had to apply it twice a day. So you open up an incredible can of worms, if you will, when patients are changing their dressing once or twice a day all sorts of things can go wrong. Where this would not happen with this product, because this product has the ability to stay in place and elute antibiotic over that long period of time. And I would defer to the PolyPid folks to talk about the actual pharmacokinetics of the release and the carrier. So you eliminate that variable right off the bat. You eliminate the variable of the patient having to change their own dressing multiple times a day, and thus every time they open the wound, that exposes the wound to more bacteria. I reviewed a case recently where a diabetic foot got badly infected with an organism that is only found in cats' mouths. And the theory was that the cat was either licking the wound or the cat hair was all over. All sorts of variables occur when you have the patient changing their own dressing and opening the wound twice a day. That's not happening here. I think also the other lesson we learned in the pexiganan trial was you have to stay on top of these patients in the evaluation and who's admitted to the study and enrolled in the study and who is not. And we didn't have that ability in the pexiganan study where we live time had video on every patient or photographs on every patient to decide whether they met inclusion criteria. I'm actually working on a clinical trial now where I am looking at every patient before they're enrolled in the study to see that they met criteria. And I think the problem with pexiganan is a lot of patients did not meet criteria but were enrolled anyway. So with a well-controlled, well-designed clinical trial, I think we've learned those lessons, and we can control for that going forward with the PD01B study. Thank you very much. Very helpful and great investor event today. Thank you very much for hosting it. Thank you. Thank you. We will now take the next question from the line of Chase Knickerbocker from Craig-Hallum. Please go ahead. Great. Thanks for taking the questions. Maybe just a little bit more on what a potential registrational study would look like. Would you expect a superiority study or is the door open for non-inferiority? Then just to be clear, the thought would be that this is an add-on to systemic therapy compared to systemic therapy in the control arm. I understand a lot of that's probably yet to be discussed with the agency. Then if you could discuss the primary endpoint per guidance document, that'd be great. Thanks. Hi, Chase. Okay. Good morning. Thank you for that. I think maybe the most important thing for investors to understand, especially investors that have been following the PolyPid story all along and following us through the SHIELD I and SHIELD II studies, this is a treatment product, and those are treatment phase III studies. We are not talking about studies of 1,000 patients like we needed to perform when we had a prophylactic drug, a prevention drug. All the patients that are enrolled to the study are already with a DFI, and when you look at these kind of studies in order to show statistical meaning and efficacy, you see studies that are around 100, 200 patients. So those are relatively smaller phase III. With regards to whether we will be looking at superiority or non-inferiority, this will be dependent on our first study that we plan, the first in human, that is planned for next year. At that point, and also as part of the discussion with the FDA, the pre-IND meeting, we will be able to answer that. There are pros and cons to both strategies, and we will be able to say more once we see the feedback from the discussion. I think you were also asking about what will be the endpoint of this study. The guidelines around DFI are always relating also to wound healing. In addition, if you look at the very simplistically, but if you look at patients with DFI, you have three parameters that need to happen in order for the infection and the wound to heal. You have the first portion, which is the portion of the debridement of the wound to clean the wound. Then you have a portion of treatment, treating the infection, and then you have the wound healing. Now, it's not really one after the other. Some of those stages are happening in parallel. The endpoint in terms of the agency is the wound healing. But what our portion is around is treating the infection. So we'll need to discuss this also with the FDA and see whether we could have the primary as treating the infection, or we'll also need to show wound healing. But that's something, again, that I will be able to answer after we hear feedback from the FDA. Understood. Yeah. Maybe just any initial thoughts on what this first-in-human study could look like. Do you expect it to have a control arm? It will be single arm. Just any thoughts there. We are looking at that. It is a relatively small study, and we are considering whether this study will have a control or not. But the idea is really here, in addition to preclinical work that we have, is to make sure we have an understanding that can support an approval study in terms of the patient journey, in terms of the efficacy of the product, or the safety of the product. All of these elements we would like to see dosing. I can't tell you now if it will have and what kind of control it will have. But the idea is to end this first-in-human with better understanding on what we need for an approval study. Got it. And just last maybe for Dr. Joseph, could you just give us maybe a little bit more detail on your workflow today with these patients. Which patients are you treating with antibiotics for an active infection? How severe do they need to be? And then what antibiotics are you using particularly? How often are they changing their dressings as well? All that would be helpful. Sure. It really varies based on the severity. As for the infection itself, if there is an infection in the foot, we're treating with antibiotics. You can't get away, in most cases, with just, say, wound debridement and offloading if there's an actual infection. You can certainly get away with that if you're just looking at the wound healing aspect. And then in those cases, sure, you debride, you offload, you use whatever dressings you're going to use, and the endpoint is healing of the wound. In an infection, when we're looking at infection, we have to use antibiotics. Because we don't really have an effective topical at this point, in most cases, we're looking at systemic antibiotics. And those systemic antibiotics, it varies based on if it's a mild infection, you can certainly get away with oral therapy. Most common oral therapies would be something like cephalexin, first-generation cephalosporin. Keflex is the well-known brand name on that. That's if you're not concerned about having MRSA. If you're concerned about having MRSA, right off the bat, doxycycline has been my go-to antibiotic for a very long period of time, because not only is it active against MRSA, it's also active against regular run-of-the-mill methicillin-susceptible staph. It's active against many streptococci. It has some gram-negative coverage, relatively limited, but it works against the organisms that we have in diabetic foot infections, particularly if we've got patients we're concerned with MRSA. And as I mentioned, because it also works through as an anti-inflammatory, it does a nice job of knocking out the clinical signs and symptoms of infection, the redness, the swelling, that sort of thing. So cephalexin, Keflex, if you're not concerned about MRSA. If you are concerned about MRSA, certainly doxycycline, I think, is first line. Many people use Bactrim, trimethoprim sulfamethoxazole. I am not a big fan because of the side effect profile of that. If the patients have a moderate infection, again, you can go oral antibiotics, pretty much the same drugs. Sometimes if it is a mixed infection, you may have to use combinations of therapies. If you have a mixed gram-positive, gram-negative, you may need to use something like a cephalexin with a quinolone, a fluoroquinolone if you have gram-negatives. Finally, if you are looking at severe infections in the patients in the hospital, and they are systemically unwell, they are septic, then you are going to use intravenous antibiotics. You have drugs like the carbapenems, ertapenem, meropenem. Some of the penicillins like piperacillin-tazobactam. Vancomycin is probably the number one used IV drug in the hospital. I hate it with a passion. There are just too many renal issues with it, especially when you combine it with pip-tazo. Different topic for a different lecture at a different time. You were using either oral or IV antibiotics, and they are some of the most commonly used drugs that we would use because we just do not have a reliable topical at this point. Very helpful. Thanks all. Sure. Thank you. We will now take the next question from the line of Jason Butler from Citizens JMP. Please go ahead. Hi. Thanks for taking the questions and appreciate you hosting the event today. One question for the company, and then I have a couple for Dr. Joseph. Diego, can you maybe talk about the preclinical data you have generated so far and any data you have around the PK profile? Specifically, when you think about the platform, how do you think about the predictive value of translating from a preclinical profile to a clinical PK profile and ultimately drug exposure from the wound site? Effectively, as you mentioned before, you are not starting from scratch here, but what can you learn from D-PLEX100 that kind of speaks to the predictive value of early data for PD01B? I will start with the latter in terms of what we can learn, and there is quite a lot of things we can learn from D-PLEX100. Not just learn, but also shorten the development path. In terms of what we can learn, a lot of it is around safety. Because our approach in D-PLEX100, and the same goes to PD01B, is long-acting, many of the safety aspects was around that, around showing that the product is safe and that the excipients are safe on a month basis, on a long-term basis. All of that are things that we believe will not need to repeat and show how the drug is acting in the tissue, whether it is all dissolved and disappear. These are things that we have a lot of safety on them in terms of the overall approach. We also have a lot of knowledge and a lot of basis in everything that has to do with the development, all the CMC processes. Since we are building on the knowledge that we have on methods that have been developed here for over a year, we can use those methods, we can use all of these validation processes for PD01B. You were also asking about? No, go ahead. Yes. That is great. Think about it as a product that has a basis for all the CMC as well as for safety and preclinical work. The extra work that needs to be done is in the specific indication, preclinical work in terms of efficacy and the specific indication, and specific dosing. Great. Thanks. Dr. Joseph, can you maybe dig in a little bit more on the profile of patient who could benefit most, or is it the greatest amount of whom need here? When you think about a therapy like PD01B, how do you think about use expanding beyond the most severe cases treated by wound or infectious disease specialists to becoming more like a standard of care? Could that ever compete with an oral for a mild infection? Thanks. Oh, yeah. Absolutely. I think that's a great question. We need something that can be used even for mild infections topically, because the orals that we're using now, again, we have orals that will work, and they do work, but when you have to give an antibiotic orally, just like when you have to give it through an IV, you do run the risks of adverse events, and you do run the risk of resistance development. There have been studies that have shown a single dose of some of the most commonly used penicillins just can really screw up your gut flora and can lead to massively increased rates of C. diff colitis, for instance. I would say this would absolutely have a place in mild infections where we don't necessarily want to or need to go oral. If we expand, PolyPid in particular is looking at moderate infections. If you're looking at moderate infections, these are patients that you frequently will have to put in the hospital, and treat them with IV antibiotics, even though the guidelines do also talk about orals. A lot of people are more comfortable putting these patients in and treating them with IV antibiotics. If we have a product, if there's a product that's developed and shows efficacy in the treatment of an infection that is at least not inferior to using an IV antibiotic, you eliminate the need for the IV line. It's about $5,000 just to place a PICC line. You eliminate the hospitalization. We know that hospitalizations are, A, very expensive, and B, a hospital is about the least favorite place anybody wants to be, and it's just a hotbed of resistant organisms. If we have something that can be used in the outpatient setting, in a clinical setting, where it can be placed by a clinician, and then the patient doesn't have to play around with it, if you will. They don't have to be changing their own dressing because it will elute antibiotic over that 30-day period of time into the wound. I think we can keep the patients out of the hospital, keep them off systemic antibiotics. That's a big stewardship play because we're going to help prevent resistance. The CDC just came out today. I get daily emails from the Infectious Diseases Society of America. The CDC just came out today with their list of multi-drug-resistant organisms and the problems with drug resistance, and just stated that 50,000 Americans per year are dying in hospitals because of multi-drug-resistant bacteria and fungi. If we can prevent that use of the systemic antibiotic which can drive the resistance development, I think that's a positive thing. Certainly if they want to look back at mild, that's a good way to go. Moderate infections, absolutely, if we can keep the patients out of the hospital. For the severe infections in patients that are septic, I think they're going to need concomitant systemic antibiotics until they become systemically stable. Sorry, just one more for Dr. Joseph. How significant a risk is elevated placebo rates in DFI trials, and are there measures that you would recommend to mitigate the risk of elevated placebo responses? Well, the problem with that's a great question. That's what we really had to deal with a lot in the pexiganan trial, because the pexiganan trial was the first ever placebo-controlled study of an actual infection. People were like, "You can't do a placebo-controlled trial on an actual infection. How's that going to work?" It's like, "Mrs. Jones, you have a foot infection. We're either going to give you an active antibiotic, or we're going to give you one that's not active. We're just going to stick a little cream on your foot or give a sugar pill and hope that you don't lose your leg." You have to build in. I have not talked to PolyPid. They have not engaged me to discuss actual study design at this point. We talked about, overall, the properties of this product and diabetic foot and where this could fit in. We haven't gotten to whether or not this would be a placebo design. I think that would be extremely difficult to do. We can do it in a mild infection, and we showed that. You really, I think, would have troubles doing that in a moderate to severely infected study. There are ways you can minimize risk, and that tends to be extremely aggressive patient follow-up. We're talking about from treatment day one, seeing the patient also on treatment day two, and then maybe treatment day four, treatment day six. This is unlike studies that you can go a week, two weeks between visits. Especially if you're looking at a placebo control, you have to follow these patients extremely aggressively to make sure that they don't go downhill very quickly, because as that New England Journal of Medicine one-page article showed you, they can go downhill quickly. That all has to be built into the trial design. If you're looking at a placebo-controlled trial, and again, I don't know if that's where PolyPid is going with this, but you can build that in. At least you can build in some of these guardrails to try to make it safer. Great. Thanks for taking questions, and appreciate you hosting the event. Jason, I will just add to that, as you remember, in D-PLEX100 phase III studies, we did not have a placebo arm. Again, because of the risk of jeopardizing the patient's health that are under the standard of care arm, the placebo arm. But there are ways to make sure that the study is well-designed, and surgeons see the patient on an unblinded basis. So having a placebo or not is really minor to the need to make sure that the study is well-controlled, and physicians are blinded for whether the patient is on the standard of care arm or the treated arm. And this is something that we have very good experience in. Thank you. We will now take the next question from the line of Boobalan Pachaiyappan from ROTH Capital Partners. Please go ahead. Good afternoon, and thanks for taking my question. I have the first question for Dr. Joseph. Dr. Joseph, you talked about the standard of care in DFI. I am just curious, maybe you can talk a little bit about what proportion of treatment failures result from, say, inadequate antibiotic penetration rather than, let's say, poor glycemic control or residual necrosis or ischemia or other factors. Also, if PD01B has to go to clinical trials, is this something you wanted to sort of hit the primary endpoints? On top of that, do you want to see some level of wound closure or a reduction in amputation in order for you to change your practice? Then I have some follow for management. Yeah. Let me do the second question first. Absolutely. I think when we are dealing with diabetic foot infections, those of us who have made our professional careers on this basically are looking at limb salvage. We are looking at preventing amputation for all the reasons we talked about in some of those studies that have been done. If we can prevent amputation, we can increase the patient's quality of life, we can increase the patient's lifespan. That is why we do this. So yes, we are trying to reduce the rate of amputation. As I talked about the natural history of disease in my lecture, going from neuropathy to ulcer to infection to amputation, and I said the only way to keep these from getting infected is to heal them. That is why healing is another important endpoint. Now, again, the agency has kind of requested healing endpoints in other studies, both on a positive and negative. They do it, A, to see that it is not inhibiting healing, but they can also do it to show that a particular product is encouraging healing. With a doxycycline, a topical doxycycline product, I think you are going to have the latter. I think that it will actually help enhance wound healing because we know that topical tetracyclines can do that. So if we can heal the wound, we can prevent the wound also from getting infected further down the line and prevent the amputation. So I would absolutely love to see both an amputation prevention and a wound healing endpoint built into any study. As to the first part of your question, it is a little bit harder to answer. I think a lot of these patients have poor glycemic control. If I had to worry about poor glycemic control and preventing infections in every one of my patients, I would never heal one because they all come in with A1Cs in the teens. It is the hemoglobin A1Cs in the teens. It is pretty amazing what their controls, the poor level of control in some of these patients. Some of it is due to that, but not all. We can kind of get that under control once the patient is enrolled in a trial. We certainly cannot bring the A1C down that quickly. You can bring the serum glucose down. You also have the vascular side of it. These patients have peripheral arterial disease. They have poor circulation, some of them at least. That is why some of these ulcerations are called neurovascular ulcerations. We have to worry about not only the neuropathy, but we also have to make sure that the patients are perfused. In those cases, I think you can build into any clinical trial, a vascular exclusion criteria. Every clinical trial which I am aware has a vascular exclusion criteria. If the patient has particularly significant peripheral arterial disease, they are excluded from the study. If the patient has really good control of their glucose, and the patient has significant or sufficient perfusion to the limb, that the antibiotic can get down to the foot, and the wounds are properly treated and debrided, in other words, cleaned up and offloaded, the pressure is taken off them, we can get pretty good results just using an oral antibiotic. That has been shown. A number of studies have looked at healing wound infection rates in the 70%-80% range, if you can control for all of that. But again, I am not looking at oral antibiotics or systemic antibiotics because they fail. I am not looking to replace them with a topical because they fail. I am looking to replace them with a topical to prevent adverse events, to prevent drug resistance. I do not know how many of you. I used to talk a lot about the drug amoxicillin-clavulanic acid or AUGMENTIN. I used to say, "Oh, yeah, that is a really great drug to take for oral antibiotics for diabetic foot infections," until I had to take it myself for a dental infection. It ripped the heck out of my stomach. Then I tried ampicillin, amoxicillin, same thing. I am looking at the benefits of using a topical to prevent the side effects and the stewardship issues with oral and systemic as much as I am for treating the infection. Thanks for the very comprehensive answer. Maybe for the management, obviously you are prioritizing PD01B, so I am just curious, what would be the incremental cost to take this program to randomized proof of concept? Also, I am curious to know the status of the GLP-1 program you unveiled sometime middle of last July. Then I have one more if there is time. Hi. Good morning. In terms of the cost of the phase III, as I said before, we need to remember that these are relatively smaller study to what we have seen with D-PLEX100. D-PLEX100, we had phase III of 1,000 patient study. It is too early to be exact in terms of numbers of phase III now, of course, but definitely it is smaller study. Same goes to a lot of the investment that we did in D-PLEX100 as part of the development in robust preclinical studies and all the CMC manufacturing processes. This product goes into our manufacturing processes almost seamlessly to any other product in terms of what it needs to be modified or adjusted in the process. So we have the facility in place. We have the ability to manufacture GMP product or drug vials that will support both preclinical and clinical work, so all of that. I think that what is important to see in terms of the investment, and I will not go into the cost of the phase III study, because, again, we do not know how this study will look like. We do have an idea of the breadth of the study. But if you look at the next two years and what needs to be done in terms of getting into this point and starting recruiting, those are relatively minor cost. You were also speaking about us. Go ahead. About GLP-1. Yeah. With GLP-1 data, we are in preclinical work, and this is the formal name in our development pipeline, is PD03A, and preclinical work is ongoing. The extending of the release of peptide over a long period is obviously demanding formulation work. It is not similar to the bridging that needs to be between D-PLEX100 to PD01B. It is a new development. But I think what is important for us in this program and for us at this stage is that the endpoint here for us is robust preclinical data. We are not looking to take this program in the same way that we did with D-PLEX100 or what we plan for PD01B. We are not looking to take this program all the way through the development path, all the way through the clinic. And with that, it is very encouraging to see how much interest there is across industry in long-acting delivery from these drugs. Also, I could say that this program is what's creating interest around the delivery platform. Okay. Yeah, maybe one final question. Obviously, the PDUFA is exactly one month from today. I am just curious whether there are any outstanding CMC questions or anything related to inspection that you can reveal at this point. Also, touch upon a little bit on Azurity, how they are preparing for the early launch. Thank you. First, we were all here thinking that this question will be the first question that will be asked. So it is nice to see that what we prepared in terms of the R&D Day created a lot of traction in terms of question. But I am very happy to say, as you mentioned, and as you all know, we are exactly one month away from the PDUFA. We are now on the 28th. The PDUFA date is 28th of November. And what you can also imagine that by this point of the process, review milestone has either occurred, or we have set dates for them to support this date. So I can say that we are very happy with the process. We see the process that is being done in line with the dates, in line of supporting and on track. Not much more than we can say, obviously, at this stage. But again, I am repeating what I said. We, at this stage of the process, the review process, review milestones have either occurred, or we have set date to them in support of the PDUFA date. All right. Thank you very much for your presentation, and thanks so much for the clarity. Thank you. Thank you. We will now take the next question from the line of Les Sulewski from Oppenheimer. Please go ahead. Great. Thank you for taking both my questions. First for Dr. Joseph, where would a local antibiotic such as PD01B fit within the treatment setting? Is it inpatient, outpatient, or podiatry office? Secondly, on formulation, do you see this as a physician or patient-administered product? How many treatment courses or duration of this topical treatment would you expect for a typical DFI patient? I have a follow-up for management. Yeah, there's some interesting questions. I think that this would be outpatient. The benefit of a product like this would be to not have to put the patient in the hospital. Now, if the patient is in the hospital because they have an abscess that also has to undergo an incision and drainage procedure, for instance, then I could perhaps see it being used at that point, much like they're using their current product with the surgical incisions and closing an incision after doing a drainage of an abscess. But I think for just the infected foot that doesn't need hospitalization, the goal would be to keep the patient in an outpatient setting. And I think it would have to be physician applied. This would not be patient applied. I think we learned our lesson when we're having patients doing things, especially on a really regular basis, since this would be probably a monthly because of the 30-day elution, a monthly application. I don't think that's too onerous for a clinic to be doing that. I think you'd be looking at podiatry offices. I think you'd be looking at wound care centers. They would be the two most common, and there's some overlap there. A lot of podiatrists work in wound care centers, and a lot of podiatrists are doing wound care in their offices. But they're primarily outpatient because I think the goal of a topical is to keep the patient out of the hospital, except like I mentioned, except perhaps in a situation where the patient has to be admitted to hospital for a surgical procedure and then using it after that. As for how many applications, hopefully one's enough. You would think, especially if you have that prolonged elution and significant enough levels of the antibiotic in the local tissues, that I would hope that that would clear the infection. But it's too early to really say. But that would be if I had an ideal If I was looking for trying to design what I would do with this, yes, outpatient single application would be ideal, but we have to see what the data ends up showing. Thank you. Very helpful. Perhaps for Dikla, maybe from a high level, given your 2030 viewpoint, are you willing to provide any long-term financial targets for PolyPid at this time, either across D-PLEX100 or the PD01B, or perhaps more broadly, how should we expect the P&L profile to look like as you exit the decade? Thank you. Thank you. Looking at our projection, I think once we have sales that are starting to ramp up, which will take a few months, at that point, we would like to start giving sales projections. I do not see this happening in 2027. We will need to evaluate as we get to the end of the first year and then see at that point. This really will allow investors to understand how revenues are going to grow, how to evaluate the companies, and D-PLEX100. As for the aspects of PD01B, as I said before, at this stage, at the first year and a half, those are relatively minor expenses in overall R&D work and operational work of PolyPid. Thank you. Thank you. We will now take a final question from the line of James Molloy from Alliance Global Partners. Please go ahead. Hey, guys. Thank you very much for taking my questions. Thanks for putting on the presentation as well. A quick question for Dr. Joseph. When you look at your patients, how would you stratify some of the best patients to put these on? I know you are looking for moderate to severe. Do you see any challenges to enrolling this clinical trial going forward? Then kind of like, what do you need to see for a clinically meaningful benefit of this procedure to, again, it goes through trials and works to use at your practice? Yeah. Meaningful benefit right off the bat would be to avoid or minimize. Sometimes you can't minimize, you might have to use in combination. Avoid or minimize the use of systemic antibiotics. That would be my overall goal, because avoiding the use of systemic antibiotics, I think, is kind of the Holy Grail. If we can just do something topically and avoid all, as I mentioned before, the adverse events and the potential development of resistance. As for the first part of your question, interestingly enough, from an enrollment standpoint, moderate infections is probably easier than mild infection to get enrollment. Because enrolling patients with mild infections in clinical trials, I will tell you, takes a lot longer and is a lot harder than you would expect, because it's a slice in time. We got to saying this when doing the pexiganan trial. You're looking at a kind of this little slice in time between a non-infected wound and a patient with a moderate to severe infection, where they fulfill that criteria, that IDSA, IWGDF criteria for a mild infection. Less than 2 centimeters of surrounding cellulitis, induration, pain, tenderness, purulence, drainage, pus, all of those. That can jump, as you saw in that New England Journal paper, that can jump really quickly from being non-infected to a moderate to severe infected with almost missing the whole mild transition. I do think that finding patients with moderate or worse infections will be easier from an enrollment standpoint than finding patients who meet the very strict criteria laid out by the IDSA, IWGDF for a mild infection. So enrollment, it's kind of paradoxical, but enrollment, I think, is actually easier for that group of infections than it is for mild infection. Okay, thank you. A quick follow-up for Dikla. Have you spoken about the expected cost of this group of trials to get through to approval? How would the experiences of the SHIELD trials sort of informed the expectations for running these trials and sort of avoiding any pitfalls that might come up? Hi, James. What we did indicate in the call, and I'll repeat this again because I think this is very important. SHIELD studies were, D-PLEX100 is designed for prevention of surgical site infection. So those are phase III prevention studies, meaning that we were recruiting 1,000 patients for the phase III. Here, we're looking at much smaller efficacy pivotal studies. So we're looking at studies that were done in this field. We're looking at around 200 patients where products could show efficacy with statistical significance. I don't want to commit now to the number of patients because it is too early. Just to give you a sense in terms of what was the breadth of the study that we ran on SHIELD I and what we are looking into now. Other thing that is important, follow-up is relatively short. There are some studies that were done that looked at anti-infection and wound healing after 2 weeks. So again, we are not looking into follow-up that is looking into months. And once we will have better understanding on the size of the study and the design after the pre-IND that we have mentioned we are going to have with the FDA, we will be able to give a better reference to cost. Well, great. Thank you very much for taking the questions. Thank you. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.