Great. Welcome, everyone, to another session here at Oppenheimer's 35th Annual Life Sciences Healthcare Conference. I'm Leland Gershell on the Biotech Equity Research team, and very delighted to have with us as our next presenting company, PolyPid. PolyPid is an innovative company that's working in the area of treating inflammation and infection with its novel delivery technology that we'll hear more about during the talk. We have with us the Chief Operating Officer, Ori Warshavsky. He will walk us through the slides. We should have some time at the end for some Q&A, so please submit any questions you like, and I can work those in with my own. With that, I'll hand the mic over to Ori. Thank you, Leland. Good morning, everyone. Yes, Ori Warshavsky, Chief Operating Officer. I'll take you through the story. I think you will see that this is an asset that's really at the final stages of phase three. A relatively simple story on one hand, on the other hand, a large addressable market with very near-term catalysts. PolyPid is an Israel-based startup company with its own proprietary drug delivery platform, what we call PLEX. PLEX stands for Polymer- Lipid Encapsulation Matrix. What PLEX can do is basically take many types of APIs from small molecules to chemotherapy and all the way to peptides and large antibodies and turn them into a local, high-concentration, prolonged-release delivery. Just to compare, how do we differentiate from some of our competitors? When our competitors say prolonged release in the local space, they talk about 72 hours, maybe 96 hours. For us, prolonged means days and weeks and even months of constant release. Really a completely different scale. We have our lead product in Phase 3, and I'll go over the results and the timelines in a minute. We have an earlier program in oncology that uses PLEX for treating solid tumors. Both the platform and the products are very well protected by a large number of patents. We have about 65 employees, all in Israel, starting from the R&D to regulatory, clinical, and manufacturing. We're traded under the PYPD ticker. Quickly, very simplistic way, how PLEX works. If you think on a nanometric level, a structure like in onions, of layers of layers of polymer, which serves as a backbone, and then lipids that surround the API and protect the API from enzymes, from body fluids, from the harsh conditions in the body. Every time the outer layer of the structure comes in touch with body fluids, it peels off or disintegrates, and then the API is released. Then the next layer comes in touch with body fluid, and the API is released again and again and again. We can control the number of layers, and that is how we control the release duration, depending on what the need is of the product. If a product needs three weeks of release, it is a set amount of layers. If it is two months of release, then there are more layers. We can control that and customize that. This peeling mechanism allows for the same amount of drug to be released all the time, which again is different from what we see in some of the competitors, which usually there is a large spike in release and then a very long tail. That's how they get to the 96 hours. For us, every layer releases the same amount, so it's really a flat line or a linear release of the product over time. We finished one Phase 3 trial in 2022. We are now towards the end of a second Phase 3 trial. We expect to have results in Q2 this year, coming in a few months. Of course, we have plans of expansion, how we increase the label and increase the market. Our lead product, D -PLEX 100, basically takes our platform PLEX and combines it with doxycycline, known, approved, safe broad-spectrum antibiotics indicated for the prevention of surgical site infections or SSI. SSIs are basically infections that come when a patient comes into the hospital for a major surgery, whether it's a joint replacement or colorectal surgery or even a C-section. They come in without an infection, and then they leave the hospital with an infection. Now it's an SSI. It's a hospital-acquired infection. There are implications both from how doctors deal with the infection and how a hospital is paid for this infection. The CDC defines every surgery, every infection that comes within the first 30 days post the index surgery as SSI. That is why we customize the release of D-PLEX 100 for 30 days. The definition is any infection within 30 days. Our product releases antibiotics in a linear manner over 30 days. It's a 505(b)(2) approval. We have breakthrough therapy for the product. We have fast-track designation for the product, and we have QIDP designation. QIDP stands for Qualified Infectious Disease Product. What QIDP gives us is additional five years of market exclusivity, which means that D-PLEX 100 will have, once approved, three years for the 505(b)(2), plus another five years for QIDP, plus a pediatric extension of another six months. All in all, eight and a half years of market exclusivity unrelated to the patent situation. You can see on the right side here the total addressable market. It's a large market. We like to look at this in two buckets. One bucket is the surgeries that have a high infection rate, those abdominal surgeries, colorectal resection, hernia, complex hernia repair, appendectomies, and some of the gynecology and urology, hysterectomies, and any kind of gynecology related that is access to the abdomen. Those are about half the procedures and surgeries with a high infection rate. The other side, the other group here are the surgeries that maybe have not as high infection rate, but if there is an infection, the consequences are really terrible, both from a clinical perspective. For example, if there's an infection in the sternum bone in an open heart surgery, there's a 40% chance of mortality. In orthopedic surgery, if there's an infection in the bone, in a knee replacement or a hip replacement, that could mean four to five weeks in the hospital and tens of thousands of dollars of cost for additional surgeries, taking the old infected hardware out, putting new hardware in. It's really a huge burden on the health system from a clinical perspective and an economic perspective. This is what D-PLEX 100 looks like in surgery. These are the last few minutes of an open heart surgery. The white powder you see here is D-PLEX 100. Basically, when it's time to close the incision, once the doctor finishes the surgery, D-PLEX 100, which comes as a powder, is dumped into a mixing bowl mixed with saline. It turns to a consistency of almost like a toothpaste in a way, and then applied directly on the incision, either with the fingers or with an applicator or some sort of spatula, but really goes all the way from the, in this case, as an open heart surgery, from the sternum bone all the way up to different tissues, the fascia, muscle, fat, all the way up to the skin. Very intuitive, very simple to apply. There's not much training that needs to happen to have this applied. There's not much change to what surgeons do today to administer D-PLEX 100. What you see here, once the incision is closed, from this point on, the D-PLEX 100 is in the incision, and it starts working and releases over time. It is kind of a one-shot, put-and-forget type of administration. There is no need to reapply. There is no need to come in and wash or take anything out one time and then protection for the entire duration. In terms of where we are on the clinical path and our timelines, we are now going through SHIELD II. SHIELD II is an 800-patient trial looking at the standard of care, which in 99% of the cases is IV antibiotics. Compare that to D-PLEX 100 in addition to standard of care. We are not looking to replace any of the standard of care today. This is why it's in addition to standard of care, we are adding another layer of protection, another tool in the toolbox for a surgeon in the prevention of surgical site infection. The trial looks at the primary endpoint is reduction in SSI, reduction in reintervention, and mortality over the 30 days of the efficacy of the product, plus another 30 days of safety. In terms of timeline, we announced in our Q4 call that happened this morning that we're past the 700 patients. We need to get to 800. We recruit about 20 patients per week. Before the end of Q1, before the end of March, we will be with a fully recruited trial. We expect to have top line by Q2, towards the end of Q2. I will say that we had an interim analysis of the data, an unblinded interim analysis done by the DSMB, the Data Safety Monitoring Board. We were still blinded, but the DSMB saw the data on an unblinded basis back in December of 2024. The outcome is really positive from our perspective. First, the DSMB saw the data, and they saw there was an efficacy signal, which kind of removes any scenario of futility from the trial. Second, the DSMB, their goal was to resize the trial to be the most effective with the highest probability of success. They sent us to the lowest station they could. They could have sent us to anywhere between 800-1,100 patients. They chose the lower bar, which again means for us, once the product works, we went for the minimal number. From our perspective, very positive. We believe increases significantly the probability of a successful trial. As I mentioned, we will have the results coming on very soon. In terms of how this relates to the previous Phase 3 trial, SHIELD I, if we look at SHIELD I, this large incision subgroup that you see here, this is exactly the subgroup that is measured in the current trial. We are really comparing apples to apples, same patient population in really almost the same trials for the most part, in almost the same centers in the trial. As you can see on the right column here, really across the board, in all the different parameters of the previous phase 3 trial, we saw a nice reduction both in the primary endpoint, in the secondary endpoint, reduction in infection, reduction of mortality of 40%, reduction in reintervention in 55%. Really a nice efficacy signal across all parameters, which again has both clinical implications and pharma economic implications for us. Another interesting point here that related to the previous trial and kind of starting to think of commercial, we looked as a post-hoc analysis, we looked at SHIELD I, and we wanted to see what is the impact on high-risk procedures and high-risk patients. We know that there are certain patients that are in high risk for infection, for example, the diabetics, the high BMI, the smokers, and some procedural-related risk factors like long incisions and long duration of trial. As you can see here, in 800 patients out of the total 1,000-patient trial, we showed a nice reduction, a 37% reduction in the primary endpoint with a very low P-value. When I'm kind of putting my commercial hat on, this is a good signal and a good story for the pharmacy director in the hospital. This is a patient population that the hospital already has a problem with. They know that this group is at high risk of infection and a higher cost to the hospital. We come in with a message of a well-defined patient population that we show nice reduction in primary endpoint, and we can save the hospital both a lot of money and a lot of time and bedtime. That is kind of the clinical development, maybe a few points on the commercial, and then I'll stop for questions. I spoke already about the 12 million surgeries in the US. The equivalent for that in Europe is about 8 million procedures. The current trial, SHIELD II, is designed to answer the requirements of both FDA and EMEA in terms of kind of the requirements for approval. We are eligible for a centralized procedure. Once we submit the file in Europe, we will have approval across the continent. Maybe one more word about the pharma economics. I spoke about this quite a lot, but there are a few levers here that we can pull on the pharma economic side. Because we're looking at hospital-acquired infection and inpatient procedures, all the cost of an infection is completely borne by the hospital. The hospital will receive a lump sum of money from the payer to perform a surgery. If the operation went well, the hospital will make money. If there's an infection and now the patient is another 10 days in the hospital, all this additional cost is borne by the hospital. The hospital has an incentive to reduce infection. In addition to that, there are kind of federal programs, CMS programs of improving quality and reducing infection. The worst offenders, this is all public, the hospitals need to report their infection rate. The bottom quartile in terms of infection rates get penalized by CMS on their Medicare reimbursement. Now, add to that what you see on the right side of the slide here, we are eligible for NTAP, which stands for New Technology Add-on Payment. NTAP will give the hospital up to 75% reimbursement on the product. On one hand, we are saving money for the hospital on hospital days. On the other hand, the product will be reimbursed up to 75%. When we kind of pull all this together into pharma economic models, it's pretty straightforward and clear to see how we can benefit the hospital. In terms of go-to-market, we are looking for partners. We understand that selling into the hospital is not an easy task for a small company from Israel. We are looking for partners that know how to sell to the hospitals, know how to call on surgeons to get products on P&T. We already have a partner for Europe, ADVANZ PHARMA, that will commercialize the product all over Europe. This was a deal that's signed in 2022, over $150 million in upfront payment milestones, development milestones, and sales milestones, plus royalties, plus margin on the transfer price. Very nice deal and a deal structure that we are looking to duplicate in other territories starting from the US. We believe once the top line data comes out at the end of Q2, these conversations, these discussions on commercialization will ramp up and we'll be able to sign something relatively quickly. Two final points. One, we have our own manufacturing suite, fully GMP, enough capacity to meet the requirements of the market for the next few years with an option to expansion. It went through a European inspection about a year and a half ago, and it's ready for commercial sales from a European perspective. It will go through FDA inspection as part of the NDA once we submit. Final point on the financials, we raised money together with interim analysis back in December 2024, 15 or just under $15 million. We announced on the quarter today that we ended Q4 with just over $15 million, which will take us into Q2 this year, so beyond the clinical trial. The entire trial is fully funded. In addition to the money that we raised, there was also just over $25 million of warrants that are exercised 10 days post-top line data. Post-top line data, there is another $25 million that will be available, assuming all the warrants are exercised. Plus, there will be some milestone payment from ADVANZ connected to the commercialization agreement. All in all, we should have by the end of the trial enough cash to take us all the way to NDA approval. I think that's it, Leland. I'll open it to you for questions. Great. Thanks very much for that review, Ori. I guess as we think about expectations for what the label is going to look like, right? Assuming this works and you get approved, how will that read in terms of the actual indication? Yeah. There are a few layers to this. First, I think some of it will depend on the efficacy coming out from the trial. We plan on, as soon as possible, to go to an end of Phase 3 or pre-NDA meeting with FDA to start these discussions on the label. Our going assumption is that we will start with colorectal resection or colorectal resection, high risk for high-risk patients because this trial is done in high-risk, large incisions because we have the previous data on high risk from patient-related high risk. That is our starting point. We have a well-defined expansion plan to expand to all abdominal. Partially, it will be kind of PK safety studies and then expand beyond that into all soft tissues and other surgeries. I think it's also important to note that because this is inpatient procedure, once the product is on formulary and the doctor starts to kind of test and pilot the product, you may see usage beyond just the label. We've seen this with other products. I heard these comments from other companies as well. The inpatient is less restricted to the label in this case. Got it. Okay. You had the interim analysis. I think that was driven by 430 patients for that. You have an incremental 270 that you had mentioned. I'm just wondering, are those patients very similar? Are there any differences we should be aware of with the subsequent cohort? Yeah. First, we are blinded, right? All we see is aggregated data. Our kind of assumption and belief is that there's not much difference. It's the same sites. The majority of the patients were recruited once all the sites were open. It's really the same sites. All we know is that there's kind of the same split in terms of male-female. It's about 70% colorectal patients, which was before as well. All in all, from what we can see, it's really a similar breakdown. Got it. Okay. Good. We should be hearing completion of enrollment soon and then the data next quarter. I mean, you'll be looking for commercial partnering. If you could just, I know there's a lot of potential partners, I guess, out there. Obviously, you're going to be in sort of the hospital space. Any kind of particular characteristics that you are prioritizing? Yeah. There are kind of two buckets of two types of partners that we are looking for. One is kind of the large device companies. If I'm Medtronic, Solventum, these guys have infection prevention units. They have infection prevention teams that call on surgeons. They have actually products in this space. Some of them have a hernia mesh, which is right kind of the exact same surgeon that we're talking to. That would be, and they get really good exposure, a lot of time, good conversation time with the surgeons, which is our main customer here. The other group are pharma, of course. Again, the pharma that knows their way around the hospital, knows how to talk to surgeon, knows how to get on P&T to talk to the ID specialist, someone like Pacira, for example, Baxter, Pfizer, these are B. Braun. These are kind of the names that are in the space. It's not a big list of companies that are kind of in this space. Probably, I'd say maybe 20 or so it targets. Very good. Great. We look forward to upcoming events. Thank you, Ori. Thank you all for zooming into this presentation with PolyPid. Enjoy the rest of the conference. Thank you so much.