PolyPid Ltd.

Greetings and welcome to the PolyPete fourth quarter 2024 conference call. At this time, participants are in listen-only mode. As a reminder, this call is recorded, and I would now like to introduce your host for today's conference, Brian Ritchie from LifeSci Advisors. Mr. Ritchie, you may begin.

Thank you all for participating in PolyPete's fourth quarter and full year 2024 earnings conference call. Joining me on the call today will be Dikla Chakchis-Axelbrad, Chief Executive Officer of PolyPede, Johnny Misalawan, PolyPede's Chief Financial Officer, and Ori Warshawski, Chief Operating Officer, U.S. of PolyPede. Earlier today, PolyPede released its financial results for the three and 12 months ended December 31st, 2024. A copy of the press release is available in the Investors section on the company's website. www.polypeed.com. I'd like to remind you that on this call, management 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 potential efficacy of D-Plex 100 and the probability of success of the trial, that the gross proceeds from the company's recent financing extend the company's cash runway into the third quarter of 2025, beyond the expected top-line results from SHIELD2, the expected timing for completion of enrollment of the SHIELD2 trial, the expected timing for top-line results from the SHIELD2 trial, potential NDA submission, accelerating preparations for regulatory submissions, and pre-launch activities, potential clinical benefits of DPLEX-100, potential market size for DPLEX-100 in the United States, potential partnership opportunities, potential benefits from the collaboration with immunogenesis, that the exercise of the warrants from the pipe in full would result in additional $27 million in gross proceeds, that proceeds of all warrants issued in the pipe, if exercised, would provide the company with capital beyond NDA approval, opportunities for the use of DPLEX 100 in additional procedures, and the company's long-term prospects. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks described from time to time in our SEC filings. The company's results may differ materially from those projections. These statements involve material risks and uncertainties that could cause actual results or events to materially differ. Accordingly, you should not place undue reliance on these statements. I encourage you to review the company's filings with the Securities and Exchange Commission, including, without limitation, the company's annual report on Form 20F, which identifies specific factors that may cause actual results or events to differ materially from those described in the forward-looking statements. PolyP disclaims any intention or obligation, except as required by law, to update or revise any financial projections or forward-looking statements, whether because of new information, future events, or otherwise. This conference call contains time-sensitive information. and speaks only as of the live broadcast today, February 12th, 2025. With the completion of those prepared remarks, it is my pleasure to turn the call over to Dikla Chachkis-Axelbrad, CEO of Polypeed. Dikla?

Thank you, Brian. On behalf of our team at Polypeed, I would like to welcome everyone to our fourth quarter and full year 2024 earnings conference call. We are very pleased with the recent critical advancement in our business, most notably as it relates to the recommendation by the Independent Data Safety Monitoring Board, or DSMB, to conclude the SHIELD2 Phase 3 trial assessing the efficacy of DIPLEX100 for the prevention of surgical site infections in patients undergoing abdominal colorectal surgery upon enrollment of 800 patients. which is the lowest sample size reassessment stopped after the minimum planned number of patients. We view the DSMB's recommendation to conclude SHIELD2 upon the enrollment of 800 patients as a favorable outcome, as it is suggestive of positive efficacy signals from DIPLEX100. As a reminder, the data generated from SHIELD2 to date remain fully blinded to polypid and others outside of the DSMB until top line results are available. As previously reported, we concurrently announced that we entered into a securities purchase agreement for a private placement financing led by existing institutional shareholders for $14.5 million in gross proceeds. The gross proceeds from the financings extend polypedes cache runway into the third quarter of 2025 beyond the expected topline result from SHIELD2. More on this transaction in a moment. First, however, some further discussions around the DSMB recommendation and our planned next steps. Most importantly, the sample size reassessment is an opportunity to ensure the study has sufficient power to conclusively confirm 100 treatment benefit, and we believe this increases the trial's overall probability of success. The study has enrolled over 700 patients to date, and at the current enrollment rate of roughly 20 patients per week, we expect to complete enrollment of SHIELD2 next month. We anticipate reporting top line results in the second quarter of 2025. Upon potential positive phase three data, PolyPID expects to submit a new drug application, or NDA, with the advantages of fast track and breakthrough therapy designations. We are thrilled to welcome Mr. Yitrak Jacobovich to the company's board of directors. Mr. Jakubowicz is a partner and a lead healthcare analyst at AIGH Capital Management and affiliates, the lead investor from the December financing. He is also a board member at Myomo, Inc. Mr. Jakubowicz earned his MBA from John Hopkins University and is a chartered financial analyst. We look forward to completing the trial and are focused on accelerating preparations for our regulatory submissions, prelaunch activities, and expediting partnership discussions in and outside of the United States. I will now turn the call over to Ori to discuss market potential, partnering efforts, and our recently announced technology collaboration. Ori?

Thank you, Dikla. I would like to provide some additional color on our market potential for DIPLEX-100 and our related partnering discussions. We believe the total addressable market for DIPLEX-100 in the U.S. is just over 12 million surgeries per year based on IQVIA data, the leading industry source on procedure and prescription data. There are approximately 4.4 million abdominal soft tissue surgeries annually both open and minimally invasive procedures, principally comprised of hernia repair, appendectomies, and colorectal surgeries. We also believe that there is an opportunity for the use of DPLEX-100 in an additional 2.1 million abdominal procedures in gynecology and urology, including hysterectomies and related procedures. Other DPLEX-100 potentially relevant surgeries, which either have high SSI rates or have high clinical and financial costs if an infection develops, includes granotomies and joint replacements. According to the CDC, SSIs are a substantial cause of morbidity, prolonged hospitalization, and mortality. It is reported that SSI accounts for 20% of all hospital-acquired infections and is associated with a 2 to 11-fold increase in the risk of mortality, with 75% of SSI-associated deaths directly attributable to the SSI. SSI is the most costly hospital-acquired infection type with an estimated annual cost of $3.3 billion and extends hospital length of stay by 9.7 days. with cost of hospitalization increased by more than $20,000 per admission. A CDC report published in November 2024 tracking hospital acquired infections in over 3,000 hospitals showed an increase of 3% in SSIs across all surgeries in 2023 as compared to 2022. The outcome of this report confirms what we have seen in our own clinical data a reduction in SSIs in the COVID years, and subsequently an increase in SSI post-COVID. Collectively, this market data reflects a large and broad unmet need and commercial opportunity for DPLEX-100 in the U.S. without even considering the more substantial global market. If approved, DPLEX-100 could potentially significantly transform the surgical landscape where postoperative SSIs remain a costly program. Turning to our partnering efforts, we remain in active discussions with several potential partners for the commercialization of DPLEX-100 in different regions, with the U.S. being our priority after the exclusive licensing agreement already signed with Advanced Pharma for Europe. Following the recent interim results and DSMB recommendations, we have seen an uptick in discussions with potential partners And just as important, a positive shift in the tone of those conversations. We are also focused on partnering efforts centered on our proprietary drug delivery technology that enables controlled and prolonged intratumoral drug delivery. As such, last December, Polypid and Immunogenesis, a Houston-based clinical stage biotechnology company, announced a research and development collaboration focused on combining polypids technology with immunogenesis potent stimulator of interferon genes, or STING, agonist drug candidate to enhance treatment for solid tumors. STING agonists are very potent, but have a short half-life in the tumor microenvironment, limiting their ability to shrink tumors when administered alone. This collaboration aims to take advantage of prolonged drug release enabled by our delivery technology with the goal of enhanced sting antitumor activity. This strategy could potentially overcome existing challenges of uneven distribution and limited exposure in dense tumor tissues while enhancing immune cell infiltration and activation within the tumor microenvironment. We believe this collaboration could create a cutting-edge approach to immuno-oncology and will continue to explore additional opportunities to bring value to innovative partnerships. With that, it is my pleasure to now turn the call over to Johnny to review the financials. Johnny?

Thank you, Ori. We are thrilled to advance each of our initiatives from a significantly enhanced financial position As of December 31, 2024, the company had cash and cash equivalents of $15.6 million. We expect that our current cash balance will be sufficient to fund operations into the third quarter of 2025. Now, let me briefly review the highlights of the private placements we recently entered into with existing event investors for $14.5 million in gross proceeds. The investors also received warrants which will expire upon the earlier of 9 months from the date of issuance and 10 trading days following our announcement of top line results. Exercise of the warrants in full would result in an additional $27 million in gross proceeds Proceeds of all warrants issued in this transaction, if exercised, would provide the company with capital beyond NDA approval. We believe that the participation in this transaction from a leading group of life sciences-focused existing investors is indicative of the substantial transformative potential of DeepLux 100. We are grateful for this continued demonstration of confidence and support. Now let's turn to our income statements. Research and development expenses for the three months ended December 31, 2024 were $7 million, compared to $4.6 million in the same three-month period of 2023. R&D expenses in the most recently completed fourth quarter were driven by the ramp-up of the ongoing SHIELD II Phase III trial. For the full year ended December 31, 2024 and 2023, R&D expenses were $22.8 million and $16.1 million, respectively. Marketing and business development expenses for the fourth quarter of 2024 were $0.2 million compared to $0.2 million during the prior year period. General and administrative expenses for the fourth quarter of 2024 were $1 million compared to $1.2 million recorded in the same three-month period of 2023. For the fourth quarter of 2024, the company had a net loss of $8.5 million as compared to $6.4 million in the fourth quarter of 2023. For calendar year 2024, the company had a net loss of $29 million compared to a net loss of $23.9 million in the full year 2023. With that, we will now open the call to your questions.

Operator?

Thank you. To ask a question, please press star, one, one on your telephone and wait for your name to be announced. To answer your question, please press star, one, and one again. We will now take our first question from the line of Roy Buchanan from JMP. Please go ahead.

Hey, thanks for taking the question. I guess just one to start. Can you just help us think about your expectations for the label, assuming the data is positive, which we expect? And then just, I know Ori went over the TAM in pretty good detail, but just how you're expecting to target those different segments and your commercialization readiness and plans. Thanks.

Good morning Roy, thank you. So our expectation is that as the first stage we will have both in US and in Europe a labeling that is in the area of the abdominal surgery. This is how we see ourselves launching the product with a general abdominal. It could be a more focused one on Let's say, let's call it large incision or things like that. But this is where we stand in terms of our expectation. And we have a very detailed plan on how to expand that. So that's with the label. You were asking about the commercialization and marketing effort?

Yes.

Oh, you want to take the second part?

Yes, yes, I'll take it. Hey, Roy. So two parts to this answer. I went over the numbers. Like we said, about half of the total addressable market is related to soft tissue, abdominal, then gynecology, urology, some of the, you know, C-section can go in there. Breast reconstruction can go in there. I think the point is from our perspective is really finding a strong partner that can drive these, you know, have these conversations both with surgeons, with pharmacy directors, with infectious disease specialists. I think it's important. We understand that selling into the hospital is a complex task and we need the right partner for that. And this is really kind of top of mind, at least for me and for all of us, is to find the right partner for that that can really have these conversations. But it'll be gradually, right? It's not day one, all these 12 million surgeries or even just the abdominal. We're starting our foot in the door in the colorectal and then expanding just like Nikla mentioned on the label, gradually expanding. I can tell you anecdotally from my conversations with surgeons, what I heard is once the product is on formulary, They understand that if an incision is made in the abdominal for a colorectal resection or an incision is made for appendectomy, it's the same incision in a way, broadly speaking. And once it's on formulary, they will use it more broadly and get experience with the product.

Okay, perfect. Thank you. I'll jump back in here.

Thank you. We will now take the next question from the line of Chase Nickelbroker from Craig Hallam. Please go ahead.

Good morning, everyone. Thanks for the question. So I guess just to start, can you give us a general idea of kind of how similar these kind of subsequent 270 patients, you know, from a baseline kind of characteristic perspective that, you know, like geographies of the facilities that are enrolling these patients, et cetera. You know, when you compare it to the 430 that informed the interim analysis, just trying to get a sense of kind of the, you know, how similar these patients have been to the kind of interim analysis patient from a baseline perspective. Thanks.

Sure. Thank you for the question. So it is in line with our expectation. We are blinded, so we don't really know how the infection rate is divided between the two arms. But we don't see anything that is alarming us in the sense that it is not in line with our expectation or what we've seen up until now along the recruitment and in the interim. Also, the interim was blinded, but as an overall. And in terms of geography, again, it's very similar. Since all the centers were open and recruiting at the time that we recruited the patient for the interim data, so we don't have new geographies or new centers. So this is also continuing. We are very pleased with the rate of the recruitment, and I expect that within a few weeks, we will be announcing last patient in.

Great.

And so, yeah, on those enrollment dynamics, so you kind of return to that, call it, you know, 80 patients per month, and then just a second, you know, after the kind of Christmas time slowdown and holiday time slowdown. And then just second, on the readout timing. So just so we kind of understand on the primary, obviously a 30-day follow-up and then kind of post that, we should think a month or two for, you know, kind of data cleanup and all the normal things. So, you know, fairly confident if you, you know, finish enrollment next month that we're talking to, you know, call it late 2Q kind of readout on the top line. Thank you.

Yes. Yes. Very confident. I would expect that we will be announcing in March, hopefully the beginning at the first half of March, last patient in. And from that point, exactly as you said, two months for follow-up or one month for follow-up for the primary and some time for the cleaning of the data. So a quarter from the time that we announce the last patient in. This is around the time that we will be announcing top-line results.

Great, thanks. Thank you, Chase.

Thank you. We will now take the next question from the line of Ram Selvaraju from HC Wainwright & Co. Please go ahead.

Thanks very much for taking my questions. Firstly, on the commercial front, I was wondering if you could give us some more insight into what you expect the properties of an ideal commercial partner to be specifically in the US for Dplex 100. And also, if you could give us some sense of, you know, if we think about a hypothetical ideal scenario, how the responsibilities might be divided between yourselves and a potential commercial partner. Would you expect to have any involvement in sales and promotional activities? If so, in what specific sales and promotional activities would those be targeted to a specific subpopulation of prescribers, for example? And also, if you could elaborate on the extent to which you expect to have sole control over the manufacturing and supply of D-Plex 100 for the U.S. market. Thank you.

Sure. Thank you, Ram. Good morning. So, the ideal partner is a partner that has presence in the surgery suite and the hospital in the surgery suite that has frequent visit to the surgeon and the broader the sales force within the surgery suite within the hospital the better and You could look at the companies that has presence in this way divided in a way into two arms one are the large pharma companies and And the other are the large med device companies. Both are very good partners that can, and speaking with them frequently for the last few years, I can tell you that they're looking at the area of surgical site infection. Many of them, it's part of their strategy. where they're looking to expand their pipeline. And in general, when you look at the, you know, surgical site infection is a subsection of hospital acquired infection. And when you look at the days post-COVID, you see product that were approved, drugs that were approved in this area of hospital acquired infection. after many years where we didn't have any new drug there. And I can tell you that those are being adopted very nicely by clinics and hospitals. And we see ourselves being the first in the area of surgical site infection alongside those new launches that were looking at other things, not necessarily of the portion of SSI. You were also asking about manufacture. So we definitely see ourselves manufacturing the product as part of partnership. We believe this is one of our strengths, bringing a full solution, bringing a product that is fully, that being a fully integrated biopharma company. we spent a lot of efforts and time these days to get ready to this stage this is something that we understand that requires efforts and investment in order to be ready for the commercial stage we did had about a year and a half ago a gmp review commercial stage gmp review by the european and Israeli healthcare, and we're getting ready for the FDA inspection that obviously will be after we submit the NDA. And this is, in all of our discussions, something that is in our advantage. And also, one maybe important thing, manufacture is very unique here. It's a septic. It's unique. There is a lot of know-how around the manufacture. And we think this is one of our strengths. Ori, you want to touch briefly on the aspect of what we believe will stay in our hands and what will be part of the responsibility of the partners?

Yes, I'll take it. Hey, Ron, good morning. So first, I think a lot of this will depend on the partner and what capabilities the partner brings. But I think in the ideal scenario and our preferred scenario, everything that has to do with the day-to-day activities, the boots on the ground, the sales reps, the MSLs, the national accounts that go into the hospitals are by the partner. And what we do is more a global view of the global activities, meaning looking into expansion of indication, looking into global medical activities, publications, HEOR, kind of global review, and looking forward at what else can be done with D-PLEX beyond prevention of COVID-19. prevention of SSI. There's quite a lot that can be done with the product. So kind of if you look at it in terms of a traditional pharma, kind of the global marketing will stay with us, the global medical affair will stay with us, and the global HUR and the day-to-day on-the-ground activity will be with the partners.

Thank you. That's very helpful. Just two other quick items, if I may, on the R&D front. Could you perhaps remind us of some of the existing approved APIs for which you already have knowledge, data, evidence that your platform would be able to effectively reformulate, potentially reposition, and optimize those approved APIs beyond what is in DPLEX-100? And then also if you could just elaborate with respect to immunogenesis, the collaboration that you have there, you know, what specific clinical development activities are currently ongoing with their candidate, how you expect your technology to be integrated into the future development plans for that candidate, and how broadly they expect to develop that asset and in combination with what drugs. And, you know, you mentioned previously that sting agonists have historically been difficult to deploy as monotherapy because of the short half-life. But do you also think that potentially pairing immunogenesis as candidate with your platform would actually enable it to be more combinable with other existing approved, for example, checkpoint inhibitor modalities for the treatment of solid tumors? Thank you.

Thank you. In terms of the PLEX platform and other approved drug that we have worked with in the past and are working on. I can only relate to those that have been disclosed. We do have in our pipeline some new programs that were not disclosed yet around approved drug and known compounds. But I can mention chemotherapy that we've worked with and we have on complex with chemotherapy we've been doing in the past some work with growth factors and steroids as well as with analgesics all have been tested pre-clinically in vivo in vitro and i think the potential here is literally we've we've not even touched the The beginning of what could be done around that. And this is the only thing that's where these close. We are also did. Some work with things that are not yet approved. For example, some peptides. Proteins as well as be specific. So those are in terms of looking at the capability of the platform. We have all of that. in our tool kit and there are some new things that we've been working on in the last two years and we are waiting for the top line to share this with investor and continue to develop that and hopefully also do that in some sorts of collaboration in area that are very lucrative So that in terms of the capability of the PLEX. In terms of the sting agonist, so sting in general has, as you said, have short life, but also tends to be deployed from the tumor very quickly. And we think that this together with the overall very potent immune response that the stink has, being able to deliver the drug locally at the tumor site, avoiding most of the systemic exposure together with having it on a prolonged and continuous basis could overcome those challenges. Both immunogenesis thought that this is a good approach to overcome those challenges and make the drug much more efficacious. But that is always with or potentially will be also with other modalities and other therapeutic agents. As good as the drug will be, I think patients will only benefit with something that with a combination with immune checkpoint. So that's definitely something that when we get to the preclinical stage, we will be looking on that as well together with immunogenesis. What's the best model to show the efficacy of the combined product?

Thank you so much.

Thank you. As a reminder, if you wish to ask a question Please press star 1 and 1. We will now take the next question from the line of Brandon Foltz from Rotman and Renshaw. Please go ahead.

Hi, thanks for taking my questions and congratulations on all the progress. Maybe just firstly from me, you talked about the potential label language, right, being sort of maybe just abdominal surgery or large incisions. Can you just talk about the pushes and pulls that we should expect in terms of the different label language possibilities? You know, is it just how compelling the Shield 2 results are? How much color do you think you get sort of post-Shield 2 in terms of where that label may be going or, you know, how much color a partner may get post-Shield 2 versus sort of

this just being regular way you submit the NDA for the broader syndication and sort of during regular way approval process kind of that's where you get the color on the label so I'm not sure I got all your points we had here some gap in the line but if I if I missed anything please Brandon add repeat some of that. I think that obviously the most important thing is the Phase III data and how efficacious it will be. If you recall, we also had in Shield 1 on this pre-specified subgroup that is now the basis of Shield 2 an effect on re-intervention. and mortality that could also make an influence on the way the agency see the data. We also have in these studies a group of patients that are not part of the primary endpoint, but that had smaller incisions. So about 170 patients out of SHIELD2 that are not part of the primary, They are on top of the 800 that are the primary, had smaller incision. So, we'll need to look at the data together with the agency, but our plan is to immediately meet the FDA to pre-NDA meeting. And obviously, once we sit with the agency, we will also start the discussions around label and label expansion.

Thanks, Dick. That's very helpful.

And then maybe just secondly, just a bit more sort of strategically, post the partnership, how do we think about Polypid's capital allocation and development strategy? Obviously, we expect you to sort of deploy funds into future development of your indications across the platform, which you partner out. But Do you look to take those molecules through the approval process as you've done with D-Plex 100, or do you look at perhaps a partnering strategy earlier stage, given the validation that a D-Plex 100 approval would bring to the platform? Thank you.

Thank you. That's a very good question, and it's important to stress this. We look at the partnering earlier stage, not just because, obviously because of the validation that we have from DPLEX 100, but also because of the area that we are choosing for our next in line, those that we've disclosed and those that we have not disclosed yet, that are in area where pharma companies are partnering at a much earlier stage. So we look to partner earlier and have most of the heavy lifting in terms of the clinical development done either by the partner or together with the partner.

Great. Thanks very much, and congrats on all the progress.

Thank you. Thank you. I would now like to turn the conference back to Axel Brat for closing remarks.

Thank you for joining PolyPEAT's fourth quarter and full year 2024 earnings conference call. We remain highly confident in our long-term prospects, especially the potential of our promising late-stage product candidate, DPLEX 100, and look forward to enrollment completion and top-line results. As always, we are grateful to our team members, shareholders, and all external partners for their commitment to our mission and support in continuing to advance toward our goal of bringing DPLEX 100 to healthcare providers and patients as quickly as possible. We look forward to speaking with you again on our next conference call.

This concludes today's conference call. Thank you for participating. You may now disconnect.