PolyPid Ltd

NASDAQ:PYPD

Good day, and thank you for standing by. Welcome to the PolyPid First Quarter 2025 Conference Call. [Operator Instructions].



Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Brian Ritchie. Please go ahead.

Thank you all for participating in PolyPid's First Quarter 2025 Earnings Conference Call. Joining me on the call today will be Dikla Czaczkes Akselbrad, Chief Executive Officer of PolyPid; Johnny Missulawin, PolyPid's Chief Financial Officer; and Ori Warshavsky, Chief Operating Officer, U.S. of PolyPid.



Earlier today, PolyPid released its financial results for the 3 months ended March 31, 2025. A copy of the press release is available in the Investors section on the company's website, www.polypid.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-PLEX100 and the probability of success of the trial, that the gross proceeds from the company's last financing extend the company's cash runway into the third quarter of 2025 beyond the expected top line results from SHIELD II, the expected timing for top line results from the SHIELD II trial, potential NDA and MAA submissions and the timing thereof, preparations for regulatory submissions, finalization of CMC and nonclinical NDA modules, potential clinical benefits of D-PLEX100, potential market size for D-PLEX100 in the United States, potential partnership opportunities, the potential to receive up to an additional $27.0 million from the exercise of the warrants from the recent financing, the company's anticipation that with such additional funding, its runway would be extended beyond anticipated NDA approval, opportunities for the use of D-PLEX100 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 20-F, which identifies specific factors that may cause actual results or events to differ materially from those described in the forward-looking statements.



PolyPid 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, May 14, 2025.



With the completion of those prepared remarks, it is my pleasure to turn the call over to Dikla Czaczkes Akselbrad, CEO of PolyPid. Dikla?

Thank you, Brian. On behalf of our team at PolyPid, I would like to welcome everyone to our first quarter 2025 earnings conference call.



We were thrilled to recently successfully conclude enrollment of the SHIELD II Phase III trial assessing the efficacy of D-PLEX100 for the prevention of surgical site infections in patients undergoing abdominal colorectal surgery. As a reminder, this significant milestone followed an independent Data Safety Monitoring Board or DSMB recommendation to conclude the SHIELD II Phase III trial of D-PLEX100 at the lowest sample size reassessment stop 800 patients after the minimum planned number of patients. We are now rapidly approaching the availability of top line data by the end of next month. To reiterate what we have said previously, we view the DSMB's recommendation to conclude SHIELD II upon the enrollment of 800 patients as a favorable outcome as it is suggestive of positive efficacy signals from D-PLEX100. Of course, the data generated from SHIELD II to date remain fully blinded to PolyPid and others outside of the DSMB until top line results are available.



Upon potential positive Phase III data, PolyPid expects to submit a new drug application or NDA with the advantages of the Fast Track and breakthrough therapy designations in early 2026. With a marketing authorization application or MAA submission in the EU anticipated shortly thereafter.



Importantly, as a result of our December 2024 $15 million financing, we are funded into the third quarter of 2025 beyond the expected top line results from SHIELD II. Further, data triggered warrants from this financing, if exercised in full, would result in an additional $27 million. We anticipate that with such additional funding, our runway would be extended beyond anticipated NDA approval. While we await the SHIELD II trial top line data readout, we are intensely focused on advancing the preparation of our regulatory submissions. With the anticipated NDA filing time line of early 2026 in mind, CMC and nonclinical NDA modules are currently being finalized.



Additionally, we continue to progress prelaunch activities and expedite partnership discussions in and outside the United States. Importantly, identifying a U.S. partner is the path we have strategically identified as the most effective commercial course for D-PLEX100. Finding the right partner with an existing dedicated hospital product sales force with significant resources will best enable D-PLEX100 to maximize its sales potential in the U.S., which we believe is substantial. To this end, as Ori will detail shortly, U.S. partnering interest in D-PLEX100 is gaining meaningful momentum amongst multiple parties as we approach our pivotal data readout.



With that, I will now turn the call over to Ori to revisit the D-PLEX100 market potential and review our partnering efforts. Ori?

Thank you, Dikla. As we get closer to the end of the SHIELD II trial, I would like to reiterate the market potential for D-PLEX100 and provide an update on our partnering discussions.



To begin, as we discussed previously and as it relates to SHIELD II, 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. This important data confirms the increase in SSIs post-COVID following the decrease in SSIs during the COVID years that we observed in the SHIELD I study.



From a commercial perspective, as I reviewed on our last quarterly conference call, -- based on IQVIA data, we believe the total addressable market for D-PLEX100 in the U.S. is just over 12 million total surgeries annually, with approximately 4.4 million of these being abdominal soft tissue surgeries and additional 2.1 million abdominal procedures, principally in gynecology and urology.



I would like to dive a bit deeper into these surgeries. Our recent market research flagged 4 groups of surgeons as potential users for D-PLEX100 beyond colorectal surgeons. These are general surgeons, hepato-pancreato-biliary surgeons, urology surgeons and oncogynecology surgeons. The surgeons who took part in the research were mainly clinical department heads and have flagged several high-risk procedures, including exploratory laparotomy and mastectomy in general surgery, while procedure in hepato-pancreatic-biliary surgery, cystectomy and nephrectomy in urology surgery and C-section, hysterectomy and ovarian tumor removal in the onco-GYN space.



These 8 surgical procedures represent an area of great unmet need with a total of close to 1.5 million inpatient open procedures per year in the U.S. and can serve as a starting point for piloting and championing D-PLEX100 post launch in major hospitals across the country. We are optimistic that the U.S. market is substantial and that it represents a viable and attainable commercial opportunity for D-PLEX100. The larger global market offers additional room for growth. And if approved, D-PLEX100 could potentially significantly transform the surgical landscape where postoperative SSI remains a burden on the health care system as well as on patients.



Moving to our partnering discussions. We continue to intensively seek partners to support commercialization efforts of D-PLEX100 with the U.S. market being our main priority. The upcoming top line results of SHIELD II represent a major milestone, and it creates a healthy competition among potential partners to be ready to advance into further negotiation and deal making once the study outcomes are known. As a result, we are in advanced discussions and due diligence stage with multiple potential partners in the U.S. and expect others to join the process once the top line data is released.



Regarding Europe, as a reminder, we already have an exclusive licensing agreement in place with Advance Pharma to commercialize D-PLEX100 in all European countries, and we are currently actively working together to plan and start implementing prelaunch activities to maximize D-PLEX100 anticipated launch in Europe.



With that, it is my pleasure to now turn the call over to Jonny to review the financials. Jonny?

Thank you, Ori. We are pleased to be in a solid financial position as we await the top line results of the SHIELD II trial expected by the end of the current quarter. As of March 31, 2025, the company had cash and cash equivalents of $8 million. We expect that our current cash balance will be sufficient to fund operations into the third quarter of 2025.



Now let's turn to our income statement. Research and development expenses for the three months ended March 31, 2025, were $6.1 million compared to $5.1 million in the same three-month period of 2024. R&D expenses in the most recently completed quarter were driven by the ramp-up of the ongoing SHIELD II Phase III trial. Marketing and business development expenses for the first quarter of 2025 were $0.3 million compared to $0.2 million during the prior year period. General and administrative expenses for the first quarter of 2025 were $1.2 million compared to $1 million recorded in the same three-month period of 2024.



For the first quarter of 2025, the company had a net loss of $8.3 million as compared to $6.4 million in the first quarter of 2024.



With that, we will now open the call to your questions. Operator?

[Operator Instructions] And the first question comes from the line of Roy Buchanan from JMP Securities.

I guess to start, can you just discuss how you're thinking about the price per vial for D-PLEX 100 because I think it's substantially above our model today. And then just remind me the vials per procedure. And how did you arrive at the price that you're at today?

So first, we have not finalized the pricing strategy and pricing I will start with that, and thank you for the question. We have not finalized the pricing strategy at this stage. We did some preliminary research along the development stages, and we will do another study once we have the top line data in the very near future as we would want to refine things, pricing has changed, index has changed and having enhanced the actual efficacy on SSI, on mortality and on reintervention could affect the pricing here.



Also, I think that as we've developed the product and started to get results and speaking with more and more surgeons, we have a better understanding of the target market opportunity. This is what Ori was elaborating on so we can better identify those specific patient and surgeries that are at most need of a product like ours. Saying all of that and maybe adding to that the dosing, the dosing is between one to three vials depending on the length of the incision where minimally invasive surgeries will need one vial and larger surgeries will need between two to three vials. Our assumption is that in average, we will see 2.5 vials, again, going to the model. I think that for the purpose of the modeling at this stage, we are looking at the pricing of $600 per vial. But as I said before, this is something that is on the go and in process to be refined. And also since we are planning to commercialize the product with a partner, obviously, this will also be a discussion that we will have with the potential partner.

Okay. Great. That makes sense. And then just a follow-up, I guess that for SHIELD II, was there a strict requirement for the number of vials used per procedure? And I know you're looking at incisions over 20 centimeters, but it seems like maybe things might change during the surgery. So will you have any subjects, I guess, with smaller incisions -- or were there absolutely none, there is a strict requirement on the -- on the incident?

So, yes. The patient population that is combining the ITT and the primary endpoints and all the statistical analysis for that are part of those are very restrict. All of them are with long incision and with three vials exactly. We had a handful of patients around 170 patients that were recruited for other purposes, safety and expansion of indication, and those combines minimal invasive and other, but they are not part of the primary endpoint. So all the statistical analysis for the sake of the primary endpoint doesn't take them into account. They are on top of the 800.

We will take our next question, and the next question comes from the line of Chase Knickerbocker from Craig-Hallum.

Maybe just first on kind of NDA filing timing. I mean, looking further ahead, can you just walk us through what will be required between data and NDA filing that leads to the expectation that it takes a couple of quarters to prepare the filing?

So the NDA is composed or there are three modules that are part of the NDA submission. Two of them are more technical. The other three are the CMC, the preclinical data and the clinical data. As we said in today's call, we are in finalization stages of the CMC and the preclinical. And once we'll have the top line, we'll start working on the clinical module. Obviously, we are not standing by and waiting, we are starting to prepare outline of that and working on everything else that is needed that is coming from SHIELD I or previous studies.



We are planning to meet the FDA for the pre-NDA meeting. We think that this is the right course. It's not a must, but we think that this is the right course in order to get to an agreement with the FDA on how we're going to submit some questions that we want to ask prior to submission to really maximize the chances to have it right at first time. And the thinking is that we will be able to meet the FDA with top line by the end of June, before the end of this year, and immediately after meeting the FDA and implementing whatever comments they will have, start submitting in early 2026, the first quarter of 2026.

Got it. And then just on the CMC module, can you remind us kind of your plans to prepare there? What's kind of the work then with consultants? Are you planning to do some mock audits in the months after the data, et cetera?

Of course, of course. So once we submit the NDA, the FDA will come and inspect our facility. This is standard, and we are in the process of having exactly what you referred to, having several mock inspections done by an external ex-FDA adviser who can prepare us. We actually met yesterday someone who is really probably one of the most, if not the most, experienced in the country in FDA reviews, with hundreds of reviews on his shoulders, with several decades of work around QA in the pharmaceutical industry, and we are aligning all the team to get to that.



We have a detailed plan on that in terms of what we need to do in preparation, and how we can best prepare for this. This is post submitting the NDA, this is the most important thing or the most important milestone prior to commercialization in the continuous development on bringing D-PLEX into the market.

And then just a little on kind of what we should expect from top-line data in the coming weeks, months. Should we be just expecting kind of top-line data? Are we going to get some of the key secondaries? Are we going to get some of the -- obviously, specific drivers within the primary? Are we going to see some data from the smaller incisions, too? I mean, just kind of walk us through what we should expect from that release when it comes.

Sure. So first, I must tell you that everyone here at PolyPid are super excited getting to this point. This is really something we've been working towards for years. And now that things are coming in together in terms of getting to finalizing day 60 of all patients and getting to the point when we lock the data and soon, we will be able to unblind the data and share it with investors as well as with all of our external partners and the discussions that we have. We expect to have top line and key secondary endpoints. and expect to share these with investors once we get it. Obviously, we will not have all the data, but we do expect to have top-line as well as secondary endpoint.

[Operator Instruction] Your next question comes from the line of Boobalan Pachaiyappan from ROTH Capital.

Congratulations on completing the SHIELD II enrollment. This is an important milestone. So, a few questions from us. So I wanted to follow up on the expectations or the top line for the SHIELD II data. And when you report your top line, so will you report a composite endpoint comprising SSI reduction, reinfection and readmission for both placebo and D-PLEX group patients? And also in that regard, can you remind us if an efficacy threshold of 30% or above in all 3 metrics is necessary to consider this trial a success?

So we will report the primary endpoint. And the primary endpoint is the combination of SSI, mortality, and reintervention. We are counting all of these events. This is how the primary is composed. And this is -- obviously, we will report the primary as a whole. We will also report the secondary. Secondary relates to surgical site infection alone. So you could see how we've met the baseline requirement of having an alpha level below 0.05 with the primary as well as some of the effect.



We'll need to see. Our plan is to report the data as soon as possible after we are unblinded. We will need to see how much of this can be digested in a way and presented in a meaningful way within hours from getting the data. But the plan is to share as much as possible, have an investor and analyst call, post the data. And then as we get more and more data, obviously, find the venue to share additional data.

All right. That's very helpful. And then switching to commercial manufacturing. So let's assume you are getting the priority review. So what are your preliminary thoughts with regards to inspection readiness? And also with respect to your capacity, can you give us some idea how do you expect to assess the demand, at least for the couple of years? And how do you expect the capacity to satisfy those demands?

Sure. So with regards to the inspection, this is our top priority these days. We are in the process of getting ready for this inspection, including having in place a detailed plan of things that we will need to be doing, time line for mock inspection. We plan to do several mock inspection prior to FDA review. We also are engaging consultants ex FDA that can help us and guide us through the process. We really reaching or outreaching this process in the mind of getting it right at the first time. So that's in terms of all the preparation for the CMC. The fact that the CMC pack modules is in finalization mode is very helpful because a lot of the actual work needed for the submission in terms of stability and all the rest of it is in finalization mode.



As for overall capacity, we did not disclose the capacity of the facility because at this stage, we believe, it is information that should be kept in-house, especially since we are in commercialization discussions in different geographies. But we did say that our assumption is that the facility will be sufficient for the first 4 to 5 years from launch, which gives us sufficient time to expand or to build an expansion elsewhere once we see that there is a need for that.

Okay. That's very helpful. I know, Ori, you mentioned about the November 2024 SSI data. Can you maybe provide that in context with what the SSI was observed pre-COVID? So essentially, I wanted to see if you can compare the SSI pre-COVID versus the November 2024 data.

Yes. So just to clarify, the data that I cited was CDC data that is comparing 2023 to 2022, and that showed a 3% increase in infection. I don't have off the top of my head the number pre-COVID, but what we know is there was a steady decline in or steady to flat rate of SSI before COVID and then a significant drop 2021, '22. And really 2023 is the first time that we see an uptick reported. And it is reported. So the 3% is really across all procedures that CDC tracks. So if you can obviously, there's some that jumped quite a lot, some of them that did not jump at all. So, on average, it's quite a large increase over the COVID time.

There seems to be no further questions. I would like to hand back for closing remarks.

Thank you for joining PolyPid's First Quarter 2025 Earnings Conference Call. We remain highly confident in our long-term prospects, especially the potential of our promising late-stage product candidate, D-PLEX100, and look forward to reporting the top line results of the SHIELD II Phase III trial in the very near future. 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 towards our goal of bringing D-PLEX100 to health care 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.