Greetings and welcome to PolyPid SHIELD II topline results conference call. At this time, participants are in a listen-only mode. As a reminder, this call is being 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 PolyPid's conference call discussing the top-line results of the SHIELD II phase III trial. Joining me on the call today will be Dikla Czaczkes Akselbrad, Chief Executive Officer of PolyPid, Dalit Hazan, Deputy CEO, Executive Vice President R&D, Clinical and Regulatory Affairs, Ori Warshavsky, Chief Operating Officer, United States, and Jonny Missulawin, Chief Financial Officer. Earlier today, PolyPid issued a press release announcing that the phase III SHIELD II trial successfully met its primary and key secondary endpoints. A copy of the press release is available in the investor 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 safety, efficacy, and benefits of D-PLEX100.
The expected submissions of a new drug application, or NDA, to the U.S. Food and Drug Administration, or FDA, any marketing authorization application, or MAA, and the timing thereof, and the company's expectation that the data results should be a substantial catalyst for expediting its ongoing global partnership discussions. 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. 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.
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, June 9th, 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. Good morning and welcome, everyone. It is a very proud moment for all of us at PolyPid today as we share the outstanding top-line results from the phase III SHIELD II study. I'd like to begin by thanking the patients, principal investigators, and study staff who made the study possible, as well as our team at PolyPid, especially Dalit Hazan, our Deputy CEO, Executive Vice President of R&D, Clinical and Regulatory Affairs, who led the excellent execution of this phase III trial, and whom you will hear from shortly. Before that, I will take you through the design of SHIELD II and describe the study's patient demographics. Following this, I will review the key outcomes from SHIELD II's primary and all key secondary endpoints, and then discuss our view on the significant unmet medical needs we believe D-PLEX100 addresses and our planned next steps.
At the conclusion of Dalit's remarks, we will open up the call for questions. With that, let's dive in and review the trial design. As seen on slide three, SHIELD II is a prospective multinational randomized double-blind phase III trial designed to assess the efficacy and safety of D-PLEX100 administered in conjunction with standard of care, which includes prophylactic systemic antibiotics compared to the standard of care alone arm, in the prevention of surgical site infection in patients undergoing abdominal colorectal surgeries with large incisions of at least 20 centimeters. In the intent-to-treat, or ITT population, a total of 798 patients were included, consisting of 405 subjects in the D-PLEX100 treatment arm and 393 patients in the control arm. Importantly, SHIELD II was designed based on FDA guidance.
Now that we have reviewed the overall trial design, let's talk a little more about the standard of care on the next slide. In SHIELD II, all patients received standard of care, both in treatment and control arms, which included IV antibiotics with or without mechanical bowel prep, or with all antibiotics combined with mechanical bowel prep. Here you can see the standard of care IV antibiotics that were used, given within 60 minutes prior to surgery and discontinued at a maximum of 24 hours post-index abdominal surgery. Each study site used the same predefined standard of care for all its subjects in the SHIELD II study, aligned with SSI prevention guidelines. Moving on to the study population, as seen on slide five, demographics and surgery characteristics were well balanced between the two treatment groups in SHIELD II. Median age, BMI, and other demographics were similar in both groups.
With respect to surgical characteristics, there were no significant differences between the D-PLEX100 and the standard of care treatment arms. You will also notice the majority of patients are cancer patients. Overall, the SHIELD II population was quite homogeneous. With these background details now complete, let's move on to the top-line results. We will begin, of course, with the primary efficacy endpoint of SHIELD II, which is the combination of deep and superficial SSI, all-cause mortality, and surgical reinterventions at the same target incision of the original index surgery, all measured within 30 days of the index surgery. On slide seven, we see that the study successfully met its primary efficacy endpoint.
In the ITT population, the surgical site administration of D-PLEX100 plus standard of care resulted in a significant decrease in the primary efficacy endpoint of 38% compared to standard of care alone, which is clinically meaningful and statistically significant, with a p-value lower than 0.005, well below the standard 0.05 required p-value. Let's now move to each of the key secondary endpoints on the next slide. The first key secondary endpoint, the SSI rate in the ITT population, showed a substantial reduction of 58% in deep and superficial surgical site infection rates among patients who received D-PLEX100 plus standard of care versus those who received standard of care alone, with a statistically significant p-value lower than 0.005. This 58% reduction in surgical site infection rate from 9.5% to 3.8% showed D-PLEX100 among the most effective prophylactic interventions for prevention of SSI in abdominal colorectal surgery.
For context, this moved the surgical site infection rate while using D-PLEX100 well below what most surgeons see even in lower-risk procedures. What makes these results particularly compelling is the consistency we're seeing. It isn't just one positive signal. As you will see in our remaining endpoints, we have observed a consistent and comprehensive clinical benefit. Moving on to the next slide, the second key secondary efficacy endpoint, combined SSI, mortality, and reintervention, is evaluated in the primary endpoint in the full set of 975 randomized patients with the surgical incision longer than or equal to 7 centimeters, meaning it includes an additional 177 patients with smaller incisions enrolled prior to the 2023 SHIELD II protocol change. Of note, the vast majority of these additional patients had laparoscopic surgery.
In this full 975 randomized patient population, the D-PLEX100 arm achieved a 36% reduction of the events versus standard of care alone, with a p-value lower than 0.005. This is also statistically significant. On slide 10 now, we can see the third and final key secondary endpoint, which is the number of patients with an asepsis score greater than 20. This is a universally accepted clinical tool used to objectively assess surgical wound infection. This score adds further clinical information to the SSI endpoint as it reflects the severity of the wound infection and the consequences of the infection itself in terms of both wound management and hospitalization. We can see a clear reduction of 62% in the D-PLEX100 arm compared to standard of care alone, again with a statistically significant p-value lower than 0.05.
I'd like to switch gears a bit here and discuss how we view D-PLEX100 addressing the current unmet needs in the surgical setting. SSIs represent a significant burden on patient outcomes and hospital systems, which are penalized for hospital-acquired conditions. SSIs are a large part of these conditions, and they are associated with a 2-11-fold increase in the risk of mortality, depending on the type and location of infection. Moreover, SSIs generally are estimated to cost the U.S. healthcare system up to $10 billion annually and extend hospital length of stay by 9.7 days on average, with the cost of hospitalization increased by more than $20,000 per patient admission. Decreasing the incidence of SSIs is of critical importance to patients, surgeons, hospitals, and payers.
Based on its compelling profile and the collective data generated to date, we believe D-PLEX100 can provide a tangible and crucial improvement in infection events following abdominal surgery. Looking ahead on the next slide, our next steps include a pre-NDA meeting with the U.S. FDA planned by the end of 2025, followed by an NDA submission in early 2026 and an MAA submission in Europe shortly thereafter. Our regulatory pathway is further strengthened by D-PLEX100's breakthrough therapy, fast-track, and QIDP FDA designations, which combined to position us for priority review eligibility and an additional five years of market exclusivity. Moreover, we expect these clear and compelling phase III results to be substantial catalysts for expediting our ongoing global partnership discussions for D-PLEX100.
In closing, I would like to congratulate and sincerely thank our extremely talented and dedicated team of employees, advisors, and consultants on a job well done. Now, I'd like to turn the call over to Dalit. Dalit?
Thank you, Dikla. Today's positive SHIELD II phase III study results mark a critical inflection point in PolyPid's journey, further validating our drug delivery platform to address unmet medical needs. I would like to sincerely thank all of the patients, investigators, nurses, and caregivers, as well as our service providers and partners involved in the phase III trial for the continued support.
Let me reiterate that what excites all of us the most, and I'm speaking on behalf of the entire PolyPid team, is the clinical impact of D-PLEX100 and its potential as an effective and transformative therapy for patients undergoing abdominal surgery, where the prevention of serious SSIs remains under-addressed with current approaches. We are already preparing our comprehensive data set for presentation at major medical conferences, where we expect these results to generate significant attention from the surgical community. Please stay tuned. With that, I will now ask the operator to begin our Q&A session. Operator?
Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Please stand by while we compile the Q&A roster. Thank you. We will now go to our first question. One moment, please. Your first question comes from the line of Chase Knickerbocker from Craig-Hallum. Please go ahead.
Good morning, and congrats on the excellent data here, and a big day for the company. First, just on the 58% reduction on SSIs, great to see. Is the data available on the other two proponents of the composite primary, or can you just at least confirm whether there was a numerical advantage in favor of D-PLEX in reinterventions and mortality?
Hi, good morning. Thank you, Chase. The data will be available. We just received the top line that the three key secondary endpoints this Friday, and as soon as possible, got them out. I can confirm that we saw a numerical reduction both in mortality and reintervention. Yes, when we were saying that it is all consistent, this is exactly what we were referring to. It is within the primary. Each of the components show numerical reduction, and overall, together, we have very robust data.
Great. In your upcoming pre-NDA meeting, as you've had a little bit of time to just get the data here, how are you thinking about your guys' positioning as it comes to a potential label? Can you just, I guess, remind us of your most recent thinking and expectations there?
As we said also in today's release, we plan to meet the FDA for a pre-NDA meeting later this year, and we were strategically waiting to discuss these aspects with the FDA once we have more clinical data. We think that this data positions us well to discuss the FDA's potential label, which we think could definitely be a broader label than just a colorectal. We are targeting the abdominal. By the way, with the European authority, we already got indication from them that they view the colorectal open resection as severe, the most severe abdominal in terms of SSI, and they will see this as a way to approve a broader label.
Got it. Under the partnership with Advanced, can you just remind us what this data makes you eligible for in terms of a milestone under that agreement?
Sure. We did not disclose the breakdown of the development milestone. We did indicate that there is about overall $25 million of development milestone payment, and definitely part of those development milestones is associated with phase III data.
Got it. Congrats again.
Thank you, Chase. Good to hear you.
Thank you. Your next question comes from the line of Roy Buchanan from Citizens Bank. Please go ahead.
Hey, great. Thanks for taking the questions. Yes, congrats on the success on the trial. Obviously, it was executed really well, so kudos to the clinical team and the whole company. First question—sorry, I missed if Jonny was on—but can you just remind us the warrant exercise provisions? How much is out there, the strike price? If they are all exercised, how long of a runway that provides? Also, is there a cashless provision for the warrants?
Sure. First of all, there's no cashless provision for the warrants. There are 6.7 million warrants with a $4 exercise price. They have a 10-day trading until they expire, so next Friday they do expire. With that, cash comes into the company, so with such funding, it will be beyond approval.
Okay. Great. Just, I guess, any changes in your confidence? What is your level of confidence in the U.S. partnership based on these results? Is there any scenario where you might promote this yourself?
I can take this. Hi, good morning, Roy. First, we took the strategic decision to find a partner with the understanding that selling into the hospital is a complex selling pathway, and we need a partner that really understands how to operate in the hospital, how to talk to surgeons, how to get products on P&T. This has not changed. We believe that going with a partner, a well-established partner, is the right way to go. What we know is that there are a number of potential partners that are already in different stages of due diligence. There are others that were waiting for top line to increase their engagement. We expect that to shift into gear even more. Next week, Bio International is happening, and we have a full roster of meetings there.
All in all, I think from now on, we'll see even greater engagement in the partnership discussion.
I would just say.
Okay. Great. I'll jump back in. Sorry, go ahead.
I would just add that from our perspective, the level of engagement that we had prior to data was surprisingly meaningful, and we definitely see the data as supportive of a greater and faster. We obviously cannot commit to timeline on that because it's not all in our control, but I think what was proven through SHIELD II and the data that D-PLEX demonstrated in this phase III is the commercial attractiveness of the product.
Yeah. Okay. All right. That sounds great. Yeah, the product definitely looks approvable, and I suspect it will sell. Thank you. Jump back in.
Thank you. Thank you. Your next question comes from the line of Brandon Folkes from H.C. Wainwright. Please go ahead.
Hi. Thanks for taking my question, and congratulations on some very good data here. A few from me, maybe just firstly coming back to the label. When I look at the incision length above 7 centimeters, data obviously looks very compelling there as well. Can you firstly just remind us of the discussions you've had to date with the FDA about SHIELD II and how they view SHIELD II data in terms of approvability versus the broader data set, including SHIELD 1?
I will let also Dalit add to that, but I think if we review the discussions with the FDA, the most important thing to start with is that SHIELD II was designed with the guidance from the FDA. We consult with the FDA prior to initiating the study in this format, and we got their feedback on that, which was very important for us, including obviously the FDA is not committing to anything, but also the understanding that this SHIELD II could serve as our pivotal study for approval, and this is reassuring. In addition to that, the product has received several designations from the FDA, starting from the breakthrough therapy designation to fast-track and three different QIDP, which also get the agency engaged in this development to a greater degree.
With regards to the labeling, we had some discussions looking at it through the QIDP to other things, but we strongly believe that the level of efficacy that we have now, combined with the three key secondary endpoints, that all of them are also statistically significant, opens the room here for discussion that will tailor the label for the benefit of patients together. Dalit, you want to add to that?
Just to add to that, as we just discussed before, we plan to meet with the FDA in the pre-NDA meeting with this successful top line results of the study. We will discuss also the broad labeling of the product. We have these plans, and we will do that, and we will know it in the upcoming months.
Great. Thanks. Maybe just a follow-up as well on this. In terms of the potential for as broad a label as possible, can you just remind us of the safety database you have, especially in terms of sort of local administration, and maybe just any additional work from a safety perspective, or even just broader between now and the filing, any gating factors we should be on the lookout for?
First, again, I remind everyone, we received the top line and the three key secondary endpoints. We are still on the wait for all safety data. All in all, we had, along the study, along the two years, several committees reviewing the safety, and no safety concerns were raised. I can also say that we see supportive data on that in the mortality. There is a numerical reduction in mortality in the treated arm. We are very comfortable with that. The overall number of patients that have been recruited in different clinical studies that were performed with D-PLEX100 is over 2,200. We are in a very good position in terms of exposure to patient population.
Great. Sorry, one more if I may. I apologize, and I'll hop back in.
No, no. We are here for this purpose. Feel free to ask as many questions as you want.
All right. Great. I do not know if you could answer this one, but as I take a step back and look at PolyPid as a whole, obviously, tremendous focus on D-PLEX100 , but it is really underpinned by the PLEX technology platform. If we think about what this does, it somewhat validates the platform technology here. How do we think about your timing strategically in terms of how you think about maybe additional partnering on new molecules or sort of internal development? Obviously, the focus, I am sure, number one, two, and three right now is getting D-PLEX100 across the line and getting a partnership there. When do you—how should we think about timing on when you may consider additional business development opportunities being sort of companies looking for partners of a technology that is now de-risked and validated? That is it for me. Thank you.
Thank you for this question. We have been doing a lot of work in the last few years around the platform and about prioritizing our pipeline. Obviously, we did not want to convey any message that this is a diversity from D-PLEX , but rather build the infrastructure for the point that we are now, to have the first product validated in a robust phase III, which will allow us now to have broader discussion. We plan to share with investors some of these developments in the next few months. Investors have seen a few months ago the agreement that we've signed with Immunogenesis around the STING agonist, but we have other products that have been developed in our pipeline that we would want to share with investors in different areas. I totally agree with you.
This was exactly our line of thinking, that having a robust phase III data with statistical meaning will be best validation of the approach and the platform.
Great. Congratulations again on the data, and thanks for taking all my questions.
Thank you.
Thank you. As a reminder, if you would like to ask a question, please press star one and one on your telephone keypad. We will now go to the next question. Your next question comes from the line of Boobalan Pachaiyappan from ROTH Capital. Please go ahead.
Good morning, team, and congrats on the diligently executed SHIELD II study and positive data. This is truly an achievement, and all the great questions from my colleagues. Just a few more from our end. With respect to slide number eight, SHIELD II was conducted outside the pandemic, Vilsarov, and SHIELD 1 was conducted in the middle of COVID-19. I'm just curious, did the SSI data in the standard of care arm meet your expectations?
Yes, definitely. This is a good point to look at. When you conduct a phase III study, obviously, it is within a more sterile environment, and not in the sense of sterile in the hospital, but there are exclusion-inclusion criteria that are not mimicking the real world. For example, the patient population were elective surgery. There are a number of emergency surgeries within the colorectal resection.
It's very hard to include those surgeries in a clinical trial because it's hard to get consent from patients undergoing an emergency surgery. I would refer everyone to today's press release and the quote that was given by Professor Charles Edmiston that is from recent data indicating that you would expect to see in real world in colorectal a much higher infection rate overall. I think that what is most important from the SSI, which is obviously what the product is designed to do, and this is what we were out to do, to show over 50% reduction in infection, that we D-PLEX , the reduction using D-PLEX with patients that all patients got standard of care, which has a lot of value for the patient, we are getting the level of SSI below what surgeons are expecting to see in minimal invasive.
This is really the power of what we do. They are out to do a quite complex surgery, open, large incision with patients that are most of them cancer patients, and they end up with lower than what they would expect to see in a minimal invasive laparoscopy surgery.
All right. Thanks for the clarity. Are you in a position to discuss SHIELD II efficacy results in high-risk population? These are the patients with high comorbid conditions such as obesity. Is that data available? If it is not available, what do you expect to see in this population?
Definitely, there are many additional secondary endpoints that we would want to see and would want to share with investors, with the clinicians, and with the scientific community. We are gathering this data, and it will be added in batches to everything that we received up until now.
It's one of the things that we are looking for. In terms of expectation, I expect to see a similar trend, probably even a better alpha P-value. Not that I think it could be much better than 0.005, but what we saw along all the clinical studies is that the harder the patient is, the harder the procedure is, the higher the level of infection that is expected. This is where the gap or the effect of D-PLEX is best seen.
Great. With respect to potential FDA meeting that could occur in the fourth quarter of this year, are there modules that are part of the CTD that are in your control that remain pending?
Actually, right now, we are starting working on the clinical model because we just received the top line results, and all the others are already in the final stages of completion. It is more the clinical part that we are starting to work right now on the results.
All right. Okay. And then, with respect to your partnership, so you've given some broader thoughts on it, but let's just say, assuming this partnership occurs after your FDA approval, let's just say sometime in the second half of 2026, how easy or difficult it is to launch the drug in early 2027?
The process in the hospital is one that takes time to get traction in the hospital. It's something that is not similar to a retail product. It takes time. Whether we sign the partnership earlier or later, it's a process that takes time. We have to find the champions in the hospital. The product needs to go to P&T. P&T sometimes meets every month, sometimes every quarter. This is a product, and this is kind of our expectation, somewhere between six to nine months from approval to start seeing traction in the hospital and see minimum sales. Again, finding a partner that already has the hospital infrastructure, that has teams that call on surgeons, that has the outreach into the P&T will make the process more expedited.
Okay. Maybe one last question. This is with respect to the commercial capabilities of Advanced Pharma. Let's say, yeah, as soon as you file your NDA, of course, you'll be beginning your preparations for the EMA. I want you to comment on two things. Firstly, does SHIELD II positive data satisfy the EMA requirements? That's number one. Number two, how soon could Advanced Pharma launch D-PLEX100 in the U.K. and EU?
We believe it.
After.
Thank you. Thank you. We believe that SHIELD II should be sufficient for approval with the EMA. We actually aligned the requirement between the FDA and the EMA along the years, and it is our understanding that this will be sufficient based on all our written communication with them. In terms of the timeline, we expect, as we said previously, we expect to submit the NDA early next year, early 2026, and shortly after that, we will submit to the EMA. The timeline for approval is about a year from the time that we submit with the European authorities. Around that time, Advanced will be able to launch the product.
I can tell you that all along, since we've signed with Advanced, we have been working together on a biweekly timeframe to make sure we have all the pre-launch activities aligned, from little things as packaging to other things. Advanced has several not similar products, but products that are being sold to the hospital. Some of them are also in the anti-infective space. They definitely have the capabilities to launch this product in the U.K. and in Europe.
All right. That's it from us. Congratulations and well done.
Thank you.
Thank you very much.
Thank you. There are no further questions. I will now turn the call over to Ms. Czaczkes-Akselbrad for her closing remarks.
Thank you again, everyone, for joining us today. We look forward to providing updates on our next conference call, and we truly appreciate your continued support of PolyPid.
Thank you, ladies and gentlemen. This concludes today's presentation. Thank you once again for your participation. You may now disconnect.