PolyPid Ltd. Q2 FY2022 Earnings Call

Greetings, and welcome to the PolyPid Second Quarter 2022 Conference Call. A reminder, this call is recorded. And I would now like to introduce your host for today's conference, Bob Yedid from LifeSci Advisors. Mr. Yedid, you may begin.

Thank you all for participating in PolyPid's second quarter 2022 earnings conference call. Joining me on the call today will be Dikla Czaczkes Akselbrad, Chief Executive Officer of PolyPid; and Ori Warshavsky, Chief Operating Officer for PolyPid's U.S. Operations. Earlier today, PolyPid released financial results for the three and six months ended June 30, 2022. A copy of the press release is available in the Investors section on the company's website. 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 our ongoing clinical trials, our expectations regarding the timing of top-line results from the SHIELD I study and potential NDA submission and MAA filing, potential milestone payments under the license agreement with ADVANZ PHARMA, potential future additional commercial partners, and our ability to maximize the value of D-PLEX100, the commercial potential for D-PLEX100, market opportunity in Europe, the strength of our financial position, and our expectation that our cash balance, together with the upfront payment from ADVANZ PHARMA and the proceeds from the Kreos loan, will be sufficient to fund operations through the end of the second quarter of 2023. 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. Our results may differ materially from those projections. These statements involve material risks and uncertainties that could cause actual results or events to differ materially. Accordingly, you should not place undue reliance on these events. I encourage you to review the company's filings with the SEC, including, without limitation, the company's 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. The conference call contains time-sensitive information and speaks only as of the live broadcast today, August 10, 2022. With the completion of those prepared remarks, it's my pleasure to turn the call over to Dikla, CEO of PolyPid. Dikla?

Thank you, Bob. On behalf of our team at PolyPid, I would like to welcome everyone to our second quarter 2022 earnings call. I'm thrilled to have the opportunity to provide you with a corporate update today during such an exciting time for PolyPid. I will begin with the recent exclusive license agreement we signed with ADVANZ PHARMA for the commercialization of D-PLEX100 for the prevention of surgical site infections, or SSI, in abdominal and cardiac surgeries in Europe, which provides further validation for the significant sales potential of D-PLEX100 and represents substantial value for PolyPid. Under the terms of the agreement, PolyPid is entitled to receive an upfront payment immediately upon signing of the agreement, additional potential development-related milestones for a total of up to $23.5 million, and up to $89 million in sales-related milestones. We will also supply D-PLEX100 to ADVANZ PHARMA for a negotiated transfer price and receive royalties on net sales in double-digit percentages of up to the mid-20%s. ADVANZ PHARMA is backed by Nordic Capital, one of the most active and experienced private equity investors in health care. ADVANZ PHARMA's expertise in marketing hospital-based therapies, mainly after the recent acquisition of Intercept, has more than doubled their commercial and medical teams across major EU countries and the U.K., which will prove invaluable in extending access to D-PLEX100 and delivering this much-needed therapy, if approved, to patients. To understand our excitement for this licensing agreement, it is important to put into perspective the opportunity of D-PLEX100 in Europe. Surgical site infections represent a major unmet medical need in Europe. SSIs are one of the most common hospital-acquired infections and occur in up to 15% to 20% of major surgical procedures such as open colorectal resection. We are also talking about a very significant market opportunity. According to IQVIA, the addressable market opportunity in selected abdominal surgeries in the big five European countries represents approximately 3 million annual surgeries. Moreover, there are an estimated 450,000 open-heart surgeries in the big five EU countries every year. As a result, it is not surprising that the World Health Organization estimates the significant economic burden that SSI represents. The WHO estimates that SSI results in up to EUR11 billion of traditional hospital costs per year in Europe. This deal is the first step in our strategic approach to commercialize D-PLEX100 in terms of additional potential collaborations in the U.S. and the rest of the world. We remain in dialogue with several other large and midsized pharmaceutical companies that we believe would be ideal commercial partners. Like ADVANZ PHARMA, these companies are leaders in selling pharmaceutical products to hospitals, often with a current portfolio of marketed products, have strong established commercial infrastructures, exhibit a deep understanding of clinical benefits and health economics in the hospital channel, and maintain strong relationships with hospital, medical, and administrative staff. Importantly, there continues to be a high level of interest in D-PLEX100 from additional potential partners. While there is currently no formal timeline related to executing any additional potential collaborations in the U.S. or the rest of the world, our most critical objective is to maximize the value of D-PLEX100 in any potential transaction, as we believe we have done in the ADVANZ PHARMA agreement. If and when we do finalize additional collaboration agreements, maximizing the value of D-PLEX100 will be the key determining factor. With that, I will now provide a brief update on the status of our pipeline. Let's begin with SHIELD I, our Phase 3 study evaluating D-PLEX100 for the prevention of abdominal soft tissue SSI. As we announced in May this year, the independent Data Safety Monitoring Board, or DSMB, recommended concluding this trial subsequent to the enrollment of 950 patients, which is the minimum number of targeted patients in the study protocol. This recommendation was based on the unblinded interim analysis by the independent DSMB of efficacy data from the first 750 enrolled patients. The enrollment of the last patient was subsequently announced in late May 2022. As a reminder, the SHIELD I study of D-PLEX100 in the prevention of SSI in abdominal tissue surgery is designed to demonstrate at least a 50% reduction in incisional SSI in the D-PLEX100 treatment arm compared to the control arm, with 90% power to detect the difference between the two arms and an alpha level of less than 0.05. Patients in this study have been enrolled across approximately 60 centers in the United States, Europe, and Israel. Importantly, SHIELD I is the largest infection prevention trial in colorectal surgery conducted in more than a decade, which we believe enhances the importance of disease data. Full top-line results are anticipated by the end of the current quarter, followed by potential NDA submission to the FDA and European Union MAA filing. Resulting from the Breakthrough Therapy Designation, D-PLEX100 is eligible for rolling NDA submission targeted to start early 2023. Before we provide an update on OncoPLEX and PolyPid financials, Ori will provide color on key takeaways from market research we recently completed for D-PLEX100 in the U.S. and how this work was further supported by the real-world commentary provided by two KOLs during our recent webinar focused on managing the cost of SSI. Ori?

Thank you, Dikla. As other partnership discussions progress, we continue our launch preparations for the U.S. market. Last month, we concluded an in-depth market research study aiming to explore current SSI prevention practices and understand how D-PLEX100 will fit within these practices. Our market research indicates that current treatment bundles used by surgeons to prevent SSIs are primarily based on surgeons' clinical experience and institutional protocol, not on a strong body of evidence-based studies. Moreover, all surgical specialties across various types of procedures agree that there is a significant unmet need to reduce infection rates regardless of how well controlled the rates are today, since even a few infections can be catastrophic and devastating. Importantly, surgeons have a fair amount of latitude to create a personal preventative bundle as they see fit for their cases, provided nothing is too outlandish or costly, and their SSI rates stay within the institution or network standards. In the independent market research, when presented with an expected product profile for D-PLEX100, almost all surgeons who participated in the study indicated that they see room for D-PLEX100 in their SSI prevention protocol. When asked about the use of D-PLEX100 at launch, the surgeons indicated that they would likely first use the product on patients with a high risk of infection; for example, patients that are smokers, have a high BMI, or uncontrolled diabetes, before expanding to the broader patient population. The surgeons indicated that approximately 40% of their patients are considered high-risk patients. Much of this market research was further supported by two real-world experts, Dr. Kyle Cologne of USC Medical Center, and Dr. Elliot Goodman of Mount Sinai Health System, who participated in our recent webinar on the cost of managing SSI last June. Dr. Cologne provided a surgeon's view in a general hospital perspective on the cost of managing SSI, and Dr. Goodman discussed the impact SSI had on quality measures and performance from an IDM perspective. Dr. Cologne noted that all hospitals are looking at infection rate data and comparing their performance to peers. From a financial perspective, avoiding complications, including infections, means that the hospital can keep more of their reimbursement money received from payers. Dr. Cologne believes that the use of D-PLEX100 will be appropriate for approximately half of surgical patients. Dr. Goodman noted that Mount Sinai's infection control team tracks infections in real-time. An infection triggers a detailed investigation because it has to be reported to the State Department of Health. The inspection team wants to know if every aspect of the SSI prevention bundle was followed. Every three months, Dr. Goodman's institution reviews internal data related to compliance with prevention bundles. This includes drilling down to individual doctors' practices and understanding why certain surgeons may not be following these bundles. Moreover, infections and readmissions are part of the annual faculty evaluation. As Dr. Goodman put it, surgeons are called to the principal's office if their infection rate is over the department's baseline. Importantly, infections are increasingly being reported and rates are rising due to the strict monitoring process currently in place. Collectively, we believe these trends and insights indicate strong commercial potential in the U.S. for D-PLEX100. And with that, I will hand the call back over to Dikla.

Thank you, Ori. As we prepare for the targeted NDA submission and potential commercialization of D-PLEX100, we also continue to make progress with OncoPLEX, our lead intratumoral product candidate in oncology, applied as a paste on a tumor resection area during surgery. Most recently, animal studies demonstrating that locally administered OncoPLEX potentially decreases the likelihood of tumor reoccurrence with reduced side effects compared to systemically administered chemotherapy agents were published in an abstract in the ASCO 2022 meeting abstract book. Switching gears, I would like to discuss changes to our Board and management team. I'm pleased to announce today that I have joined PolyPid's Board of Directors. Additionally, Jonny Missulawin has been promoted to Senior Vice President of Finance. He has been with PolyPid for eight years in roles of increasing responsibility in the finance group, most recently as Director of Finance. Prior to joining PolyPid, he was Senior Editor at Ernst & Young. Jonny earned an MBA from Tel-Aviv University in Financial Management, a BA in Accounting and Economics from Bar-Ilan University, and is a Certified Public Accountant in Israel. With that, I will now review our financials. From the perspective of our balance sheet, you will recall that in the first quarter, we obtained a nondilutive secured term loan facility of up to $15 million that broadens our financing options and provides us with access on a nondilutive basis to significant additional capital, which bolsters our ability to invest in our commercial capabilities for D-PLEX100 as well as fund further advancement of our unique PLEX technology platform. As a reminder, the loan facility is comprised of three tranches in the amount of $10 million, $2.5 million, and $2.5 million respectively. The first tranche of $10 million was drawn in April 2022, the second tranche of $2.5 million was available once we obtained results from the interim analysis of SHIELD I, and the third and final tranche of $2.5 million will be available subject to obtaining positive top-line results from the SHIELD I trial or if other conditions are met. As of June 30, 2022, the company had cash, cash equivalents, and short-term deposits of $23.8 million, excluding the second tranche of $2.5 million from the loan, which was drawn in July 2022. Also as it relates to our balance sheet during the second quarter of 2022, we sold approximately $300,000 worth of ordinary shares from our existing at-the-market facility. This action, combined with the upfront payment from ADVANZ PHARMA and the loan agreement with Kreos Capital, extends our cash runway throughout the end of the second quarter of 2023. Investors should note that this cash runway excludes additional potential development-related milestones from ADVANZ PHARMA as we announced last week, including a potential payment of up to $12.5 million contingent upon positive top-line results of the SHIELD I Phase 3 study and additional development-related milestones of up to $8.4 million. Now let's turn to our income statement. Research and development expenses for the three months ended June 30, 2022, were $8.4 million compared to $7.4 million in the same period in 2021. The increase in R&D expenses resulted primarily from the increased cost incurred in the SHIELD I Phase 3 clinical trials. Marketing and business development expenses for the second quarter of 2022 were $923,000, up modestly compared to $739,000 for the same period of 2021. General and administrative expenses for the second quarter of 2022 were $2.2 million compared to $2.4 million recorded in the prior year period. For the second quarter of 2022, the company had a loss of $11.1 million compared to a loss of $10.5 million in the prior year period. This was primarily driven by a strong rate of patient recruitment in the SHIELD I Phase 3 clinical trial. We will now open the call to your questions. Operator?

Your first question comes from the line of Gary Nachman from BMO Capital Markets.

Okay. Great. Congrats on all the progress. So, the license agreement with ADVANZ in Europe, just talk more about their capabilities in the hospital space in Europe. What countries will they focus on initially, and what are the market opportunities in those countries? And when are you expecting to file in Europe? Will it be at the same exact time as the U.S.? What are the criteria there?

ADVANZ PHARMA, in general, is a Nordic Fund-backed company. They were bought about a year ago by Nordic Fund for $850 million, and they are focused on the hospital space, on specialty products. They also have two anti-infective specialty products. This is their sweet spot, and this is where they are strategically targeting. They have built a robust sales force and medical access force in Europe, specifically in the big five countries and in Western Europe versus Eastern Europe, but very much from our perspective and from what we've learned and worked together in the last few months of discussions and negotiation, they're focused on the right patients and the right physicians for a product like D-PLEX.

Okay. And then, the filing, the timing of that?

The process in Europe is a bit different in terms of timing. The filing is expected to be more or less the same time, maybe slightly after. But generally, we're looking at the same time of filing. The review time is distributed differently, but both approval and filing should be more or less at the same time. We're talking about not more than a quarter difference in terms of the filing and probably then the review.

Okay. And then, for the rolling submission in the U.S., if it's initiated in early next year, just when will it be completed? Are there any gating factors on the CMC side? Is that all buttoned up? And is there going to be any additional clinical data outside of SHIELD I that you're going to supplement in that package?

I'll start with the later part. Yes, we will be submitting SHIELD I and also our Phase 2 trial, which is part of our clinical development agreement with the FDA. The supporting data will be the Phase 2 that they've already seen and the Phase 3. The rolling submission is expected to start early in the year, and our assumption is that not more than six months from the first model, we should be submitting the last model. Everything is in process; all those models are getting ready to be submitted. There are some CMC aspects required in terms of having six-month stability. I'm sure everyone on the call remembers that last year, we increased our manufacturing capacity and more than doubled it. In the last few months, we validated the facility and got to the stage where we can start preparing for GMP manufacturing and have stability processes in place. This is again on track, but you're right that this will probably be the last model to be submitted.

Okay. That's helpful. And then, the last question, probably for Ori. Just when you think about potentially launching in the U.S. and how you're preparing for that, it sounds like there are partnership discussions ongoing. Do you think it is more or less likely that you'll have some sort of commercial presence in the U.S.? And how big of a commercial presence would you be willing to have? What are some of the different scenarios that you're thinking of in terms of co-promote or just completely licensing out the opportunity in the U.S.?

I think we believe that it's important for us to keep some level of control in the U.S. for the product in the U.S. market. It's the biggest market for us, where our focus and attention are. The strategy is to find a partner for co-promotion, not just licensing. The structure of the deal will not look like the deal with ADVANZ. How this would look depends a lot on the partner, but we do see — first of all, we bring the manufacturing into this discussion since we're backward integrated and manufacture our products. We bring the knowledge of the product, some of the medical knowledge around the product and the need. We are developing a lot of the capabilities and many of the prelaunch activities necessary for launching. As time progresses, we build more and more around this. I think strategically, it is important for us to control or to have some level of control over pricing, definitely on the brand strategy, how the product is positioned, who we call on, and how we expand the label, and so on. But at the end of the day, it will be dependent on the partner. We are looking for partners that know the way around the hospital, around P&T committees, and around the surgery suite. Then depending on what the partner brings in, I think this is how the structure will end up.

Okay. Great.

And the question comes from the line of Brandon Folkes from Cantor Fitzgerald.

Congratulations on all the progress. Maybe just following on from the question on the new opportunity. Can you talk about how infection rates may differ in country by country in Europe and how this compares to the U.S.? Similarly, in terms of standard of care in the EU, how does that compare to the U.S. and maybe between countries?

Yes, sure. In general, you would see in Europe, in major surgery, a 15% to 20% infection rate, especially in surgeries such as open colorectal procedures. Generally, our understanding, looking at the historical data, the infection rate in Europe might be slightly higher than in the U.S., again, on average. When considering specific countries, you could see differences. We do not experience it prominently yet, but we will also need to see, in our Phase 3 study, what the differences are between different countries within Europe. I can tell you that what we saw, and this was observed in market research that was conducted as part of this deal, is that you see the level of infection everywhere. It's not that in the U.K., they don't have surgical site infections; it's not only in Eastern Europe. The average and the numbers of 15% to 20% that occur in major surgical procedures, this is in all of Europe. There are some slight differences between countries, as you will see in the U.S., also between hospitals, but it’s not just geographic.

Great. And maybe just one more question, if I may. Can you remind us of the expectation of the D-PLEX label initially? And then, Dikla, I did hear you talking about SHIELD I and the Phase 2. Is what was agreed to be submitted the only data? Given the exposures in SHIELD II, do you think there’s any potential at that pre-NDA meeting for the FDA to submit the exposures from SHIELD II, and could we potentially explore a broader label at approval? Or do you think this is very much pushed to the side, and we should think about it as an sNDA?

This is a very good question, and we are putting a lot of effort into preparing for that. We aim for a broad abdominal indication with both the FDA NDA and EMA MAA submissions. This is our target. We believe that with some indications that we have received and the data we have gathered, this is a reasonable target. However, we are also preparing a backup. There are some slight differences between Europe and the U.S. in terms of what was already agreed with us and what we expect to be the pathway forward. But SHIELD II, as you mentioned, is much more of a backup; if needed, it could be submitted in a few months' time post-NDA approval to expand to a broad labeling. So, we aim for a broad labeling, and there is a possibility that we may receive that based on the data submitted at the NDA submission. However, we already have 200 patients in SHIELD II, and we could add a few hundred more to get this broad label for broad abdominal indications. We believe this is feasible within the short term. Additionally, there is a plan for expanding beyond just broad abdominal indications into external and other orthopedic indications but again, I think it’s a bit too early to discuss that. We'll wait until the end of this quarter for the top line, and then we can give a more reasonable plan going forward.

The question comes from the line of Elliot Wilbur from Raymond James.

This is actually Michael Parolari on for Elliot. So, to start off, I know you guys detailed a little bit of the background about your commercial partner in Europe. But are there any key different perspectives that ADVANZ is bringing to the table in terms of pricing, reimbursement, or targeting that's impacting the way you're viewing the EU opportunity and how you might view the U.S. opportunity?

Maybe, Michael, I can take this one. When you look at pricing, just to remind everyone, when we tested pricing in the U.S., we looked at a range of somewhere between $200 to $600 per vial, further testing $400 per vial as a proxy to some of the other locally administered products like EXPAREL and ZYNRELEF. We saw that at $400, what came out from research is that there’s broad acceptance. This is what we heard in the research from surgeons. Our assumption is, and I'm sure you’ll see this in your research as well, that the prices in Europe will be slightly lower; that's our going assumption. But as we work on our prelaunch activities and ADVANZ does the same, we'll be able to sharpen this number. As an initial thought, slightly lower than $400 is probably a reasonable assumption. In terms of the access point, ADVANZ is responsible for getting or doing all the commercial activities, including access and reimbursement. That said, we are working together. We will work together on generating some of the health economics piece, which is a bigger driver in European countries than in the U.S. We are collecting data as part of the trial and have a plan in place for the pharma economics piece, which will be developed and executed together with ADVANZ.

Got it. That's helpful. And then, looking towards the expected top-line readout on SHIELD I, we are obviously expecting a readout on the primary endpoint, but should we also be anticipating any updates on any of the key secondary endpoints along with that readout?

Yes. So we are expecting to have both the top line and the first secondary endpoint updated. We will be able to update on both the first key secondary endpoint. Probably within a few months' time, we'll also have the full Clinical Study Report. The primary endpoint, just as a reminder, includes both infection and mortality, and the key secondary is just infection.

Got it. And then the last one for me is, I know you provided an update on the OncoPLEX program in your prepared remarks, but just wondering if we should expect to see any further progress points before the year-end, and how you guys are thinking of evolving that program as you get closer to the commercialization of D-PLEX and being able to shift some attention there.

So we are very much focused, both in terms of resources and attention, on D-PLEX100 and this large trial. People here are concentrated on cleaning the data and meeting the timeline, as well as the day after the top line, which will trigger a robust plan required for approval and manufacturing. All of this has occurred here in the last two years. For those reasons, OncoPLEX has progressed nicely. But I must say, on a personal level, that I hope we will be able to progress it much more aggressively. This is what we hope to achieve, as having the top-line results very soon will enable us to put more effort and time into OncoPLEX. It’s hard for me to say at this stage if we will have substantial updates before the end of the year, but I’m sure we will be able to share more on the plan and the next steps before year-end.

And the question comes from the line of Balaji Prasad from Barclays.

Just two for me. I guess just on the competitive side of things, have there been any new developments with similar use cases to D-PLEX? Or any updates on potential timing of new entrants?

You want us to take the — Ori, you'll take the competition part, and I will relate to additional dialogues and discussions on commercialization.

Yes. Mikaela, on competition, first, let me make the point that what we see in the market today, even the existing players don't have that level of evidence, the size of the trial, the significant data that we expect to get from SHIELD I. When you compare what the existing prevention measures are, they don't compare to the level of evidence we have. That said, to remind, the trial is D-PLEX on top of standard care. So at least as the first go, none of the existing prevention measures are direct competitors. We're not changing a doctor's behavior or taking anything away from the tools or procedures they use to prevent SSI. Looking into pipelines, as far as we can tell, we don’t see anything in the FDA databases or in literature that is in clinical trials. There are small preclinical attempts in SSI prevention, but nothing that is really in the near-term horizon, even in the midterm horizon.

With regards to the timing of future collaboration and commercialization, we have the track record of giving the sense of the presence of those obviously being less than two months from top-line. We do not expect to announce additional partnerships this summer. However, we sense that this partnership we have already established will accelerate some of the dialogues and discussions that we are in.

Our next question comes from the line of Roy Buchanan from JMP Securities.

First one, Dikla, you mentioned the powering and the alpha level of less than 0.05. I wondered if you could tell us what the minimum threshold is needed for the primary endpoint to be statistically significant.

The actual one, you mean, below the 0.05% — yes, correct, very much. The penalty that we paid for the interim, as you can see, is minimal, 0.048%.

And then, sorry to stretch beyond the discussion you just had on OncoPLEX. Last call, I think you mentioned potentially partnering OncoPLEX as well as the platform. I know you've had partnerships with other companies looking at their molecules before. I wonder if you could look out in the future a little bit. Any thoughts on partnering the platform more broadly, maybe something like what Halozyme does, partnering with proprietary molecules?

When we look at our vision, and the vision we all hold at PolyPid, is feasible for both our own proprietary pipeline and also collaborating with novel molecules, peptides, and antibodies. This is part of our vision and the way we would like to explore or extract the most value from the platform and our approach. This will take more time. To give you investors a roadmap, I think first, we'll have the top line and some additional progress along with more preclinical data from our oncology program with OncoPLEX, which will open the door for those kinds of collaborations and licensing of the platform. Unlike what we had six or seven years ago, which was purely research, we will be much more mature in terms of the stage and the commercial aspects of those collaborations.

There are no further questions. So I'd like to hand the conference back to the speakers for closing remarks.

Thank you for joining our second quarter earnings conference call. I would like to emphasize how excited we are about the progress we have achieved to date. As we transform from a research and development company to a commercial organization, potentially earning milestone payments and royalties from D-PLEX sales by our European partner, we remain grateful to our team members and all external partners for their commitment to our mission and their support in continuing to advance towards achieving our goal of bringing D-PLEX100 to healthcare providers and patients as quickly as possible. We look forward to speaking with you again shortly on our next call.

This concludes today's conference call. You may now disconnect.