Greetings, and welcome to the PolyPid Second Quarter 2022 Conference Call. [Operator Instructions] 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 3 and 6 months ended June 30, 2022. The 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 a truly 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 represent substantial value for PolyPid. Under the terms of the agreement, PolyPid is entitled to receive an upfront payment immediately upon signing of the agreement an 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 expertise in marketing hospital-based therapies, mainly after the recent acquisition of Intercept, that more than doubled their commercial and medical teams across major EU countries and the U.K. will prove invaluable in extending access to the 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 in 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…

Thank you, Dikla. As other partnership discussions progress, we continue our launch preparation 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' own clinical experience and institutional protocol and not on 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 and "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, has 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 2 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…

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 administrated OncoPLEX potentially decreases the likelihood of tumor reoccurrence with reduced side effects compared to systemically administrative 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 Board of Directors. Additionally, Jonny Missulawin has been promoted to Senior Vice President of Finance. He has been with PolyPid for 8 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. Johnny earned an MBA from Tel-Aviv University in Financial Management, 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 an up to $15 million nondilutive secured term loan facility 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 3 tranches in the amount of $10 million, 2.5 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…

[Operator Instructions] 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 the market opportunities in those countries? And when are you expecting to file in Europe? Will it be 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 2 anti-infective specialty products. And that's where -- this is their sweet spot. This is where they are strategically targeting. And they have built a very nice sales force and medical access force in Europe -- only in Europe. They quite dramatically increased their capability, doubled their sales force just in the last few weeks buying all of the out of U.S. business of Intercept. So now they are with a few hundreds of sales reps and market access personnel in Europe. Of course, more so in the big 5 countries and in the 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 [talks] and negotiation, very much focused on where we want to be and open the doors for a product like D-PLEX to the right patients and to the right physicians.

Okay. And then, the filing, the timing of that? [Technical Difficulty]

So, the process in Europe is a bit different in time. 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. And the way the review time is distribute differently. But again, 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? And are there any gating factors on the CMC side, is that all buttoned up? And is there going to be any additional data -- clinical data outside of SHIELD I that you're going to supplement in that package?

So I'll start with the later part. So, yes, we will be submitting SHIELD I and also our Phase 2 trial, which is part of our clinical development agreement with the FDA that the supporting data will be the Phase 2 that they've already seen and the Phase 3, so this will be [one]. The rolling submission is expected to start early in the year. And our assumption is that not more than 6 months from the first model, we should be submitting the last model. Everything is in process, all those models are in process and are getting ready to be submitted. There are some CMC, as you mentioned, aspects that are required in terms of having 6-month stability. I'm sure everyone on the call remember that last year, we have increased our manufacturing capacity and more than doubled the capacity. And in the last few months, we validated the facility and got to the stage where we can start, get prepared for -- again, for GMP manufacturing and have stability process in place. So 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 is it 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? And 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. -- or the product in the U.S. market. It's the biggest market for us. That's where our focus and our attention is. And so, the strategy is to find a partner for co-promote, and not licensing. So, the structure of the deal will not look like the deal with ADVANZ. How this would look like? A lot of it will depend on the partner, but we do see -- first of all, we bring the manufacturing into this discussion since we're backward integrated and manufacture on products. We bring the knowledge of the product. We bring some of the medical knowledge around the product in the need. And we are developing a lot of the capabilities and a lot of the prelaunch activities that are needed to launch. And as time progresses, we build more and more around this. I think strategically, it's important to us to control or to have some level of control on pricing, definitely on the brand strategy, how the product is positioned, who we call on, 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, around the surgery suite. And then, depending on what the partner comes 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 maybe just talk about how infection rates may differ in country by country in Europe and how this compares to the U.S.? And similarly, in terms of standard of care in the EU, how does that compare to the U.S. and maybe between countries?

Yes, sure. So, in general, you would see in Europe in major surgery, 15% to 20%, especially in -- such as open colorectal procedure, you'll see 15% to 20%. Generally, our understanding, looking at the historical data, the infection rate in Europe might be slightly higher than in the U.S., again, in an average on a very broad basis when you look at specific countries, you could see difference. We don't experience it so much yet, but we'll need also to see in our Phase 3 that there is -- what's the difference between the different countries within Europe. I can tell you that what we saw and also this was seen in market research that was done as part of this deal. You see the level of infection everywhere. It's not that you will say, well, in the U.K., they don't have surgical site infection, it is only in Eastern Europe. So, this average and the numbers of the 15% to 20% that occur in major surgical procedures, this is in all Europe. Obviously there are some slight differences between countries. And as you will see in the U.S., also between hospital to hospital, it's not just geographic at all.

Great. And maybe just one more question, if I may. Can you just remind us of the expectation of the D-PLEX label initially? And then, Dikla, I did hear you talking SHIELD I in the Phase 2 is what's agreed to be submitted. But given the exposures in SHIELD II, do you think there's any potential at that pre-NDA meeting for the FDA to, say, submit the exposures you have in SHIELD II and we could potentially explore a broader label at approval? Or do you -- is that very much put 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 are aiming for a broad abdominal indication both with the FDA, NDA, MMA -- and this is -- sorry, MIA. And this is what we are aiming to. We believe that [Technical Difficulty] with some indications that we have received and the data that we have gathered, this is a reasonable target, but we are also preparing a backup. And there are some slight differences between Europe and the U.S. on that in terms of what was already agreed with us and what we expect will be the path forward. But SHIELD II, as you mentioned, this is very much a backup that if needed could be submitted in a few months' time post-NDA approval to extend to a broad level. So, we are aiming for a broad level. There is a possibility that we will get that based on what the data that will be submitted at the NDA submission, but we already have 200 patients in the SHIELD II, and we could add additional few hundred, 1 or 2, to get this broad labeling of broad abdominal indication. This is very much something that we see feasible within the short-term. And later on, there is a plan also for expanding beyond just broad abdominal on external and other orthopedic indications. But again, I think it's a bit too early to discuss it. 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 is there any key different perspectives that ADVANZ is bringing to the table in terms of pricing reimbursement or targeting that's impacting the way that you're reviewing the EU opportunity and how you might view the U.S. opportunity?

Maybe -- Michael, maybe I can take this one. So, when you look at pricing, just to remind everyone, when we tested pricing in the U.S., we looked at the range of somewhere between $200 to $600 per vial with -- and further tested $400 per vial as -- with proxy to some of the other local administered products like EXPAREL and ZYNRELEF. And we saw that at $400, what came out from research is kind of broad -- no restriction news. This is what we heard in the research from surgeons. Our assumption is -- and I'm assuming -- 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 kind of sharpen this number more. But I think, as an assumption for now, slightly lower than $400 is probably a good assumption. In terms of the access point, so first, just from a, let's call it, deal structure, ADVANZ is responsible for getting -- or doing all the commercial activities, including the access and reimbursement. That said, we are working together. We will work together on generating some of the health economics piece, which, as we know, is a bigger driver in European countries than in the U.S. And we're collecting the data as part of the trial. There's 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, 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 redo]?

Yes. So we are expecting to have both the top line and the first secondary endpoint. So we will be able to update on both the first key secondary end point. And probably within a few months' time, we'll also have the full CSR. The primary end point, just as a reminder, it's both infection and mortality and the key secondary is just infection.

Got it. And then last one for me is, I know you guys 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 commercialization of D-PLEX and being able to shift some attention there.

So we were very much, both in terms of resources and attention, very much focused as a company and as a relatively small company on, of course, D-PLEX100 and this large trial. And also now, people here are really very much concentrated on cleaning the data and meeting the time line, as well as the day after the top line, which will just trigger a very robust plan that was required for approval and manufacturing. And all of this is happening here in the last 2 years. And obviously, for those reasons, OncoPLEX has progressed very nicely. But I must say on a personal level that I hope we will be able to progress it much more aggressively. And this is what we are hoping to be able to that having the top line results, again, very soon as you said, will enable us to have more effort and more time on OncoPLEX. It's hard for me to say at this stage if we will have substantial update before the end of the year. But I'm sure that we will be able to share more on the plan and the next steps before the end of the year.

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

This is actually [Mikaela] on for Balaji. Just 2 for me. I guess just on the competitive side of things, has there been any new developments with similar use case to D-PLEX -- or I guess, any updates on potential timing of new entrants? And then, just circling back to the ongoing partnership conversations, I guess just when can we expect an update on this?

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], so on competition, first, maybe 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. So really when you compare what the type of tools of the prevention measures that exist today, really they don't compare to what we have from a level of evidence. That said, just to remind, the trial is D-PLEX on top of standard of care. So, at least as the first go, none of the prevention measures that exist today are direct competitors. We're not changing a doctor's behavior or taking anything away from the tools or the procedures in their bundles that are used for preventing SSI. Looking into pipelines, as far as we can tell, we don't see anything in the FDA databases or in literature everything that's 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.

And with regards to the aspect of timing on future collaboration, commercialization, I think that we have the track record on giving the sense of the actual presence of them, those obviously being less than 2 months from top line. Obviously we do not expect to be able to announce additional partnerships this summer. But what I can say, and again this doesn't imply on the actual timing, we do think that -- and we sense it already that this partnership that is already established will accelerate some of the dialogues and the discussions that we are in. I think that's the only thing I can say at this stage on timing.

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

First one, Dikla, you mentioned the powering and the alpha less than 0.05. So I was just wondering 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 0.5% -- [0.478% -- 0.048], yes, so very much. The penalty that we had to pay for the interim, as you can see, is very minimal, 0.048%, below 0.048%.

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

So, I think that's really when we look at our vision and the vision that we're all here in PolyPid believe is feasible and possible for the FLEX platform and their approach. This is where we are aiming to have not just our own proprietary pipeline, but also collaborating with novel molecules, peptides, antibodies could be also additional things. And this is really part of our vision and the way we would like to explore or to extract the most value from the platform and from the approach. I think that this is something that will take additional time. If I need to kind of give you investors the road map to that, I think first, we'll have the top line, we'll have some additional progress and some additional preclinical data from our oncology program, from the OncoPLEX, and this will open the door for those kind of collaboration and licensing of the platform. But as opposed to what we had probably 6, 7 years ago, which was purely research, they 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 as well as potentially earning milestone payments and royalties from D-PLEX sales by our European partner, we remain grateful to our team members and all of our external partners for their commitment to our mission and their support in continuing to advance towards achieving our goal of bringing D-PLEX100 to health care 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.