Zealand Pharma A/S (ZEAL) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to Zealand Pharma R&D Conference Call. [Operator Instructions] I must advise you that this conference is being recorded today, Friday, 5th of March of 2021. I would like to hand the conference to our first speaker today. Emmanuel Dulac. Please go ahead, sir.

Thank you for joining this Q&A session of our R&D Day. I hope you found the presentations insightful and worthy of your time. I am honored to introduce this session. And before we jump to fit first in the session to answer your questions, we have 4 slides we would like to share. If you turn to Slide 2. You will see the Q&A participants. I am joined by Adam Steensberg, our Head of R&D; Danilo Verge, Head of Medical Affairs; Matt Dallas, our CFO; and Rie Schultz Hansen, our Head of Discovery and Innovation. On Slide 3, I want to remind everyone that during this presentation, we may make some forward-looking statements which are subject to change and only represent executive management point of view. Next slide, Slide 4, and my last, is about our vision. In 2020, despite the global pandemic and thanks to our employees' dedication, we kept our company, our labs and our trials running and also completed our transformation into a fully integrated biotech company with a commercial presence in the U.S. We are now set up for our potential first independent launch in 2021. And we are boldly pursuing our ambition as a fully integrated biotech company, with the goal of having 5 commercialized products on the market by 2025. So while commercializing will be a key pillar in our corporate development, investing in our R&D engine has proven to be a great choice, a great bet. And we intend to continue to develop our R&D capabilities. So I want Adam to walk you through the strategy pursued in this area.

Thank you, Emmanuel. And I also want to thank you all for joining the call and hope you have enjoyed the presentations, which hopefully have provided more clarity on not only the late data assets, but also the new early assets that we talked about. And lastly, setting the direction for the next 5 years in R&D. If you turn to Slide 5, then at this moment, I think it's important to just remember that Zealand Pharma has actually more than 20 years of experience in pioneering the engineering of novel peptide drugs. And we've really taken our innovation from endogenous peptides towards more complex structures, of which we have focused even more on those in recent years. And that really has created the opportunity for us to target completely novel innovation and also target new therapeutic opportunities, which really excites us and provide the opportunities for us to excel our innovation which is going to be a key part of the Zealand Pharma in the next 5 years as Emmanuel just said. If you go to the next slide, then as we're approaching our potential first launch of a product that has been fully developed by Zealand Pharma, we also have to realize that our pipeline has never been stronger. We have a robust set of late-stage assets, which are also approaching the final stages. And at the same time, as we have revealed here during the R&D day, that we have the new value drivers getting close to the clinic. So you should really expect to see this pipeline we develop -- having had significant development over the next years. And what we can say from our end is that we have a very strong commitment to continue to deliver as we have done in the last years. If you take Slide #7, then we have 3 key focus areas for R&D. And of course, the most important thing for Zealand Pharma R&D organization is to deliver on the late-stage assets where '21 is said to be a key year for us. Following that, we will make sure to progress the next value drivers into the clinic and really also expect to see a read-out for some of the earlier clinical assets this year, and thereby, set the direction for what the pipeline will look like in the years also ahead of us. We will also keep investing in the peptide platform. We will actually increase our investments in the peptide platform, reflecting that our opportunities in this space has actually broadened out in recent years, and we think timing is right for us to do this also to reflect that Zealand Pharma is going to be a different company in 5 years from now. If you take the next slide, and that's my last slide. Then, as Emmanuel presented here and also discussed during the prerecorded sessions, then he has set a very clear vision for Zealand Pharma and with an ambition of having 5 products on the market in 5 years from now. And as we are recognizing that, then we also have to recognize that the pipeline is -- then behind that ambition needs to reflect that, and that is that we will be a very different company. And from an R&D perspective, we are also going to be very ambitious. So we will make the investments necessary to establish a next-generation peptide platform, which will take our innovation capabilities to new levels. We will -- you should expect to see more all-peptide opportunities in the future. And then if we take into the therapeutic areas, then we will leverage our strong foothold in the metabolic and GI space, but we'll expand the focus towards -- from hypoglycemia and type 1 diabetes towards obesity and associated metabolic diseases in the metabolic area and in the TI area. We will go from focusing only on SGS towards IBD and also other chronic inflammatory diseases where we see a number of opportunities in our late preclinical pipeline that could address some significant unmet medical needs for these patients. And with that, I think it's time to actually open up for the Q&A session, and we would like to hand over to the operator for questions.

[Operator Instructions] And sir, your first question comes from the line of Michael Novod from Nordea.

It's Michael from Nordea. A few questions. First of all, to the obesity strategy. And first, with the BI-45. Can you please give us a bit more color on where we would expect to see, first of all, the Phase I data from Boehringer? And then also the overall plans for the Phase II data and whether that would likely enable Phase III going into 2022 for at least some of the indications? And then secondly, also on obesity. Maybe you could elaborate a bit on your partnering strategy, whether you have a partnering strategy for the GIP and amylin analogs? Or how we should sort of look at those 2 assets in the early-stage pipeline when they move into more medium-stage clinical trials? And then lastly, maybe a question for Matt, regarding the sort of the financials going forward. I know you haven't guided for 2021 yet. But maybe just to get an understanding of how we should forecast the spend and the burn going forward, given that you also have this bold ambition of having 5 products on the market in 2025?

Thank you, Michael. I will address -- this is Adam. I will address your 2 first questions, and then I will hand over to Matt to see if he has some comments on that one. But if we take the [indiscernible] to look on asset that we have with BI, then first of all, we are extremely excited, of course, to be able to announce that they now -- you can basically see that they are initiating 2 additional Phase II studies, one in obesity and one in NASH, really showing their strong commitment to this asset. And I think also reflecting what they saw in Phase I. When we can expect to see these data? It is our clear understanding that we should expect to see the Phase I data, which included 16 weeks exposure, actually, in the multiple ascending dose part later this year, which hopefully will set, you can say, the baseline for what you could also expect from the next studies. On the ongoing Phase II and type 2 diabetes, we do not have insights into when they expect to reveal those data. And we can also not comment at this stage on their next development steps. It is really up to BI to do that. So -- but we are really, really happy to see the progress there. I think you also asked about the partnering. Potential partnering strategy for the 2 obesity assets that Danilo revealed, also on the call, the one is our once weekly amylin, and the other one are once weekly GIP. We see these 2 as high-profile targets in obesity, and they're basically complementary to other treatments in development or on the market for obesity today. And what is unique about the approach, and this is, again, back to our design -- design capabilities and focus on how we like to make drugs at Zealand Pharma, then we have designed these molecules, so they can be co-formulated. They have the same PH spend as other some of these molecules that we all know. And therefore, of course, it opens up for partnering strategies. But you can also turn it around and say that these molecules can -- could also hold promise as a standalone molecule. But the opportunity for Zealand right now is to progress these molecules towards into Phase I and 2, Phase I. There's already proof-of-concept by a competitor that these entities are important -- potentially important assets in metabolic diseases. And then you can say, we will make decisions later if it's only going to be monotherapy or if we are going to partner up with other companies for potential co-formulations of our molecules with other assets in development or on the market. So you can say it's probably a dual strategy. We can decide to push this forward as a monotherapy or engage in partnerships as we go for combination therapies. Matt, would you like to answer the last question?

Sure. So going forward, what I'd like to refer to you, Michael, is on March 11, we'll announce our 2020 full year earnings. With that, we'll include guidance for 2021 operating expenses, which will include the cost for these programs we've kind of outlined here, going forward, as it impacts 2021. Also, a lot of the -- where this company is building, we're building infrastructure that can support multiple programs, so as we're building our commercial infrastructure. It's being built not just for, hopefully, our upcoming launches and the V-Go support, but it's also as we look to have that commercial infrastructure that we can utilize for launches #2, 3, 4 and 5. So we have a lot of synergies built in with our planning.

Sir, your next question comes from the line of Thomas Bowers from Danske Bank.

Yes. A couple of questions from me here. So just on glepa. And then I will also ask a few questions on CHI. So just turning to glepa. So the time lines now is 2022. So can you maybe give a little bit of color on recruitment status? And then have you done all -- consider any trial amendments to sort of speed up the process? And then secondly, that -- the trial that started a few years ago now and your move for the East free extension. So can you maybe just comment on the first patients you recruited in EASE-1? Are these or majority still on, you can say, longer-term glepa treatment? And then regarding the EASE-4 trial, I understand it is to completely replicate the Phase II data. But can you maybe just explain what the goal is here compared to what you have done in the pivotal EASE-1? Is this sort of label amendment maybe, or how should I understand this trial? And then, lastly, just on -- well, I note that the patients in the EASE-3 trial is only going to be once weekly, so I'm just wondering whether this is a confirmation that you sort of now have a once-weekly profile compared to the twice weekly you also have in the EASE-1? I think I'll stop there and then ask a few CHI questions afterwards.

Thank you, Thomas. I will address this. This is Adam. You're correct that we are providing guidance now for our results in '22 for EASE SBS 1, which is the pivotal Phase III study that we expect to file on. And you can say we actually removed the guidance at our quarterly call in November because we were unsecure about how things would go to the COVID over the winter. And it was a tough time, I would say, with regard to randomizations in that point. But as I also said in the call, what we have seen here starting in late January, but especially in February and into March, is actually that we are back to pre-COVID recruitment speed, which we are really, really happy to see. Right now, we guide for '20, but we are not more specific on '20 because we need to just see the next one in '22 because we need to see the recruitment in the next few months before we will be more specific during '22. On EASE SBS 3, this is a study that we start because EASE SBS 2 -- there's, of course, multiple reasons, but EASE SBS 2, which patients in EASE SBS 1 rolled into, that's a 2-year study. So we could decide to extend that study or start a new study. EASE SBS 3 will be more simple to participate in. There will be less, you can say, procedures for the patients and so also for the clinic. And then importantly, this is where we will actually introduce the auto-injector, which is a feature that also differentiates glepa from other treatments. And we also selected a once-weekly profile. We have all the time -- all the time, they've had a lot of confidence in the once-weekly profile, and that is probably what you see here. But we have no new data to support that confidence. So this is just part of how we see the development program. For EASE SBS 4, that is a super interesting trial for us. It's a smaller trial, but it's interesting in the sense that there has not been these longer-term studies that looked into energy and fluid uptake for more than 3 to 4 weeks. And right now, here, we are actually doing a study, which is long term, 26 weeks, to extract the full potential when it comes to that PD marker. And it's not clinical, you can say -- recognized as a clinical outcome, but it's actually recognized as the main effect of the drug. So this is something that will inform more, you can say, patients on how glepa is working. And if you want to add to that, then in this study, we will actually allow both patients with intestinal failure and patients with intestinal insufficience. So in the EASE SBS 1, it's only SBS patients on parental support. But in the EASE SBS 4, we also allow SBS patients who are just borderline and do not get parental support. So of course, ultimately, it is something that could broaden out the use of the product like this.

Perfect. And then just on the CHI. So I understand that the FDA team, the CGM end point which will have, you can say, poor sensitivity, at least back when you've designed the trial. So when we get the 17103 trial readout with the CGM as the primary endpoint, I'm just wondering, will this potentially be an issue, you will need to discuss with the FDA in sort of the prefiling meeting? Or was the CGM endpoint agreed upon prior to the 103 trial starts? And then secondly, I'm just wondering, the sensitivity of the CGM, did this approve -- sorry, improve after you actually had the FDA recommendation to go for the SMPG? So well, any chance it will be accepted as a supportive endpoint for the 109 trial in the filing process as well?

So maybe just one clarifying question. When you talked about the primary endpoint in 03, did you mean 06? The study we did report or the one that we still have ongoing?

Yes, the ongoing -- well, sorry.

Okay -- yes, I can address that question, and then maybe Danilo is here. He can talk a little about the glucose sensor and how we see SMPG versus CGMs. But if we take of the 03 study. We actually don't use CGM as the primary endpoint. We -- that's a study in neonates from 7 days to 12 months of age. And they are all in the hospital and they're hooked up to IV glucose infusions because they have so severe hypoglycemia that they need to have infusions of glucose to stay out of hypoglycemia. And the primary endpoint in that study is the ability to reduce the glucose infusions. So it's actually not a CGM measure. So a very different endpoint, which, of course, we appreciate after we saw the 06 data, which demonstrated the issues with SMPGs. So but -- so it's a different endpoint for [ 06 ], and we don't see the same issue. Danilo, maybe you can discuss it, on the SMPG question?

Yes. Very quickly, Thomas. So CGM technology has actually progressed quite substantially in the last couple of years. So much so that the -- all of the automated insulin delivery systems with Medtronic and Tandem and Omnipod, et cetera, are highly reliable on the ability of CGMs to be find the information so that the system can adjust automatically. So that's one piece. The second piece in terms of the CGM potential acceptance by the FDA, our strategy based on the results of 103, as Adam just talked about, is to go for the totality of evidence. This is an auto rare disease, it's an orphan disease for which there is no real treatment. And so what we intend to do is to make sure that we have all the evidence available, of which CGM will be part of when we go to the FDA to ask for registration of this study. Okay.

So we've got another question comes from the line of Graig Suvannavejh from Goldman Sachs.

I'm just going to focus my questions on the BHAP program. I've got several questions around it. My first is just in terms of the competitive landscape, could you just remind us who also might be working on a similar artificial pancreas-like concept? I'm just trying to get a sense of the competitive landscape here. And then my second question just has to do with the clinical trial design. And I'm wondering if you can provide any initial thoughts on how long do you think it might take to enroll these patients? I think the primary endpoint is at 26 weeks. And based on that, is it more realistic to think about data in perhaps middle of next year or second half of next year or maybe even 2023? I just don't know how long it takes to enroll these types of studies. Another question just has to do with, as you look at the clinical trial design, where are the areas of risks that you see in terms of how the trial has been designed? And is it more about towering? Is it more about just the conduct of the clinical trial and quality control and measurements? And then maybe the last question I'll ask is just in terms of -- if I were to try to then think about the potential revenue opportunity, any initial thoughts on how many -- as you look, cartridges are typically going to be used? What does that kind of recurring revenue stream look like? Just any sense of how we should be thinking about it. I don't think many of us have it in our model, or at least I don't. I'm just trying to get a sense of how to think about that.

Yes. Thank you, Graig, for your questions. I'll take the first one on the landscape, and then Adam will actually carry on, on the design to be designed. On the competitive landscape for the development front, the best benchmark today that exists is actually the insulin pump market, which is in the U.S., around 60% -- 50%, 60% of the patients. And some of them have different states. I mean, here, we're talking about a smart closed-loop pump. Not all the pumps today in the market are this type of pumps. But that's actually the next best thing, I would say, in this market. I mean, of course, to power such a dual-hormone pump, you need a liquid stable glucagon. And to our knowledge, to date, I mean, there is only one per generation glucagon analog, which is the dasiglucagon. There is actually a liquid stable glucagon solution that exists, which to date hasn't been advanced into the dual-hormone project. And I think the company that has this liquid stable glucagon, second-generation can -- didn't talk about it at all. So I don't know what their plans are right now, but we don't see -- we don't see any other players in the field right now in the clinical side. And then for the clinical design?

Yes. Thank you, Emmanuel. And yes, so on the clinical design, I think, a good benchmark, and I think you started out asking about what we should expect with regard to enrollment. And as we have also discussed before and shared, then we are working together with Beta Bionics, who are developing this dual bi-hormonal artificial pancreas, the iLet, which is really a unique system in that it takes the -- I mean, all the things that a patient has to do and put that burden on the pump. And they -- so it's running in an automated manner. But that system can actually run in an insulin-only system, and it can also be in a bi-hormonal system. And right now, they are doing the insulin-only pivotal study that will serve their registration study and a study to get the pump approved in an insulin-only mode. So they're randomizing 440 patients into that study. They manage to screen all of these patients throughout, actually, May, June last year, and then they saw some delays, as all of us there, due to the COVID situation. But right now, they are actually randomizing. And my understanding is that, that is going extremely well. So I would put that as a benchmark that they started randomization very, very late this year, and they are well into the randomization now. So that can inform you how quick randomization into such a study can be, and we have high expectations for the bi-hormonal study, which is set to enroll in both of adults and children over 300 patients into each arm. So we cannot give you more flavor if it's -- for the specific when we will have the readout. But right now, we are guiding on starting the study in the second half, and it is a 6-month endpoint, as you said. But -- so you will have to put adjustment there. But we expect fast enrollment into this study also because we actually expect these 440 patients who are in the insulin-only study. They could be candidates to our study as well. Then we talked about risk into the program. And maybe I can discuss with you the risk, and then Danilo can discuss a little bit on the importance and the clinical relevance of the primary endpoint. Because I think that's a key thing. When we built this for the first time after having agreed with the FDA on the -- during the end of Phase II meeting that our primary endpoint is going to be HbA1c superiority versus the insulin-only mode, that's a very important notion because this is where the iLet has continuously demonstrated, in smaller studies, the ability to provide better glycemic control when running in a bi-hormonal setting than in an insulin-only setting, and by far, meeting standard of care, which we are also going to compare to in the study. Of course, we have the normal risks of doing a clinical study, but we actually consider some of those less here because it's a fully automated system, so there's less buyers from patients and compliance, and those issues, you'd normally have to deal with. So -- and really reducing the primary endpoint to HbA1c, which is -- which Danilo can talk more about. That takes a lot of risk out of this program, instead of if you also have to include SMPGs in a primary -- co-primary endpoint or so on, as we learned in the CHI study. So we actually are extremely happy with the agreement we have reached with the FDA so far on the trial design and really support our efforts to get this important product forward to patients. But Danilo, maybe you want to talk a little bit about HbA1c and then [ comment on that in detail ].

Sure. And I can also come back a little to expand on what Emmanuel saying in terms of the market because there's no doubt that A1C remains the end all, be all in terms of treatment of type 1 diabetes patients, given complications. The beauty of the bionic pancreas, the bi-hormonal system is the fact that you can allow the system to continue to provide insulin because you will not have -- with the availability of glucagon, you do not have the potential or you basically decrease markedly the potential for hypoglycemia. And no matter how good the algorithms are, no matter how sensitive the pumps are in terms of being able to deliver minute amount of insulin, which you see with some of the automatic insulin delivery systems that are in the market, closed loop, hybrid systems that are in the market and that are actually in development, you will always be limited by the fact that if the system senses that the patient or the person with diabetes is going to hypoglycemia, insulin stops being delivered. That is not the case with the bi-hormonal pump. Because if glucose starts to go down, and then glucagon kicks in, and insulin does not stop being delivered. So -- and that's why we saw -- we believe, of course, that we need to confirm a Phase III. That's why we saw in the Phase II that you actually get 90% of the patients using the bi-hormonal pump down -- to 9% down to an equivalent A1c of 7, so CGM of less than 154. And you only saw 50% of the patients with the insulin-only model. So we are -- we're pretty excited about the fact that not only that, but also the fact, as Adam said, that the algorithm of Beta Bionics allowed for just putting the weight for the patient into the system, and then machine learning within the algorithm takes care of adjusting the amount of glucagon and insulin delivery.

And then maybe just the last question you had on the number of cartridges. That, of course, depends on the amount of glucagon that each patient will use. But on average, we expect a patient to use 1 cartridge per week. So it's a 4-milligram solution we have in the 1 milliliter cartridge. So that would be the average expected amount. On pricing, we cannot communicate on that yet. We need to see the Phase III results to be able to get all the information into the value of the drug.

Maybe Emmanuel, maybe just a follow-up. What is current insulin cartridge pricing? And I realize that may not be a good comp, but at least it's something, if you know it. And then maybe I might have missed it in the answers before, but in terms of when we could expect to see that primary endpoint data, 26 weeks?

Yes. Maybe on the last one, on the primary endpoint data, it will, as you say, it will at least take 3 months to recruit the patients, and then it's a 6-month endpoint, but it could also take longer. So that's why we are not guiding on when we will have the results yet. We need to see Beta Bionics completing the insulin-only study, which, as I explained, they are well into the randomization of that study, and that's a 3-month study. So we would expect the data later this year from that study. And once we have that, then we also have, you can say, the operational benchmark, which will allow us to communicate when we expect results from the bi-hormonal. But what we are seeing right now and how they're doing on the insulin-only, we are very impressed. On the insulin cartridge, I think it's a very difficult comparison. I guess the list prices are between $7 and $10 per day, but then you also know there's huge rebating there due to competition and so on. So it could be a little difficult to compare that.

Another question comes from the line of Jesper Ilsoe from Carnegie.

I had a question on your platform. You mentioned for the first time, at least for me, that you will potentially expand into all formulations. So what technologies do you have in-house that could make your peptides formulated in tablets? Or should we understand it as you plan to partner up with some, say, biotech firms that have this technology in-house? The reason for asking is, of course, peptides have been shown difficulties in doing this. And I know Novo has had some success, but it's really not easy. So what do you have in-house that could enable this? And can you -- if you have it, can you use that on your current products? Or will it only be on future pipeline products?

Yes. So I will let Rie answer this question. But maybe just -- of course, we have alpha4-beta-7 that we already discussed, and which is designed as an oral peptide and which we anticipate to take into the clinic. So -- but Rie, will you comment on our strategy for the oral platform activities?

I can. I think it's a good thing to bring that alpha-4-beta-7 into the mix here because it is a peptide that has been designed with oral bioavailability in mind. And that's actually our strategy, is to focus on the actual engineering and design of the peptide and then render it already in the, you can say, on the molecule more orally available. So we do not plan to make like semaglutide linearly, analogs of hormone peptides orally available. Actually, the new generation -- the next-generation of peptides that we envision will be -- obviously, we'll also have to use Novo's formulation technologies. It's a really dynamic field. As you mentioned, semaglutide has been -- I mean, that has really been demonstrated, that has been notoriously difficult to make a peptide orally available. But now it's possible with them now. We believe that if we also, in the initial design of the peptide, make it orally available, then in a combination with these Novo technologies, we actually will be able to reach a meaningful bioavailability.

Any other question?

So do you have that technology in-house to make them oral, just so I understand it? Or do you need, for example, if you want to make a new obesity product or if you want to make the amylin analog much more differentiated, can you actually do some stuff to the molecule and use some technology in-house? Or do you need to partner that up?

The answer is for all the projects that, we always look at what we can do in-house and always combine with what is externally available, which kind of technologies, that really depends from project to project on how we would approach this. But I'll just say -- I mean, just to repeat again, we're not looking to taking the analogs of our peptide hormones that we already have in the clinic. That's not the strategy right now to look at that to make that orally available. But it's really the next-generation peptide that we're focusing on, which is oral bioavailability.

I think, yes, maybe also to add on this, there has been a lot of progress on the understanding, the formulation technology that could be used for all therapies. And as Rie said, sema is a good example of something that was almost impossible to overcome, but yet, it was -- it became possible. What we are doing is we're going to use our extensive peptide design capabilities and focus on these new modalities, which are -- where we build in the ability to be orally available in the molecule itself, and then we're going to complement it with combination technologies. And those can be either in-house, which we already are working with some or through partnerships. And so it's going to be a combination, but we're really going to leverage, you can say, how much innovation that's been in this space over the last 10 years. And that's why we think this is a unique moment for Zealand to combine these technologies and actually do what we have shown over and over again that we are best at. And that is to not only do the discovery, but also the development phase of medicines that have the profiles that we need.

Okay. Very clear. Just one last question. So just on the Alexion partnership. For me at least, it's been a while since we've heard something there because it's still, of course, preclinical. Has that changed with the Astra acquisition of Alexion? Or do you still have as much, say, collaboration with Alexion? And when will we actually see some clinical updates there? So when will you move into Phase I? When -- how -- when could we actually see some data and some updates there?

Yes. We would also like to be able to communicate more on this. I mean, what we can share is that we are very excited, and we see very good progress together with Alexion and, of course, soon to become Astra. We have not seen any signs that this should not be a high-priority project in the new consolidation. And so -- and we, of course, hope and expect to be able to communicate more throughout the year on this collaboration and the progress we are making. But I think we also have to recognize that they are in the middle of finding their ways of operating. And that's, unfortunately, how it is right now with regard to what we can communicate. So we are excited. We see strong progress, and we hope to be able to communicate more this year on where we are and next steps.

Our next question comes from the line of Lucy Codrington from Jefferies.

A few left from me. Just going back to the first question, really. I just wanted to talk more about the strategy for the co-formulation and the obesity products. I'm just wondering whether it's -- are there possible once-weekly GLP-1s that you could actually consider in lighting for co-formulation with your assets? And then, secondly, on the amylin product and similarly, ZP10000, how are those going to be differentiated from products that are already further ahead, the new in the clinic. And specifically, with ZP10000, obviously, we had some morphic holdings, or small molecule data this week. So just interested to see how you think you might be differentiated there. And then just finally, on the artificial pancreas Phase III, just to confirm that you won't need the 52-week data for filing, you'll be able to do that on the 26-week data?

Yes. Thank you for your questions, and there are actually one with to their [ BCT ] strategy. And I think Danilo, he will provide some answers to that. And then as a follow up, [indiscernible] and then I'll just hand over to you Rie to you as well. But maybe on the [PF ], the 52 versus the 26, the primary endpoint is at 26 weeks on HbA1c. Then because it's also, you can say, an approval of dasiglucagon for chronic use, then FDA requires that we submit 1-year data as well. But that does not mean that we, of course, have to have all those data before we can start the process, meaning from your half results until you submit, there's always a certain period, you need to have your end of phase III meeting and so on. So we will include the 1-year data in the submission, but we do not anticipate that it will delay things to any significant degree. So for us, it's really the 26th week that starts the clock for when we can submit. On alpha-4-beta-7 and how it differentiates compared to competitors, you are right that there's been some quite encouraging data from some competing programs. And we see that as highly encouraging also for our program. And Rie, maybe you want to talk a little bit about why we're excited about our approach for alpha-4-beta-7.

And it's just -- I think it's just really important to remember that it's, I mean, vedolizumab, this is a bit on the motivation, has a very high receptor occupancy that bind really the type 2 [indiscernible] of the alpha-4-beta-7. We see the same with our smaller compound, the ZP10000. I actually also think one of the competitors has a similar efficacy, but it is a small molecule. And I think it's really key for these binding molecules that they have to be selective. So I think it's also something that we are exploring more the selectivity of our compounds. And an important part is also that it's a little bit more on the specific. It is on how the activation and inactivation of the integrin. And actually, we have a different mode of action here, also our ZP10000, but definitely something that we are exploring in this preclinical phase as well. While, as Adam said, we are really encouraged by the competitors taking forward as well because it does demonstrate that it is possible to get a really high efficacy also in the clinical setting.

Yes. And I think probably what we should all expect is that there will be more a test a different immunomodulatory target that has proven successful with antibodies in the years to come because as we try to explain also in the presentation, because really from a peptide perspective, right now, opening up that we have the tools that allows us to go after target that were otherwise only accessible for antibodies as injections. And here, as we -- I mean, we are -- that's why we are so excited about this all strategy and trying to go with some of these targets. And so we should expect to see more competition. And as Rie said, we believe we have our differentiators. Danilo, do you want to address the...

So if I recall correctly, there were 2 questions. One, whether we would consider in-licensing a GLP-1 receptor agonist. And the other one was how do we differentiate our amylin and GIP assets. So when it comes to partnering up, if you will, our peptides, GIP or amylin, with potentially a GLP-1 receptor agonist, I think that we are open to all kinds of avenues. Right now, our focus is progressing amylin to Phase I this year and progressing GIP to Phase I next year. And the fact that these 2 are differentiated enough from competition, we believe, because of the fact that they can be co-formulated with pretty much any other peptide. And if you saw the presentation that I provided yesterday, it is pretty clear that dual pharmacology or triple pharmacology even is what is going to be needed to be able to achieve the levels of weight loss that bariatric surgery actually achieves. And there's no question that with a pandemic, the clinical obesity of almost 800 million people, there's going to be room for a lot of different players and a lot of different approaches. We are very confident that our approach is going to be one that, that is going to be differentiated. And that other people may want to partner with us on.

Do you have more questions, Lucy?

And your next question comes from the line of Etzer Darout from Guggenheim.

This is Paul on for Etzer. So first one, for the amylin analog 8396, can you provide a little bit more color on your planned Phase I, maybe on the size and scope of the trial and potential initiation time? And then a second question for your 2 preclinical IBD programs, it's early, but hoping you could help us understand the opportunity in IBD as you see it, where you see these therapies working in the current treatment algorithm? Is it more sort of complementary or to replace certain treatments that are already on the market?

Thank you. So this is Adam. I think I will just address first. On the amylin Phase I, you should probably expect a very classical Phase I study. We are focused, as Danilo said, on progressing this part through the early clinical phase. There's already some clinically proven concept and learnings from the programs that has been -- that are in front of us taking the same target. And of course, that's something we can leverage. So that is [indiscernible]. On the IBD assets, there are, of course, different strategies with these. If you take the alpha-4-beta-7, then it's obvious to think about vedolizumab, how that has differentiated its [ open ] . And we are trying to make a similar molecule that has the same mode of action that you could speculate have the same benefits, but then it's an oral -- it's a tablet instead of an injection. So that would provide a very clear market segment and market opportunity. For Kv1.3, it's actually a very different story. And maybe Rie will actually -- can discuss a little bit more on that. But reality, that is a broad anti-inflammatory target that -- and the reason that we are so excited about this is that it also provides the potential for some news-bearing activities. But for that asset, our lead indication right now is IBD, but you could also take it forward, as I explained yesterday, into other diseases, such as psoriasis, rheumatoid arthritis and multiple sclerosis, et cetera, because of the broad nature of the interaction with the immune system. So there, we could envision a very different strategy and, really, multipurpose as the alpha-4-beta-7 is really targeted towards IBD. But Rie, we do want to -- a little bit more in Kv1.3.

I was saying, this is -- we are progressing this into the IND-enabling drugs now also, so it's ready for the clinical setting. And obviously, it is a target that is found on the of effector memory T cells, which play a really important role in several autoimmune disease. We are open for also other indications to cover. Right now, we do have really good evidence also within ulcerative colitis. So that, of course, is a really good focus point for us, but there are many other opportunities there. I think what you said also about the immunosuppressive effect being really located to the effective memory T cells. It's so important because it actually demonstrates that it is immune sparing going forward. And then again, it's an offering for patients who are suffering from these inflammatory diseases, while you are saving the rest of the immune system and can be -- that can still be active in defending, again, pathogens. So I think that it -- it has a lot of potential, and we are definitely exploring that also as we are progressing towards the clinic.

We got another question comes from the line of Joseph Stringer from Needham & Company.

Question on hyperglycemia and then a follow-up on SBS. So just wondering if you could comment on sort of the market dynamics around the rescue hypoglycemia market. It appears that the rescue syringe kit holds the majority market share despite the relatively recent entries of competitor intranasal and also an auto-injector. So I guess my question is, how do you sort of see that -- those market dynamics playing out if and when HypoPal gets to market? And is there an opportunity to sort of switch those syringe kit stations over to, say, HypoPal's -- have that switch occur faster, number one? And then number two, would there be an opportunity -- I think you alluded to this to some extent in your presentation posted yesterday. Would there be an opportunity to grow the overall market? And then I have a follow-up in SBS.

Yes. Joseph, thank you. So regarding the hyploglycemic market, that's a market that for the last 20 years, hasn't seen any innovations and 0 promotion. So it's been a bit flat in ZP. And so what we know today, that in the U.S. alone, it's a $300 million market and there's around 500,000 patients buying, on average, 2 kits. The potential for this market in the U.S. alone is over 6 million patients. So the introduction of Novartis last year, we saw an increase -- an immediate response from the market. But that's not enough. It takes time to actually develop the market. However, the market to date, I think, is growing by around 10%. So we've seen, actually, a very nice response from the market. And there is no doubt that these novelties will slowly replace these old kits and, potentially, as well that more patients will equip themselves. Now the crystal ball will tell us how fast these development will take place. But the more players there is in this market, the more noise and awareness there is. We believe that we're advancing a compound, which is a very strong chance to meet the entire, I would say, requirements from the patients. So we are very excited by the approaching PDUFA date from the FDA, and we hope to be able to launch this product right after that. So that's the vision for this market. And then I -- yes?

Sorry. I have a quick one on SBS enrollment for glepaglutide and your kind of timing around -- guidance around timing for results in 2022. Is that -- you're talking about enrollment nearing pre-COVID levels. But I also want to get your thoughts on -- is that sort of results timing and that enrollment -- in the current enrollment rate and maybe future enrollment rate for glepaglutide, does that sort of factor in any competitor Phase III trials into that sort of guidance on timing?

Yes. It factors in our best estimate. And I would even say that we could perhaps even do with less patients that we saw in the last month to meet this. So this factors in our best estimate, considering all aspects of the SBS and global inputs. I think we have -- so that -- yes. I think I cannot say most of that, that we feel confident around this now.

We got a follow-up question comes from the line of Graig Suvannavejh from Goldman Sachs.

It's probably a couple of quick ones. One, just on the C3 collaboration. Just wanted to know if you're anticipating any potential changes with that collaboration, given the impending acquisition by AstraZeneca? And then just on the C3 program itself, there are a lot of companies that are also interrogating C3 for dry AMD. And so I'm wondering, just as you think about that collaboration, what is the scope for which you think such a once-weekly or longer-acting might -- could be applied to. So -- just some color there would be great. And then the other question I had was just on the amylin program. I think you had mentioned that there's a long-acting amylin program in Phase II. I'm just not really smart on that space. Could you just remind us which program that is and what they've shown? And what do you think you need to show with your program to be either competitive or better?

Yes, Graig, I mean, regarding our collaboration partnership with Alexion, I think what Adam was sharing is that we're not really -- because of what's going on right now, we're not really commenting too much on what the matters for Alexion. What we are very positive about is the compound. And we're very positive of what we have and our ongoing relationship with Alexion. But related to Alexion and what their plans are, I think we cannot really discuss right now because of this. And then for the amylin long-acting, I'll ask the Danilo to respond.

Sure. So what I made mention of in the presentation yesterday was the fact that there's another amylin compound in development right now in Novo, actually has amylin Phase II. And the beauty of it is that there's clinical proof-of-concept that they provided with amylin. So we know amylin works. We believe that our amylin, which, again, we're excited to actually bring into a finish this year. Our amylin is different because the pipeline can be co-formulated, and therefore, would provide an advantage if the data pans out compared to what Novo is actually developing right now. But in a way, it kind of derisks our entry into the space. But yes, we're really excited to actually see this go into human trials.

Yes. Anything else on your mind, Graig?

Sir, the line of Graig has already gone. And we got a follow-up question for the line of Thomas Bowers from Danske Bank.

Just a few quick follow-ups here. Just on the bi-hormonal. Can you just clarify, in regards to the Phase III design. Do you need to hit the primary endpoint in both the adult and pediatric trials in order to be able to file for approval? And then -- well, you can say now the Phase III design is sort of in place, so I'm just wondering if this is -- you can say, the milestone you have been looking for in order to trigger potentially other, what you call, non-exclusive deals with some of the other device makers to put more validation into this bi-hormonal concept? And then just a final one HypoPal. Of course, I assume you have concluded the late cycle meeting with the FDA now. So is there anything you want to share in regards to the label discussions? And then maybe primarily in regards to the rabid PDR that's could -- would that potentially become a claim for superiority or just something that you expect, of course, will be included in the label?

So thank you for your questions, Thomas. And I think as you can probably appreciate, it's difficult for us to comment on these negotiations with the FDA as we are approaching the PDUFA date here for March 27. What we can, of course, say and what Danilo also shared yesterday that across our Phase III studies, we have seen that we have a very, very consistent readout of 10 minutes to recovery, which we think is outstanding and not only from the speed, but also how robust that has been reported across studies. So we cannot comment more on that due to the sensitivity of where we are, but yes. On the -- your question on the bi-hormonal artificial pancreas studies, we would expect that we would -- should meet both the primary endpoint in the adult and the pediatric study in order to get approved. That would constitute 2 studies, which is normally required to have new medicines approved in a U.S. context. Having said that, of course, we should also all recognize that [indiscernible] they have a breakthrough designation from the FDA for this use because FDA understands unmet medical need and what you can say this device, including dasiglucagon, could actually bring to the market. But our current base case is that we meet the primary end point in those studies, and that would be needed. On the potential partnering, you're also correct that we have a nonexclusive collaboration with Beta Bionics. Right now, they are the ones that we are collaborating with. We are having shared meetings with FDA. We are progressing this with the same diligence and excitement. And of course, we would expect that other device companies would start to -- once they start to see the moves here, would also need to at least consider that defensive moves against something which we believe could completely transform the management of Type 1 diabetes. But we cannot comment more on that Beta Bionics. Those are the guys we are collaborating with. They want to have, in our mind, the most exciting system right now, and for sure, the most progressed in these situations. And so that's where we are.

We have reached the top of the hour, and I would like now to pass the call back to Emmanuel Dulac to close the call. Please go ahead, sir.

Thank you, operator. Thank you, everyone, for joining this Q&A. We're very, very excited by the presentations that we were able to provide and put together and bring some -- shed some light around the early pipeline, which remain a bit, I would say, in the shadow of the late-stage pipeline for the entire 2020 year. So as you can see, we're well on our way to meeting our ambitions. We were very excited as well to see the number of people that registered for this conference, and this is still growing. We wanted to remind you as well that these presentations will remain live on the website for a few more days so that we make sure that if you want to go back to it, you can actually look at them and check. And again, with that, I hope to see you soon all. I hope you're doing well as well. Stay safe. And this is basically closing this session. Thank you very much. See you soon. Bye.

That concludes our conference for today. Thank you for participating. You may now all disconnect.