Ladies and gentlemen, thank you for standing by and welcome to Zealand Pharma R&D conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask questions during this session, you need to press star one on your telephone. I must advise you that this conference is being recorded today, Friday, 5th of March, 2021. I would like to hand the conference over 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. Before we jump two feet first in the session to answer your questions, we have four slides we would like to share. If you turn to slide two, 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, Henriette Wennicke, our head of discovery and innovation. On slide three, 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 four, 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 five commercialized products on the market by 2025. So why 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. 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-stage assets but also the new early assets that we talked about. And lastly, setting the direction for the next five years in R&D. If you turn to slide five, 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. We have really taken our innovation from endogenous peptides towards more complex structures, of which we have focused even more on those in recent years.
That really has created the opportunity for us to target completely novel innovation and also target new therapeutic opportunities, which really excites us and provides the opportunity for us to excel our innovation, which is going to be a key part of Zealand Pharma in the next five years, as Emmanuel just said. If you go to the next slide, then as we are 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. At the same time as we have revealed here during the R&D days, then we have the new value drivers getting close to the clinic.
So you should really expect to see this pipeline be developed, have 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 number seven, then we have three 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 2021 is set 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 readouts 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 have 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 five 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 pre-recorded sessions, then he has set a very clear vision for Zealand Pharma and with an ambition of having five products on the market in five years from now. And as we are recognizing that, then we also have to recognize that the pipeline that is behind that ambition needs to reflect that. And that is that we will be a very different company.
From an R&D perspective, we are also going to be very ambitious. We will make the investments necessary to establish a next-generation peptide platform, which will take our innovation capabilities to new levels. You should expect to see more oral peptide opportunities in the future. If we take into the therapeutic areas, we will leverage our strong foothold in the metabolic and GI space, but we will expand the focus from hypoglycemia and Type 1 diabetes towards obesity and associated metabolic diseases in
the metabolic area. In the GI area, we will go from focusing only on SBS 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. With that, I think it's time to actually open up for the Q&A session. We would like to hand over to the operator for questions.
Thank you, sir. And once again, if you would like to ask a question, just press star one on your telephone and wait for your name to be announced. And if you want to cancel your request, just press the hash key. Once again, please press star one for a question. And sir, your first question comes from the line of Michael Novik from Nordea. Please go ahead. Your line is open.
Thank you very much. It's Michael from Nordea. A few questions. First of all, to the obesity strategy. And first, with the BI 456906, can you please give us a bit more color on where we would expect to see, first of all, the phase one data from Boehringer and then also the overall plans for the phase two data and whether that would likely enable phase three 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 two assets in the early-stage pipeline when they move into more medium-stage clinical trials. And then lastly, maybe a question for Matt regarding 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 five products on the market in 2025. Thanks a lot.
Thank you, Michael. This is Adam. I will address your two 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 one glucagon 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 two additional phase two 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 one.
When we can expect to see these data, it is our clear understanding that we should expect to see the phase 1 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 2 and type 2 diabetes, we do not have insights into when they expect to reveal those data. We can also not comment at this stage on their next development steps. It is really up to BI to do that. We are really, really happy to see the progress there. I think you also asked about the potential partnering strategy for the two obesity assets that Danilo revealed also on the call. One is our once-weekly amylin and the other one, our once-weekly GIP.
We see these two as high-profile targets in obesity, and they are 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 peptide design capabilities and focus on how we like to make drugs here at Zealand Pharma, then we have designed these molecules so they can be co-formulated. They have the same pH span as 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 could also hold a promise as a standard-owned molecule. But the opportunity for Zealand right now is to progress these molecules towards into phase one and through phase one. There's already proof of concept by competitors that these entities are 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 11th, we'll announce our 2024 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 they impact 2021. Also, a lot of the way 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 HypoPal support, but it's also as we look to have that commercial infrastructure that we can utilize for launches number two, three, four, and five, so we have a lot of synergies built in with our planning.
Okay. Okay. Thanks a lot.
Thank you, Michael.
So your next question comes from the line of Thomas Bowers from Danske Bank. Please go ahead. Your line is open.
Yes. Thank you very much. A couple of questions from me here. So just on glepaglutide, and then I will also ask you a few questions on CHI. So just turning to glepaglutide, so the timeline now is 2022. So can you maybe give a little bit of color on recruitment status? And have you done or considered any trial amendments to sort of speed up the process? And then secondly to that, the trials have started a few years ago now, and you opened up for the EASE III extension. So can you maybe just comment on the first patients you recruited in EASE I? Are these or majority still on, you can say, longer-term glepaglutide treatment? And then regarding the EASE IV trial, I understand it is to completely replicate the phase two data.
But can you maybe just explain what the goal is here compared to what you have done in the pivotal EASE I? Is this sort of label amendment maybe, or how should I understand this trial? And then lastly, just on, well, I know that the patients in the EASE III 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 I. I think I'll stop there and then ask a few CHI questions afterwards. Thank you.
Thank you so much. I will address this with Adam. You're correct that we are providing guidance now for our results in 2022 for EASE- SBS 1, which is the pivotal phase three study that we expect to file on. You can say we actually removed the guidance at our quarterly call in November because we were uncertain about how things would go due to COVID over the winter. It was a tough time, I would say, with regard to randomizations at that point. As I also said in the call, what we have seen here starting 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 2020, but we are not more specific on 2020 because we need to just see the next win in 2022 because we need to see the recruitment in the next few months before we will be more specific on 2022. On EASE-SBS III, this is a study that we start because EASE-SBS II, there's, of course, multiple reasons, but EASE-SBS II, which patients in EASE-SBS I roll into, that's a two-year study, so we could decide to extend that study or start a new study. EASE-SBS III will be more simple to participate in. There will be less, you can say, procedures for the patients and also for the clinics, and then importantly, this is where we will actually introduce the Ultra Injector, which is a feature that also differentiates Gleepa from other treatments.
We also selected a once-weekly profile. We have all the time had a lot of confidence in the once-weekly profile, and that is probably what you see here. We have no new data to support that confidence. This is just part of how we see the development program. For EASE- SBS 1, that is a super interesting trial for us. It's a smaller trial, but it's interesting in the sense that there have not been these longer-term studies that looked into energy and fluid uptake for more than three to four weeks. 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.
It's not a 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 Gleepa 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 insufficiency. So in the EASE- SBS 1, it's only SBS patients on parenteral support. But in EASE- SBS 1, we also allow SBS patients who are just borderline and do not get parenteral support. So of course, ultimately, it is something that could broaden out the use of a product like this.
Perfect. And then just on the CHI, so I understand that the FDA deemed the CGM endpoint to have, you can say, poor sensitivity at least back when you designed the trial. So when we get the 17103 trial readouts 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 pre-filing 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 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?
The ongoing trial. Oh, sorry. Yeah.
Okay. So yeah, I can address that question. And then maybe Danilo, this year, he can talk a little about glucose sensor and how we see SMPG versus CGMs. But if we take the '03 study, we actually don't use CGM as the primary endpoint. That's a study in neonates from seven days to 12 months of age, and they are all in the hospital, and they are 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 it's a different endpoint for '03, so we don't perceive the same issue. And you maybe can discuss it on the SMPG versus.
Yeah, very quickly, Thomas. So CGM technology has actually progressed quite substantially in the last couple of years, so much so that all of the automated insulin delivery systems with Medtronic and Tandem and Omnipod, etc., are highly reliable on the ability of CGMs to be able to provide that 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 ultra-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 of the evidence available of which CGM will be part of when we go to the FDA to ask for registration of this study.
Okay. That's great, and thank you for clarifying. Thank you very much.
Yeah. Thank you, Thomas.
Sorry, we got another question. Comes from Graig Suvannavejh from Goldman Sachs. Please go ahead. Your line is open.
Yeah. Good morning. Good afternoon. Thanks for hosting this Q&A session. I'm just going to focus my questions on the BHAP program. I've got several questions just 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 and 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 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? Is it more about powering? 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 gas and glucose 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. Thanks.
Yes. Thank you, Greg, for your questions. I'll take the first one on the landscape, and then Adam will actually carry on on the design. On the competitive landscape for the dual-hormone pump, the best benchmark today that exists is actually the insulin pump market, which is in the US, around 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 on the market are these types 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 today, I mean, there is only one third-generation glucagon analog, which is dasiglucagon.
There is actually a liquid-stable glucagon solution that exists, which to date hasn't been advanced into the dual-hormone pump project, and I think the company that has this liquid-stable second-generation glucagon didn't talk about it at all. So I don't know what their plans are right now, but we don't see any other players in the field right now in the clinical side, and then for the clinical design, yeah.
Thank you, and yeah, 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. As we have also discussed before and shared, then we are working together with Beta Bionics, who are developing this dual biohormonal artificial pancreas, the iLet, which is really a unique system in that it takes the, I mean, all the things that the patient has to do and put that burden on the pump. It is running in an automated manner. That system can
actually run in an insulin-only system, and it can also be in a biohormonal system. Right now, they are doing the insulin-only pivotal study that will serve as their registration study to get the pump approved in an insulin-only mode. They are randomizing 440 patients into their study. They managed to screen all these patients throughout actually May, June last year, and then they saw some delays, as all of us did, 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 biohormonal study, which is set to enroll in both adults and children, over 300 patients into each arm. So we cannot give you more flavor 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 six-month endpoint, as you said, but so you will have to put the adjustment there.
But we expect fast enrollment into the 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 a few of the risks, 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. We revealed this for the first time after having agreed with FDA during the end-of-phase two 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 biohormonal setting than in an insulin-only setting and by far beating standard of care, which we are also going to compare to in the study. Of course, you have the normal risk 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 bias from patients and compliance and those
issues you normally have to deal with, really reducing the primary endpoint to HbA1c, 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 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 FDA so far on the trial design and really supports our efforts to get this important product forward to patients. But Danilo, maybe you want to talk a little bit about HbA1c and then forms of that in the study.
Sure. And I can also come back a little to expand on what Emmanuel was saying in terms of the market because there's no doubt that A1c remains the end-all, be-all in terms of treatment for type 1 diabetes patients with complications. The beauty of the bionic pump or the biohormonal 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. 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 minimal amounts 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 being 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 into hypoglycemia, insulin stops being delivered. That is not the case with the biohormonal pump because if glucose starts to go down, then glucagon kicks in, and insulin does not stop being delivered. And that's why we saw, we believe, we believe, of course, that we need to confirm in phase three.
That's why we saw in the phase two that you actually get 90% of the patients using the biohormonal pump down to 90% down to an equivalent HbA1c of 7, so CGM of less than 154. And you only saw 50% of the patients with the insulin-only model. So we are pretty excited about the fact that not only that, but also the fact, as Adam said, that the algorithm of Beta Bionics allows for just putting the weight of the patient into the system, and then machine learning within the algorithm takes care of adjusting the amount of glucagon and insulin that is delivered.
And then maybe just the last question we 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 one 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. Yeah. We need to see the phase three 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?
Yeah. Maybe on the last one, on the primary endpoint data, as you say, it will at least take three months to recruit the patients, and then it's a six-month endpoint. But it could also take longer. So that's what we are not guiding on when we'll 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 three-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 biohormonal. But what we're seeing right now on how they're doing on the insulin-only, we are very impressed. On the insulin cost, 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.
Okay. Thank you. I'll go back into the queue.
Thank you, Graig, again.
We get another question comes from the line of Jesper also from Carnegie. Please go ahead. Your line is open.
Thanks so much. I have 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 if you have it, can you use that on your current products, or will it only be on future pipeline products? Thank you.
Yeah. So I will re-answer this question, but maybe just, of course, we have Alpha- 4 beta- 7 that we already discussed, which is designed as an oral peptide and which we anticipate to take into the clinic. But will you comment on our strategy for all 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 orally available, so we do not plan to make semaglutide's linear analogs of hormone peptides orally available. It's actually the new generation, the next generation of peptides that we envision will be. Obviously,
we'll also have to use novel formulation technologies. It's a really dynamic field. As you mentioned, semaglutide, it has been, I mean, that has really been demonstrated that what has been notoriously difficult to make a peptide orally available, but now it's possible with Sema. We believe that if we also, in the initial design of the peptide, make it orally available, then in combination with these novel technologies, we actually will be able to reach a meaningful bioavailability.
Thank you. Yes.
Any other questions?
Yeah. So do you have that technology in-house to make them all, 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?
I think for all the projects that we do, we always look at what we can do in-house and always combine it with what is externally available, which kind of technology. So it 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 take 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 peptides that we are focusing on with this oral bioavailability.
I think, yes, maybe also to add on this, there has been a lot of progress on 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 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 formulation 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. That's why we think this is a unique moment to see and 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, pre-clinical. 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 we move into phase one? When could we actually see some data and some updates there? Thank you.
Yeah. 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 constellation, 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.
Thank you. Thank you so much.
Thank you again.
We get our next question comes from the line of Lucy Codrington from Jefferies. Please go ahead. Your line is open.
Hi there. Thanks for taking my questions. There's 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 for the obesity products and just wondering whether it's are there possible once-weekly GLP-1s that you could actually consider in-licensing for co-formulation with your assets? And then secondly, on the Amylin product and petrelintide, ZP10000, how are those going to be differentiated from products that are already further ahead than you in the clinic? And specifically with ZP10000, obviously, we had the Morphic Holding oral 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 three, 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. Thank you.
Thank you for your questions, and there are three ones with the obesity strategy, and I think Danilo, he will provide some answers to that, and then I'll go forward on survodutide and then the biohormonal, and I'll just hand over the word to you, Rie, as well, but maybe on the biohormonal, 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 one-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 you have results until you submit, there's always a certain period you need to have your interface meeting and so on.
So we will include the one-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 26-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 maybe you want to talk a little bit about why we are excited about our approach to Alpha- 4 beta- 7 in the future.
I think it's just really important to remember that, I mean, really, this is a bit on the mode of action, has a very high receptor accuracy. It binds to the alpha- 4 beta- 7 receptor. 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. But 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 then actually, we have a different mode of action here, also our ZP10000. So it's definitely something that we are exploring in this pre-clinical phase as well. While, as Adam said, we are really encouraged by the competitor taking forward as well because it does demonstrate that it is possible to get a really high efficacy also in a clinical setting.
Yeah. And I think probably what we should all expect is that there will be more attempts to have different immunomodulatory targets that have proven successful with antibodies in the years to come because as we tried to explain also in the presentation, this is really from a peptide perspective right now opening up that we have the tools that allow us to go after targets that were otherwise only accessible for antibodies as injections. And here, as Rhea said, I mean, that's why we are so excited about this oral strategy and trying to go for some of these targets. And so we should expect to see more competition. And as Rhea said, we believe we have our differentiators. Danilo, do you want to address the other questions?
Sure. So if I recall correctly, there were two 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 on progressing Amylin to phase one this year and progressing GIP to phase one next year. And the fact that these two 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 is no question that with the pandemic 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 is going to be differentiated and that other people may want to partner with us on.
Thank you. Do you have more questions? Lucy?
Sorry. Thanks. That was very clear. Thank you.
Thank you.
Your next question comes from the line of Etzer Darout from Guggenheim. Please go ahead. Your line is open.
Hi. This is Paul on for Etzer. Thanks for taking our questions. So first one, for the Amylin analog, ZP8396, can you provide a little bit more color on your planned phase one, maybe on the size and scope of the trial and potential initiation time? And then a second question for your two pre-clinical IBD programs. It's early, but hoping you could help us understand the opportunity in IBD as you see it. Where do 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.
Thank you. So this is Adam. I think I'll just address first. On the Amylin phase one, you should probably expect a very classical phase one study. We are focused, as Danilo said, on progressing this fast through the early clinical phase. There's already some clinical proof of concept and learnings from the programs that are in front of us taking the same target. And of course, that's something we can leverage. So that is classical forward. On the IBD assets, there are, of course, different strategies for these. If you take the Alpha- 4 beta -7, then it's obvious to think about with Vedolizumab, how that has differentiated itself. And we are trying to make a similar molecule that has the same mode of action that we could stimulate, have the same benefits, but then it's an oral 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 Rhea will actually discuss a little bit more on that. But really, that is a broad anti-inflammatory target. And the reason that we are so excited about this is that it also provides the potential for some immune-sparing 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, etc., 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 do you want a little bit more on Kv1.3?
Yeah. I'll just say, I mean, we are progressing this into the IND-enabling studies now also so it's ready for the clinical testing. And obviously, it is a target that is found on the effector memory T cells, which play a really important role in several autoimmune diseases. We are open for also other indications to go ahead. Right now, we do have really good evidence also within ulcerative colitis. So that is also 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 effector memory T cells is so important because it actually demonstrates that it is immune-sparing going forward. 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 still can be active in defending, again, pathogens. So I think that it has a lot of potential here, and we are definitely exploring that also as we are progressing towards the clinic.
Great. Thanks very much.
Thank you. Do you have more questions or should we elaborate on?
No, that was great. Thank you.
Thank you, Etzer.
We got another question. It comes from the line of Joseph Stringer from Needham & Company. Please go ahead. Your line is open.
Hi everyone. Thanks for taking our questions. A question on hypoglycemia and then a follow-up on SBS. So just wanted to get a comment on sort of the market dynamics around the rescue hypoglycemia market. It appears that the rescue syringe kit still holds a 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 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? 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. Regarding the hypoglycemic market, that's a market that for the last 20 years hasn't seen any innovations and zero promotion, so it's been a bit flat and sleepy, and so what we know today, that's in the U.S. alone, it's a $300 million market, and there's around 500,000 patients buying on average two kits. The potential for this market in the U.S. alone is over 6 million patients, so the introduction of Zegalogue last year, we saw an increase and immediately a response from the market, but that's not enough. It takes time to actually develop a market. However, the market to date, I think, is going by around 10%. So we've seen actually a very nice response from the market, and there is no doubt that these Zegalogue 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 this development will take place. But the more players there are in this market, the more noise and awareness there is. We believe that we're advancing a compound which has 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. Great. Yeah. Joseph?
Sorry. Thank you for that detail. I have a quick one on SBS enrollment for glepaglutide, and you're kind of timing around guidance around timing for results in 2022. 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 and the current enrollment rate and maybe future enrollment rate for survodutide, does that sort of factor in any competitor phase 3 trials into that sort of guidance on timing? Thanks.
Yeah. It factors in our estimate. And I would even say that we could perhaps even do with less patients that we saw in the last months to meet this. So this factors in our best estimates considering all aspects of the SBS and global inputs. I think we have, so yeah. I think I cannot say more to that, that we feel confident around this now.
Okay. Fair enough. Thanks for taking our questions. Appreciate it.
We got a follow-up question. It comes from the line of Graig Suvannavejh from Goldman Sachs. Please go ahead. Your line is open.
Yeah. Thanks. 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 lots 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 2. I'm just not really smart on that space. Could you just remind us which program that is and what they've shown? What do you think you need to show with your program to be either competitive or better?
Yes. Graig, I mean, regarding our collaboration and 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 matters for Alexion. What we are very positive about is the compound. And we're very positive about 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 Danilo maybe 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. Novo actually has Amylin in phase 2. 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 the clinic this year, our Amylin is different because of the fact that it 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 de-risks our entry into this space. But yeah, we're really excited to actually see this going into human trials.
Okay. Thank you. Thank you very much.
Yes. Anything else on your mind, Graig?
Sir, the line of Graig is already gone, and we got a follow-up question for the line of Thomas Bowers from Danske Bank. Please go ahead. Your line is open.
Yes. Thank you very much. Just a few quick follow-ups here. Just on the bi-hormonal, can you just clarify in regards to the phase three design? Do you need to hit the primary endpoint in both adult and pediatric trials in order to be able to file for approval? And then, well, you can say now the phase three 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 on HypoPal. Of course, I assume you have concluded the late cycle meeting with FDA now. So is there anything you want to share in regards to the label discussions and then maybe primarily in regards to the rapid TTR? Would that potentially become a claim for superiority, or is this just something that you expect, of course, will be included in the label? Thank you.
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 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 three studies, we have seen a very, very consistent lead 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 yeah. On your question on the bi-hormonal artificial pancreas studies, then we would expect that we should meet both the primary endpoint in the adult and the pediatric study in order to get approved.
That would constitute two 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 Beta Bionics, they have a breakthrough designation from the FDA for this use because FDA understands the 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 endpoint in both studies, and that would be needed. On the potential partnering, you're also correct that we have a non-exclusive 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.
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 their 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 are the ones who have, in our mind, the most exciting system right now and for sure the most progressed in these situations. So that's where we are.
Great. Thank you very much.
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 are very, very excited by the presentations that we were able to provide and put together and shed some light around the early pipeline, which remained a bit, I would say, in the shadow of the late-stage pipeline for the entire 2020 year. So as you can see, we are 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. Staying safe. And this is basically closing this session. Thank you very much. See you soon. Bye.
This concludes our conference for today. Thank you for participating. You might now all disconnect.