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

Good morning. Good afternoon. I am Emmanuel Dulac, CEO of Zealand Pharma. And on behalf of the entire organization, I am glad to welcome you to Zealand Pharma R&D Day. As 2020 monopolized all attention on operations, we are excited today to share the leap we have made in our R&D platform as well as R&D projects. 2021 promised to be a special year for Zealand Pharma, as we are planning to build and to turn into a highly performing commercial organization, while remaining a strong R&D-driven organization. So without waiting, I'm going to cover the agenda for today. Right after me, Adam Steensberg, Head of R&D, will cover with you the R&D strategy going forward. Danilo Verge, Head of Medical Affairs, will zoom in the metabolic portfolio. Steven Russell, Associate Professor of Medicine at Harvard Medical School, will walk you through in detail on the Dasiglucagon Bihormonal pen program. After that, Adam Steensberg will come back to cover in detail the gastrointestinal portfolio. And Rie Schultz Hansen, our Head of Discovery and Innovation, will walk you through the improvements we're making on our R&D platform as well as some of the progress we've made on earlier research programs. Finally, Adam and I will come back to wrap it up on the corporate strategy, corporate vision as well as R&D ambitions. I want to remind you that during this presentation, we will be making forward-looking statements, which are only engaging the management of the company, and are subject to change. Now 2020 has been a turbulent year for the society, and while the crisis is not behind us, I think we've spoken enough about it. So now let's look ahead and plan for going back to normal. At Zealand Pharma, we are already exploring what changes to keep and what changes to roll back. For example, we've all benefited for an improvement in productivity by cutting on long commutes, by adding flex work and flex time for employees. We've actually adopted and gained a lot of maturity on digital tools, such as telemedicine, trial management or tools, which are helping us to remotely engage with customers and/or manage patients. But what really excites me is that not only Zealand Pharma weathered through a storm, but at the same time, we have the great fundamentals to execute going forward. We have a clear vision. We have a strategy which is embraced by all our employees. We have a rich and well-balanced pipeline. We have an organization with strong values. And we have healthy finances to help us carry us through our ambitions. So let's look at what 2021 has for us. In January, we successfully executed on the largest capital raise of the company's history, providing us a solid foundation to pursue exciting opportunities. Right around the corner, we have the PDUFA date for the Hypopal Dasiglucagon rescue pen, which we are expecting it to be a major event for the company, not only because it's the first approval of the company, but as well, it will be the first launch. We need to turn our organization, which is creating for new challenges, into a high-performing commercial organization. And to that effect, we've invested a lot of time and resources in the past year to build our U.S. capabilities. Today, I'm excited to disclose to you that we have the team to execute on this launch. 2021 is also a very important year for us in terms of activities on the pipeline as well as milestones in the clinical development pipeline. And in a minute, Adam, Danilo and Rie will come and present to you in more detail these progresses. My vision for 2025 is clear. We need to become a fully integrated biotech company to leverage the full potential of our products in order to benefit our patients and our investors. With the acquisition of V-Go, the potential launch of Dasiglucagon Hypopal rescue pen and the highly-advanced late-stage pipeline, we have made a significant step in the ambition of having 5 commercialized products by 2025. It's a bold vision. And to get there, not only we need to build an outstanding commercial organization, but we also need to pursue our R&D efforts, keep investing in our platform, keep advancing our programs through clinical development. We are animated, at Zealand Pharma, by addressing the challenges and the unmet medical needs of the patients in metabolite and gastrointestinal disease. And we have a moral obligation to all the patients and families joining our clinical studies. So with that, let's introduce now Adam Steensberg, so that we can carry through the rest of the presentation and talk about the R&D strategy. Thank you very much.

A warm welcome to this Zealand Pharma Research and Development Day. My name is Adam Steensberg. I'm the Chief Medical Officer and Head of Research and Development at Zealand Pharma. I'm truly excited about the opportunity to share the recent progress in our pipeline and in our peptide platform, and also, to set direction for the 5-year ambition for R&D at Zealand Pharma today. I'm joined by my 2 good colleagues: Rie Schultz Hansen, who is heading up research and early innovation; and Danilo Verge, who is our Head of Medical Affairs. This is a very unique moment in Zealand's history. We are approaching our first potential launch of a medicine that has been discovered and fully developed by our team. And at the same time, our product pipeline has never been stronger, and we have a very robust peptide platform. So for more than 20 years, Zealand has been pioneering the engineering of novel peptide drugs that meets the needs of the patients. Lixisenatide was one of our first invention. It's actually one molecule for the treatment of Type-2 diabetes. And today, this molecule is marketed globally by Sanofi. Since then, we have continued to pioneer the engineering of novel peptide drugs and taking more than 10 molecules into the clinic, and we have many more in the late preclinical phase. We have several sources of inspiration and use a variety of techniques to achieve the biological effects and other attributes that we want to build into our peptides. And before we get further into the presentations today, I would like to share a short video about what makes us Zealand. [Presentation]

As you can see, we have broadened our innovation space in recent years beyond endogenous peptides, such as GLP-1, GLP-2 and glucagon. So we now get our source of inspiration from a variety of sources, such as toxins, face display and in silico design. This allows us to focus on disease targets that are otherwise difficult to reach by other modalities, such as antibodies or small molecules. And it really sets us in a situation where we're uniquely positioned to excel our innovation and discovery and be much more productive in the future. We are more than 190 people working in R&D, focused on delivering on our commitment to patients. I'm really proud to share that we still have one of our founders, Bjarne Due Larsen, with us, who, by the way, is a brilliant peptide chemist. It's the experience of people like Bjarne and the many talents that have joined us over the years that make's Zealand unique. I personally believe that our success comes from the fact that we always focus at what we are best at, making peptides into drugs that meets the needs of patients. We have seen a significant evolution in our pipeline over the recent years, and we have a strong commitment to continue to deliver. As we are approaching our first potential launch, we have a number of Phase II and III programs. And today, you will also learn much more about the early programs that we are approaching as the next value drivers in research and development. For the year, we have 3 focus areas. Number one is to deliver on the late-stage assets. Number two is to progress the next value drivers towards the clinic. And number three is to increase our investments in our peptide platform. And by focusing on these 3 pillars, we believe that we will not only secure a strong pipeline progress over the year, but also, secure Zealand's ambitions of breaking -- of building a long-term, high-value pipeline. Our ambition is to continue to drive innovation and establish a next-generation peptide therapeutic platform and a high-value product pipeline. With this, we'll continue to expand our leadership in the peptide drug discovery and development by enhanced use of novel technologies, of which we have already started to implement some, which you should learn much more about later today. In order to secure the long-term value creation of Zealand Pharma, as we establish our commercial footprint in the U.S., with the potential for 5 products marketed in 2025, we will also expand the therapeutic focus in R&D. In the metabolic area, we'll expand towards obesity and associated metabolic diseases, and in TI, we'll expand towards IBD and other chronic inflammatory diseases. And with that, I hope that you will enjoy the next set of presentations, which will give you a much deeper understanding of what we are doing in R&D and our ambition for the company in the next 5 years. Thank you.

My name is Danilo Verge, Head of Medical Affairs. Zealand started its history in the metabolic space with the discovery of lixisenatide, a GLP-1 receptor agonist, co-developed with and commercialized by Sanofi. This therapeutic area is part of the company's DNA, and as such, one of the main areas of focus for our research and development activities. In the near future, we're aiming to address a spectrum of hypoglycemic conditions based on our Dasiglucagon platform, starting with the approval and launch of our Hypopal rescue pen in the United States. In the medium term, we're working with our partner, Beta Bionics, to make the bihormonal bionic pump, a reality for people with Type-1 diabetes. And in the long term, we expect to advance the development of peptide design and formulations targeted obesity. Amylin is a particularly attractive candidate, which we plan to move towards Phase I later this year. When one thinks about hypoglycemia, insulin treatment immediately comes to mind, as it is the most common side effect of insulin therapy and one of the most dreaded conditions for people with diabetes. But while iatrogenic hypoglycemia is the most common manifestation of low blood glucose events, there are other less non-conditions that can lead to serious hypoglycemic attacks in all age groups and in a variety of settings. The analog nature of dasiglucagon allows for a stable aqueous formulation, enabling it as the only glucagon to potentially be used across the spectrum of hypoglycemic conditions. In the next few slides, I'll highlight the unmet medical need in each of these 4 conditions and Zealand's plans to address them. The International Hypoglycaemia Study Group defined 3 levels of hypoglycemia severity. Level 1 refers to blood glucose levels below 70 milligrams per deciliter, and alerts the patient to ingest simple sugars to avoid progressing to Level 2. At this level, blood glucose is below 54 milligrams per deciliter, and the patient is at very high-risk of losing consciousness, which is defined as Level 3 or severe hypoglycemia. The ADA recommends that glucagon be available to any individual at risk of Level 2 hypoglycemia. Glucagon rescue therapies have been available for more than 30 years as kits for reconstitution. Despite their availability and the seriousness of severe hypoglycemia, patients are not comfortable with glucagon administration due to the cumbersomeness of these kits. As you can see on this slide, in a 2019 survey of primarily highly educated privately insured adult participants on insulin pumps, i.e., people that can afford these medications, most patients with Type-1 diabetes had been prescribed glucagon. However, 1/3 did not have a current prescription for glucagon, 1/3 did not receive education on glucagon use and only 1/3 of those that did fill their prescription carried glucagon with them at all times. Moreover, the majority of glucagon prescriptions are in pediatric age groups as it is parents asking for glucagon to treat hypoglycemia in their kids and/or trains themselves on reconstituting and administering glucagon. As you can see on the graph, the flat part of the curve, adults experiencing hypoglycemia themselves, do not seem to be as aware of the consequences of severe hypoglycemia, be those cardiovascular, be those metabolic or cognitive, or they don't find available glucagon presentations easy to use or to have a spouse or relative be trained on how to administer it. The fact remains that even after the introduction of newer formulations of glucagon in the past couple of years, there is still a large unmet need for insulin-treated patients, both Type-1 and Type-2, to have glucagon available at all times. The next-generation glucagon analog, Dasiglucagon, would be the first glucagon product to be provided in a ready-to-use stable aqueous formulation. Like glucagon, Dasiglucagon is comprised of 29 amino acids, where 7 amino acid substitutions have been introduced to improve physical and chemical stability. This allows it to be stored at room temperature, and it makes it available for immediate use in the event of a hypoglycemic attack. Dasiglucagon was studied in 3 Phase III studies versus placebo, 2 in adults and 1 in children between the ages of 6 and 18 years of age. In the first adult trial and the pediatric one, the market in glucagon kit was used as a reference. Across all 3 studies, there was a consistent 10-minute response time in plasma glucose, which was measured as an increase of 20 milligrams per deciliter from baseline, and this was defined as plasma glucose recovery or PGR. To the right of the slide, you can see that 2/3 of all patients in all 3 studies achieved PGR by 10 minutes, with almost 100% by 20 minutes. The safety and the tolerability of Dasiglucagon was in line with that observed for the glucagon kit in the 2 studies in which it was included as a reference. Now this data forms the backbone of the FDA submission, and we believe that if approved, it will provide with a very attractive alternative for patients and providers alike. Changing gears a little bit, Congenital Hyperinsulinism, CHI, is a rare disease affecting mainly newborns and toddlers. It is caused by a defect in pancreatic beta cells, resulting in insulin overproduction and leading to persistently and dangerously low blood sugar levels. CHI develops in 1 out of 50,000 or fewer children, which corresponds to approximately 300 children diagnosed in the U.S. and Europe every year. The most severely affected children need to have their pancreas surgically removed within a few months of birth in order to prevent hypoglycemia. This invariably results in the development of Type-1 diabetes, which will follow them for the rest of their lives. And current treatment options are insufficient. Less than 1/3 of newborns and less than 2/3 of older children respond to approved medical therapy. The burn of disease is significant, not just for the affected children, but for their families and caregivers, and it represents a significant unmet medical need. The aqueous formulation of Dasiglucagon provides it with stability, and it makes it very well suited for chronic administration through pen systems. We have designed a comprehensive Phase III program addressing various clinical situations, endpoints and children ages. Trial 17109 evaluated children from 3 months to 12 years of age with a current incidence of more than 3 hypoglycemic events per week, despite previous near total pancreatectomy and/or maximum medical therapy. And it compared Dasiglucagon versus standard of care. Based on FDA advice, the primary endpoint of the study was the rate of hypoglycemic events as detected by SMPG or self-monitoring of blood glucose. Since the agency at the time deemed continuous glucose monitoring or CGM to have poor sensitivity in capturing low glucose values, however, in accordance with the FDA, we still included CGM as a secondary endpoint using Dexcom's Platinum 4 CGM meters. Now the results of the study show no difference in hypoglycemia rates as measured by SMPG, but almost a halving of rates as measured by CGM. We are conducting additional analysis and consulting with experts to understand the data better. It is very important to remark that 31 out of the 32 patients included in the study chose voluntarily to continue on to the 17106 study, in which all patients receive Dasi and which I will talk about in a couple of seconds. Now trial 17103 is currently evaluating the use of Dasiglucagon in neonates up to 12 months of age. In contrast to the previous study, these children are newly diagnosed with CHI. Dasi or placebo is administered for 48 hours, at which time the treatments crossover. At the end of the crossover, all children are treated with Dasi for 21 days. The primary endpoint is intravenous glucose infusion rate, which in contrast to SMPG, is much more objective and sensitive, and a very good indicator of the effect of continuous infusion of Dasi. Hypoglycemic events will be captured both through CGM and SMPG as part of a wide range of secondary endpoints. And finally, trial 17106 complements the safety gathering data for Dasiglucagon by allowing all those children and their families who choose to continue to be treated with Dasiglucagon for up to 2 years from the end of the first study. Finally, in terms of other hyperglycemic conditions, we have the ability -- the potential ability to use mini-doses of Dasiglucagon in other conditions, such as – Post Bariatric Hypoglycemia. This is hypoglycemia that occurs after bariatric surgery, primarily Roux-en-Y Gastric Bypass, and this is increasingly encountered by clinical endocrinologists. And although, the reported prevalence varies between 5% and 15%, the true frequency of this condition remains uncertain due to several factors, including a relative lack of patient and physician awareness and understanding of this condition, since most of these patients don't have diabetes. Post Bariatric Hypoglycemia can be severe and disabling for some patients with neuroglycopenia, resulting in alter condition, seizures, loss of consciousness, and all of these leads to falls, motor vehicle accidents, job and income loss. Moreover, repeated episodes of hypoglycemia can result in hypoglycemia unawareness, further impairing safety and requiring the assistance of others to treat hypoglycemia. As you can see on the left-hand side of the slide, presentation with PBH or Post Bariatric Hypoglycemia, first occurs approximately a year after surgery, and symptoms usually present after eating, with a marked postprandial glucose peak, followed by hypoglycemia 1 to 3 hours after. That is the cornerstone of therapy, aimed at reducing the stimulus for these glycemic spikes and the corresponding insulin secretion. But in many patients, this is not enough to prevent hypoglycemic episodes. An unmet need, therefore, exists to prevent and treat severe hypoglycemia in these patients. On the right, you can see that in a study that was presented at the European Association for the Study of Diabetes last year, Dasiglucagon was shown to achieve higher nadir plasma glucose levels in postsurgical Roux-en-Y Gastric Bypass patients with confirmed symptomatic postprandial hypoglycemia. This was a double-blind, triple crossover study that showed that a single dose of Dasi, either 80 or 200 micrograms, effectively ameliorated postprandial hypoglycemia, and all of this provides the basis for an upcoming Phase IIb study in an outpatient setting to be started later this year. The other condition that mini-doses could potentially address is exercise induced hypoglycemia. This can occur during, shortly after or many hours after exercise, and therefore, patients should remain vigilant for its occurrence, including frequent use of SMBG or CGM, measures to reduce early post-exercise hypoglycemia include carbohydrate ingestion and reducing insulin doses, which can result in weight gain and hypoglycemia, respectively. So a better approach is needed to prevent and to treat this condition. Dasiglucagon was studying-ed in small doses, ranging from 30 micrograms to 600 micrograms or 0.6 milligrams, which coincidentally is the dose that will be used in the rescue pen. And this was studied in patients with Type-1 diabetes in a hypoglycemic state, as you can see from the y-axis on the graph. And it showed a consistent and dose-dependent increase in blood glucose levels. Another study to be presented at the ADA later this year is comparing Dasi 80 and 120 micrograms to carbohydrate replacement, and it showed a faster and more durable response with Dasiglucagon data, which hopefully you'll be able to see at the ADA meeting. All of this data has led us to embark upon another Phase II study evaluating a low dose of Dasi administered by a pen device scheduled to start later this year. This study will recreate real-life conditions for people with Type-1 diabetes to investigate how they would choose Dasi as a non-caloric alternative to manage their plasma glucose in everyday life, including exercise. As a matter of fact, patients are requested to exercise regularly during the study, and they are free to decide when to administer treatment, either before, during or after the start of aerobic exercise. Let's now talk about what Zealand Pharma is planning to help out with the treatment and the management of persons with Type-1 diabetes. It is very well established that maintaining mean blood glucose concentrations near-normal range prevents many complications of Type-1 diabetes and reduces mortality. However, most people with Type-1 diabetes are not able to maintain mean blood glucose in this range, and intensifying treatment to achieve therapeutic goals increases the risk of both symptomatic and life-threatening hypoglycemia. An unmet need exists for better methods to manage glycemia. So I would now like to have Dr. Steven Russell, from Harvard Medical School, explain in more detail the gap that remains in achieving normal glycemia as well as the potential of the Bihormonal Bionic Pancreas to help people with Type-1 diabetes reach that goal, while reducing the need for ongoing physician intervention or user input and monitoring so that the pump operates effectively. Dr. Russell?

Hi. My name is Steven Russell. I'm the Associate Professor of Medicine at Harvard Medical School. I'm on the staff of the Massachusetts General Hospital Diabetes Center. In addition to my medical practice caring for people with diabetes, I have been doing clinical research on automated insulin delivery for more than 15 years. In the course of doing the pre-pivotal feasibility studies of the Bionic Pancreas, I have received research funding from Beta Bionics and Zealand Pharma, and I am a consultant for Beta Bionics. I'm also a principal investigator and the clinical study director for the NIH-funded investigator-initiated insulin-only Bionic Pancreas pivotal trial, and I will be directing the upcoming Bihormonal Bionic Pancreas pivotal trial. From my perspective as a clinician, automated insulin delivery systems are the current state of the art therapies for Type-1 diabetes. But as good as they can be, there's potential for clinically important benefits from adding automated delivery of glucagon. Why is that? One of the important benefits of the automation of insulin is that insulin delivery can be decreased or suspended when glucose is falling towards the hypoglycemic range. However, even rapid-acting insulin formulations are absorbed and cleared fairly slowly after infusion. So suspension of insulin delivery isn't always sufficient to prevent hypoglycemia. Users must always have fast-acting carbohydrates at hand for treatment at lows. To minimize the number of these episodes, control systems must be conservative with insulin dosing, and this limits how low on average glucose can be achieved. In contrast to insulin-only artificial pancreas systems, the normally function in pancreatic iLet don't rely on insulin alone to regulate blood glucose. Even though, the pancreas has the benefit of much faster insulin delivery and can be achieved with subcutaneous infusion, glucagonis an integral part of the way it controls glucose. glucagoncounters the action of insulin on the liver, where it can cause the breakdown of glycogen and release of glucose into the bloodstream. The pancreas releases glucagonduring fasting when glucose returns to the bottom of the normal range after rising from a meal and during exercise. The iLet bionic pancreas, an investigational device developed by Beta Bionics, can automate delivery of both glucose-regulated hormones used by the pancreas. If suspension of insulin delivery alone isn't sufficient to prevent hypoglycemia, then microdoses of glucagoncan be given automatically. Since the insulin delivery was already suspended by this point, these tiny doses are usually sufficient, and there's no need to eat carbohydrates to treat at all. And it makes sense that mimicking the approach of a normally functioning pancreatic iLets could improve glucose control, and data from small feasibility studies that I've directed suggests this is true. We compared the bihormonal configuration of the iLet delivering both insulin and glucagonto the insulin-only configuration of the iLet. In these studies, the insulin-only iLet achieved outcomes similar to those reported for other insulin-only systems. But there are 50% of study participants achieving an average glucose at or below the American Diabetes Association glycemic therapy, which corresponds to a hemoglobin A1c of 7%. The amount of time in the hypoglycemic branch was low and consistent with the ADA guidelines. This was much better glucose control than is achieved by the population of people with Type-1 diabetes at large, but many people with diabetes won't meet goals with the therapy with insulin-only systems. Therefore, even if insulin-only systems were used universally, an important unmet need would remain. In contrast, because the bihormonal configuration of the iLet can be more aggressive in dosing insulin without an increase in hypoglycemia, it was able to achieve lower average glucose values in these studies, with about 90% of study participants achieving the 88 goal for average glucose. There was less hypoglycemia than with the insulin-only iLet configuration, and less need to eat carbohydrates to prevent or treat hypoglycemia. In my opinion, these are important differences, both in terms of risk of long-term complications and also for quality of life. The participants in the trial seemed to agree, rating their experience using the insulin-only iLet highly, but the Bihormonal iLet even more highly. As compelling as the benefits of glucagon were in our feasibility trials, the use of human glucagon is not practical for widespread use in the Beta Bionics' iLet. In order to take advantage of glucagon's potential to take automation of glucose controls to the next level, a more chemically stable glucagon formulation was needed, and that is what Zealand has developed. Small feasibility trials that I've directed found that the Zealand glucagon analog, Dasiglucagon, worked similarly to human glucagon in the bihormonal iLet. With all of this as background, I'm pleased to be moving forward soon with the next step in making these technologies available to people with diabetes, that is, to begin the Bihormonal Bionic Pancreas pivotal trial, which will evaluate the safety and efficacy of the iLet and Dasiglucagon working together.

Various data sets published in recent years show that in spite of newer instruments and better administration systems, the vast majority of people with Type-1 diabetes, around 80%, are unable to reach glycemic goals as defined by the American Diabetes Association. The proportion who do meet the ADA therapy goal increases slightly with age from young adults, which is only 1 in 8, to mature adults, approximately 1 in 5, to other adults, approximately 1 in 4. The slide we're looking at basically shows a red line corresponding to the measures of CGM readings. And it shows a histogram for each one of the groups being evaluated that shows the distribution of the A1c values obtained across that population. And you can see, as I said before, that the number of histograms -- the number of bars below the ADA target really correspond to the people that achieved the ADA glucose target. And it is pretty clear that this part of the slide shows that targets are not being achieved. Well, what about other studies, where there's more intensified treatment? These are representative trial, the first one on the middle, targeting more intensive glucose management. And this intensified usual care resulted in around 40% of participants achieving therapy goals. The last panel or next to last panel on the right shows the Bionic Pancreas, the iLet device, that operated in the insulin-only configuration. And here, it was able to achieve therapy goals in around 50% of those same participants. But as you see on the last panel, with a bihormonal configuration, where participants received insulin and Dasiglucagon based on their individual needs, more than 90% of participants achieved therapy goals across these studies. And what makes these studies or the results even more striking is that participants also experienced less hypoglycemia in the bihormonal configuration, as the Bionic Pancreas automatically and proactively corrects both high and low blood sugar levels every 5 minutes throughout each day. And finally, what you can see, as you move from left to right, culminating with the Bionic Pancreas, there's a striking reduction in inter-subject variability, where the Bionic Pancreas is not noteworthy relative to usual care and the general population, as evidenced by the tight clustering of the histograms in the 2 Bionic Pancreas arms compared with a much more spread out histograms seen from the usual care arm data and the general population data. Zealand is collaborating with Beta Bionics on developing Dasiglucagon for use with Beta Bionics' iLet Bionic Pancreas, which you can see to the right of the slide. There is a purpose-built, pocket-size, dual-chamber, autonomous glycemic control system. It is designed to mimic a biological pancreas for a person with diabetes by calculating automatically and dosing automatically, both insulin and Dasiglucagon as needed every 5 minutes based on data from their body-worn continuous glucose monitor. Results from a Phase II study in people with Type-1 diabetes, which you can see on the left, comparing the Bihormonal iLet configuration using Dasi to the insulin-only iLet configuration, were presented at the ADA and Diabetes Technology meeting last year. The study enrolled 10 adult participants with Type-1 diabetes in a crossover design, where each participant used the insulin-only iLet for a week and the bihormonal iLet for another week in randomized order. The analysis of the CGM glucose endpoints show that the bihormonal configuration using Dasiglucagon provided superior glycemic control or the insulin-only configuration, with mean CGM glucose levels being 10 milligrams per deciliter lower on the Bihormonal iLet, where 90% of participants on the bihormonal iLet had a mean CGN glucose level of less than 154 milligrams per deciliter. This is a level that corresponds to an A1c level of 7%, which, as I said before, is a therapeutic goal for people with Type-1 diabetes recommended by the ADA. In contrast, on the insulin-only arm, only 50% of participants achieved this mean glucose level of less than 154. But despite the much tighter glycemic control, participants spend less time in hypoglycemia when using the bihormonal iLet as compared to the insulin-only iLet. Now the good news is that we've had a very productive end of Phase II meeting with the FDA and we expect the pivotal Phase III trials to be initiated in the second half of this year. So let me talk a little bit about what we're planning for Phase III. The Phase III program will consist of one pivotal adult trial -- one pivotal trial in adults with Type-1 diabetes and one pivotal trial in children with Type-1 diabetes. There's approximately the same number of adults and children, around 350 in each group, and they will be randomized into the studies. The primary outcome measure for both studies is superiority on A1c on the bihormonal iLet configuration or the insulin-only iLet configuration at week 26. A usual care arm, which you see at the bottom and top, respectively, with the adult trial and pediatric trial arms, will be included for secondary comparisons on A1C and various CGM outcome measures. Participants in the insulin-only and the bihormonal iLet arms will continue treatment until week 52 to establish long-term safety data. And upon completion of the randomized period at 26 weeks, all usual care participants will be allowed to enter a 26-week extension study for treatment with a bihormonal iLet configuration with Dasiglucagon. Finally, upon completion of all 52 weeks of treatment with the insulin-only iLet configuration, these participants will be allowed to enter a 13-week extension study for treatment with the bihormonal configuration with Dasi. Overall, the program has been designed to demonstrate the clinical outcome of utilizing Dasiglucagon in the bihormonal iLet versus the insulin-only iLet, while also comparing these results to intensified usual care. In this final part of my presentation, I will be describing the plans we have at Zealand Pharma to expand beyond diabetes and hypoglycemia into obesity and associated metabolic diseases. In 2019, The Journal and The Lancet commissioned a group on obesity, which advanced the conation that obesity is a pandemic, closely related to those of undernutrition and climate change. Subsequently, a New England Journal of Medicine paper, published last November, highlights that the global prevalence of obesity has tripled since the mid-1970s, with 650 million adults and 124 million children and adolescents suffering from obesity. In the U.S. alone, more than 40% of the population are considered obese. While awareness of obesity has risen, based on its increased prevalence, there's an underappreciation by the public health community of the links between obesity and other health outcomes, including Type-2 diabetes, non-alcoholic fatty liver disease and NASH, certain types of cancer and various manifestations of cardiovascular disease, among others. Medical treatment of obesity will be one of the cornerstones of addressing this pandemic, and Zealand's peptide expertise can contribute with the development of some of these medicines. In terms of obesity, the goal of therapy is to prevent, treat or reverse the complications of obesity and improve quality of life. Health benefits have been reported with weight loss of as little as 5% of bodyweight. But many patients have a weight loss goal of 30% or more below their current weight, a goal that is often not achievable without bariatric surgery. Medical treatment, based on single-receptor target pharmacology, has been shown to reach up to 10% to 15%, but it is clear that to achieve levels of weight loss approaching those of bariatric surgery, dual or even triple pharmacology is needed. At Zealand, we have the ability of designing single peptides with dual agonism action, such as the GLP-1 glucagon receptor agonist being developed in collaboration with Boehringer Ingelheim, which I will discuss in a second. And we also have the ability of designing mono-agonists that can be co-formulated with other peptides targeting other receptors, such as amylin and GIP. As I said before, the concept of targeting more than one receptor in treating obesity is illustrated in this picture. Activation of the GLP-1 and glucagon receptors lead to complementary actions in terms of appetite suppression and increased energy expenditure, respectively. Preclinical models and early human studies show these effects to be additive. Zealand's collaboration with BI is advancing, with BI having completed Phase I studies for the dual agonist, in which clinically significant weight loss was seen for the dual agonist. Detailed results of this data will be communicated by BI at upcoming scientific meetings later this year. The Phase II program for both obesity and Type-1 diabetes -- Type-2 diabetes are underway as well as plans for investigating the dual agonist in NASH. Moving on to amylin. Amylin is a very interesting peptide. It is actually derived from beta cells in the pancreas and it's co-secreted with insulin. It both regulates blood glucose by delaying gastric emptying after meal ingestion, and it directly modulates satiety signals in the brain. Preclinical studies also suggest that amylin, like glucagon, can increase energy expenditure contributing to its weight loss effect. However, human amylin tends to aggregate and form amyloid fibrils, which makes administration of the native hormone very difficult. Along acting analog of amylin by another company is currently in Phase II studies, and the proof-of-concept has been shown because it's shown both its effect as monotherapy and in combination with the GLP-1 receptor agonist. At Zealand, we developed an amylin analog, which we call, ZP8396, that has a half-life allowing for once-weekly administration, and unique to this peptide for co-formulation with other antiobesity peptides, such as GLP-1 receptor agonist, GIP, PYY, et cetera. As you can see on the slide, in a preclinical model of obesity, one of our other amylin analogues showed marked weight loss compared with liraglutide, the only marketed GLP-1 receptor agonist currently prescribed for the treatment of obesity. We do anticipate starting Phase I trials with the ZP8396 analog later this year. And finally, GIP or glucose-dependent insulinotropic peptide, this is also a particularly interesting peptide to explore in treating obesity. It is synthesized by K cells, which are found in the proximal intestine, and it circulates as a biologically active 42 amino acid peptide. GIP receptors are expressed in many organs and tissues, including the central nervous system, enabling GIP to influence regulation of appetite and satiety while showing antiemetic effects. Thus, GIP can contribute to the efficacy of other anti-obesity peptides, both by a complementary effect and by providing an improved and wider therapeutic window of the other peptide. This, in fact, was the approach taken by Eli Lilly in designing their GIP/GLP-1 dual receptor agonist, which has shown promising weight loss in Phase II studies, and again, showing proof-of-concept. We do have our own GIP agonist, ZP6590, and it has shown, as you can see on the graph, additive effects when co-administered with a GLP-1 receptor agonist in an obese mouse model. We expect to bring the analog to Phase I next year. And like our amylin analog, this can also be co-formulated with any other peptide targeting obesity. So to summarize, metabolism continues to be a pivotal area of focus for Zealand. We're exploring the use of Dasiglucagon across the spectrum of hypoglycemic conditions, starting with the rescue pen to be launched this year. We're working closely, together with Beta Bionics, in getting the Phase III program for the Bihormonal Bionic Pancreas, starting before the end of 2021. And finally, we're expanding our focus to obesity, with plans to put our amylin analog in Phase I later this year. As illustrated by Robert's testimony, our focus continues to be on addressing unmet medical needs.

Our strong commitment towards patients with short bowel syndrome is the foundation for our gastrointestinal franchise. We are making significant progress on this end. Today, I will also share some new assets, and thereby, set the direction for where we will take this franchise in the future. We are developing 2 molecules for short bowel syndrome. Glepaglutide, our long-acting GLP-2 analog and Dapiglutide, our long-acting GLP-1 and 2 receptor dual agonist. We have 2 new assets, a Kv1.3 blocker and a4ß7, which targets IBD, and they are progressing towards Phase I. We also have a complement C3 inhibitor. And together, these 3 assets represent our leading assets towards IBD and other chronic inflammatory diseases. The complement C3 inhibitor, we have licensed to Alexion, and we are making very good progress on the -- in this collaboration, and Rie Schultz will share more of that when we get to her part of her presentation. Turning to short bowel syndrome. Marianne is living with short bowel syndrome, which is the result of a long-standing Crohn's disease and multiple intestinal surgeries. As she has said herself, getting SBS was her worst nightmare. A few of us can imagine how it would be to one day wake up and find out that you could no longer absorb the fluids and energy you need to survive, and that you have now become dependent on parenteral support for the rest of your life. This means that people will be hooked up to IV infusion lines for up to 17 hours every day to survive. Marianne, however, is also lucky, not only because she's one of the strongest persons and have the most positive inspiration around her, but also because she lives next to a Center of Excellence with healthcare professionals who know how to help her manage her complex condition. Marianne and the many people who have shared their stories with us at Zealand give us the energy and focus to continue to progress new medicines to help them ease their conditions. There are approximately 40,000 people living with short bowel syndrome in U.S. and Europe. The condition is defined by having less than 2 meters of short intestines, leaving the patients with too little absorptive capacity to get the nutritions and fluid they need. When people with SBS eat and drink, they will experience diarrhea, and around half of the patients will become dependent on home parenteral support for the rest of their life. Yes, we have seen some progress in the management of SBS with the introduction of the short-acting GLP-2 analog, teduglutide. However, there remains a huge unmet medical need for faster, more effective and more reliable treatments that can take reductions in parenteral support to a new level, and ultimately, get patients to regain full enteral autonomy. Glepaglutide is our long-acting GLP-2 analog, with an effective half-life of approximately 50 hours that we have in Phase III development as either once-weekly or twice-weekly injection. The unique design of this molecule has allowed us to develop it in a stable and accurate solution, and thereby, also progress the development of an auto-injector for easy and simple injections, as you can see down to the left of this picture. If you look to the right, then you can see the main results of our Phase II study, which demonstrated that the 2 higher doses of glepaglutide increased intestinal absorption of fluid. We also observed changes on a number of other effect parameters, and concluded glepaglutide to be safe and well tolerated in the study. As a result of the increase in intestinal absorption of fluid, we also saw increases in urine production in the Phase II study. That's a very important observation because increases in urine production is directly related to their ability to reduce parenteral support in clinical practice, but also in our ongoing Phase III study. If you look to the right of this slide, we have applied the algorithm that we used to guide reductions in PS in our Phase III study to the data we achieved in our Phase II study. And it's striking to see that only following 3 weeks of treatment with glepaglutide, 71% of the patients would have had a reduction in their parenteral support and perhaps even more striking 57% of the patients would actually have met the responder criteria of a more than 20% reduction in PS defined in this study. EASE SBS 1 1 is our pivotal Phase III study that is set to enroll 129 patients with SBS. Following 6 months of treatment, they are then offered to roll over into EASE SBS 1 2 , which is a long-term 2-year study where all patients get active treatment. The primary endpoint in EASE SBS 1 1 is the reduction in parenteral support as measured by the end of the study. As already announced, enrollment of patients into this study has been impaired by COVID-19. We are, however, happy to say -- to see that recruitment is getting back to pre-COVID conditions here over the last few months, likely due to the introductions of vaccinations. And pending a continuous positive development in recruitment, we expect to see results in 2022. While our focus is on securing patient enrollment into EASE SBS 1 1, I'm also excited about the opportunity to share that we are starting 2 additional Phase III studies. One study, called EASE SBS 3,will allow patients who are completing EASE SBS 2 to roll into a further 2 years of treatment here actually in being dosed via the auto-injector. In EASE SBS 4, we are evaluating 24 weeks treatment effects on intestinal absorption of fluid and energy, and thereby, confirming in a long-term study the data we have observed in our Phase II study. And we believe the full program that is displayed here is very well set to highlight the benefits of glepaglutide, and we look so much forward to see the pivotal Phase III data next year. I would now like to turn to dapiglutide, which is our long-acting GLP-1 and GLP-2 analog that we are also progressing for treatment of short bowel syndrome and potentially other GI diseases. The concept of a dual-acting peptide stimulating both the GLP-1 and the GLP-2 receptor have already been demonstrated in short-term clinical studies. While GLP-2 increases the absorption across the intestines, the GLP-1 component is believed to reduce the gastric motility, and thereby, allowing more time for the nutritions and fluid to be absorbed. And we, therefore, believe that the dapiglutide has the potential to take treatment of SBS to a completely new level and really get many more patients towards that ultimate goal of full enteral autonomy. Last year, we completed a Phase Ia study, where we concluded dapiglutide to be safe and well tolerated in doses up to 7.5 milligrams. We also observed a plasma half-life of 120 hours. This allowed us to start the Phase Ib study, which is ongoing. I'm happy to report that we have completed the second dosing cohort in the Phase Ib, and expect the full results of the study later this year. At this time, we also expect to announce the next development steps for the molecule. Over the last few years, we have expanded our resource activities into IBD and other chronic inflammatory diseases. Peptide drugs have proven their effectiveness in other therapeutic areas, such as diabetes and obesity. And, we believe they hold great potential as novel and innovative treatments in chronic inflammatory diseases as well. It's an area that has otherwise been dominated by antibodies for many years. The programs we are progressing towards the clinic represent high-profile targets, with Kv1.3 and Complement C3 have been proven very difficult to block by small molecules or by antibodies. And the a4ß7 goes for a target that has already clinical evidence in that -- antibodies have been shown to provide benefit to patients living with IBD. One of the first immunomodulatory molecules we are progressing towards Phase 1 is our Kv1.3 ion channel blocker. Kv1.3 is a central ion channel to the T effector memory cells, which plays a key role in autoimmunity and chronic inflammation by the release of pro-inflammatory cytokines. These factors recruit more immune cells to the inflamed area and causes tissue damage, as you can see, schematically presented to the left of this slide. The anti-inflammatory effects of blocking Kv1.3 has been demonstrating numerous preclinical models of autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, psoriasis and IBD. The illustration to the right shows the engagement of a leukocytes to the activation of the T cell receptor. Pending the nature of this leukocyte, different ion channels are engaged. Naive and central T memory cells are dependent on KCA3.1 ion channels, whereas the T effector memory cells are dependent on the Kv1.3 ion channel. The efflux of potation to these channels activates the cells and cause the release of pro-inflammatory cytokines. The specific and selective location of Kv1.3 to the T effector memory cells makes it a high-profile target, in that, it preserves the immune system's other parts, and therefore, we are very excited to bring this molecule forward. So our lead candidate is a potent and selective Kv1.3 blocker with a potential to treat a broad range of autoimmune diseases. Currently, we are progressing the molecules into IND toxicity studies and aim to take the molecule inflammatory bowel disease as the first indication. The graph to the right shows one example of the link between Kv1.3 and pro-inflammatory cytokine production. In this study, we demonstrated that our lead molecule can inhibit the production of IL-2, IL-17 and interferon gamma stimulated from whole human blood cells, and thereby, providing a direct link to humans from the preclinical evidence we have for this molecule. We expect to take the lead molecule into Phase I next year, and we look very much forward to share additional scientific data over the year on this molecule. On this slide, you can see some of the data we have generated for ZP10000, which is our oral a4ß7 inhibitor. a4ß7 is a clinical validated target, and many patients with IBD have already seen improvement in their disease when they were treated with vedolizumab, which is an antibody for either IV infusion or subcutaneous injection. Some of the success of vedolizumab is ascribed to the gut restrictive nature of the immune suppression with this target. ZP10000 is a peptide inhibitor of that same target with binding kinetics on par with what we see from antibodies. In preclinical models of inflammation, the compound is effective in decreasing the inflammation after all administration, as you can see, one example, off to the right in this slide. And what is striking is that the molecule has been designed to have all bioavailability from the start, and what we are focused at right now for this molecule is to optimize the clinical formulation of the molecule. This is our first goal with an all available peptide. And as such, it's also leading the way and our ambition to develop many more peptides with all bioavailability that we hope to progress into the clinic over the next years. This concludes our session on the gastrointestinal and chronic inflammation portfolio. We are committed to progress new assets into this area and have made significant progress getting new both late and early assets forward. Glepaglutide and dapiglutide represent our opportunity to change the management of people living with short bowel syndrome. And the early assets I shared represent opportunities for totally new innovation in an area of IBD and chronic inflammation. Our long-standing commitment to patients living with short bowel syndrome is the foundation of our efforts, and the new assets opens up for a completely new value creation by Zealand Pharma. And with that, I would like to hand over to Rie for her to take us through our peptide platform.

My name is Rie Schultz Hansen, and I'm Head of Discovery and Innovation here at Zealand Pharma. I'm very pleased to give you a talk through our expertise in peptide design and engineering. And I'm proud to say that for more than 20 years, we have been the drivers of innovation in designing peptide drugs. We have established our next-generation peptide platform on our innovative capabilities. For my part of the presentation, I'll give you a walk-through of the technological solutions that we have applied for selected programs. I'll talk about how we use our rational designer proscesses for dasiglucagon and dapiglutide. I'll talk about how we engineered nonhuman peptide starting points into a selective drug candidates in the Kv1.3 and the C3 programs. And finally, I will talk about how we are taking peptide drug discovery to the next level by advancing potential oral treatment for IBD patients based on the known mode of action of blocking a4ß7. But first, I'll give you a short presentation of peptides and our innovative peptide platform. Peptides are made from amino acids, which are kind of nature's building blocks, and peptides are drug class on its own. They are more specific in inhibiting protein-protein interactions than small molecules, and they do have superior tissue penetrants when we compare them to antibodies. Peptides can regulate cellular processes by being agonist or antagonist of biological function and is even possible to engineer dual pharmacology into a peptides. At Zealand Pharma, we see our scientists as an integrated part of our discovery platform because it's really built on a deep understanding of rational peptide design of how to order the amino acid sequence to enhance certain purposes. We're continuously adding several other relevant technologies to our platform, for example, libraries of venoms or molecular display, which I'll come back to a bit later; our silicon modeling or computational chemistry that we're also using; and very importantly, also novel oral formulation technologies because we believe that together with designing the peptide made for all delivery, this holds a very exciting future promise. So during this presentation, I'll use examples of how we have exploited these technologies, starting with our Phase III asset, dasiglucagon where our rational design processes were key. Dasiglucagon is a demonstration of our abilities to improve drug purposes of peptide. Native glucagon has been a treatment offering for severe hypoglycemia for more than 30 years, but it's a highly unstable peptide that is prone to aggregation and it needs reconstitution from powder, which really limits its clinical use. So here, the ambition was to make a ready-to-use product to make an analog of glucagon that is stable in an aqueous solution. But how did we approach that? So we know that creating electrostatic reposes in a molecule will prevent them from getting close to each other and form aggregates. So we needed to make a more charged molecule that could prevent this aggregation. And we did this by replacing only 7 of the 29 amino acids. On the graph to the left, you can see aggregation, which is measured as an increase in the fibrils signal. On the blue graph, you can see native glucagon that aggregates into fibrils within days. But dasiglucagon, as you can see on the red graph, is not aggregating at all. So we managed with our replacing of the 7 amino acids to make a peptide that is not aggregating. But of course, it's also key to ensure that the potency and specificity for the glucagon receptor is maintained. On the graph to the lower right, you can see the effect of dasiglucagon in an aqueous solution in the hypoglycemic rat model. On the red graph, you can see dasiglucagon that elicits a rapid increase in blood glucose, the same effect is seen with native glucagon on the blue graph, but of course, that has to be reconstituted before use. If we use DMSO as a stabilizer, we can also elicit a response with native glucagon, but this has a delayed onset of action. So in summary, the Dasiglucagon is a really good example of how we used our deep understanding of peptides to design a drug with excellent stability while maintaining the desired physiological properties. Now I'd like to turn to how to make peptides with dual agonism. As you know, we have 2 dual-acting clinical candidates, a dual GLP-1 glucagon that BI is advancing and a dual GLP-1, GLP-2 analog dapiglutide. And with the dapiglutide, our ambition was to engineer a peptide with dual pharmacology and a long plasma half-life. So native GLP-1 and GLP 2 only share 33% amino acid homology. And we rationally replaced 10 amino acids in the GLP-2 sequence to add GLP-1 activity. So we really obtained here a balanced receptor potency. On the graphs on the left, you can see a dual dose-dependent effect in a mouse model. And you can see on to the left, the intestinal transit time dose dependently is decreased, that's a hallmark of GLP-1 effect. And on the right side, you can see the rate of the small intestine is increased, and that's a hallmark of GLP-2 effect. So really here, we managed to combine the 2 biological effects in one peptides. Now as mentioned, the scaffold here is the GLP-2 peptide. And native peptide has short half-life in plasma, and that needed to be addressed, too. Attaching an acylated fatty acid to the peptide makes it able to bind to human plasma albumin, and human plasma albumin has a plasma half-life of 19 days. So with this binding, the peptide is then protected from degradation and from fast renal filtration, and furthermore, it's really gradually released into circulation. And on the graph to the right, you can see a bioanalysis study, where subcutaneous administration at dapiglutide has been administered to the dog. And what you can see is in the dog, it has a half-life of about 35 hours, and that is the effect of the isolation. This roughly translates into a half-life of about 120 hours in humans. So really, we designed dapiglutide to be a dual GLP-1, GLP-2 agonist that is suitable for once-weekly administration in the clinical setting. As a first example of a program where no humans starting currently exist, I would like to discuss the Kv1.3 blocker. Kv1.3 is a potassium ion channel that is upregulated in inflammatory conditions and no human starting points exist for this channel. When we work with ion channel, we know that selectivity is key. This is really difficult to obtain with small molecules and antibodies are selective, but they are really difficult in entering the channel pool. So peptides, they are ideal ion channel blockers, but as mentioned, no human starting point exists. So we needed to find a peptide starting point, and we know that venoms are rich source of bioactive peptides. Animals such as spiders, lizards and scorpions use their toxic cocktails to engage their prey. And we had access to libraries of these bioactive peptides and we screened for peptide hits. We find -- found such a peptide hit, and it was optimized by evolution to inhibit the Kv1.3 channel. Now venom starting points are really complex peptides. They're inherently soluble, but the challenge here is to enhance the selectivity and stability of the peptide while maintaining the soluble 3-dimensional structure. But by rational design as in silicon modeling, we obtained to increase the Kv1.3 selectivity. We maintained the potency, and we also dialed in the stability and maintained the soluble nature of this peptide. On the graph to the right, you can see the candidate peptide, and it prudently blocks the Kv1.3 in an enricher setup while maintaining a high selectivity towards other very similar ion channels. Also, this peptide is optimized for large-scale production, and we're really eager to take this venom -- the right candidates through the IND-enabling studies to further explore its clinical potential. So we are devaluing a C3 peptide inhibitor in collaboration with Alexion Pharmaceuticals. Alexion Pharmaceuticals is a company that is specialized in Complement diseases. I use this program to illustrate how other sophisticated laboratory technologies can be used to generate peptide drug starting points. Now the Complement system is a part of the innate immune system and C3 is a very central component. C3 interaction sites with this target molecule is too small for antibodies, but it has to just right size for peptides. But again, here are no natural peptide inhibitor exists. The face display library technology is really well suited for this kind of targets, and we have implemented this technology at Zealand. Face display is a powerful molecular biology screening technique that can generate libraries of random -- of millions of random peptides, and we can use those libraries to identify ligands to proteins such as C3. In this case, the starting point for molecular was from molecular display, but it was publicly available, and we knew the binding site and the confirmation. We used our structural knowledge and in silicone model to rationally replace amino acids, and we obtained an optimal balance between potencies, the ability and solubility, while keeping the peptide affinity for C3. On the graph to the left, you can see surface plasma resonance data, and we can see the concentration dependent binding kinetics to C3, and it demonstrates that the candidate is a very prudent C3 binder. Our candidate is also half-life extended, it has the potential to be the best-in-class. We have now selected the candidate molecule, and we are together with progress in this into the next stage of development. As a last example, I would like to discuss the a4ß7 integrin inhibitor. a4ß7 is located on the surface of T cells. And the inhibition prevents the interaction with MAdCAM1, which is placed on the endothelial cells. And this interaction between a4ß7 and MAdCAM1 plays a very critical role in immune cell recruitment to the intestinal tissue. This is a mode of action that's clinically validated in inflammatory bowel disease by marketed antibodies, but most IBD patients would really prefer an oral tablet treatment. Due to its size, this interaction surface between a4ß7 and MAdCAM is a very attractive target for peptides, but again here, no natural peptide ligand exists. We know that the MAdCAM1 mimetic peptide structure is published, and we use this structure to design peptide ligands that selectively bind to the a4ß7. This design was guided again by in silicon modeling, and we also incorporated proboscis of oral bioavailability. On the graph to the right, you can see the concentration dependent properties of our compound, ZP10000, that again here is measured by surface plasma resonance. What is really remarkable here is that the binding purposes are on par with marketed antibodies. That is something that is really extraordinary to obtain with a peptide this size. We have also demonstrated oral bioavailability in vivo, and currently, we are exploring the optimal oral formulation for this compound while we are progressing the program. So in summary, our peptide platform is founded on more than 20 years of know-how of how to rationally design peptide analogs. The chemistry of several of our newer programs is guided by in-silicon modeling and computational chemistry, a technology area that is rapidly evolving in the peptide space and that we continue to invest in. Combining this with technologies like venom libraries and molecular display has increased our bandwidth to include targets outside of the traditional peptide receptor area. And also, with the addition of our first oral program, we're exploring and investing new formulations that can enhance oral exposure, in combination with focused design of smaller peptide that has a building propensity for oral bioavailability. I would like to emphasize that we remain determined and committed to design and engineer druggable peptides for any high-value target where peptide drugs can make a difference. We have been pioneers in the peptide world for 2 decades, and we see a large untapped potential in this class of molecules, and we are dedicated to develop the next-generation peptide drugs that are designed to address unmet medical needs.

I hope you have enjoyed the presentations today, and are excited and energized by all the progress we have made across the pipeline and the peptide platform. We have set a very high ambition for our R&D organization over the next 5 years. And we're excited about delivering on our promise to the patients. As we enter into 2021, we will focus on 3 areas. Number one is to deliver on the late-stage assets. Then we'll progress the next value drivers into the clinic, and we'll increase our investments in the peptide platform. So we have some very exciting years ahead of us, and can't wait to get going. And with that, I would like to hand over to Emmanuel for his closing remarks.

Thank you, Adam. Zealand has made extraordinary progress over the past 2 decades, but I believe, our next chapter is our best yet. I am thrilled to be leading Zealand Pharma through the next development. I hope this R&D Day brought to you the same excitement that fuels our team daily. And I am honored that we were able to actually bring you all the milestones and information regarding to our R&D development. I am thrilled to show you the one-of-a-kind Zealand Pharma is turning into, a company that cares and thrives for the care of patients in metabolites and gastrointestinal disease. Thank you for your attention, and we look forward to having you joining our Q&A session.