Zealand Pharma (NASDAQ:ZEAL.CO), a biotechnology firm specializing in metabolic and gastrointestinal disorders, has reported significant progress in its obesity and rare disease programs during its latest earnings call. The company highlighted positive Phase 1 results for petrelintide in treating obesity and the advancement of Survodutide into a Phase 3 program by their partner, Boehringer Ingelheim.
With a strong cash position of DKK 4.1 billion, Zealand plans to boost investment in its obesity and rare disease candidates and expects key clinical outcomes and regulatory approvals in 2024. Despite reporting a net financial loss of DKK 137 million for 2023, the company has refined its ESG strategy and is expanding its workforce to support growth.
Key Takeaways
- Zealand Pharma reported positive Phase 1 results for its obesity treatment, petrelintide, and is advancing other rare disease products.
- Partner Boehringer Ingelheim has seen positive Phase 2 results for Survodutide and is moving it into Phase 3.
- The company expects important clinical results and regulatory approvals in 2024.
- Zealand has a strong financial position with a cash reserve of DKK 4.1 billion and plans to increase investment in key programs.
- The workforce is set to expand by 30% in 2023 to support growth.
- Zealand reported a net financial loss due to loan repayment but has taken steps to strengthen its balance sheet, including raising DKK 1.5 billion in April 2023.
Company Outlook
- Zealand Pharma anticipates important clinical results and milestone achievements in 2024.
- The company plans to increase investment in obesity programs and continue progressing rare disease product candidates.
- Zealand is committed to refining its ESG strategy and operating a responsible business.
Bearish Highlights
- The company reported a net financial loss of DKK 137 million in 2023 due to loan repayment and termination.
Bullish Highlights
- Zealand has a robust cash position, extending its financial runway into 2027.
- Positive clinical trial outcomes for petrelintide and Survodutide bolster the company's portfolio.
Misses
- Specific plans for the Phase 2b trial of petrelintide were not disclosed during the call.
Q&A Highlights
- Executives discussed the benign side effect profile of Survodutide and its potential advantages in satiety and muscle wasting prevention.
- The possibility of combining amylin analog with GLP-1-GIP assets was mentioned.
- Boehringer Ingelheim plans a large Phase 2b study for petrelintide to refine dosing before Phase 3.
- The company is considering partnering for Phase 3 of petrelintide.
Zealand Pharma is poised for a pivotal year in 2024, with the company focusing on advancing its clinical programs and potentially bringing new treatments to market. The firm's commitment to addressing the obesity pandemic and associated comorbidities, coupled with its strong financial footing and strategic investments, positions it as a notable player in the biotechnology sector.
As the company expands its workforce and refines its ESG strategy, investors and stakeholders will be watching closely for the top-line results from clinical trials and regulatory developments that could shape Zealand's future in the years to come.
InvestingPro Insights
As Zealand Pharma (ZEAL.CO) forges ahead with its promising obesity and rare disease treatments, the financial metrics from InvestingPro paint a detailed picture of the company's market performance. With an adjusted market capitalization of $5.79 billion, Zealand's financial clout is significant in the biotech industry. Despite a negative P/E ratio of -51.65, reflecting the company's current lack of profitability, the substantial revenue growth of 267.38% over the last twelve months as of Q3 2023 indicates a rapidly expanding business.
InvestingPro Data:
- Market Cap (Adjusted): $5787.92M
- Revenue Growth (LTM as of Q3 2023): 267.38%
- Gross Profit Margin (LTM as of Q3 2023): 102.49%
Investors may also be intrigued by the impressive gross profit margin of 102.49% during the same period, suggesting that Zealand is highly effective at converting sales into profit. Moreover, the company's stock has experienced a remarkable one-year price total return of 176.29%, signaling strong investor confidence in its future prospects.
InvestingPro Tips:
- Zealand's significant revenue growth and high gross profit margin could be seen as indicators of the company's potential to capitalize on its clinical advancements.
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Full transcript - Zealand Pharma ADR (ZEAL) Q4 2023:
Operator: Good day, and thank you for standing by. Welcome to the Zealand Pharma Results for Full Year 2023 Webcast. At this time all participants are in a listen-only mode. After the speaker's presentation there will be a question-and-answer session. [Operator Instructions]. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today Anna Krassowska, VP of Investor Relations. Please go ahead.
Anna Krassowska: Thank you, operator. Welcome, and thank you for joining us today to discuss Zealand's results for the full year of 2023. With me today are the following members of Zealand's management team. Adam Steensberg, President and Chief Executive Officer; Henriette Wennicke, Chief Financial Officer; and David Kendall, Chief Medical Officer. You can also find the related company announcement and annual report on our website at zealandpharma.com. As described on slide two, I caution listeners that we will be making forward-looking statements that are subject to risks and uncertainties. Moving to slide three, I will turn the call over to Adam Steensberg, President and CEO. Adam.
Adam Steensberg: Thank you, Anna, and thanks for everyone for joining today. 2023 was an extraordinary year for Zealand. I'm very proud of our team's performance to deliver significant progress across our obesity and rare disease assets, while building a strengthened financial position. In obesity we reported positive Phase 1 results for petrelintide that support our conviction for amylin potential as a monotherapy and an alternative to the GLP-1-based therapies. With dapiglutide, we have a truly differentiated GLP-1 containing molecule and we are very excited about the trials evaluating its potential to address not only obesity, but also low-grade inflammation associated with metabolic diseases. Our partner Boehringer reported Phase 2 results for Survodutide in obesity and advanced the molecule into a global Phase 3 program and yesterday's top line results in MASH [ph] provide evidence of clear differentiation that potentially positions Survodutide to become a leading GLP-1 containing weight loss medication. And finally with two NDA submissions we progressed our rare disease products into the regulatory phase towards patients who need them. Moving to slide four, Zealand is well positioned to achieve significant milestones in 2024. We look forward to important clinical results for both of our wholly owned and differentiated obesity assets that we anticipate will position us to expand our efforts and advance into substantial Phase 2b trials. We will work closely with the FDA during the NDA review of our two rare disease assets dasiglucagon in congenital hyperinsulinism and glepaglutide in short bowel syndrome. For these assets, we also expect to progress our partnership discussions further. This year we also expect two of our preclinical programs targeting inflammation to move into first in human trials. Moving to slide five, I will now turn over the call to our CMO, David Kendall to discuss our R&D pipeline. David.
David Kendall: Thank you, Adam. Today I'd like to focus my remarks on the continued progress of our obesity programs and also provide an update on the regulatory progress with our rare disease assets. Turning to slide six, and beginning with petrelintide, our long-acting amylin analog many of you are aware that we presented data demonstrating a mean weight loss of more than 5% in healthy lean and overweight people after weekly doses at both 0.6 milligrams and 1.2 milligrams administered for six weeks. Data presented in full at Obesity Week 2023. We are both excited by the opportunity that our amylin analog represents and are very encouraged by the significant weight loss observed, which we believe is on par with the results reported in the initial short-term studies of GLP-1 based therapies. Importantly, we also believe that the side effect profile and tolerability of petrelintide offer the opportunity for a considerable improvement as compared to the adverse event profiles reported with Incretin or GLP-1 based treatments. In addition, amylin agonism provides a unique alternative mechanism for achieving weight loss in those with overweight and obesity by reducing food intake, restoring leptin sensitivity and inducing satiety, which is a mechanism distinct from the appetite suppression observed with GLP-1 based therapies. Furthermore, non-clinical data support that amylin agonist like petrelintide may offer the potential for preservation of lean mass and as such a higher quality weight loss as compared to incretin based treatments. In addition, both our own and clinical observations with other amylin analogs have demonstrated improvements in cardiovascular risk factors, such as C-reactive protein, lipids, blood pressure and heart rate, supporting a potential for cardiovascular protection from this class of therapy. This profile supports our conviction for developing petrelintide as monotherapy to achieve and maintain weight loss and thus provide an alternative to GLP-1 based therapies, with the potential for improved tolerability, preservation of lean body mass, and improvements in cardiovascular risk. The next key readout for our petrelintide program will be the top line results from the 16-week multiple ascending dose trial, exploring significantly higher doses of petrelintide using a dose titration scheme, with data anticipated later in the first half of 2024. We expect these results will further inform our plans for a large Phase 2b trial planned for initiation in the second half of 2024. Turning to slide seven, and turning our attention to dapiglutide, our first in class and only in class dual GLP-1, GLP-2 receptor agonist, we await data readouts from two clinical trials to be reported in 2024. In the first half of 2024, we anticipate top line results from the investigator-led DREAM trial, evaluating not only the potential of this therapy to provide significant weight reduction, but also assessing dapiglutide's potential to address both the low-grade inflammation associated with metabolic disease that drives organ damage, and achieve improvements in gut barrier function, which may play an important role in the management of those with obesity-related metabolic diseases. In the second half of 2024, we also look forward to top line results from the 13-week dose titration trial, evaluating higher doses of dapiglutide than are currently being explored in DREAM and the previously reported Phase 1 multiple ascending dose trial, in which a mean relative reduction in body weight of 4.3% was observed after weekly dosing over four weeks. We furthermore anticipate that these results will inform and lead to the initiation of a large Phase 2b trial planned for start-up in the first half of 2025. Turning now to slide eight in the Survodutide program, the glucagon/GLP-1 dual agonist being developed by Boehringer Ingelheim. As was reported earlier this week and at prior scientific congresses, Survodutide has demonstrated efficacy in treating obesity, and now has demonstrated a positive effect in individuals with metabolic dysfunction associated steatohepatitis or MASH. We are particularly excited with the recent reported top line results from the Phase 2 trial in MASH, which demonstrated that 83% of participants treated with Survodutide showed a biopsy-proven improvement in liver disease due to MASH, stages F1 to F3, after 48 weeks of treatment when compared to placebo. Importantly, there were also significant improvements in all secondary endpoints and the significant improvements in measures of fibrosis, a key secondary endpoint in this trial. These exciting and important results provide evidence for clear differentiation of Survodutide amongst current GLP1 containing weight loss medications, and we look forward to detailed results of this MASH study, which will be presented at an upcoming medical congress. Now turning to slide nine and to offer an update on our rare disease programs. For Dasiglucagon and congenital hyperinsulinism, we’ve had productive and informative interactions with regulatory authorities and now have greater clarity on the path forward for these regulatory submissions. This information puts us on track for resubmission of the NDA Part 1 or Original 1 for up to three weeks of treatment. The resubmission follows the complete response letter issued by the FDA in December last year, related to deficiencies identified at a third-party manufacturing facility that are not specific to Dasiglucagon. We look forward to responding to and resubmitting the information to the FDA before the end of the first half of 2024. In addition, we anticipate completing and submitting Part 2 of the NDA for the use of Dasiglucagon in CHI beyond the three weeks of treatment, also in the first half of 2024. Our plan is in place to submit the additional analyses requested by the FDA from existing continuous glucose monitoring data sets that were included as secondary outcome measures in the Phase 3 program. These additional data will support use of Dasiglucagon beyond three weeks of treatment, something the vast majority of children with CHI will require. We believe that Dasiglucagon, if approved, can be an important and effective treatment option for this rare and devastating disease. This program represents a significant opportunity for Zealand to address a major unmet medical need for these children and their families. We plan to make Dasiglucagon available to U.S. healthcare professionals and patients as soon as possible after regulatory approval and expect to continue to engage with potential partners for future commercialization. Turning to slide 10, in glepaglutide, our long-acting GLP-2 that we believe has the potential to be the best in-class therapy for the treatment of adult patients with short bowel syndrome who are dependent on parenteral support. The NDA for glepaglutide was submitted in December 2023 and now has been accepted for full review. We anticipate notification of a PDUFA date in the coming weeks. And with that, I would now like to turn the call over to our Chief Financial Officer, Henriette Wennicke, to review our financial results for the full year 2023. Henriette?
Henriette Wennicke: Thanks, David, and hello everyone. Let's move to slide 11 and the income statement. Revenue for the full year of 2023 was DKK 343 million. This was mainly driven by a EUR 30 million milestone payment from Boehringer Ingelheim, as well as a U.S. $10 million milestone from Sanofi (NASDAQ:SNY). Operating expenses for the full year of 2023 were DKK 896 million compared to DKK 941 million in the same period of 2022. The decrease was driven by lower sales and marketing expenses, as well as lower admin expenses due to the cost reduction efforts following the restructuring announced in March 2022. This was partly offset by higher R&D expenses. In fact, 76% of OpEx was allocated to R&D activities in 2023, driven by the progression of the late-stage rare disease assets towards submission and significant investments in the advancement of our wholly owned obesity programs. We expanded our workforce by approximately 30% in 2023 to support these efforts. Net financial items for 2023 resulted in a loss of DKK 137 million, driven by the final repayment and termination of the loan with Oberland Capital in May 2023. Let's move to slide 12, and the cash position. In 2023, we have taken significant action to strengthen our balance sheet. In April, we raised DKK 1.5 billion in progressive proceeds from a private placement of new shares. In May, we settled and repaid the debt facility with Oberland Capital. Also in May, we established a DKK 350 million with revolving credit facility. In December, we obtained a EUR 90 million debt facility with the European Investment Bank. And finally, early January 2024, we raised DKK 1.45 billion in gross proceeds from a private placement of new shares. As a result of these actions, we now have a cash position of approximately DKK 4.1 billion. I must say I'm very satisfied with our financial position, which now takes our runway into 2027. This solid foundation allows us to expand our investment in our wholly owned obesity programs, to ensure we have the right speed and quality in the advancement of these assets as we conclude Phase 1 and initiate Phase 2b. At the same time, we will continue to invest in progressing our rare disease program product candidates through the regulatory phase, while engaging in partnership discussion. And this takes me to slide 13, and our financial guidance. In 2024, we will increase our investment and be guided for net operating expenses of between DKK 1.1 billion to DKK 1.2 billion. We do not provide guidance on revenue anticipating from existence and potential new license and partnership agreements due to the uncertainty related to the timing as well as the size of such revenue. Let's move on to slide 14 in our ESG strategy. Beyond the clinical and financial progress we made in 2023, we also refined our ESG strategy and initiated preparation for the CSRD requirements. At Zealand, we are committed to changing life with next generation peptide therapeutics, and we do recognize the importance of operating a responsible and sustainable business as we grow and expand our pipeline. Therefore, we have identified three pillars within sustainability which are affected by our activities. First pillar is our patients. We leverage innovation to advance the health and well-being of patients. Our work is to develop patient-centric treatments that solve severe unmet medical needs, which is why the vast majority of our resources are allocated to this. Second pillar is our people. We strive to foster an engaging, enriching and inclusive workplace for our people, which we measure through engagement scores and turnover rates. Both of these measures came out very positively in 2023 with an engagement score of 8.8 on a 10 point scale. The third pillar is our operations. We take responsibility for our impact of our operation and focus on minimizing and mitigating our climate impact, while having proper controls in place to avoid adverse events. For each pillar, we have a well-set clear goals and ambitions to ensure that Zealand continues to act responsibly and sustainably. And with that, we will move to slide 15 and I will turn the call back to Adam.
Adam Steensberg: Thank you, Henriette. Looking ahead, I expect an exciting next 12 months with several key events and catalysts across our therapeutic areas. In obesity, we expect top-line results from the 16-week clinical trial with our amylin analog, petrelintide. Later in the first half, we expect these results will further inform our plans for a large Phase 2b trial planned for initiation in the second half of the year. For dapiglutide, we expect top-line results from the investigator-led Phase 2 trial in the first half, followed by top-line results from the 13-week trial in the second half of 2024. In rare diseases, NDA submissions allow for potential regulatory approvals in 2024. And in chronic inflammation, we expect two preclinical programs to advance into the clinic this year. So in summary, I look very much forward to a phenomenal 2024 that has the potential to elevate Zealand into a new league. We are progressing our product candidates in obesity and rare diseases with quality and speed, backed by a solid balance sheet and our engaged, experienced, and enthusiastic employees who are committed to deliver throughout the year. And with that, I will now turn over the call to the operator for questions.
Operator: Thank you. [Operator Instructions]. Our first question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead. Your line is open.
Rajan Sharma: Hi. Thanks for taking my question. First one, just on the NASH trial yesterday, and I realize that kind of we'll see the data at a medical conference, but I was just wondering if there are any exploratory endpoints which look at fibrosis improvement with no worsening of NASH? And then secondly, just on petrelintide, I'm just wondering if you could give us some color on how you are thinking about the buffer efficacy at 16 weeks in the context of some competitor data that we've seen this morning? Thank you.
Adam Steensberg: Thanks for those questions, Rajan. So first on the NASH data, on survodutide data, it really is up for Boehringer to release these further insights into these data at a scientific conference here in the first half. So we can unfortunately not provide more flavor on the data, but we look very much forward to Boehringer sharing these data later in the first half. And we are, as I think is clear from also press releases, extremely excited with the top line results that has been released and believe that the server looks extremely promising here. For petrelintide, our amylin analog, maybe I'll just start here and then hand over to David. As you mentioned, we expect to have 16-week data coming out in the first half of the year. And I think it's incredibly important to understand that what we are developing petrelintide for is, as an alternative to the GLP-1. So for us, it's really about passing the bar for weight loss, the weight loss that patients are looking for. It's not like we are competing with the GLP-1 class. So our bar is really relating to achieving GLP-1 like weight loss, then we would be more than happy. And if you look into some of the early studies, that is in the range of 7% to 9% weight loss. And that for me would be definitely enough to define petrelintide as a potential future winner in this space, because it's an alternative for those patients who cannot tolerate a GLP-1 or would like to try something else. The data that just came out this morning on a GLP-1 GIP, we have honestly not had the time to look into the details of those data, but I would expect them to look similar to other GLP-1 GIP containing molecules as they are built on the same concept. David, any additions to this?
David Kendall: Yeah, I'll just add. Thanks Rajan. Some flavor to Adam's comment for petrelintide, and I think the long-acting and we think more potent amylin agonists, at least in these short-term trials, 12 to 16 weeks, I would anticipate that high single-digit weight reduction. But having seen in the six-week low-dose part one of the trial previously reported, achieving in excess of 5%, I think that for us would give us a clear indication that it meets the threshold that Adam described. Obviously, both for petrelintide and other amylin agonists, extended treatment out beyond 24 to 36 weeks will be what is necessary to get the clearest read on both the dose response to this therapy, and give us insights into whether we achieve weight loss that as Adam says, we anticipate to be on par with GLP-1s. I think there's one historic reference, which is older studies with high-dose Pramlintide, now a shorter acting agent, which as you may recall, achieved nearly 10% weight reduction in Phase 2 studies. So I think without trying to predict trial results, those are the range of responses that in a 16-week trial we would be looking for to fit with the pattern that we would anticipate for this drug.
Rajan Sharma: Brilliant. Thank you very much.
Operator: Thank you. We'll now move on to our next question. Our next question comes from the line of Lucy Codrington from Jefferies. Please go ahead. Your line is open.
Lucy Codrington: Hi. Thank you for taking my questions. I appreciate there's limited information you can give on the MASH data, but perhaps you could remind us of the rationale for including the F1 patients within this trial and, I guess, any idea if what the proportion of the F1 patient were in the trial. And I appreciate, again, we may need to wait for this with the detailed data, but is it fair to say that the NASH improvement is maybe a potentially easier endpoint, I would assume, than NASH resolution? And any reason to expect that the NASH resolution endpoint would be materially worse than what we've seen with the likes of tirzepatide, which reported on NASH resolution as opposed to NASH improvement? And then on the amylin, understood on what we're looking for in terms of efficacy. It seems to me that tolerability here is perhaps even more important. And I guess what's your bar here? Do we want to see all mild adverse events when it comes to GI or will some moderate events be okay as long as we're not seeing significantly severe events and/or discontinuations? Thank you.
Adam Steensberg: Thanks, Lucy. I will provide some color first and then maybe David, you can add in. For the for the trial results with survodutide, we can really not provide more flavor on the data until they're presented at the scientific conference. It is really up for our partner, Boehringer, to do this. You are correct that patients with F1 to F3 was included in this study. I think it's important to understand that all studies are – you cannot – you should always be careful when you compare across trials. There were also other differences. For instance, Boehringer did not have BMI requirements into their study, which were actually required into the former studies, so that there are differences. I think what excites us a lot is, this is the first molecule that has reported statistical significant effects on fibrosis. And trust me, others have tried to achieve that as well. So we are extremely excited about that outcome. And then I would say once we have the full data disclosure that at upcoming scientific conferences, that I think is the appropriate time to discuss the differences in more detail. For the upcoming data with petrelintide, I think you are right to the extent that the side effect profiles look benign when we look at our early data. And beyond that, just the fact that it's a different mode of action, it works in satiety and not just on suppressing appetite. It has the muscle wasting potential of preventing of that and then other aspects. I think it's the totality of data that will be important for us as we move forward. But clearly, we expect to see a more tolerable profile compared to the GIT-1 class, because that was what we observed in the six-week study. But David, maybe you want to add something here.
David Kendall: Yeah, I'll make one. Thanks, Lucy, for your question. On the fibrosis question, as Adam said, we will not and cannot go more deeply into these data until such time as our BI colleagues present this. But I think it is important to note that while F1 is considered mild fibrosis, fibrosis is an abnormal reaction. We do not fibroses our liver under healthy circumstances, so reversal even of F1 fibrosis can be considered a significant advance. As Adam said, reversal of fibrosis has sort of been the bugaboo, maybe the Holy Grail, beyond removing fat, reducing inflammation, diminishing the ballooning that's observed. So I think, like you, we're excited to see the details on these data and get an understanding of what changes in fibrosis and improvements in MASH scores are, in a sense, both dependent on no worsening in fibrosis, which was included, and improvements which achieve statistical significance. So I think those are important points to remember as we await the full data set. Secondly, intolerability. Again, there are historical data, some from previous studies with Pramlintide, others with Cagrilintide, that would support that the GI side effects that are observed are both, less intense, less severe, and less frequent than with GLP-1 therapies. I would be premature to say, I dream of a world with only mild adverse events. But given what we've seen in the early trials, I think certainly a more favorable profile, both less frequent and potentially less intense GI side effects could be observed, but ultimately, the data will be the teller of that tale. So we await the 16-week data to give you a much clearer answer on that.
Adam Steensberg: And maybe just to follow-up, I would, as we have been saying for some time, we really think what is needed in this space of weight loss and weight maintenance is differentiated molecules. We have to go beyond just looking at weight loss, and it's about how well do you address comorbidities like MASH, which is one of the most important comorbidities. And then it's of course, can you provide tools to patients who need something that is not based on a tier-one backbone? So, I think our clear focus is to go beyond weight loss. We need to have enough weight loss, but then key to success for future medicines that are going to be launched. That is how well they address comorbidities and provide differentiation beyond weight loss.
Lucy Codrington: Thank you.
Operator: Thank you. We'll now move on to our next question. Our next question comes from the line of Charlie Mabbutt from Morgan Stanley. Please go ahead, your line is open. Charlie Mabbutt, your line is open. Please go ahead.
Charlie Mabbutt: Hi, can you hear me now?
A - Adam Steensberg: Yes.
Charlie Mabbutt: Hi. Charlie Mabbutt from Morgan Stanley. Thanks for taking my questions. I guess firstly, I'd be interested to hear your thoughts on what's actually causing the fibrosis improvement. I guess it'll be interesting to know – do you believe it's the case that all high efficacy obesity treatments are able to achieve fibrosis improvement eventually and that we are seeing that earlier with glucagon agonists given the rapid depletion of liver fat from the very start of the trial, or do you believe that glucagon is actually doing something else special from a fibrosis perspective? And then secondly, I guess just thinking about NASH more broadly, how important do you believe non-invasive biomarkers will be to the success of Survodutide in terms of actually being able to identify suitable patients in that subgroup for the class of therapies? Thank you very much.
Adam Steensberg: Thank you. Again, I will start Charlie and then maybe David can add something. If I should address your first question, again, we definitely expect that Boehringer will also provide more insights into the specific mechanism of action of this drug, and they are already now very clear that they do believe that glucagon contributes to this, and I think they've also published preclinical evidence to support the glucagon component. As a general notice, I would just say, when it comes to fibrosis, we think there's much more in this than just pure weight loss. Of course, we already know there's benefits of weight loss when it comes to liver health. But for the specific effects of each individual molecule, there's much more to it. And I personally believe that Boehringer have a very strong case for the involvement of glucagon on some of the specific pathways that should be more beneficial in fibrosis. When it comes to MASH and the non-invasive biomarkers versus biopsies and so on, I would put it this way again. If you have a weight loss medication that also achieves strong data in MASH, for me, this will be as important as if you have strong data in cardiovascular outcome studies. If you are an obese and overweight individual, 75% of those have [inaudible], so increased level of fat in the liver, and 35% have NASH, some degree of NASH and this is just how it looks today. So that is based on data of obese individuals in the last few years. If we fast forward 10, 20 years, those numbers I expect to go up significantly. So when a physician will see an obese patient in the future, there's a very high likelihood that such a patient will have features of NASH. And there, in that situation, you can say biopsies and biomarkers becomes more important. It becomes the same concept as understanding that the reason that we treat this patient whose obese is actually to prevent a liver failure or liver end-stage organ, just as we have data today to support use of GLP-1s in preventing cardiovascular disease. So I think when you are talking about this category of drugs that also address weight loss and provide additional health into organs, I think these markers will be less important, just as it is the case for probably cardiovascular disease. But David, I don't know if you want to add some flavor to this.
A - David Kendall: Yeah, Charlie, I'll add just a couple of things on the fibrosis front. I think again, we will await the presentation of the formal data set from our BI colleagues. I look forward to that as you do. But as Adam alluded to, glucagon specifically and its effects on free fatty acid trafficking, the ability to clear liver fat and continue to promote liberation of energy from the liver, including energy that's stored as fat, likely plays an important role in reducing the overall injury that comes with fatty liver disease. Fibrosis, again, is a response to injury. A regression of fibrosis would suggest that the mechanism of action reduces that injury profoundly. Your earlier comment that just profound weight loss agents or agents that achieve significant weight loss should also be expected to reduce fibrosis, has not borne out, at least in the Phase 2 trial programs with more potent GLP-1 agonists where weight loss alone without the glucagon component has been used. So I think these are, as our colleagues said, groundbreaking in terms of the prevention and regression of fibrosis. I would at least mechanistically ascribe a lot of that potential to the added glucagon activity. And then to the non-invasive approaches, I think this is a maturing science, and the use of FibroScan and other markers of hepatic injury are still relatively in their infancy. But I would anticipate that as these assets come to market, to Adam's point, the pre-test or prior probability of having a MASH in these individual patients is so high that you'll need convincing. But I think this will certainly be a very important adjunct to use non-invasive testing. Biopsy obviously is what the agencies, the regulatory authorities are looking for, because it is the most definitive in clinical trials. In the future, clinical reality may allow us some degrees of freedom to use these non-invasive tests.
Charlie Mabbutt: Great, thank you very much.
A - Adam Steensberg: Thank you.
Operator: Thank you. We'll now move on to our next question. Our next question comes from the line of Jesper Ilsøe from Carnegie. Please go ahead, your line is open.
Jesper Ilsøe: Thank you so much. A couple of questions, firstly, on Survodutide MASH data. Can you just remind us what you see the base case is moving forward? So will it be a large Phase 3 trial or is there a potential for an accelerated approval? A reason for asking is just that Boehringer Ingelheim interviews has been a bit unclear with indications that will be CMS that will first be launched. Secondly, on the amylin upcoming readout, can you just remind us how you intend to announce results? Do we expect you to top line weight loss results, but not give any detailed safety results? And just on that topic as well, in theory, would your amylin analog be able to be combined with a GLP-1 GIP asset or is it mainly for GLP-1? I fully understand that you guys want to position it as a monotherapy, but just in a partner perspective, whether or not it could be combined as well with a GLP-1-GIP. Thank you.
Adam Steensberg: Thank you, Jasper. And again, it's really hard for Boehringer to also communicate on the future plan for Survodutide in MASH. I think they have been very clear that they are moving forward as fast as possible with this indication. And as you also said, communicated that it's unclear which of the two, obesity or MASH could be the first indication, which again is just in our minds, a strong testament to the commitment to this program. So of course, there's a huge unmet medical need here and Boehringer together with regulators will try to push this forward as fast as possible. But we cannot comment on the timeline, but of course we expect to have more clarity on this throughout the year. So for us, it's just exciting to see these statements. And I would say for Amylin, we will as we always do when we send out top line results, provide a balanced, you can say, review of the top line. So that would of course include both, efficacy and some safety observations or tolerability observations. Combination, it's not like we don't want to combine Amylin, our Petrelintide with other GLP-1s and we also see an opportunity to do so later. We, just as we have said a lot of times, actually believe that there is a much larger need for alternatives to the GLP-1s that are just combination products. But having said that, we will also pursue combination therapies once we have a good understanding of the dosing regime and we are moving into Phase 3 with our Petrelintide or Amylin analog. It has been designed with the opportunity to co-formulate, because it's stable at the same pH levels as the GLP-1s we know of at least. So it is a fantastic opportunity to pursue that opportunity for those patients who need that additional amount of weight loss. But really, we are such firm believers that in a world five years from now, the world will more be looking for alternatives than more of the same. And that is again why we keep highlighting Petrelintide as a crown jewel in our pipeline, because it is one of the most promising alternatives non-increasing weight loss agents in development. Soon there will likely be a lot of GLP-1 containing molecules on the market. They will have to differentiate on how well they address different comorbidities it's not just going to be about how much weight, but at that time the world we believe will really need alternative therapies that can help those patients who don't get the right benefit from a GLP-1 based therapy. David?
David Kendall: Yeah, one other comment to Adam's response around combinations, Jesper as you may recall, we have published preclinical data looking not only at the stability of co-formulation of our petrelintide molecule with GLP-1 based therapies, both semaglutide and tirzepatide, and have shown additivity in the clinical effect, at least in animal models of overweight obesity and that goes back again to historic Pramlintide data which showed additivity even with the – I'll call them now first generation oral therapies like sibutramine, Phentermine. So we fully expect additivity of petrelintide, but I will re-emphasize that Adam is spot on and our thinking is that alternatives with unique mechanisms, potentially with this improved tolerability profile is really our primary focus with the opportunity to do exactly as you say to consider combinations as part of the life cycle management of this asset.
Jesper Ilsøe: Thank you.
Adam Steensberg: Thank you.
Operator: Thank you. We will now move on to our next question. Our next question comes from the line of Suzanne van Voorthuizen from VLK. Please go ahead your line is open.
Suzanne van Voorthuizen: Hi team. This is Suzanne from Kempen. Thanks for taking my questions. Again, congrats on yesterday's data for survo. I think we're also looking forward to the amylin data. Can you elaborate already a bit on the Phase 2b that you are planning for petrelintide. What are your preliminary results on trial design, sample size, patient population, end points, etc. And also if you can share some color on how you are currently thinking about the timing of potentially partnering this asset? What are the considerations on your mind? Thank you.
Adam Steensberg: Thanks Suzanne and thanks for the question. So we cannot provide the details of the Phase 2 design yet. What we have committed to and also communicated is it is going to be a very large Phase 2b study and as we also alluded to at our R&D day, for us it's actually extremely important to do this right, because we think we have potential best in class amylin analog. We think we have the potential to create a new category for weight management, which in our minds with the days that we have seen thus far acknowledging its early days, looks to be a very, very potential strong future category. So we want to do this right and that means of course a last Phase 2b study, not trying to cut corners and making sure we hit the doses right and also have the right extent of exposure before concluding on how to progress into Phase 3. So for us it's important to do it right. Having said that, we will also seek to keep momentum and then I can reassure you that we are deeply engaged in preparing for this study under the anticipation of positive data readout later in the year, so that is our thinking on that one. With regard to partnering for amylin, it is really our ambition to now start the Phase 2b study and hopefully also get to data readout. We think we can build in a lot more value in this asset. We have a very clear strategy for how to progress this asset and then before entering Phase 3, it is in our minds a logical time to initiate a partnership where we have to make large investments into manufacturing and also make sure you have a true global reach. But at that time, we would seek to have strategic rights and stay involved in the program. We think we have a lot to contribute with and also would like to contribute. Yeah, hope that – the next question.
Operator: Thank you. We will now move on to our next question. Our next question comes from the line of Julian Harrison from BTIG. Please go ahead your line is open.
Julian Harrison: Hi. Congrats on the progress, and thank you for taking my question. I'm curious if you could talk more about the payer supported and self-pay segments of the obesity market, your overarching strategies and addressing both. And if there are any specific mechanisms of target profiles that are more amenable to one over the other.
Adam Steensberg: Thanks for that question Julian, and I think it's highly relevant to consider these things. At least our observation is that there's such a deep patient engagement in these new medicines, because of the huge desire for patients to lose weight. And in the future environment we do expect this to stay, you can say as a very significant segment, the patients who are willing and can afford to pay themselves for these therapies. So ultimately, we do believe that you will of course also have more access from the payer side, because – but that will need, you can say, clear data on organ protection, clinical outcome data, so you can you can describe the full value that that society gets from these weight loss medications. We think it's highly likely that we will see these positive clinical readouts with a number of these molecules that are in development, because we already know that losing weight today is associated with health benefits, and by adding some of these novel modalities that we have discussed today into the this phenomenon, we think there will be a lot of positive clinical outcome data that will support the payer segment. But the segment of patients who will be willing to pay themselves to achieve the weight loss that they have been trying to achieve for many years without being successful, we think will remain a big category. And as a society I truly believe we should be very happy with that, because ultimately that should lead to better health outcomes and a more healthy population. So it's something we are very focused on, when we develop these medicines and also to make sure that we make the right choices, to be able to address the needs and desires from all the stakeholders, but the ultimate goal really is to secure that we will not be hit with this tsunami of comorbidities that associated with the obesity pandemic we are seeing right now. So I think it's a unique – the self-paid segment is a unique opportunity in this space that we really want to embrace in the future.
Julian Harrison: Excellent. Thank you.
Operator: Thank you. We'll now move on to our next question. Our next question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead your line is open.
Rajan Sharma: Hi. Thanks taking my follow-up questions. I'm just – actually on a – from a competitive perspective on the rare disease side, we notice that there's a Phase 1 trial for apraglutide in graft versus host disease, which is expected to read out in the first half of this year. So I was just wondering, to what extent that could be informative to future development plans with glepaglutide. And also potentially, to what extent it may be informative of potential inflammation benefits with dapiglutide, given that also has a GLP-2 component. Thank you.
Adam Steensberg: Thanks for that question. And it is interesting that we discuss the rare disease as it's so little these days, but of course we understand that. And with glepaglutide as we – as David also alluded to in the prepared remarks, we really believe we have a best-in-class GLP-1 analog that has now been accepted for review by the FDA and we have also been very clear to the market that we are looking for companies to commercialize, not only CHI, basic long-term CHI, but also glepaglutide for short-bowel syndrome. And I think one of the reasons is of course, we truly believe there's more to this and with a future partner it would of course be wonderful if they would also look into expanding the label with future studies in future indications. So we truly believe there's much more in this, in GLP-2 than what we have seen just in the first generation GLP-2 gadget that was launched into SBS, and it would be our hope that a future partner would also look into expanding the opportunities with what we believe could become a best-in-class GLP-2. And the whole information aspect of GLP-2 is something that has been heavily understudied. Luckily we're starting to see more and more data of not only indirect effects of GLP-2, but direct anti-inflammatory effects of GLP-2 coming out. And for dapiglutide, it is really for us a unique opportunity with dapiglutide to leverage the GLP-1 effects on weight loss and metabolic benefits and then adding that anti-inflammatory component of GLP-2 into the molecule. In theory, that should be hugely beneficial for not only cardiovascular disease, but also MASH as we discussed before, Alzheimer and other diseases. In general, if you have metabolic challenged organs, you will always see inflammation along that. And we believe with dapiglutide, we have a unique opportunity to address that to a larger extent than some of the other GLP-1 containing molecules.
Rajan Sharma: Thank you.
Operator: Thank you. There are no further questions at this time. So I'll hand the call back to Adam Steensberg for closing remarks.
Adam Steensberg: With that, we would like to thank you all for attending and for your questions. We look very much forward to future announcements and to updating, and connecting in the coming weeks and months. Thank you.
Operator: This concludes today's conference call. Thank you for participating, you may now disconnect. Speakers please stand by.
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