In a recent earnings call, Zealand Pharma (NASDAQ:ZEAL), a biotechnology company focused on the development of peptide-based medicines, reported a robust start to 2024 with a strong cash position and significant progress in its clinical trials. CEO Adam Steensberg highlighted the company's satisfaction with its financial performance in the first quarter, along with the ongoing clinical trials and regulatory interactions. With a cash runway extending into 2027, the company remains committed to advancing its obesity and rare disease programs.
Key Takeaways
- Zealand Pharma reported Q1 2024 revenue of DKK15 million and a solid cash runway until 2027.
- The company completed Phase 1b trials for petrelintide and a titration trial, expecting top-line results in Q2.
- Positive Phase 2 trial results for survodutide in MASH were reported by partner Boehringer.
- The FDA has accepted Part 1 of the NDA for dasiglucagon with a PDUFA goal date of October 8, 2024.
- The NDA for glepaglutide is under review, with a PDUFA goal date of December 22, 2024.
- Zealand Pharma is engaging in pre-launch activities for glepaglutide and seeking a partner before launch.
- The company is in discussions with potential partners for its obesity drugs, focusing on those with a strong ambition to lead in the market.
Company Outlook
- Zealand Pharma aims to develop petrelintide as an alternative to existing GLP-1 based therapies for weight management.
- They anticipate the submission of additional analyses for glepaglutide dosing beyond three weeks in the second half of 2024.
- The company is optimistic about the potential of its assets to play a significant role in treating obesity and addressing unmet medical needs.
Bearish Highlights
- No bearish highlights were provided in the summary.
Bullish Highlights
- The Phase 1b trial for amylin is expected to show a 7-9% weight loss.
- The addition of glucagon to weight loss programs like survodutide may provide additional benefits for liver health.
- Petrelintide has a unique mechanism of action and tolerability profile, positioning it as a promising candidate in weight management.
Misses
- The company did not disclose the full number of cohorts in the Part 2 of the MAD study for petrelintide.
Q&A Highlights
- Executives expressed confidence in finding partners with the right ambition for the future of obesity management.
- They emphasized the importance of dose differentiation in the petrelintide program.
- Baseline characteristics such as gender and baseline weight will be important factors in interpreting weight loss data.
- The initial readout for petrelintide will focus on the impact of body weight by dose and dose titration scheme.
Zealand Pharma (ZEAL.CO) continues to strengthen its position in the biotechnology sector with its focus on innovative treatments for obesity and rare diseases. As the company moves forward with its clinical trials and regulatory submissions, the market will be closely watching for the outcomes of their efforts to provide new therapeutic options for patients.
Full transcript - None (ZLDPF) Q1 2024:
Operator: Good day, and thank you for standing by. Welcome to the Q1 Financial Results Interim Report First Quarter 2024 Conference Call. 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, Vice President, Investor Relations and Corporate Communications. Please go ahead.
Anna Krassowska: Thank you, operator. Welcome, and thank you for joining us today to discuss Zealand's results for the first quarter of 2024. 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 announcements and interim report on our website at zealandpharma.com. As described on Slide 2, I caution listeners that, we will be making forward-looking statements that are subject to risks and uncertainties. Moving to Slide 3, I will turn the call over to Adam Steensberg, President and CEO. Adam?
Adam Steensberg: Thank you, Anna, and thanks to everyone for joining today. I'm very pleased with the performance of our business in the first month of 2024. The progress we have made sets us up for an extremely exciting next few months with key clinical results from all our programs targeting obesity and continuous productive interactions with the FDA on our two rare disease programs. We have completed the Phase 1b multiple ascending dose trials with petrelintide and the investigator-led DREAM trial with titration trial. Both programs are on track for top line results here in the second quarter. For petrelintide, we aim to develop this molecule as an alternative to the GLP-1 based therapies for weight loss and importantly weight maintenance. As we believe the specific mode of action could provide a better patient experience and address some of the shortcomings associated with GLP-1 based therapies. With titration trial, we have a truly differentiated GLP-1 containing molecule is designed to provide significant weight loss with the added potential to address the low grade inflammation associated with metabolic diseases. Through the DREAM trial, we expect to mainly gain mechanistic insights into the effects of the GLP-1 and GLP-2 receptor components. As this trial only included lower doses of dapiglutide and thus will be less informative on the weight loss potential in the second half of the year. However, we expect top line data from a 13 week dose titration trial investigating significantly higher doses of dapiglutide. In February, our partner Boehringer reported groundbreaking top line results from a Phase 2 trial with survodutide in MASH providing evidence of effect on fibrosis and thus a clear differentiation that precision survodutide as a potential future leading increasing based weight loss medication. Results from this trial will be presented at the ease of progress here in early June. In rare diseases, we now have PDUFA Gold Days for dasiglucagon in congenital hyper insulin and for glepaglutide in short bowel syndrome in the fourth quarter. Lastly, we significantly strengthened our balance sheet through a private placement with two renowned international investors in early January, securing a runway into ‘27. Moving to Slide 4. With the strong start of the year, we remain on track to deliver on our key priorities for 2024. We look forward to important clinical results for both petrelintide and dapiglutide that we anticipate will position us to advance into large comprehensive Phase 2b trials and thus significantly expand our efforts towards developing the next generation of obesity treatments. To address what we believe is the largest healthcare challenge we have seen in modern times. For the past year, we have already made significant investments into the organizational capabilities required to deliver on this next development phase, and we expect to accelerate those air force as we progress through the year. Our true rare disease at dasiglucagon in congenital hyper insulin and glepaglutide for short bowel syndrome are an active value by the FDA with the PDUFA date in Q4. In parallel with the regulatory process, we are engaging in partnership discussions for future commercialization. We are also advancing our preclinical programs targeting chronic inflammation towards the clinic and expect to initiate first in human trials with our Kv1.3 ion channel blocker this year. We intend to provide an update on the potential next steps with the complement C3 inhibitor in due cause. Moving to Slide 5, I will now turn over the call to our Chief Medical Officer, David Kendall to discuss our R&D pipeline. David?
David Kendall: Thank you very much, Adam. Today I would like to focus my remarks on the continued advancement of our obesity program and also provide an update on the regulatory progress with our two rare disease assets. Turning to Slide 6, I will begin with petrelintide, our long-acting amylin analog. Amylin agonism provides a unique and distinct mechanism for achieving weight loss in people with overweight and obesity, and represents an exciting potential alternative to incretin-based treatments. Amylin agonism reduces body weight by enhancing satiety and restoring leptin sensitivity in contrast to the reductions in appetite and prospective food intake that are observed with GLP-1 based therapies. Furthermore, non-clinical data have demonstrated that amylin agonists, including petrelintide, offer the potential to preserve lean body mass and therefore provide higher quality weight loss when compared incretin-based treatments. In addition, both our own observations and clinical observations with other amylin analogs have demonstrated improvements in cardiovascular risk factors such as blood pressure, lipids, and markers of vascular inflammation without increasing heart rate, supporting the potential for improving cardiovascular risk. We have previously presented data demonstrating a mean weight loss of more than 5% in healthy, lean, and overweight and obese individuals after weekly doses of both 0.6 and 1.2 milligrams administered for six weeks. With these data presented in full at obesity week 2023. We remain both optimistic and excited about the potential for our amylin analog and are very encouraged by the significant weight loss observed, which is similar to results reported in initial short-term studies of GLP-1 based therapies. Importantly, we also believe that the tolerability profile of petrelintide offers the opportunity for a considerable improvement compared to the adverse event profiles reported in clinical trials and experienced in real world settings with incretin-based treatments. We are on track and expect to report top line data from the 16 week trial of petrelintide late this quarter. In this Phase 1b trial, we are exploring significantly higher doses of petrelintide using a dose titration scheme, and we anticipate this trial will inform both doses and dose titration schemes plan for a comprehensive Phase 2b trial, which is expected to initiate in the second half of 2024. In line with Adam's initial remarks, GLP-1 like weight loss after 16 weeks would reinforce our conviction that petrelintide has the potential to be an effective monotherapy and may represent an appealing alternative to GLP-1 based therapies for both achieving and maintaining weight loss. We truly believe that with petrelintide, we have a unique opportunity to establish a new class of therapies for the treatment of overweight and obesity. Turning to Slide 7, and turning our attention to dapiglutide, our first-in-class and only-in-class dual GLP-1, GLP-2 receptor agonist, dapiglutide is designed as a potent GLP-1 agonist targeting significant weight reduction, and offers the potential to also leverage GLP-2 pharmacology and improve gut barrier function, as well as addressing the low grade inflammation associated with metabolic disease, representing a truly differentiated incretin asset. In obesity, low grade inflammation is thought to further drive many common comorbidities, and we believe that dual GLP-1, GLP-2 receptor agonism can play an important potential role not only targeting weight loss, but also directly affecting a number of key obesity-related comorbid conditions, including liver disease, cardiovascular disease and neurodegenerative disease, including Alzheimer's. We anticipate reporting top-line data from the investigator-led Phase 2a DREAM trial in the coming weeks. DREAM was specifically designed to provide an initial assessment of the potential of dapiglutide to both reduce body weight and target low-grade inflammation as well as address the well described abnormalities in gut barrier function. The initial top-line data will focus on weight loss as well as safety and tolerability and we look forward to further detailed results, assessing inflammatory markers and gut biopsy findings, which will be presented at future scientific meetings. Speaking to the weight loss potential of dapiglutide, it is important to highlight that the DREAM trial is exploring dose strengths of dapi up to 6.0 milligrams, which were also assessed in the previously reported multiple ascending dose trial, where a mean relative reduction in body weight of 4.3% was observed after weekly doses over four weeks. In the ongoing Phase 1b trial, we are exploring significantly higher doses of dapiglutide over 13 weeks of treatment using a dose titration scheme and expect top-line data in the second half of 2024. These data will be used to more fully inform plans for the larger Phase 2b trial, which is expected to begin in the first half of 2025. Turning now to Slide 8 in the survodutide program, the glucagon GLP-1 receptor dual agonist being developed by Boehringer Ingelheim. Boehringer reported the exciting and impressive top-line data from the Phase 2 trial with survodutide in people with metabolic dysfunction associated steatohepatitis or MASH in February. These data demonstrated that 83% of participants treated with survodutide showed an improvement in biopsy measures of MASH without worsening of fibrosis, stages F1, F2 and F3 after 48 weeks when compared to placebo. Importantly, survodutide also met all secondary endpoints, including a statistically significant improvement in liver fibrosis. This is the first report demonstrating an improvement in fibrosis with a GLP-1 based therapy, providing evidence for differentiation among GLP-1 containing weight loss medications. We look very much forward to seeing these data presented in full at the upcoming European Association for the Study of the Liver Congress in Milan on June 7th. Based on the positive results from the 46 week Phase 2 trial in people with obesity and overweight presented last year at both the American Diabetes Association and the European Association for the study of diabetes as well as the positive results from the previous 16 week Phase 2 trial in Type 2 diabetes patients, survodutide is now in Phase 3 for the treatment of obesity and overweight with recruitment into the trials progressing very well. Boehringer have also communicated that they anticipate moving forward with Phase 3 studies in MASH as quickly as possible. Now turning to Slide 9 for an update on the regulatory status of our program for dasiglucagon in congenital hyperinsulinism. Following the complete response letter issued by the U.S. FDA in December of last year identifying deficiencies at a third-party manufacturing facility that were not specific to dasiglucagon. We have now resubmitted Part 1 of our NDA, so called original one, which targets dosing of Dasiglucagon of up to three weeks duration. This NDA has now been accepted by the U.S. FDA with the PDUFA a gold date October 8, 2024. This represents a significant opportunity for Zealand to address a major unmet medical need for these children and their families. If approved, we plan to make dasiglucagon available to U.S. healthcare professionals and patients as soon as possible and continue to actively engage with potential partners for future commercialization. We also expect to submit the additional analyses requested by the FDA from existing continuous glucose monitoring data sets in support of part two of the NDA for dosing beyond three weeks in the second half of 2024. We anticipate that longer term therapy will be necessary for the vast majority of children living with congenital hyperinsulinism. Turning to Slide 10 and glepaglutide are long-acting GLP-2 analog that we believe has the potential to be the best in class therapy for the treatment of adult patients with short bowel syndrome and intestinal failure who are dependent on parenteral support. As we have previously shared, the NDA for liraglutide was submitted in December, 2023 and is now under active review at the FDA with the PDUFA Gold date of December 22, 2024. As with our CHI program, we are actively engaged in partnering discussions for glepaglutide. And with that, I would like to now turn the call over to our Chief Financial Officer, Henriette Wennicke to review financial results for the first quarter of 2024. Henriette?
Henriette Wennicke: Thanks, David, and hello everyone. Let's move to Slide 11 and the income statement. Revenue for the first quarter of 2024 was DKK15 million. This was mainly driven by the license and development agreement with Novo Nordisk (NYSE:NVO) for Zegalogue. Operating expenses for the period were DKK266 million driven by research and development expenses, which represented 72% of Zealand OpEx. The increase in research and development expenses compared to the same period last year is driven by the clinical advancement of our wholly owned obesity pipeline and activities supporting the regulatory review by the U.S. FDA of the late stage rare disease assets. Selling and marketing expenses primarily led to activities associated with dasiglucagon, which seen and will make available to patients in the U.S. once approved. The increase in admit expenses is a result of the straightening of the IT infrastructure and organizational capability is in selective corporate functions as well as legal expenses related to our patent portfolio. Net financial items in the first quarter of 2024 of DKK26 million are mainly driven by interest income, common investment in marketable securities. Let's move to Slide 12 and the cash position. As of March 31st, cash, cash equivalent and marketable securities were approximately DKK3.2 billion and DKK3.6 billion, including the undrawn credit facility. In Q1, the balance sheet was significantly straightened. In January, we raised DKK1.45 billion from a direct issue and private placement of new shares, and in March trends a of the loan facility the European investment bank was dispersed representing EUR50 million. With a cash runway into 2027, Zealand has never been in a stronger financial position, and this solid foundation allow us to invest in our old wholly-owned obesity program with the right speed and quality. As we conclude Phase 1 and embark on initiating last Phase 2b trials. At the same time, we are in a strong position to continue the more detailed partnering discussion power rare disease programs. And this takes me to Slide 13 on our financial guidance. Let me keep this brief. As our guidance is unchanged, we continue to guide for net operating expenses of between DKK1.1 billion and DKK1.2 billion. And with that, I will move to Slide 14, and turn the call back to Adam for concluding remarks.
Adam Steensberg: Thank you, Henriette. We are rapidly approaching some of the most exciting weeks and months in the history of Zealand. Our differentiated obesity assets holds a transformational potential and could elevate the company into a new leak for petrelintide. Specifically, we have an opportunity to create an entirely new class of medicines for weight management and thus play an important role in framing the future landscape for treatment of obesity. Within the next 12-months, we expect to be well into large and comprehensive Phase 2b trials for both petrelintide and dapiglutide. We have invested significantly in setting up the organization for this next phase of development. Zealand is ready to move ahead with speed and quality. Also, within the next 12-months, our two rare disease programs will have completed the regulatory review process in the U.S. with both dasiglucagon in congenital, hyperinsulinism and glepaglutide. In short bowel syndrome, we have an opportunity to address major unmet medical needs for patients. Finally, our next wave of peptide innovation targeting chronic inflammation will have ended early clinical development. Thank you all. I'll now turn over the call to the operator for questions.
Operator: [Operator Instructions] Your first question comes from the line of Rajan Sharma from Goldman Sachs.
Rajan Sharma: I think it's actually the second quarter in a row that there's been kind of new obesity data on the day of your quarterly results. So similar question to last quarter. Could you just provide, your thoughts on the extent to which the Roche data this morning as well as kind of other competitor readouts recently changed the dynamics in terms of the profile that you think you need to achieve with petrelintide and dapiglutide, if at all. And then just kind of a second follow up on partnering discussions on dasiglucagon and glepaglutide. Now that you have the PDUFA dates for both and more clarity on the competitive landscape in short bowel syndrome specifically, should we expect updates on those processes during 2024? Is that likely to come after the respective PDUFAs?
Adam Steensberg: Thank you all again for those questions. I will start and maybe, David will add some flavors also on the -- you can say data readout on the BC -- in the big BC space. If I start with the updates on the rare disease programs and partnering discussions, then -- at this call, we now communicate our PDUFA date for the Original 1, which a 3 week indication and also our intention to submit Original 2 in the second half. And we continue to have good dialogues there, in parallel, as in the year there also, the experts and David as well, we are preparing for making this product available to patients once approved and continue partnership discussion with the ambition of having a commercial partnership established at the right time. So we have a good dialogue. On dapiglutide, we have just started those discussions following the acceptance of the PDUFA file and also data readout from one potential competitor. We are happy with where we are in those discussions. They have been now started, and we have a significant interest, as you can imagine, with a potential to have a best-in-class molecule to address unmet medical needs for patients with short bowel syndrome that is of high interest, I would say. So we will, of course, communicate to the market once those discussions materialize, but we will not provide specific guidance on when. I will share that also that, we are, of course, in parallel with those discussions also making all the commercial preparedness to be able to launch the product, but we will provide updates as we progress those discussions. Regarding clinical data readouts, I think it is no surprise to us and I don't think it should be to any that, we will continue to see more and more data readouts in this space, as we see more players being active here. An important thing for Zealand Pharma is that, we are truly focused on developing differentiated assets and not, you can say, things that are carrying the same mode of actions of medicines that you already have on the market on late-stage development. And I think that is where, from our point of view, data sets regarding molecules that are based on a GLP-1 TIP backbone is not something that really changed our view on how we would position or develop our molecules, because you can say, it is already you already have, you can say, products like that either on the market or in development. Our focus is to come up with novel differentiated products that either target comorbidities to obesity in a differentiated way compared to the existing nicotine base and that is mainly for products where we have GLP-1 as a backbone bone like with survodutide or with dapiglutide. And then, of course, as we continue to discuss more and more about amylin as an alternative and novel class. And here, I would say the data for any GLP-1 would not change our scope here and opportunity to develop something for those patients who don't have perhaps the optimal experience in the GLP-1. We don't think any of the other GLP-1s would be among many of those patients the obvious choice, but a novel non-inquetine based mechanism would be. For us, it doesn't change our plans. And I would also say, in my mind also, it doesn't change the future healthcare space of it, you can say, in the sense that, there'll be plenty of opportunity to differentiate with novel modalities in the future. David, do you want to add anything to this?
David Kendall: Yes. Thank you, Adam. I agree wholeheartedly that these data from Roche and other recent reports with GLP-1 based therapies do not substantively change either our perspective or the landscape. It's a follow on to what has now been reported with tirzepatide in many settings. But to Adam's point, I think for us, the data readouts and the advancement of information, for example, of Lilly's amylin agonist, and the amylin or combined amylin GLP-1 program at Novo have added further strength to our position, which is that our amylin agonist petrelintide still has a very important potential role to play. And so this unique mechanism as Adam referred to with distinctive mechanisms of action and potentially a distinctive tolerability profile with efficacy that we would hope would at least mirror that of the GLP-1 alone class. For us, that is really the information that has added strength to the story that we believe petrelintide and amylin agonism can play a critically important role.
Operator: Your next question comes from the line of Lucy Codrington from Jefferies.
Lucy Codrington: Just then following on amylin, and we've obviously seen Lilly move into Phase 2. Just wondering if you could talk us through the relative importance of activity on amylin and calcitonin, all these long acting amylin assets and how you think petrelintide may be differentiated from some of the other assets out there? Secondly, I noticed Boehringer has started a small non-bio based Phase 3 study in obese subjects with MASH. I presume this is separate to a larger study that would be planned. I just wonder if -- I appreciate, it's not your study, but any thoughts on the rationale for that specific study? Then just on the recent collaboration with Beta Bionics and Xeris and what the potential implications are for dasiglucagon in an artificial pancreas, given that their deal does appear to be exclusive for use of -- future glucagon and whether we should therefore, what that would mean for the Phase 3 that may or may not start this year. And then, sorry, one more quick one just on glapa, I presume given that the lack of commentary that unlike dasiglucagon this isn't something you would consider making available whilst you wait to seek a partner. Just confirmation there.
Adam Steensberg: Maybe I will start and then David will add as well to this. If we start with glepaglutide, you can say engaging in the pre-launch activities needed to be ready to -- that any party would need to initiate to be ready to look at the product. And this is of course, our clear ambition to have a partner on board before we launch the molecule. And we have good discussions here and it is a different, you can say animal, if you will, and launching into an ultra-rare indication like, CHI. So, you're correct on those assumptions on the Beta Bionics collaboration, we also expect to provide further updates in the coming months to the market as we progress discussions with Beta Bionics. I think it's important to note that we have a non-exclusive collaboration, meaning that we could work with any company in this space. And our understanding is that Beta Bionics Xeris has now engaged in an exclusive collaboration regarding their glucagon. With that does, should not change our, you can say collaboration, but they -- again, for us, it's important to have non-exclusivity to work with any pump manufacturer in the future for this indication. And we'll provide updates as we progress through the year on this one. I can also, on your observation on the phase smaller Phase 3 study of these individuals with survodutide who also have MASH. That is also our understanding that this is more a program that is targeting the obesity indication and we should expect additional activities, specifically related to MASH development. But again, it will be helpful for to comment on those things. Lastly, and I'm sure that David will add something here as well, on the amylin and calcitonin, we, of course, have a very good idea what we have, and we also have some idea about petrelintide, because we have -- that has been around for a long time, and at least our believers that you have to have the most effective molecules, you need to be addressing both receptors both in the right balance. And we will provide further updates to the market on how we have addressed that relative balance, and other aspects of the molecule for the Lilly molecule and other molecules, we don't have the same insights yet. And you can say ultimately, I guess clinical data will inform us. What I can say is that the translation that we have observed from the animal studies into the initial clinical evidence of weight loss has been very reassuring in our minds that we agreed onto something that looks very right. David, any comments to that?
David Kendall: Yes, happy to add a couple of notes to that, and Lucy, your U.S. colleagues provided a short summary, the other day on, the importance of understanding the receptor biology. I think we're in the early stages of that understanding. But to Adam's point, we do believe that, this complex receptor system with amylin calcitonin that activation at both receptors, not true decas but the amylin mimetic compounds activating both amylin, pure amylin receptors, pure calcitonin receptors, that we believe is one of the components that is important for promoting significant weight loss. And as Adam also alluded to, we will provide further characterization over time of our molecule. And I think that also ties back to other components of these molecules beyond receptor biology. Long half-life with stable drug exposure or pharmacokinetics has demonstrated in other classes of medicines and we believe will be demonstrated with long-acting amylin analogs. That will be another important contributor to the impact on body weight. And then finally the mechanisms I alluded to in my prepared comments, namely that this is a very distinct mechanism, the mechanism of satiety versus the loss of prospective food intake or the desire to eat with GLP-1 or incretin-based therapies, as well as the leptin sensitizing nature of amylin agonism, we believe can contribute both to the experience at the patient level in terms of how they feel, when they're taking the medication. The side effect profile, we've already talked about, and then maintaining that weight loss through each of those mechanisms. So for us, it is uniquely positioned based on much more than just the receptor biology. But an important question nonetheless. So thanks for your questions, Lucy.
Operator: Your next question comes from the line of Thomas Bowers from Danske Bank.
Thomas Bowers: Thank you very much. A couple of questions here from my side. So kicking up with amylin. The Phase 2b trial design, I don't know I'm a bit early out here, but I'm just trying to get a bit of understanding on future timelines here. Are you potentially targeting 40 plus minus weeks? Or could you maybe even see a potential reduction given that you might be able to try trade faster? Just to get a feeling on how to advance as fast as possible toward the pivotal trials here? And then just on -- I'm just wondering whether you had the mid-cycle review yet. And do you have any indication from the FDA regarding a possible outcome here? And then on Dapi, you mentioned it in your prepared remarks, but I just wanted to double check. With the top-line data we get from the DREAM that, there's not going to be any information data at all in those top-line data. That will only be safety and weight reduction. And then just lastly, very quickly here, just on the complement C3, is there something in that, that you see that you want to advance on your own? Or, let's say, the competitive environment changed given that Astra is not pursuing this after all?
Adam Steensberg: Thanks for your questions Thomas. I will start with C3. We cannot provide further, you can say, comments on these programs. We are negotiating the return of the asset with Astra. We will provide updates as those discussions are being completed. For dapiglutide, it will be the top-line weight and safety data from the lower dose that will be recorded, and the mechanistic data will be presented at later scientific conferences. You are correct in that note. And then, of course, in the second half, you will have the Phase 1b with titration and significant higher dose exposure that will also be reported this year. And for Glepaglutide, the mid cycle revenue is still ahead of us, but it's of course approaching and we have no indications of that both yet. And then for amylin, again, it's a bit early for us to provide all the comments on the Phase 2b design. What we have said and what we also maintain is that, this will be a very large and extensive Phase 2b study, which really has designed with quality in mind. It's hand speed, of course. I would say, it will also require the number of weeks needed to fully understand the potential of a molecule like amylin before we move into Phase 3 with this opportunity and also the appropriate titration and so on. You can expect a very thorough Phase 2b study.
Operator: Your next question comes from the line of Laura Hindley from Berenberg.
Laura Hindley: Hi. Laura from Berenberg. Thanks for taking my question. My question is on your partnerships in obesity. Has there been any change in the cadence of your interactions with potential partners for your obesity drugs so far this year versus last year? Can you remind us of what you see as the ideal time to see them to find partners for petrelintide and dapiglutide? And then, how your thinking is evolving on this and do your competitor readouts have any bearing here? And then as a follow-up on amylin, is there a floor value for weight loss that you'll need to see in this Phase 1b trial to go ahead with your planned Phase 2b. And final one on NASH. So Novo has been confident that -- can deliver a statistically significant fibrosis benefit in NASH in its larger and longer Phase 3 trial. If -- does show the significant benefit, how confident are you that server -- can still differentiate?
Adam Steensberg: I will again start and then maybe David have some additional comments. If I start with the partnership discussions, our minds have not changed here in the sense that we for some time of course have had informal discussions with a number of large pharma companies, and trying to understand their views on this market and where it should go. And of course, I think it should be of no surprise to anyone that there's a huge interest in this space as such. So, we have had those discussions, but we have also been very clear that we didn't want to move on to more concrete discussions until we have the next data set. So what we are doing from an internal perspective is that we set our organization and all our efforts off so we can complete deliver on the Phase 2b programs and we will move these programs forward. But of course, as we get data here in this quarter, we will also engage in discussions and see when is the right time to find a partner. For us, it's the right time really will be also defined on that we are reassured that we have partners with the right, you can say ambition. We truly believe we have opportunities, as I said in my prepared remarks to frame the future of obesity management. We think we sit with some very unique differentiated assets and we will only partner with somebody who have an ambition of winning in this space and not just playing in this space. So we actually think that's such a unique and rare situation. We sit in here that we will be, you can say really also looking for the commitments from such a partner before defining what time is right for this. But it's clear to us that there is significant interest as you can imagine. On the amylin Phase 1b study, remember it's a small study. I think it's reasonable to expect, I mean, seven to nine then we are line with others as we have said repeatedly percent weight loss. If it's lower, we would have to look into if that could be static specific reasons for that. But I mean maybe David will provide further comments. I will just maybe beforehand also you David address the MASH trial and say, I think it's pretty well established that weight loss per se are related to MASH improvements overall. So of course, you should expect that weight loss programs will provide some MASH benefits and potentially also some improvements in fibrosis. As we have said all the time, by adding glucagon to that weight loss program, as has been the case with Survodutide then you get a liver specific reason to get energy out of the liver and thus we would at least expect general weight independent benefits on liver and thus significantly higher benefits. So we don't think it will change anything. It will just underscore, you can say the potential of indirect weight loss, but it will still, you can say precision, the product that is most effective in addressing MASH as a potential future leader because MASH is such a huge -- is going to be such a huge issue with obesity in the future. David, do you want to add something to this?
David Kendall: I'll follow on Adam, thank you. On the MASH piece, I think you're spot on that, while there is evidence that there are weight dependent effects on fatty liver and the components of MASH, as Adam alluded to targeting the glucagon receptor appropriately improves free fatty acid trafficking, the metabolism of free batty acid. So there is a unique mechanism added to, we believe the weight reducing effects of survodutide that at least allow the potential to differentiate from GLP-1 alone. So I think if there is significant improvement with weight reduction with GLP-1s, that's a positive for the entire class and then having, if you will, that second signal in this case, the glucagon signal with survodutide can and potentially will offer additional benefits over and above the benefits associated purely with weight change. And I'll go back to Adam's comment on the petrelintide program and what we would expect or at least are anticipating and refer you back to the early data with the 5-plus-percent weight loss over short exposures, I think 7% to 9% if we see with reductions in that range. That is entirely consistent with what has been reported with other amylin agonist and is on par with shorter studies, meaning these 12- to 16-week studies in weight loss with GLP-1 associated -- or GLP-1-based therapies. Similarly, I think what the pattern of weight loss will we see differentiation in doses, which is important to inform Phase 3 really is as important as the absolute number. But given what we have seen previously, anticipating something in that 7% to 9% range, for us would fit with how we have modeled this going forward.
Operator: Your next question comes from the line of Suzanne van Voorthuizen from VLK.
Suzanne van Voorthuizen: This is Suzanne from Kempen. I have one more on the upcoming petrelintide readout. Can you elaborate on the considerations around certain baseline characteristics, like BMI and general split? What we should be keeping in mind when interpreting weight loss data? And to what extent will there be information provided on the samples baseline characteristics in the top line release?
Adam Steensberg: Thank you for the question, Suzanne. And again, I will just start by putting a few comments, and then David, you can add. But of course, it's known, especially in Phase II programs at both baseline characteristics, gender amount of, you can say, the base weight and so on are quite significant, you can say, determines of how much weight or you can achieve. But so is other things related to how you guide the patients and so on. So there are so many things you put into your trial design when you move into Phase 2b, which we have not implemented in a study like this. But I think it's a fair assumption that these are healthy -- all the way to these individuals. So we have not been, you can say, specifically pushing to get the most of these patients into a study like this. So yes, if that is what the question is about. David, do you want to add something?
David Kendall: Happy to. And yes, nice to hear from you. And this reminder is a relatively small study and characteristics like gender and the baseline weight. As Adam said, these are otherwise healthy overweight and tell these individuals -- and, while we will, obviously, at this time or at a future scientific presentation, go through those data in detail. I think for us, what's critical with the initial readout is looking at, the impact on body weights, by dose, and what the dose titration scheme may have taught us. Obviously, the primary measure in Phase I, looking at safety and tolerability, as carefully as possible. This would more than likely be a more homogeneous population, and we will share those data on both the top lines and the future presentations as appropriate.
Suzanne van Voorthuizen: Got it. And then one follow-up. Can you clarify the number of dosing cohorts that are part of the Part 2 of the MAD study?
David Kendall: We haven't disclosed the full number of cohorts, but note that, there are multiple cohorts, which allowed us to, both progress and modify the dosing regimen to get these, what I'll still call, until we have top lines substantially higher doses. But, this is not a single cohort study. We are looking obviously at, significantly higher doses across multiple cohorts.
Operator: Thank you. There seems to be no further questions. I would like to hand back for closing remarks.
Adam Steensberg: Thank you. And with that, we would like to thank you all for attending and for your questions. We look forward to future announcements and updates and to connecting in the coming weeks and months. Thank you.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.
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