Zealand Pharma A/S

Good day and thank you for standing by. Welcome to the Zealand Farmer Results for Q3 2024 Conference Call. At this time all participants are in a listen only mode. After the speakers presentation there will be a question and answer session. To ask a question during the session you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question please press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today Anna Kraskowska. Apologies Anna Kraskowska, Vice President Investor Relations and Corporate Communications. Please go ahead. Thank you.

Welcome and thank you for joining us today to discuss Zealand's Results for the first nine months of 2024. With me today are the following members of Zealand's management team. Adam Steenste, President and Chief Executive Officer. Henrietta Winnicka, Chief Financial Officer. David Kendall, Chief Medical Officer and Eric Cox, Chief Commercial Officer. You can also find the related company announcement 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 Steenste, President and CEO. Adam?

Thank you Anna and thanks to everyone for joining today. I'm extremely pleased with the achievements that they have made in the first part of 2024. At Obesity Week on Tuesday, we presented detailed data from the 16-week phase 1 trial with Petrinatide, our long-acting amelian analog, which we are developing as an alternative to GOV1-based therapies for the management of overweight and obesity. We believe that these results strongly support that Petrinatide is very well tolerated and could provide a better patient experience than -creteine-based therapies while providing similar degrees of weight loss. We expect the first participant in the phase 2B trial with Petrinatide to be dosed very soon. And we are also now exploring collaboration opportunities with large pharma companies. With the right partnership, we believe we have an opportunity to not only develop Petrinatide as an alternative to GOV1-based therapies, but also a potential future foundational of first-line therapy for weight management. In that regard, I'm pleased that with us on the call today for the first time is Eric Cox, who recently joined our management team in the role as Chief Commercial Officer. Eric brings 25 years of commercial and business development experience from biotech and leading global biopharma companies. He'll be a very important contributor as we explore co-development and co-commerciation opportunities for our differentiated obesity programs. We are also very pleased to have reported positive and encouraging top-line data from part 1 of the phase 1B trial with our TLB1-TLB2 dual agonist, Dabiglutide. We believe that this candidate holds the potential to be a -in-class therapy for obesity and inflammation-related comorbidity. The reported data gives us the confidence needed to progress Dabiglutide into a comprehensive phase 2B trial, which is planned to be initiated in the first half of 2025. On the back of the impressive phase 2 data with Cervulotide in mass presented earlier this year, our partner, Werner Ingelheim, recently announced the initiation of a large global phase 3 program for Cervulotide in mass. Werner also announced that Cervulotide has received U.S. FDA breakthrough therapy designation for the treatment of adults with non-cerotic mass and moderate or advanced fibrosis. There is a significant overlap between obesity and mass. And with the clinical data reported to date, the ambitious phase 3 program and the recognition by regulators, we believe that Cervulotide holds potential as a leading -in-base therapy for obesity and mass. Turning to slide 4, I would like to emphasize the reasons why we are so excited about the potential of Pletrointide. We have seen the impact of the first two once-weekly GDB1-based therapies to be approved. In phase 3 clinical trials of longer duration, they have demonstrated potential for 15 to 21 mean weight loss in patients with obesity and positive outcomes on several obesity-related comorbidities. On the flip side, GDB1-based therapies are associated with a number of gastrointestinal adverse events, including nausea, vomiting, diarrhea, and constipation. Real-world data suggest that up to 30% of patients with obesity on a GDB1 treatment stop within a month before reaching their target dose, and within one year, only 60 to 70% of patients withdraw from treatment. With Pletrointide, we are targeting GDB1-like weight loss of 15 to 20% in longer-term phase 3 trials. With potential for higher quality weight loss and a different and better patient experience. As evidenced by recent data with Pletrointide presented at a BCTV, we are confident that Pletrointide has potential for significantly improved GI tolerability profile compared to GDB1 receptor acronyms, suggesting both lower frequency and milder severity of GI adverse events. And with that, let's move to slide 5. As I turn over the call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline. David?

Thank you, Adam. Today, I would like to focus my remarks on the continued advancement of our obesity programs and provide a brief update on our other development activities. Beginning with our novel long-acting amyloin analog, Pletrointide, let's move to slide 6. In the trial design of recently presented detailed data of part 2 of our Phase 1B trial. This was a randomized double-blind placebo-controlled Phase 1B trial, enrolling a total of 48 adults with overweight and obesity. Participants were randomized into one of three dose cohorts, assessing multiple ascending doses of Pletrointide using a dose titration scheme or to match placebo. Study medication was administered weekly for 16 weeks in an outpatient setting, followed by a nine-week safety follow-up period. I would also like to highlight that in this trial, we evaluated doses of Pletrointide up to 9 milligrams and note that the two higher dose cohorts received the maximum assigned maintenance dose for a period of only six and eight weeks respectively. Turning to slide 7. Shown here are the mean weight loss curves across each of the individual dose cohorts and placebo. Pletrointide treatment resulted in reduction in mean body weight of 4.8, 8.6, and 8.3 percent from baseline after 16 weeks of treatment across the three dose cohorts, while placebo treatment resulted in a mean body weight loss of 1.7 percent. We find these data to be even more compelling given that the study population was predominantly male with a relatively low BMI and these results were achieved in the absence of any background lifestyle modification, suggesting that the response observed may have been muted in participants included in this study. Moving to slide 8. Shown here are the individual study participant data on both adherence to study medication and to the dose escalation and scheme over the 16-week treatment period. These data demonstrate that there was both a high degree of compliance with dose escalation and adherence to and completion of study treatment for the vast majority of participants. Only a single trial participant discontinued therapy due to treatment related or Pletrointide related AHEs, which occurred after the third dose while also starting at a 1-milligram initial dose. In addition, one participant in the 9-milligram arm was maintained for an additional week on the 7-milligram dose due to reported tolerability issues. The two other participants who discontinued therapy did so for other reasons unrelated to study medication. Notably, all other subjects followed both the dose escalation steps defined in the protocol and completed Pletrointide treatment as planned. We believe that the ease with which participants achieved their target dose and the proportion of those treated who remained on Pletrointide treatment over the course of this trial support our conclusion that treatment with Pletrointide is both well tolerated and readily dose escalated, further differentiating this from Inkson-based therapies. Turning now to slide 9 and the tolerability profile. Additionally, the vast majority of treatment emergent adverse events reported, including those related to GI tolerability, were reported as mild and only a single participant in the highest dose cohort discontinued treatment due to treatment emergent adverse events. Moving to slide 10, the data reported in this phase 1B trial further demonstrated that all gastrointestinal related treatment emergent adverse events were mild except for the single event of moderate nausea and vomiting, both of which were experienced by a single study participant, the same subject that discontinued treatment. Notably, no other participant reported vomiting and there were only two reports of diarrhea, both of which were mild. Nausea was reported in up to 33% of the Pletrointide treated participants as compared to 17% reported by participants in the placebo group. Additionally, three participants in the highest dose cohort reported constipation, all episodes of which were reported as mild. These data support the observation from earlier trials with Pletrointide and further support our conclusion that Pletrointide offers the opportunity to limit issues of GI tolerability. Overall, these data support and further our ambition for Pletrointide supporting that this novel treatment offers the potential for -1-like weight loss and an improved patient experience as compared to that reported in both clinical trials and the clinical use of -1-based therapies. Moving to slide 11 and the Phase 2B design. As mentioned in the last call, we will continue to progress our development of Pletrointide as a standalone therapy in a large and comprehensive Phase 2B program. The first Phase 2B trial in persons with obesity or overweight with related, weight-related comorbidities, either hypertension or dyslipidemia, will initiate in the coming days. This larger trial with longer treatment exposure will enroll up to 480 adults and will compare multiple doses of Pletrointide or placebo over 42 weeks of treatment with five dosing arms, the highest being 9 milligrams as in the Phase 1B multiple ascending dose Part 2 trial. Participants will be continuing blinded treatment for 42 weeks with a primary endpoint of percentage change in body weight from baseline at 28 weeks. The primary completion is set for November 2025 and will enable us to more fully assess both the efficacy and safety of Pletrointide across a wide dose range to inform the doses to be used in longer-term Phase 3 studies. Note that the primary endpoint at 28 weeks will be used for regulatory interactions about registrational trials with unblinded data readout only after completion of the 42-week treatment period. Key secondary and exploratory endpoints in this Phase 2B study will include an assessment of body composition by magnetic resonance imaging or MRI, change in HbA1c, change in fasting lipids, and change in high sensitivity C-reactive protein or HSCRP. In addition to this Phase 2B study, we expect to initiate a second Phase 2B study in the first half of 2025, exploring weight loss in a population with type 2 diabetes and pre-diabetes, where data support that amylin agonism can potentially deliver weight loss comparable to that observed in non-diabetes population. Further differentiating Pletrointide treatment from GOP1 receptor-based treatments, where muting of the weight loss response has been observed in those with diabetes. Moving to Slide 12, and turning our attention to our other wholly owned obesity asset, Dapiglutide, the potential first and -in-class GLP1-GLP2 receptor dual agonist. Dapiglutide is designed as a potent GLP1 agonist, targeting significant weight reduction, and offers the potential to leverage GLP2 pharmacology to improve gut barrier function and directly address the low-grade inflammation associated with metabolic disease, representing a truly differentiated incretin acid. As we have recently reported, Dapiglutide was evaluated in a single-center randomized double-blind placebo-controlled Phase 1B trial in participants with overweight or obesity. In Part 1 of this trial, a total of 54 participants, approximately 85% of whom were male, with a median baseline BMI of 30, were randomized to receive 13 weekly doses of either Dapiglutide or placebo within three dose cohorts. At Week 13, the estimated mean placebo-adjusted body weight decreased by up to .3% with Dapiglutide treatment. Dapiglutide doses of up to 13 milligrams were assessed to be both safe and well tolerated, with GI adverse events consistent with the frequency and intensity reported in studies of other incretin-based therapies. We are both excited and encouraged by these data, and we look forward to presenting detailed results at a future scientific congress. In addition, in Part 2 of this trial, we are evaluating even higher doses of Dapiglutide, up to 26 milligrams over 28 weeks of treatment. We expect to report top-line results of this part in the first half of 2025. And note that this added component of the Phase 1B study will not impact the timing for initiation of a Phase 2B trial in people with overweight or obesity, which we expect to initiate in the first half of 2025. We will obtain valuable additional insights on the optimal dose and dose escalation scheme to inform both the Phase 2B trial and additional studies, investing the potential of Dapiglutide in obesity and selected inflammation-related comorbidities, including liver disease, cardiovascular disease, inflammatory bowel disease, and neurodegenerative diseases. Moving now to Slide 13 and Servidutide. Along with our Beringer-Ingelheim colleagues, we believe that the data from the Servidutide Phase 2 trial in metabolic dysfunction associated with steatohepatitis, or MASH, is the strongest clinical data set on improvements in MASH and liver fibrosis reported to date. Positioning Servidutide as a potential leading incretin-based therapy for the treatment of obesity in MASH. This leads me to Slide 14. We are very excited that our partner, Beringer-Ingelheim, has initiated a large Phase 3 program for Servidutide in MASH, in addition to the ongoing studies in obesity. Leverage and liverage cirrhosis are global Phase 3 clinical trials, investigating the efficacy and safety of Servidutide in adults with MASH and moderate or advanced fibrosis, and in those with compensated MASH cirrhosis, respectively. Turning to Slide 15 and a few remarks on our rare disease franchise, starting with doziglucagon for the treatment of congenital hyperinsulinism. Following the complete response letter issued by the FDA last month, which was due to the timing of findings and conclusions from the inspection of the third-party manufacturing facility, we eagerly await the new inspection classification. We remain confident in the approvability of this therapy for the substantial unmet clinical needs in CHI and are committed to working with the FDA and our third-party manufacturing partner to bring doziglucagon to patients living with this devastating disease in the months ahead. We still expect to submit the requested and detailed analysis from existing continuous glucose monitoring data sets supporting use of doziglucagon beyond three weeks by the end of the year. In addition, the US FDA has set a regulatory decision goal date of December 22nd for our long-acting GLP-2 analog glopaglitide, which possesses potential -in-class characteristics for the treatment of short bowel syndrome with intestinal failure. And with that, I would like to move to slide 16 and turn the call over to Eric Cox, Chief Commercial Officer at Zeeland Pharma, to review our near-term and future commercial opportunities for our rare disease franchise and obesity portfolio. Eric?

Eric

Cox Thank you, David,

and hello to everyone. I'd like to start briefly talking about our near-term commercial opportunities through our rare disease franchise. Our doziglucagon product is under evaluation for the treatment of congenital hyperinsulinism, an ultra-rare and devastating disease, primarily in neonates and children. Our focus is on bringing this product to patients as quickly as possible. As there are a few existing treatment options, there are a few existing effective treatment options. Our pre-launch activities are in full swing, and we're ensuring that our capabilities across the commercialization spectrum are in place so that we're ready for a U.S. launch in the first half of 2025 contingent on regulatory approval. Our goal is to serve the patients, and all effort is being focused on setting up the necessary structure and resources to accomplish this. For our glopaglutide product, which is currently under evaluation for short-term bowel syndrome, we are currently undertaking pre-commercial activities to enable a launch once approved by the FDA. As glopaglutide is expected to be launched in markets with a large commercial footprint, we're focused on finding a commercial partner for the product to reach as many patients who need these alternatives and ensure commercial maximization. Turning to slide 17, and focusing on the future commercial opportunities of the obesity programs. In particular, I want to talk about why we strongly believe that pentalatide has the potential to become a future foundational therapy, including a first-line option for weight management. With the magnitude of obesity and obesity-related comorbidities, we believe that we are facing the biggest healthcare challenge of our time. Not only is it the pandemic associated with tremendous direct medical costs, particularly to the healthcare systems, it's also the cause of too many preventable deaths. Of the 41 million adult deaths each year due to noncommunicable diseases such as diabetes, stroke, and coronary heart disease, five million are driven by high BMI, and this may be underestimated. The obesity pandemic is rapidly accelerating, and by 2030, it's expected that 50% of adults will live with overweight or obesity. Additionally, utilizing present trends, it's estimated that 40% of children between the ages of 5 and 19 are expected to live with overweight and obesity by 2035, which means this is not only a problem of today, but well into our future. Even though we've seen the first two GLP-1 therapies be approved and marketed, a huge unmet need still persists. There is a need for novel and alternative treatment options with different mechanisms of actions other than the GLP-1 based therapies approved today. The need focuses on providing a new approach to better quality of weight loss, particularly improved adverse event profiles and preserving muscle. Specifically, we see an opportunity to establish a new foundational first-line therapy for weight management. When people are looking for weight loss, we know that approximately two-thirds of adults who want to lose up to 20% of their weight and are looking for a good overall experience in their weight loss journey. However, a significant portion of adults are stopping current GLP-1 therapies early due to their unwillingness to accept gastrointestinal adverse events, including nausea, vomiting, and diarrhea. From the perspective of the healthcare professional, including primary care physicians, we know they have limited time for really complex patient situations. They seek to avoid multiple follow-ups and want overall good patient experiences. This is where pantrelatitis profiles are expected to deliver. This leads me to slide 18 and the target product profile of pantrelatide. We believe that the target product profile of pantrelatide holds a significant potential to become a future first-line foundational therapy for weight management, addressing both the needs of patients and HCPs by targeting weight loss on par with GLP-1s, but with a significantly improved GI tolerability profile and a potentially higher quality of weight loss, including muscle preservation, all coupled with its simplicity, making it easy for HCPs to prescribe and manage. We very much look forward to further evaluate the potential in the upcoming large Phase II-B clinical trial. And with that, I'd like to turn it over to our Chief Financial Officer, Henrietta Wendke, to review our financial results for the first nine months of 2024. Henrietta?

Thanks, Jere. Turning to slide 19 and the income statement. Revenue for the first nine months of 2024 was 54 million DKK. This was mainly driven by the license and development agreement with Numer Nordisk for Stigilov. Operating expenses for the period were 919 million DKK, driven by research and development, which represented 72% of the company's operating expenses. The increase in R&D expenses compared to the same period last year is due to the clinical advancements of the obesity pipeline and activities supporting the regulatory review by the US FDA of the late days where the G-set is. Selling and marketing expenses of 50 million DKK primarily relate to the pre-commercial activities associated with our Rarities assets. The increase in AdMIT expenses is a result of the additional legal expenses related to our patent portfolio, as well as the strengthening of our organizational capabilities at large. The net financial items for the period of 81 million DKK are mainly driven by the interest income from liquidity invested in market securities, which is significantly higher compared to the same period last year as a result of the recent capital increases. And that takes me to slide 20 and the cash position. In the first nine months of 2024, I am very pleased with the fact that we have secured 8.6 billion DKK through capital raises and disbursements of part of the loan facility provided by the European Investment Bank. As of September 30, 2024, cash equivalent and market securities were 9.2 billion DKK, and our strong cash position truly enabled us to make significant investments into our obesity programs. And this takes me to slide 21 and the financial guidance. I will keep this brief as our is unchanged. We continue to guide for net operating expenses of between 1.25 and 1.35 billion DKK. And with that, I will move to slide 22 and turn the call back to Adam for concluding remarks.

Thank you, Hina Jensen. I'm extremely satisfied with our progress in the first nine months of the year, which have created a very strong platform for us to accelerate our growth pursue our vision of becoming a key player in the growing obesity space, and thus play our part in addressing what we believe is the biggest health care challenge of our time. Based on the strong performance in 2024, we're also building momentum into 2025 with additional clinical progress anticipated for our preparatory obesity efforts. For patronetized, we in the first half of 2025 expect to initiate the second planned phase 2B trial while we in the later in 2025 also plan to initiate a phase 1B combination trial with patronetized and a DLB1 receptor agonist. In the first half of next year, we also will initiate a phase 2B trial for our potential first in class DLB1, DLB2 dual agonist, DAPGL type. In the same time frame, we also expect to announce top line results from a cohort of the phase 1B trial evaluating even higher doses of DAPGL type with longer treatment duration. Thank you all, and I will now turn over the call to the operator for questions.

Thank you. As a reminder to ask a question, you will need to press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 1 again. We will take our first question. Our first question comes from the line of Lucy Codrin, turned from Jefferies. Please go ahead. Your line is open.

Hi there. Thanks for taking my questions. A couple from me. Just firstly on the phase 2B design, the five dose arms, can I just confirm, sorry if this has already been said, but is that five different doses or fewer doses but with different titration regimes being evaluated across the different cohorts? And I note you said doses, plural, for the phase 3. So is the intention to take more than one dose through to phase 3 trials? Certainly, one of the competitors was showcasing initial data for their amelan assets at obesity week as well and talked about the calcetone in activity having potential case of the consequent edge could affect GI activity. But is taste diversion something that you are, something you're hearing about from patients taking Petrolin Tide? And then finally, just to clarify on the Dazaglutagone filing, is the part 2 data set already complete and it's just a case of waiting for part 1 to be de-risked? Or is there still additional work ongoing? I'm just trying to work out the timing of what's holding up filing that part 2. And any read across, at what point do we start worrying about the Glepid Leukide approval when this classification hasn't been granted? Thank you.

Yes, thank you for your questions, Lucy. I will just start by addressing the last two and then hand over to David. On the Dazaglutagone resubmission, we do expect to resubmit both, as David said, both the up to three week indication and also the chronic indication. And that, you can say, with the limited time left of the year, also means that you can say that data analysis and so on are completed for both. And we do expect, as David also mentioned, an updated regulatory status for the CMO in the near term. Of course, this is the data between the FDA and the CMO, so it's not in our control. But based on the feedback, we feel quite comfortable that they will change the regulatory status. And of course, if they don't, it could also affect Glepid signs. But again, as I said, we feel comfortable also reassured by the fact that there was no repeat findings. So the findings that caused the original inspection deficiencies have been solved. And we truly believe it is a matter of timing of the re-inspection, which came later into the year than anticipated, and it takes time to make these reports. So David, I will hand over to you on the two first questions, if you will address those.

Yeah, thank you. And Lucy, thanks for your questions. On the Phase 2B design, as I think is apparent from the schematic, what these dose arms identify is different top or maximal exposure doses. So this is classic dose ranging Phase 2 with a similar dose escalation scheme across each. And as noted in the schematic, it will be monthly step ups in the dose escalation, as is for us consistent with both clinical and pharmacy practice. And Phase 3, as I referred to it, doses. I have some experience in this space, referring back, for example, to dual glutide, the truolicity asset at Lilly. We don't obviously know until these data are available whether a single dose will declare itself as clearly the most effective and or well tolerated. So we will, obviously with the data from this trial and the 28-week readout, submit those data for regulatory review and with the agency determine if a single or multiple doses are necessary. So my reference wasn't a certainty, but keeping open the option, as is often the case, both for dose escalation and maximal top exposure dose that you have a maximum and potentially a half maximum dose. So again, the dose arms will have different top doses, but similar dose escalation scheme across the treatment cohorts. The comments on the reports from another compound and the reference to taste diversion consequences. First and foremost, we have not seen reports at all of taste diversion, either in ours. I'm not aware of them in the coagulantide nor previously in the pramlantide programs. Obviously, both coagulantide and patrolantide, at least in our hands, have significant balanced calcitonin and enamel and receptor agonism. Many of the preliminary reports and the non-clinical data that speak to this potential for taste diversion is actually not mediated through the calcitonin receptors to our reading, but actually the CGRP receptor component. In our hands, patrolantide does not have any significant activation of that receptor. So first and foremost, we do not expect unless there is CGRP activity for an asset that this would rear its head and that calcitonin receptor agonism, as we've stated previously, actually is necessary central signaling in calcitonin for the positive metabolic effects of pharmacologic exposure to amelan or amelan calcitonin agonists. So to us, not something we've observed nor is it in our mind actually specifically related to calcitonin of the CGRP receptor component.

Very helpful. Thank you.

Yeah. Thanks, Lucy.

Thank you. We will take our next question. And the question comes from the line of Charlie Hayward from Bank of America. Please go ahead. Your line is open.

Yeah. Thank you, Charlie Hayward, Bank of America. I've got two questions, please. So first is you've obviously stepped up your partner in conversations a few months ago. So I wondered if you could share any color on how the early discussions are going and what, if any, are the key debates you're having. And on that, I guess you've previously talked about targeting having a seat at the table with a co-commercialization, co-development agreement. I don't believe you stated that today, so can you confirm that's still your ambition and you remain confident in achieving that post-initial conversations? And then the second question is, we've got fairly imminent data for Cagri-Semakang. So obviously we've seen in the early data you showed superior weight loss to Cagri. I'm interested in how you think the Petri molecule compares to Cagri and what differences you'd call out there and whether you think you've been able to dose effectively higher than Cagri has in its phase three. Thank you.

Thank you, Charlie. I will address the first question and then hand over to David after that. We are very, very pleased with how our partner discussions are going as we have been popping around. We had the full, you can say, data set in the house in August from the phase one C trial, which we discussed at the BGT earlier this week. And we have started the discussions more formally here in the in September onwards. So we are making, I would say we are extremely pleased with where we are in these discussions. We do believe we have a very unique value proposition to, as discussed on the call today, to really bring forward a potential future foundational and even first-line therapy for the management of BGT, developing one of the first tools that are non-inclusive based. And I must say that we are extremely pleased with the feedback we have from the discussions with potential partners. We also believe, you can say, we have a very interesting value proposition in the sense that we are going for a co-development and co-commercialization opportunity. Remember, many large pharma companies are not deeply invested or deeply engaged yet in obesity and obesity-related diseases. We think we can offer a lot, the first part of the collaboration. And then on the request on co-commercialization, so far we have not met a significant pushback on that. I think the car parties we discussed with, they recognize that that is an important need for FEMA. The way we can develop our company the way we want. And so I do not foresee this will be a major hurdle in the discussions. We'll just have to align on how to do this. And again, as I said, it's not something we get pushed back on. Our focus will be US and potentially other major markets. So that is where we would look for profit sharing. And then you can say perhaps being less involved in other markets. So at least so far we have received a lot of positive feedback on this and also not something that I would describe as a negative part of the conversation, but deep understanding and also deep appreciation that we have to contribute based on our deep knowledge and experience in the space as we partner with large pharma partners. So overall we are extremely pleased with where we are and expect to progress these discussions in the coming months. David, will you take the other question?

Happy to, Adam, and thanks, Charlie. As regards to the CAGRES data like you, we anxiously await seeing what the potential additivity of the CAGRES with the obesity doses of samaglotide readout and report. As to comparison, obviously we have no direct -to-head comparative data. I think there are a number of characteristics that exist both from our understanding of each of the molecules and their formulation as well as what we have seen in terms of dose, dose exposure and the clinical effects. As we've stated previously and as I think many know well, CAGRES is formulated at a different isoelectric point, requires an acidic formulation to ensure and maintain stability and as such we believe that limits CAGRES dose exposure both due to injection sites, tolerability injection site reactions. There is also a greater degree of immunogenicity reported for CAGRES, whether that is dose and exposure related or related to other characteristics of the molecule. We do not know. We have to date seen no anti-drug antibodies to patrolentide. I think the most important part of this regardless of the potential causes is that we now know that patrolentide is well tolerated at doses of from 4.8 up to 9 significantly higher dose or milligram dose exposures and in our hands while both are balanced amyloin calcitonin receptor agonists, they appear to be equipotent at the receptor so we believe we can get to an up to 4x greater dose exposure than the planned maximal dose of CAGRES which is 2.4 milligrams. I think the last and perhaps most important part of dose exposure to CAGRES we believe can and will be tied to semaglutide tolerability. We know that semaglutide like other GOP1 based therapies can limit maximal dose exposure just because of GI tolerability and as a consequence of this being a fixed dose combination you may limit CAGRES exposure simply as a consequence of semaglutide tolerability. Now all of those are at least in our minds potential reasons that we believe patrolentide can and will meet or exceed what is seen with CAGRES. We think CAGRES is an effective compound no question and if the data from phase 1B bear out to see this continued reduction in body weight we fully anticipate that given those characteristics it will meet and very likely exceed the weight lowering effects of CAGRES. So I hope that's a reasonable set of reasons that can help you understand how we're viewing patrolentide as potential best in class. Many thanks. Yep thanks Charlie.

Thank you. We will take our next question. Your next question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead your line is open.

Hi thanks for taking my question. Just got a couple. Firstly on glabroglutide just could you maybe just help us understand what this potential early launch could look like from a ZLIM perspective. It sounds like there's not going to be a partnership on that one before a potential approval. So just in terms of what a -to-market strategy could look like potential investment there and whether you'd require kind of incremental SG&A costs and personnel costs from here. And then secondly Eric you talked about potential for developing patrolentide as a foundational first-line therapy in obesity. In order to do that ultimately do you think you need a -to-head against current JLP-1 agonists. Even if you didn't do you think that could be a logical trial to run just to cement the differentiation that you talked to. And then finally just one on patrolentide a follow-up from the obesity week presentation. We didn't see a split of kind of weight loss in males versus females in the presentation. So could you just confirm on the trial was there higher weight loss in female participants. I'm conscious there are only a few of them but it would be helpful to get some color on that. Thank you.

Thank you for your question John and I will just take the last one and then hand over to Eric to put a little bit more color into our thinking. But we have not shared the detailed data on gender you can say balances for weight loss yet and that will be up for a later conference. But we have indicated that you can say you should probably expect the same phenomenon as we have seen with JLP-1 that females tend to lose more weight on an amylin as well compared to males. So we will present those data at later conferences but clearly something we also believe could become the case on amylin that females lose more weight. And Eric will you take the next call on the last question on glypactotide and also on protenetide on the -to-head need for -to-head

question. I think with regard to kind of commercialization I think we first have to look at commercialization for Daziglucogone. We know that that's going to be a small footprint I think as we launch that one. As we think about GLEPA I think it will be a little bit more expanded recognizing that the prescribing population is larger but it would still not be a significantly large footprint. We would expect SG&A to go up a little bit but recognize it's a very, very focused population. We will be looking for that partner and have had several conversations with potential partners to really kind of figure out how we can expand that reach as we move forward. But overall I would say you'd still have a fairly limited footprint very similar to what you see in kind of rare diseases and probably more on the smaller end of it as well. With regard to kind of foundational therapy and -to-head I think and David you can speak to as well but I think that we are looking at it. We're looking at what is the appropriate timing and what is the appropriate place we would want to look at a -to-head. We recognize that we'll learn more out of our phase two data and really what is the appropriate dose and then we'll look at what is the appropriate timing to create that differentiation. I do think that the -to-head will be important for us to kind of better understand kind of how this stacks up relative to the GLP ones but I do think we'll start to see where we go with -to-head in the future.

Yeah thanks Eric and Rajan. I can comment as Eric mentioned critically important before we even consider such a trial that we fully understand the maximum dose and the magnitude of that response at each of the doses. I mean that's not to say we don't have confidence in the potential for a -to-head but without our understanding of what those -to-market or -to-phase three doses will be. I think you can anticipate and we're having discussions about whether phase three or phase three be the most appropriate space in which to complete those studies. I think you can understand as well the complexity how much do you force titrate and work to keep people on those doses versus doing this in sort of a real world clinical exposure setting where tolerability may impact a top dose of any assets. So yes certainly part of our conversation around the phase three and phase three be planning awaiting data from phase two as well as the phase two in those living with pre-diabetes or diabetes. So best I can tell you today is that is on the planning sheet and more to follow as we get readouts from phase two. Okay thank you very much.

Thank you. We will take our next question and the next question comes from the line of Suzanne Van Voolthuysen from VLK. Please go ahead your line is open.

Hi Dean thanks for taking my questions. My question relates to obesity week emulin data. First on the trillin side we noted that there was also a reduction in the heart rate. Curious if you have some thoughts what could explain this mechanistically and how you look at this additional interesting finding in the overall picture for the acid. And secondly on the also emulin data that was also shown this week clearly not as good weight loss and more at first defense as you compare it to patrilin tides. But could you frame what you think is behind the differences with patrilin tides assuming here different receptor potency but are there other elements such as the shorter half life that can be factors driving the difference in risk benefits. Thank you.

Thank you Suzanne. I'll just give a few comments before handing over to David. Especially if you look into the DLB1 class there's always been some concerns around increases in heart rate. I would say especially probably with some of the newer DLB1 increasing based therapies where we have seen very extensive increases in heart rate which is not normally something you would see as a beneficial thing in a metabolically cardiovascular challenge obese person. So we actually very encouraged that emulin does not seem to carry that liability and I think it's quite similar to what has also been seen with capriin tides that neutral to lowering of heart rate with the emulin class. But David can provide more flavor on that. On the astrocynica as we now saw it's of course extremely early day we saw falling from a single ascending dose. It gives us a lot of confidence in our approach to develop patrilin tide as a best in class emulin agonist. At least we note you can say a four day high half life for that program compared to the 10 days we have. We note it's also communicated that it is 15 fold more active on the emulin receptor and then we note that you can say at least a similar degree of nausea which again to us suggests that targeting both calcitonin and emulin as we do do not carry any liabilities in particular considering that you can say that one study with that competing program was stopped due to severe adverse events quite close to where they observed some We feel very comfortable and pleased to continue to develop what we think could become a best in class emulin analog. David any more flavors?

Yeah just very quickly Suzanne thanks for the question on heart rate. I can't say at least to my knowledge that we know a specific reason why emulin agonism would either with patrilin tide or other compounds reduce heart rate. I think knowing that emulin signaling particularly in the hindbrain and the effects acutely for example on gastric emptying are mediated through vagal afferents so there is the potential that some modest increase in vagal tone which would lower your heart rate could play a role but that is speculation. I think to Adam's point the increase in heart rate that comes particularly higher dose exposures of GLP-1 is something that we looked obviously to avoid through emulin agonism and clearly our early data suggests that there is no increase and perhaps this modest decrease. If that combined with lower blood pressures that have been reported in larger trials with other emulin agonists bear fruit that obviously then lowers the cardiac effort which we would expect to have a potential benefit on cardiac function and cardiovascular risk but obviously too early to tell with our assets. To Adam's point we think the prolonged half life of patrilin tide and the balanced signaling which in our mind is not only necessary but has been both Cagri and patrilin tide to not only raise fewer GI tolerability issues but clearly is a part of the benefit in terms of the metabolic effects on body weight. So very early data with the other compound that is targeted to emulin agonists we know one of the more common symptoms is a higher dose of the receptor meaning higher milligram doses may be required for the same effect but beyond that I won't try to speculate too much given the very limited amount of data available with other compounds.

Thank you. We will take our next question. Your next question comes from the line of Julian Harrison from PBTIG. Please go ahead your line is open.

Hi good morning this is Rayon for Julian. Congrats on the progress so far and thanks for taking our question. You mentioned earlier on a partnership for both patrilin tide and glupliglutide. We were just wondering what an ideal partnership term or deal would look like.

Thank you for that question and I'll hand it over to you to just give some flavors on our thinking.

Yeah and so thanks for the question. I think from a partnership perspective I think we're exploring all partners. I think at the end of the day we do know that there are some opportunities on the glapicide that are a little bit larger of opportunities. So we would want to look at a commercialization partnership as we move forward on that one. I think they would also then explore if there's other opportunities for life cycle management but it would definitely be a strong commercialization partner on the CHI or the DASI glucagon. I think it is a new market and I think people are still trying to assess the opportunity that exists so we are still looking for commercial partners and potential partners that would be willing to consider both options and to commercialize and build more of a full rare disease franchise. So we are looking for commercialization partners for the most part.

Got it thank you very helpful and just a follow up if I may. Do you expect any residual allegiance to Gattix or are you planning for most of the short bowel syndrome market to convert to less frequent treatment options?

I think there's two components on the short bowel syndrome side of things. I think you have the Gattix patients we know that they're not really well controlled so there's one option I think as we look at some of the Gattix patients as well as well as the more convenience but we still recognize there's a significant portion of patients that are not being treated and that is still an opportunity for us. So we do look at it as across the entire spectrum of all those customer segments both the Gattix side of it those people that are not well controlled those people are looking for better convenience and then those that are currently not being treated.

Thank you very helpful thanks again.

Sure thank you for the question.

Thank you we will take our next question and the question comes from the line of Prakhar Agraal from Kanter. Please go ahead your line is open.

Hi thank you for taking my questions and great presentation at Obesity Week. One thing that maybe we are still hoping to get more clarity on is on the dose response. The weight loss trajectory looks fairly similar for the 4.8 and 9 milligram dose even in the initial titration period but you clearly believe that based on individual patient data there should be dose response and longer duration so anything that you would note based on the data that drives this conviction and a couple more if I may on partnership discussions for petrol lintide what will be some of the important factors for you in the deal structure is having a co-commercial structure in the US important and then lastly just quickly on you talked about the Cadre SEMA data coming in for Q maybe just talk about the implications for petrol lintide from the Cadre Lintide monotherapy arm in the trial just wanted to understand what you are hoping to see on on that from an efficacy and safety standpoint and thank you so much.

Thank you I'll just discuss perhaps a little bit more on the partnership front before handing over to David so it is very important for us in the partnership that whoever we partner with will share the vision and ambitions of the train type to develop this as a future foundational and first time therapy and that also of course means committing to the associated investments into clinical conduct positioning and of course also manufacturing. What we would be looking for is a true partnership where we will continue to contribute and develop seed and along we can say the development of this molecule towards as it approaches the market where we would also ask to have co-commercialization right well how these are going to play out specifically is something we will discuss with the in through these partnership discussions but it will be extremely important for us to stay involved in programs who will focus as I said before on the US and potentially other major markets and and and so it will be important for us to to maintain like and also the commercial and but operate alongside a partner. Then maybe just one favor on the Cacrinitide Cacrisima data that reads out to be of course as anyone else extremely excited and to see how these data reads out and of course you can say as David has also shared several times on the call today we have a quite similar receptor biology a very different molecule with regard to formulation and other aspects but but it will be interesting for us to see also if no one always report on the Cacrinitide monoarm what the 2.4 milligram of Cacrinitide can can deliver. Of course when looking into that for us it will be important to recognize that we believe we have a significant high variability and also we know we will be dosing much higher in our studies as David shared. So while it can produce some can provide us with some guidance and insight we also recognize that we need to conduct our own phase 2b to fully understand the full potential of the train type. David would you add some more?

David Yeah happy to. Hi Prakhar. The dose response I think to your point this is obviously a limited data set 12 participants exposed in the two dose groups 4.8 and 9 but as we have alluded to it was really that early response with a lower starting dose in the 4.8 group they had a fairly robust early response and then a relatively linear mean response after those first few weeks of the titration scheme. Can I based on these data and others say that the lines will cross and 9 will continue to decline at a more rapid rate and exceed 4.8? No but I think both those observations the fact that in both groups we have a very limited number of female participants who tend to lose more but that obviously the phase 2b that we've described will allow us between that what I call mid-high dose and the higher dose 9 milligrams allow us to explore if separation is possible. So I don't want to overstate what gave us the confidence that we may see a continued decline in the 9 milligram dose. What I can say is that obviously we believe we've got at least twice and potentially up to 3 to 4x the potential dose exposure to get maximal response but like you I'm going to await phase 2b to finalize that statement on dose separation but given that we have tox coverage the evidence in rodents suggests that higher exposure will permit greater effects on body weight and at least some suggestions from the individual data that you'll see at a future congress give us confidence that at least looking in phase 2b can help elucidate the dose at or above the 4.8 to 5 milligram range that can maximize the response. Nothing more to add to Adam's comments on CAGRi. I think the monowarm will hopefully give us even greater confidence in the double digit weight loss 15 to 20 potential of the dromontide.

And maybe just one other note on the 4.8 and the 9 milligram dose. I think it's also perhaps important to recognize that these were still quite low BMI participants and in the phase 2 and on next studies of course they expect he would hire BMI so far it will be extremely important to carry you can say the full dose opportunity into phase 2b and then see which is the right dose to bring into phase 3.

Thank you. Thank you. We will take our final question. Your final question comes from the line of Thomas Barres from Thanks Good Bank. Please go ahead your line is open.

Yes thank you very much. Just a couple of questions remaining here from our side. So just on the potential side do you actually have any CRP reduction data from that phase one. I'm not sure whether you actually tested for that and also DAPI glutide. Is that something that we could expect from the phase one as well. And then just on the DLP one combination with the potential side is this going to be a combination with what you can say commercially available once weekly approved DLP one in obesity or is it something that you also have internally in the pipeline. And then my last question. So looking at the slides from obesity week. When I assume in on the efficacy curve wouldn't it be fair to sort of make a conclusion that we at least see an indication of the weight loss effect tailing off a bit after 12-13 weeks for actually both of the high dose cohorts. So I know of course it's a very small sample size here. I'm that we should be a little bit concerned about at least arguing for the 20 percent weight reduction that you are targeting or could this maybe be also an effect of a low baseline BMI for these patients in the study. Thank you.

Yeah thanks for those questions. I'll just start. CRP you should not expect that from a small study like this. But we of course know from the phase two study from no noise the carcane type that you see reductions in at least the carcane type and CRP. So we would also expect that to be this molecule. When it comes to combination therapy with the train title and here's the one I think at least our thinking is potentially quite different from the approach that our competitors taken. Since we want to develop the train type as a future foundational therapy it will be extremely important for us to number one identify you can say the effective doses amylin and then consider to add a little bit of the other one on top of that instead of using what is considered the most effective dose of the other one for weight management adding a little bit of amylin. You think it's the more patient potentially more patient friendly approach to add just a little bit of the other one on top of a maximum effective dose of an amylin then which could further you they contribute to limiting the side effects in for those patients who would potentially need combination therapies which we believe will be the most mobile. So only a smaller fraction of the larger bcp opportunity on the slope of the weight loss. It's really not something we see. I mean the what I know you have brought this up a few times it's not how we read the data. I think you are right if you have a low bmi population there's of course a limit to how much weight you can achieve in a small study. You also have to really think about this is a phase study phase one study where you don't apply to diet and exercise. So I would say all data including data from competing programs that we have looked into suggest that the weight loss will continue also for an amylin analog and so it's not a concern we share. So I hope that answers your question.

That's great thank you very much. Thank you.

Thank you. This concludes today's question and answer session. I'll now hand the call back to Adam Steensberg for closing remarks.

Yeah with that I would like to thank everyone for your participation today and we look forward to future updates and interactions. Thank you so much.

This concludes today's conference call. Thank you for participating you may now disconnect.