Q2 2024 Zealand Pharma A/S Earnings Call
Speaker Change: Good day and thank you for standing by. Welcome to the Zealand Pharma First Half Financial Results 2024 conference call.
Speaker Change: At this time all participants are in a listen-only mode.
Speaker Change: After the speaker's presentation, there will be a question and answer session.
Speaker Change: 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
Speaker Change: Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Anna Krassowska.
Anna Krassowska: Please go ahead.
Anna Krassowska: Thank you, Alfredo
Speaker Change: Welcome and thank you for joining us today to discuss Zeeland's results for the first six months of 2024. With me today are the following members of Zeeland's management team.
Speaker Change: Adam Steensberg, President and Chief Executive Officer, Henriette Wennicke, Chief Financial Officer, and David Kendall, Chief Medical Officer.
Speaker Change: You can also find the related company announcement and team report on our website at www.zeelandpharma.com As described on slide 2, I caution listeners that we will be making forward-looking statements that are subject to risks and uncertainties.
Speaker Change: 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 satisfied with our progress in the first six months of 2024.
Speaker Change: First of all, we are extremely pleased
Adam Steensberg: We were extremely pleased to report the positive top-line data from the Phase 1b 16-week trial with protreinotype, our long-acting amylin analog, which we are developing as an alternative to DRB1-based therapies for the management of overweight and obesity.
Adam Steensberg: With the potential for GLP-1-like weight loss and a significantly more benign tolerability profile, we believe that Petroleantide has the potential to become a future backbone therapy for weight management.
Speaker Change: Thank you.
Speaker Change: At the EESL Congress in June, our partner, Boehringer Ingelheim, presented impressive data with cervical types and liver fibrosis improvements.
Speaker Change: from the PHASE II trial in mass.
Speaker Change: The phase 2 program with cervical type also included separate trials in both type 2 diabetes and obesity, from which Böhringer reported very strong results as well.
Speaker Change: Servitutite is now in phase 3 for treatment of obesity and overweight and expected to advance into phase 3 trials en masse later this year.
Speaker Change: There is a significant overlap between obesity and mass, and with the clinical data reported to date, we believe Cervarutide holds potential as a leading inquisitive-based therapy for obesity and mass in the future.
Speaker Change: Following our strong top-line data reported with Petroleum Tide, we did an upsized and significantly oversubscribed equity offering, raising gross receipts of 7 billion Danish Kroner.
Speaker Change: This is the largest ever European biotech offering, with a development stage funding as primary use of proceeds.
Speaker Change: We are very grateful to both new and existing investors who share our view on the transformational potential of our differentiated obesity assets.
Speaker Change: The strengthened financial position now allows us to accelerate our investments into our obesity candidates, expanding both the depth and the breadth of our development program.
Speaker Change: For Dasik Luergon in congenital hyperinsulinism and Klepakutait in short bowel syndrome, partnership discussions are progressing very well. With our strong capital preparedness, we remain focused on securing a commercial partnership that maximizes the long-term value creation for these assets.
Speaker Change: And for Petreantype, we are now initiating dialogues with potential future partners as well.
Speaker Change: It will be important for us to find a truly committed and capable partner who shares our vision for developing Petrinatide as an alternative to the DRP1-based therapies and a potential future backbone therapy for weight management.
Speaker Change: In this regard, I'm really pleased.
Speaker Change: with the addition of Eric Cox to 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.
Speaker Change: He will be a very important capacity as we progress our development programs further and put ourselves in a strong position for partnerships.
Speaker Change: Turning to slide 4.
Speaker Change: I would like to remind everyone why we are so excited about the potential of petroleum tide.
Speaker Change: With the magnitude of the obesity pandemic and the global healthcare challenge that obesity and obesity-related comorbidities represent, we believe there is a need for novel and alternative treatment options with a different mechanism of action than the GP1-based therapies approved today.
Speaker Change: We have seen the impact of the first two once-weekly tier 1-based therapies to be approved.
Speaker Change: In phase 3 clinical trials, they have demonstrated potential for 15-21% mean weight loss in patients with obesity and positive outcomes on several obesity-related comorbidities.
Speaker Change: On the flip side, DS1-based therapies are associated with a number of gastrointestinal adverse events including nausea, vomiting, diarrhea, and constipation.
Speaker Change: Recent data suggest that up to 30% of patients with obesity on a GW1 treatment stop within a month before reaching their target dose, and that within one year, 60-70% of patients with obesity withdraw from treatment.
Speaker Change: Thus, we believe there is a need for treatments that can help patients who cannot tolerate the GLP-1-based therapies, or who would be looking for an alternative solution to maintain a weight loss.
Speaker Change: With Pertrinenside, we are targeting DLV1-like weight loss of 15-20%.
Speaker Change: with potential for high-quality weight loss implying increased preservation of lean body mass.
Speaker Change: Importantly, petroleumtide offers a differentiated mechanism of action, reducing food intake by increasing satiety for a different and potentially better patient experience.
Speaker Change: We are also confident that petroenzyte has potential for a significantly improved GI tolerability profile compared to GLP-1 receptor agonist.
Speaker Change: suggesting both lower frequency and milder severity of gastrointestinal adverse events, which is an important point of potential future differentiation in weight maintenance.
David Kendall: And with that, let's move to slide five, as I will turn over the call to our Chief Medical Officer, David Kendall, to discuss our R&D pipeline. David.
David Kendall: Thank you, Adam. Today, I would like to focus my remarks on the continued advancement of our obesity programs.
David Kendall: Beginning with our novel, long-acting amylin analog, petrolentide, let's move to slide 6.
David Kendall: As we have recently reported, Petrelentide was evaluated in a randomized, double-blind, placebo-controlled Phase 1b trial enrolling a total of 48 adults with overweight and obesity.
David Kendall: Participants were randomized into one of three dose cohorts assessing multiple ascending doses of petrolantide using a dose titration scheme or to match placebo.
David Kendall: Study medication was administered weekly for 16 weeks in an outpatient setting, followed by a nine-week safety follow-up period.
David Kendall: Note that study participants randomized to the two higher-dose cohorts received the maximum assigned maintenance dose for a period of only six to eight weeks.
David Kendall: The starting dose in the cohort with maintenance for six weeks was higher than in the other two other cohorts Importantly in this trial there was no specific lifestyle intervention provided
Speaker Change: Turning to slide 7, shown here is a summary of the key baseline characteristics of the participants enrolled in this trial.
Speaker Change: In contrast to many weight loss studies previously reported, approximately 80% of the participants in this trial were male.
Speaker Change: Median age was 49 years and median body weight was 92 kilograms with a median BMI of 29 across the study cohorts.
Speaker Change: All groups were well-matched for baseline characteristics.
Speaker Change: Moving to slide 8 and the changes in body weight observed.
Speaker Change: The reduction in mean body weight across the three dose cohorts was 4.8, 8.6, and 8.3 percent from baseline after 16 weeks of treatment, while placebo treatment resulted in a mean body weight loss of 1.7 percent.
Speaker Change: Importantly, and consistent with our observation from earlier studies with pertrellantide, every individual participant on active treatment lost weight during the 16 weeks of study, and the weight loss appeared to be on a continued downward trajectory throughout the active treatment period.
Speaker Change: In addition, review of data from individual participants supports that separation at the higher doses is possible with longer treatment duration in a larger study population.
Speaker Change: We find these data to be even more compelling in light of the fact that the study population was predominantly male with a relatively low BMI.
Speaker Change: and these results were achieved in the absence of any background lifestyle modification, suggesting that the response observed may have been muted in this study.
Speaker Change: Moving to slide 9 in the tolerability profile.
Speaker Change: In this trial,
Speaker Change: Strelentide was assessed to be both safe and well tolerated.
Speaker Change: There were no serious severe adverse events and the safety profile observed that was consistent with earlier studies. All gastrointestinal or GI adverse events were mild except for two moderate events.
Speaker Change: of nausea and vomiting reported by one participant who discontinued treatment after the third dose cohort.
Speaker Change: This participant was randomized to the cohort with maintenance for six weeks.
Speaker Change: that included a higher starting dose compared to the two other cohorts. Notably, no other participants discontinued treatment due to adverse events, and no other participants reported vomiting, and there were only two reports of diarrhea, both of which were mild.
Speaker Change: Overall, nausea was reported by 19.6 to 33 percent for active treatment groups and 16.7 percent with placebo.
Speaker Change: In addition, only a low number of participants reported injection site reactions, all of which were mild, and no anti-drug antibodies were observed.
Speaker Change: The tolerability profile reported in this trial further demonstrates the potential for an improved patient experience as compared to that reported in both clinical trials and with the clinical use of Inkerton-based therapies.
Speaker Change: We strongly believe that the mechanism of action by which caloric intake is reduced with amylan agonism, increasing satiety as opposed to reducing appetite, along with leptin sensitization known to occur with amylan agonism,
Speaker Change: can become an important differentiator in the treatment of overweight and obesity.
Speaker Change: We look forward to presenting the full results and detailed analyses from the trial at a scientific conference later this year.
Speaker Change: Turning to slide 10.
Speaker Change: These exciting and compelling data provide us with the confidence and necessary information to rapidly progress our plans for initiation of a comprehensive phase 2b trial with petrolentide monotherapy in the second half of 2024.
Speaker Change: The draft Phase IIb trial study design is shown here.
Speaker Change: This larger trial with longer treatment exposure will enroll more than 400 adults with overweight or obesity and will compare multiple doses of Trelatide or Placido over an estimated 42 weeks of treatment with up to five dosing arms.
Speaker Change: Consistent with other studies of treatments for overweight and obesity, the primary endpoint will be percentage change in body weight from baseline.
Speaker Change: And the study plans include a number of key secondary and exploratory endpoints.
Speaker Change: including an assessment of body composition as measured by magnetic resonance imaging or MRI.
Speaker Change: We are pleased and excited to advance the development of this promising asset as we truly believe that Petroleantide offers the unique opportunity to establish a new class of stand-alone therapies for the treatment of overweight and obesity.
Speaker Change: At the same time, our strength in financial position allows us to invest further in this comprehensive development program.
Speaker Change: In addition to the Phase 2b study currently planned, we are developing plans for a Phase 2 trial exploring weight loss in a population with Type 2 diabetes and prediabetes.
Speaker Change: where data suggests that amylin agonism can potentially deliver weight loss comparable to that observed in non-diabetes populations, further differentiating this treatment from GLP-1 receptor agonist therapy.
Speaker Change: We are also developing plans for investigating petrolatide in combination with a GLP-1 receptor agonist.
Speaker Change: In addition, we are fully prepared to complete all of the Phase 3 enabling study in the coming months and years.
Speaker Change: Turning to slide 11.
Speaker Change: In June, at the European Association for the Study of the Liver, Congress held in Milan, our partner Behringer Ingelheim presented exciting and impressive data from the Cervidutide Phase II trial in metabolic dysfunction associated steatohepatitis, or MASH.
Speaker Change: In this trial, 64.5% of adults with moderate to advanced scarring, that is fibrosis stages F2 and F3, achieved a biopsy-proven improvement in fibrosis without worsening of MASH after 48 weeks of Cervidutide treatment.
Speaker Change: compared to 25.8% of participants treated with placebo.
Speaker Change: These data on fibrosis improvement followed the top-line results announced earlier this year, demonstrating that up to 83% of adults treated with Cervodutide for 48 weeks.
Speaker Change: achieved a biopsy-proven improvement in MASH without worsening of fibrosis stages F1 to F3, compared to 18.2% with placebo.
Speaker Change: We believe that this is the strongest clinical data set on improvements in MASH and liver fibrosis published to date, positioning cervidutide as a potential best-in-class incretin-based therapy for the treatment of obesity in MASH.
Speaker Change: We are excited that the Beringer is anticipating to advance the Redutide into separate phase three trials in mash in the second half of this year.
Speaker Change: Moving now to slide 12 and turning our attention to dapiglutide, our first-in-class GLP-1, GLP-2 receptor dual agonist.
Speaker Change: 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.
Speaker Change: as well as address the low-grade inflammation associated with metabolic disease, representing a truly differentiated incretin acid.
Speaker Change: In obesity, low-grade inflammation is thought to further drive many common comorbidities.
Speaker Change: And we believe that dual GLP-1, GLP-2 receptor agonism can play an important role, not only targeting weight loss, but also by directly affecting a number of key obesity-related comorbid conditions.
Speaker Change: including liver disease, cardiovascular disease, inflammatory bowel disease, and neurodegenerative diseases, including Alzheimer's disease.
Speaker Change: In the second half of 2024, we expect to report top-line results from the Phase 1b dose titration trial with apiglutide.
Speaker Change: investigating the pharmacokinetic and pharmacodynamic effects of dapaglutide treatment.
Speaker Change: with doses up to 13 mg, which represents 2-3 times higher dosing than that utilized in prior clinical trials with BepiGlutime.
Speaker Change: Based on the tolerability profile observed to date, we have amended the trial to include an additional cohort in the Phase 1b trial to investigate even higher doses, up to 26 milligrams over a treatment duration of 28 weeks.
Speaker Change: Results from this added cohort will be reported in the first half of 2025.
Speaker Change: The added cohort in the Phase 1b trial will have no impact on the timing for initiation of the Phase 2 trial in people with overweight and obesity, which we expect to initiate in the first half of 2025.
Speaker Change: The data will be used to inform the potential for even higher treatment doses in Phase 2.
Speaker Change: We will obtain valuable insights on the optimal doses and dose escalation steps to inform both the Phase 2b trial and additional studies investigating the potential of dapiglutide in obesity and selected obesity-related comorbidities.
Speaker Change: Turning to slide 13 for a few remarks on our rare disease programs rapidly approaching regulatory decisions by the US FDA.
Speaker Change: Starting with doxiglucagon for congenital hyperinsulinism, we have a regulatory decision goal date of October 8 for the original one part of this new drug application, which will evaluate dosing of doxiglucagon of up to three weeks duration.
Speaker Change: In the second half of 2024, we expect to submit the requested analyses from existing continuous glucose monitoring data sets that will support the original two component of the NDA, assessing use of dozyglucan infusion beyond three weeks of dosing.
Speaker Change: If approved, doziglucagon would help address a substantial unmet medical need for newborns and children with congenital hyperinsulinism who have had either no or very limited treatment options today.
Speaker Change: Additionally, the US FDA has set a regulatory decision goal date of December 22nd for our long-acting GLP-2 analog, filopaglutide, which possesses best-in-class potential for the treatment of short bowel syndrome with intestinal failure.
Speaker Change: We are pleased to have had a successful and productive mid-cycle review meeting with the USFDA earlier this year.
Henriette Wennicke: And with that, I would now like to turn the call over to our Chief Financial Officer, Henriette Wennicke, to review our financial results for the first six months of 2024. Henriette?
Henriette Wennicke: Thanks David and hello everyone. Let's move on to slide 14 and the income statement.
Henriette Wennicke: Revenue for the first six months of 2024 was 49 million DKK. This was mainly driven by the license and development agreement with Novo Nordisk for Segaloft.
Speaker Change: Operating expenses for the period were 559 million DKK, driven by research and development, which represented 72% of the company's operating expenses.
Speaker Change: The research and development expenses are driven by the clinical advancement of our wholly owned obesity assets and activities supporting the regulatory review by the US FDA of the late-stage rare disease assets.
Speaker Change: Selling and marketing expenses primarily relate to pre-commercial activities associated with our rare disease asset.
Speaker Change: The increase in admin expenses is a result of a strengthening of the IT infrastructure and organizational capabilities in selected corporate functions, as well as legal expenses related to our patent portfolio.
Speaker Change: Let's move to slide 15 and the cash position.
Speaker Change: As of June 30, 2024, cash equivalents and marketable securities were 9.7 billion DKK.
Speaker Change: In June, we successfully raised 7 billion DKK in gross proceeds from an upsized and significantly oversubscribed equity offering.
Speaker Change: This race represents the largest ever Nordic biotech offering, the largest ever ever European biotech offering focused on development-state funding, and the fifth largest biotech follow-on ever globally.
Speaker Change: I must say that we are very proud of this transaction and extremely pleased and grateful to both new and existing investors who decided to support us in this transaction.
Speaker Change: Clearly, Zealand has never been in a stronger financial position.
Speaker Change: is such a...
Speaker Change: And this takes me to slide 16 on our financial guidance.
Speaker Change: This strong cash position enables us to accelerate investments in our obesity assets.
Speaker Change: And consequently, we have today updated the guidance on net operating expenses for the year from between 1.1 and 1.2 billion DKK to between 1.25 and 1.35 billion DKK.
Speaker Change: We now have a unique opportunity to expand both the depth and the breadth of the development programs for our differentiated obesity assets.
Speaker Change: in addition to comprehensive phase 2b trials.
Speaker Change: The capital raise of 7 billion DKK enabled us to invest further in preparing for additional studies including positioning studies and studies in related indications as well as associated CMC activities.
Speaker Change: [inaudible]
Speaker Change: Our strategy remains to enter partnership for our assets, focusing on maximizing long-term value creation.
Speaker Change: Discussion with potential partners are progressing well, but we are at the same time running the necessary pre-commercial activities.
Speaker Change: And with that, I will move to slide 17 and turn the call back to Adam for concluding remarks. Adam?
Adam Steensberg: Thank you, Henriette.
Adam Steensberg: The first six months of 2024 have been remarkable for Sedan Pharma. With impressive data across our pipeline of differentiated obesity candidates and an extraordinary capital raise, we are setting ourselves up to become a key player in the growing obesity space.
Speaker Change: For Petrinityte specifically, we have an opportunity to create a new class of medicines for weight management and thus play an important role in framing the future treatment landscape in obesity.
Speaker Change: In the near term, we also have an exciting six months ahead of us, including full results and analysis from the 16-week trial with proteinotype, as well as Phase IIb trial initiation.
Speaker Change: and top-line results from the 13-week part of the dose titration trial exploring higher doses of dapaglutide.
Speaker Change: Outside obesity, we have regulatory decisions in the U.S. for both of our rare disease programs in the second half.
Speaker Change: With both basic Luagan for congenital hyperinsulinism and glipaglutide for short bowel syndrome, we have an opportunity to address a major unmet medical need for patients.
Speaker Change: Finally, the next wave of peptide innovation targeting chronic inflammation is expected to end early clinical development.
Speaker Change: Thank you all and I will now turn over the call to the operator for questions.
Speaker Change: Thank you. As a reminder to ask a question you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question please press star 11 again.
Speaker Change: We will now take our first question. Please stand by.
Speaker Change: And the first question comes in the line of Rajan Sharma from Goldman Sachs. Please go ahead, your line is now open.
Rejan Sharma: Hi, thanks for taking my question.
Rejan Sharma: We've got a couple. Firstly on DAPI Gluta, I just wanted to understand what drove the decision.
Speaker Change: to include the higher dose cohort in the Phase 1 rather than just kind of including that in the Phase 2. And then, given that you still expect the same timeline for the initiation of the Phase 2, do you expect to use those higher doses in the Phase 2 even if the data from the Part 2 of
Speaker Change: the phase one are not available and then just longer term how high do you think you could actually go on dosing there and then maybe just staying on on DAPI
Speaker Change: What do you think would constitute a good outcome from the initial phase one data that we're expecting in the second half of the year? You kind of
Speaker Change: We're quite clear on how you were thinking about the petrolytide readout, so if you could just provide some colour around that. And then, should we expect any data on inflammation markers in the initial data set?
Speaker Change: Maybe if I could just follow up with one on petrolyntide. So I think you said that you'll be using MRI to assess body composition in the phase two. I just wanted to understand your rationale for that relative to using other measures.
Speaker Change: Do you think MRI will likely be the standard measurement across the space and will you also be able to assess bone density in that trial? Thank you.
Speaker Change: Thank you, Ajan, for those questions. I'll just start and then I'll hand over to you, David.
Speaker Change: As you highlighted, we have included an even higher cohort into the first-in-week trial and I think it's important to mention that it will not impact, as David also said, initiation of the Phase IIb trial, but it has the potential to actually
Speaker Change: ultimately be included in that trial and David can share more on that thinking later. On the expectations for outcome,
David Kendall: Again, remember that we are adding a higher dose. What we have said all the time, and that is still our position, that with codapaglutide we are aiming to achieve
David Kendall: what we would see as testicular type like weight loss. So at least crossing that, continue to believe that we can cross that 20% bar for weight loss in longer term studies, and that's what we will be looking for in the upcoming data set.
David Kendall: knowing that we are at 13 milligrams there and we will also go higher but as long as we have confidence that we can achieve that bar then we think we have a differentiated molecule with the true differentiation being on how well it addresses co-morbidities.
David Kendall: And then, David, I will hand over to you to put further light on that and perhaps also address the MRI question on protein size.
David Kendall: I'm happy to, and Rajan, thanks for your question, reiterate what Adam said, which is the higher dose.
David Kendall: As we have the appropriate tax coverage, you can...
Speaker Change: add that to understand safety and tolerability in Phase 1. So we do hope and anticipate that as the data from that amendment become available, we could
Speaker Change: amend and potentially include those doses if well tolerated.
Speaker Change: in the phase two program. Markers of information, I'm speaking without the protocol here in front of me over the 13 weeks. I do not recall the level of detail that the study protocol outlined. Clearly markers of information will be part of the clinical program.
Speaker Change: for dapiglutide throughout the other clinical trials planned in the obesity phase 2b and beyond. So I don't want to speak out of school without the protocol in front of me.
Speaker Change: spot-on that MRI or AMRA.
Speaker Change: device and technology has become the most widely used and we will
Speaker Change: certainly have.
Speaker Change: That in the next
Speaker Change: phase 2 trial and we believe that that's going to be both the most predictive and reproducible of the measures that allow us to look at body composition.
Speaker Change: And as for bone density, yes, that will be observed. So we have some understanding of the overall impact, but AMRA will be the body comp measure of choice.
Speaker Change: Thank you.
Speaker Change: Does this answer your question, Sajan?
Sajan: Yep, thank you very much.
Sajan: Thank you. We will now take our next question.
Speaker Change: Please stand by.
Speaker Change: And the next question comes in the line of Thomas Bowers from Danske Bank. Please go ahead, your line is now open.
Thomas Bowers: Yes, thank you very much for taking the question. So, first of all, in the slide presentation you highlight that 30% discontinued OPD-C treatment after one month.
Thomas Bowers: but how many do you actually believe discontinue due to tolerability issues? And maybe you're testing my luck, but how many of these patients would you think could have the needed tolerability improvement on enamelin to successfully stay on therapy? Actually, I guess that's the main goal, of course. And then also, second question on paternity, so
Speaker Change: So I remember in connection with the top line results that you argued for the expected one plus year weight reduction of 15 to 20 percent. So what data do you have to support the tail here?
Speaker Change: to my understanding, and also reading through some research material, one of the...
Speaker Change: concerns with amylin as a standalone is that you will hit the ceiling quite early on. So, is there anything I have missed here that actually proves the opposite, that you will see a GLP-1-like curve going towards those 60 and 70 weeks? And then, just lastly, just on the iron channel blocker that you're now moving into phase one, I'm just wondering whether you're talking specific autoimmune diseases, or is this something that
Speaker Change: that you actually could see more could complement the obesity pipeline. So, of course, improving potentially co-morbidities given that the link between the memory T-cells and adipose tissue. So, just a bit curious there. Thank you.
Speaker Change: Thank you, Thomas, for those questions and I'll start and then maybe David will again have some...
David Kendall: additions to this. On the tolerability profile
Speaker Change: There are recent publications from real world use that suggest that 30% drops off within a month before they reach the target dose.
Speaker Change: Within after a year, it's only
Speaker Change: 40 to 40 percent who are still on treatment. Of course, there are different reasons why people do not stay on treatment. We, our assessment is that the early drop-off, the 30 percent that you see early on, is a sign that people are not going to stay on treatment. So, we are not going to
Speaker Change: A large extent of that is due to tolerability issues for the patients and when it comes to the long stay on, there are several reasons why people go off and there's only, let's say, 30 percent on treatment after a year.
Speaker Change: I have to remind you also here, remember we have now seen the first two medicines launched into a space truly providing patients with the weight loss they're looking for and there are no alternatives. So you see these dropout rates even in an environment where there's no alternatives.
Speaker Change: So, I think the key question for me is, if there was a more tolerable and different alternative, what would the dropout rates then be? Because we know how motivated people are to achieve their weight loss.
Speaker Change: So we at least speculate that you will see even larger degrees of dropout if there was an alternative because we know how motivated people are to achieve this and still the dropout in today's environment.
Speaker Change: Volchina, Tim. [inaudible]
Speaker Change: on the weight loss curve for longer-term exposure.
Speaker Change: At least to our knowledge, you have data going out until 26 weeks and 32 weeks with cochlea inside those are probably the most
Speaker Change: long-term exposure that
Speaker Change: have been reported for long-acting amylin. And if you look into the study with the longest duration, then in type 2 diabetes patients, then norbus coagulantide at a lower dose, not the most effective dose,
Speaker Change: as a monotherapy actually provided 40% more weight loss at 32 weeks than simatrotype. They approved those and probably go with
Speaker Change: So I don't know which data you relate to when you say that there's evidence suggesting that we will flatten the curve. I acknowledge that we don't have a lot of evidence to suggest.
Speaker Change: what data will look like at one year, but I don't think the evidence exists that there should be a flattening of that curve. We speculate that we will see a continuous weight loss as that is what we have seen at least up to week 32.
Speaker Change: and we would not expect that to change in the subsequent weeks, especially not when you dose as high as we can do with protein type where, as David also shared,
David Kendall: With the highest dose of sputuantide, we saw signs of continuous weight loss that would probably, in a longer-term study, result in more weight loss than the mid-dose.
Speaker Change: And then lastly on the KV1.3 inhibitor, we have not disclosed which indications we are going for here and we will not do it on this call either but I can confirm that we are excited about its potential in different autoimmune diseases and we are also
Speaker Change: you can say, of course, have observed that this target could also play a role in some metabolic diseases.
Speaker Change: David, oh, do we have...
David Kendall: further insights to share? No, Adam, I think just reiterate what you stated, which is around the flattening of the curve with primalatide and as you noted with picrolatide, presumably because of this effect on
Adam Steensberg: satiety that perhaps as a consequence of leptin sensitization we do not at the higher doses we expect to utilize
Adam Steensberg: Ahm, per...
Speaker Change: have belief or data that would suggest this would plateau early on. That is seen with rapid weight loss, but with a satiety signal, this gradual weight loss of 8.5% at
CAGRI: 16 weeks, remembering that only 6 of those weeks were at, 6 to 8 of those weeks were on the high dose. So, all evidence, CAGRI, our own early on.
CAGRI: and other studies would suggest that the weight loss range that we at least could hypothesize is supported by both the science and the literature.
Speaker Change: Great, thank you very much for the additional color.
Speaker Change: Thank you. Thank you. We will now take our next question. Please stand by.
Speaker Change: and the next question comes in the line of Suzanne van Voorheesen from Van Lanschot Kempen, please go ahead your line is now open
Speaker Change: Hi team, this is Suzanne. Thanks for taking my questions. Allow me to start off with on the exploratory partnering discussions that you are initiating on Petroleum Tide. Can you elaborate what you wish to get out of these conversations?
Speaker Change: and give some context on what features you look for in finding, let's say, the right partner.
Speaker Change: And then my second question is on the full data for paternity that's coming in the coming months. Can you elaborate to what extent we can expect information on comorbidity, biomarkers, and the quality of weight loss?
Speaker Change: like which metrics will be reported on and which elements in there makes you most confident that your amylin is the best in class molecule. Thank you.
Speaker Change: Thank you, Suzanne. I will just start and then David he can add again. On the partnership discussions...
Speaker Change: It is, you can say, we do, as we have shared also in this call, believe that we have a very, very unique opportunity to actually frame the future management of obesity by progressing what we believe looks to be one of the first true alternatives to a TLD1.
Speaker Change: We also acknowledge that, of course, to build a new category with a potential best-in-class molecule, that requires that you go all in, not just with speed, but also with investments and a geographical reach. What we will look for in the conversations that we'll entertain in this second half is
Speaker Change: a large pharma company who shares our vision and ambition that protein side can become a backbone therapy for weight management in the future if we continue to generate data that we have seen this summer.
Speaker Change: and you can say as a minimum an alternative to the DLT1s. Then we also recognize the opportunity to combine with other DLT1s for those patients who need the highest degree of weight loss.
Speaker Change: But we would really be looking for a partner who is ready to make commitments to develop.
Petrinskij: Petrinskij as a future backbone for weight management. And that, of course, requires significant investment, not only into the development of clinical activities such as
Petrinskij: phase three studies in obesity including cardiovascular outcome studies and associated comorbidities but also
Petrinskij: willingness to do the appropriate investments into manufacturing at a stage where you will not be, you can say, hit by the same supply issues that we are currently seeing in the market. And then ultimately somebody will have a global reach so we can get out to
Petrinskij: all the areas.
Petrinskij: So it's commitment that we are looking for, and of course, having said all this, it will have to be one of the largest pharma companies of this world.
Petrinskij: that otherwise the partnership will not be interesting for us within the partnership framework.
Petrinskij: We will also ask to have, you can say, development responsibilities, to continue to have co-development responsibilities and also aim to have commercial rights, 50% commercial rights in the U.S. and all the major markets.
Petrinskij: We think it's incredibly important for our sealand and we think we have a lot to contribute with in such a relationship and we are very proud of it.
Petrinskij: A co-development and co-commercialization partnership with a very committed partner who shares our vision and ambition for Petroleum Time. That will be the focus for these discussions.
David Kendall: And on the full data set that we're going to present with Patronite, David, will you share something there? Yeah, thank you, Adam. Thank you, Suzanne. The full data set, as we said, will...
David Kendall: is anticipated to be presented in the last half of this year at a scientific congress. As to biomarkers, given that this was predominantly the safety and tolerability phase 1b,
David Kendall: design that comes with most development programs.
David Kendall: We do not have a comprehensive but have some biomarkers. Some of the most important ones we're looking at are actually not biomarkers per se, but safety markers, but also effects on blood pressure, heart rate, etc. But rest assured that the plans for Phase 2b do include a more comprehensive biomarker.
David Kendall: assessment and the previously mentioned
David Kendall: assessments with MR for the quality of weight loss and the evidence of lean tissue preservation. I would say Suzanne would give us the
Suzanne: Confidence in calling this
Suzanne: a potential best in class.
Speaker Change: Our preclinical data, the understanding that, as Adam has mentioned, we can and will go to these higher doses in Phase 2, something that has not been investigated or was not possible. For example, with cougar lentide, animal data supporting
Adam Steensberg: preservation of lean mass and targeting of fat mass which we believe not only will allow for weight loss in the 15 to 20 percent range but also
Speaker Change: may be a very effective maintenance therapy. So dosing, exposure, and the quality of weight loss that comes, we believe, broadly with AML and agonism, for us, give us the confidence that this can and will be a best-in-class medicine.
Speaker Change: Thank you. We will now take our next question.
Speaker Change: Please stand by.
Speaker Change: And the next question comes from the line of Lucy Codrington from Jeffreys. Please go ahead, your line is now open.
Lucy Codrington: Hi there, thank you for taking my questions. I have a few if I may. Just to jump on that recent comment about the aspiration for co-development and co-commercialization rights
Speaker Change: Are they, is that a...
Speaker Change: an absolute must-have for you and if that is not on the table would
Speaker Change: that prevent any kind of future discussions with possible partners.
Speaker Change: Wondering, I guess the investment required on your behalf to commercialize in such key geographies and also the willingness of a potential partner to give up those rights, just wanted to know if that's a kind of hard and fast...
Speaker Change: ambition of yours and then just on some of the other kind of follow-ups
Speaker Change: You mentioned about the deaf-imputed Part 2 being based on the tolerability observed to date. Is that based primarily on the DREAM profile or also does that include blinded data from the Part 1 ongoing data set?
Speaker Change: And just related to that, I guess, is there anything to explain why the six milligrams dose has the same degree of weight loss at four weeks as it did at 12 weeks in the DREAM study?
Speaker Change: Secondly,
Speaker Change: Obviously, lots of, quite rightly, investment in expanding the studies around your obesity programme. I guess...
Speaker Change: On that it seems to me like the weight loss with amylin does seem to be largely assured now I mean, I know we need additional studies, but
Speaker Change: Will that weight loss be relevant if you don't have a CB benefit along with it? And therefore, is that something you could consider to start evaluating sooner rather than later? Or is that only something that will be done once you start the phase three trial?
Speaker Change: and...
Speaker Change: Also, in terms of your other obesity pipelines, I wonder when we might get some visibility on any non-clinical obesity assets that you may have in development and what your priorities are there. And then a final one, if I may, I appreciate I've asked a few, but you mentioned about
Speaker Change: high percentage of male participants in the amylin data set you have.
Speaker Change: I just want to understand your confidence that with a more balanced or potentially even female dominant group, you might not risk a deterioration in the tolerability profile.
Speaker Change: given there are some data to suggest that tolerability does tend to be worse in females than men, at least with GLP-1s. Thank you.
Speaker Change: Thank you, Lucia, and I think it's probably the most challenging questions today, just due to the number of questions, but try to address them and let us know.
Speaker Change: We missed out on some. If I'm going to start with one on the co-development and co-commercialization request,
Speaker Change: You can say from our end, it is actually a must that we have both and including co-commercialization opportunities in the major markets. You can, of course, strike such deals in many ways, and we will now entertain the discussions.
Speaker Change: It's absolutely critical for Zeeland to stay involved not only in the development phase, but also in the commercial rollout. Of course, this will have to be alongside an already established large pharma company.
Speaker Change: So it is, you can say, something that we will ask for in these discussions.
Speaker Change: and we think it's absolutely important for us.
Speaker Change: If we look into DAPI, and I will just start here to say it is the blinded data observations from the 13-week study that has caused us to go for the higher dose. And then you can say adding, allowing, actually deciding to let it run for 28 weeks.
Speaker Change: gives us the opportunity to understand the full potential a little bit more and also get a very early data readout that can help us define and design the phase 3 program. So we actually think
Speaker Change: This is a major upside to the program that we also...
Speaker Change: at you can say length to this because it allows us to move faster forward ultimately while
Speaker Change: you can say get it as we get an early data readout. But it is really the blinded observations are not on tolerability in the in the phase three that sorry in the in the 13-week study that we are recording later this year.
Speaker Change: As we have shared on the weight loss after 4 and 12 weeks with the 6 mg dose, I think it is really down to small cohorts, but it's also, you can say, it's also because
Speaker Change: As we shared before, we are really at the lower end of the effective path. And we know there's a lot, you can say, more heterogeneity in how people respond if you are at the very low end of exposure response. So I think that's why you can see, expect more variability at that six milligram dose.
Speaker Change: compared to higher doses.
Speaker Change: For amylin it is going to, and I would say this for any weight loss medication, it is going to be absolutely important that you also show benefits on cardiovascular
Speaker Change: risk and other, you can say, comorbidity, stability. We are not in this
Speaker Change: developing medicines just for weight loss, but actually to improve health. So of course, again, in the partnership discussions, it will be incredibly important that a partner is also ready to commit together with us to do CV outcome studies as early as possible.
Speaker Change: and… [inaudible]
Speaker Change: David, I think I will have to let you see if you can remember the last two questions. Lucy, I wrote them down. I may have missed some of the detail, but...
David Kendall: Yeah, the question around CV benefit, as Adam said, very important one for any obesity asset, certainly cardiovascular safety.
Speaker Change #100: the first bar to pass and then.
Speaker Change #101: potential benefit. I think the preliminary data that's been seen with petrolentide and other analogs
Speaker Change #102: where blood pressure is lowered, heart rate does not increase, markers of inflammation do go down and, you know, those...
Speaker Change #102: suggest that it's at least
Speaker Change #102: less pro-inflammatory environment which may
Speaker Change #102: take existing cardiovascular disease and make it more unstable, as you well know.
Speaker Change #102: So weight loss, yes, but to Adam's point, we're in the business of.
Lucy Codrington: improving health, so these value-adds or additional benefits are going to be important for us to both assess and demonstrate. Your question, I think, Lucy, about other assets in development. We have not disclosed our discovery phase.
Lucy Codrington: assets in the obesity area, I will say we have
Lucy Codrington: commitment to what we call Obesity Plus, which is...
Speaker Change #103: looking carefully for other assets or combinations of assets that can be
Speaker Change #103: employed for the management of overweight and obesity.
Speaker Change #103: as was
Speaker Change #103: previously asked.
Speaker Change #103: given the interest in pro-inflammatory
Speaker Change #103: markers and the inflammatory environment and obesity.
Speaker Change #104: not only looking at additional weight loss.
Speaker Change #105: further improving the quality of the weight loss, but targeting inflammation in unique ways is also on our list. So more to come, but nothing disclosed beyond what we have in clinical development now.
Speaker Change #105: As for your question on male participants versus female participants, there actually are some data generated both in animal models and in humans.
Speaker Change #105: tolerability, at least in the GOP1 class for females, may actually be better, not...
Speaker Change #105: what you described, but I'm happy to trade articles so we can have a look at those data.
Speaker Change #105: that data published from a collection of the clinical programs for semaglutide, drzeptide and other assets.
Speaker Change #105: suggest that females can lose 2-3% more body weight on those pharmacologic interventions. That's also been demonstrated in
Speaker Change #105: very low-calorie diet and other approaches to weight management that women
Speaker Change #105: tend to respond.
Speaker Change #105: By a few percentage points better than men. The tolerability profile first off for petrolentide in particular
Speaker Change #106: The tolerability profile we reported was, in our opinion, so benign that we don't anticipate seeing a difference in genders, depending on what you see. But I think...
Speaker Change #107: That, to us, is a very strong portion of this asset's benefits, which is a tolerability profile that is substantially different, in our opinion, than GOP1's. So I'll leave it there. Lucy, Adam, if you have any other points, now that you know the questions, again, I'm happy to turn it back to you.
Speaker Change #108: Did we answer your questions?
Lucy Codrington: You did. Thank you so much. Sorry about that.
Speaker Change #109: Thank you. We will now take our next question.
Speaker Change #110: please stand by.
Speaker Change #111: And the next question comes in the line of Julian Harrison from ETIG. Please go ahead, your line is now open.
Julian Harrison: Hi, thank you for taking my questions and congrats on all the recent progress. First, I'm wondering if you can maybe remind us of Glupaglutide, Spark It Opportunity, and Short Bowel Syndrome and how you're thinking about developments in competitive positioning from earlier this year.
Speaker Change #113: Yeah, thanks for that question, Julia. So, yeah, I mean, we are.
Speaker Change #113: You can say excited about the profile of Dupaglutide.
Speaker Change #113: In particular, we can say we have a long-acting molecule developed in an autoinjector, so it should be easy for the patients to take it if it's approved. And furthermore, and perhaps more importantly, we think we have a very strong efficacy readout with the patient.
Speaker Change #114: significant reductions in the need for parental support and actually a very large amount of
Speaker Change #115: Thank you.
Speaker Change #115: being able to completely get rid of their parental support needs.
Speaker Change #115: So we think we have a very strong competitive profile if the product is approved. Not only, you can say, towards the existing product on the market, which is a once-daily year-to-one, but also when we compare to data presented by competing programs. So you can say
Speaker Change #115: For sure our confidence in the profile has improved significantly in the first half as well compared
Speaker Change #115: to before we saw phase 3 data from competing programs. So, as we have said for some time, we do plan to progress this asset into, and if approved, into the hands of patients and with a potential for a best-in-class profile.
Speaker Change #116: When we look into the market, I think at least our observation is that it's a market that continues to increase, and we are north of, I think, 800 or 900 million U.S. dollars now, expanding both not only in U.S., but also Europe and Japan.
Speaker Change #116: So there is clearly a market opportunity growth and we would expect that with the entry of novel and
Speaker Change #116: Longer-acting molecules you could see even further growth. So so it's definitely an attractive market And as we also see a huge unmet medical need as many patients are still not offered treatments or actually drops are off early on
Speaker Change #116: for different reasons. So we actually see a significant opportunity to grow the market with these potential second generation molecules.
Speaker Change #117: Okay, excellent, and then I guess both for SBS and CHI, are these launches you're preparing for and can initiate internally if you need to, or are you expecting partners to step in sooner than later?
Eric: You can say I think they differentiate they differ a little bit and perhaps you know at the next call when we have Eric on board He can share more After our Q3 how we think about this But but what I can say is the CHI is of course a different animal than an SPS because it's just you can see
Speaker Change #119: It's an ultra-rare indication with very few centers handling these patients. And as we also shared last year, we are, we believe, completely ready to make this product available to patients. I'll remind you that it's the three-week indication that we get approved first and we still need to submit the chronic use. So we will
Speaker Change #119: We will be working daily on the tours, making the product available to patients as we also progress partnership discussions and actually get the chronic label submitted as well.
Speaker Change #119: For SPS, we are also making all the pre-launch activities, and if need be, we would also, as an organization, be ready to make it commercially available.
Speaker Change #119: But it is a key focus for us to still, as we have communicated all the time, have a partnership in place that can, you can say, drive the commercial rollout.
Speaker Change #119: Having said that, as we also shared today, these discussions for us is really focused on long-term value creation. So we are not, you can say,
Speaker Change #119: in an urgent need to do something but we will do the right thing when time being but that in our minds is together with a partner as we do the commercial actual commercial rollout.
Speaker Change #120: Okay, excellent. And then finally, I just have a quick housekeeping question. Sorry if I missed it, but wondering if you have any updated cash runway guidance in light of the equity raise in June.
Speaker Change #120: Thank you for that question, Julian. So let me cover that. You can say before the capital raise, we got it for a runway into 27.
Speaker Change #121: and clearly with, with your cash.
Speaker Change #122: We now have a position that has been extended. You can say that we also guided for the Koss Run Raid. We did not include any potential milestones or off-runs from new or existing partnerships, which of course would add.
Speaker Change #123: So, for the time being, we are not guiding. There are so many swing factors that can impact our cash runway, but I think it is fair to say we are really well funded to progress the assets we have in the pipeline.
Speaker Change #123: Thank you.
Speaker Change #124: Good morning.
Speaker Change #125: Thank you. We will now take our next question.
Speaker Change #126: Please stand by.
Speaker Change #127: The next question comes in the line of Kerry Holford from Berenberg. Please go ahead, your line is now open.
Kerry Holford: Thank you very much, Kerry Holford-Berenberg. Two points of clarification for me, please, on petrol and tide.
Kerry Holford: So I've seen the context of your move to phase two.
Speaker Change #129: Did you mention earlier in the call that you plan to run a study looking at petrol and iodine combo with the GLP-1?
Speaker Change #129: Or did I mishear that? Is it just more the concept of...
Speaker Change #130: potentially being used in that way ultimately. And then secondly on partnerships, I wonder if you can just clarify do you have ongoing live discussions on this here today?
Speaker Change #131: and indeed whether you would clarify whether you would be happy to consider a partnership ahead of the free-to-be data readout. Thank you.
Speaker Change #132: Thank you for those questions. So.
Speaker Change #133: The Phase IIb study that we will initiate here in the second half with proteinatide focus entirely on monotherapy, establishing the right dose range for using proteinatide as a monotherapy and developing it as an alternative to the Tier 1 class of medicines.
Speaker Change #134: What David said is that also next year we are planning to start combination studies as well but that is you can say
David Kendall: that is to address you can say potential those segments of patients who would need more than 25 percent weight loss and be kind of a sub-study not included in the phase 2b study. So we are doing that and we are also planning to start a study in patients with type 2 diabetes because
David Kendall: at least early days to suggest that.
Amelie Nanloch: and Amelie Nanloch could actually provide potentially more weight loss than the GFD1s in type 2, so this is part of expanding the
Amelie Nanloch: The scope of the program, but the main focus still is the monotherapy and creating this alternative and backbone. But we of course recognize the potential for combination therapies for those groups of patients who need the most weight loss. So that will be also addressed in separate studies next year.
Amelie Nanloch: On the partnering discussions, we have had dialogues for some time and we have stepped those up now, and I would say as we move into here the second quarter, we will formalize them a little bit more. But
Amelie Nanloch: And our ambition is, of course, to have a partnership in place before we start phase 3, but we don't necessarily need to wait until phase 2b started.
Amelie Nanloch: has reported that depends on the dialogue. So I would say we are open to engaging a partnership when we have the right framework and the right partner that shares the ambition and vision for Trinityte. And those discussions will start here in the second half.
Amelie Nanloch: and I would say we would expect them to progress well into the next few months.
Amelie Nanloch: Thank you.
Speaker Change #136: Thank you. We will now take our next question.
Speaker Change #137: Please stand by.
Speaker Change #138: And the next question comes from the line of Prakhar Agrawal from Cantor Fitzgerald, please go ahead your line is not open
Prakhar Agrawal: Hi, thank you for taking my questions. Firstly, on petrolentide, Phase IIb plants, you know there's five doses in Phase IIb.
Speaker Change #140: I'm just going to confirm of the highest dose in phase one.
Speaker Change #141: is the highest you will go in phase two, or the protocol will have flexibility to go higher in dosing like you did with dapiglutide. And if you're not going higher on dosing for petrolentide in phase two B, what's the reason?
Speaker Change #141: Second question, just following up on combination strategy, obviously monotherapy is the focus right now.
Speaker Change #142: But from your perspective, which combination mechanism might be most attractive for an amyland drug from an efficacy and safety perspective?
Speaker Change #143: Obviously, some of the competitors have a different strategy with NOVA going after CLIP-1, but there seems to be some additive effects of GI rates with CLIP-1 and amylin, while Lilly is using CLIP-1-K for their amylin. So, wanted to get your perspective on combination mechanisms for amylin. Thank you.
Speaker Change #144: Thank you for those questions.
Speaker Change #145: It is the highest dose in phase 1b that we anticipate to also put forward in phase 2b and we don't anticipate to go higher. Partly because we don't think we need to, but also because this is, you can say, where we have the trust coverage to support the dosing. So
Speaker Change #145: Of course, we could consider going higher if we really felt we had to, but if you, and I think people will understand that when they see the more detailed data that we'll send it later, we think we are really where we need to be.
Speaker Change #145: and within the doldrums that is needed for Pretrinside to achieve the target product profile we are aiming for.
Speaker Change #146: On the combination therapies, I would say that we would anticipate that amyline could be a good combination partner for any GFP1-containing molecules. And that could be a pure GFP1, a GFP1-TIP, or a GFP1-TOP2.
Speaker Change #146: or DLZ1 Gluagon. So I think there are many opportunities because Amelin and DLZ1 works on different ways to reduce appetite.
Speaker Change #146: For those patients who really need the highest degree weight loss, we think it's a more logical combination than just trying to get the max out of a GP1, if you will.
Speaker Change #146: And so we have, of course, and if you look into the data, NOVO have presented the Cagri Sima. It is, of course, impressive data with a very high degree of weight loss for those patients who need that very high degree of weight loss. We think it's an attractive profile, but
Speaker Change #146: Thank you.
Speaker Change #147: Thank you. Thank you. We will now take our next question.
Speaker Change #148: Please stand by.
Speaker Change #148: The next question comes from the line of Michael Novod from Nordea. Please go ahead, your line is now open.
Michael Novod: Thank you very much. Just two short questions.
Michael Novod: With funding in place, significant funding in place, what are your considerations around
Michael Novod: oral development, oral technologies.
Michael Novod: How can it be applied to existing assets? What are you thinking around that? And when could we potentially hear something around that? And then secondly, can you talk to
Speaker Change #150: but the youth.
Speaker Change #151: sense that you have the right balance between calcitonin and amylin receptor agonism with petrolentide, also compared to competition and sort of the bang for the buck on the weight loss without causing too many side effects.
Speaker Change #151: [inaudible]
David Kendall: Thank you, Michael. I will answer the first question, and David, he can talk about the balance around amylin and cathitonin. I would say we do have activities that are also focused on oral delivery of amylin, and there are many interesting technologies out there that can help peptides getting across the intestinal barrier. But I would, however, say for us it's really life cycle management opportunities. We are in the camp that truly believes that injectables will remain the major
David Kendall: You can say administration way for a long time for these categories. We think they're quite convenient for patients once a week.
David Kendall: as compared to having to take a pill perhaps every single day and also you can say running.
David Kendall: Some of the tolerability issues with that associated with that so but we have activities and it's something that has our keen focus It's also fair to say that it's these are some of the activities. We would most likely only step up
David Kendall: significantly within a partnership, but we are making the preparatory steps for doing that. David, will you talk about the balance?
David Kendall: Happy to, and thanks for your question, Michael.
David Kendall: As we are slowly learning the understanding of the biology of both amylin receptors, particularly amylin 1 and more so amylin 3, of these
David Kendall: ramp modified
David Kendall: receptors, as well as, you know, understanding which of these receptors may ultimately contribute to clinical outcomes. I will say, before I get into detail, that
David Kendall: ultimately clinical outcomes are likely to be the point of differentiation if there is any among these.
David Kendall: But we believe, based both on rodent data and understanding the calcitonin receptors,
David Kendall: do play an important role both in the central nervous system but for
David Kendall: maintaining a positive metabolic environment.
David Kendall: If the calcitonin receptor is absent, you see...
David Kendall: physiologically, less satiety, greater weight gain.
David Kendall: in the animal models who've had the calcitonin receptor knocked out. Energy expenditure may also change.
David Kendall: So we believe quite firmly that while activating the amylin receptor
David Kendall: in a potent way it is.
David Kendall: that some calcitonin receptor agonism does actually contribute to the weight loss observed.
David Kendall: make sense to us.
Speaker Change #152: Not having seen data from so-called pure amylin analogs, it's tough to make.
Speaker Change #152: comparisons.
Speaker Change #152: So, we will await clinical data, do our own work understanding the receptor biology, but remain convinced that petrolantide certainly has a profile that we think can be very effective.
Speaker Change #153: Great, thanks a lot. Thanks, Michael.
Speaker Change #154: Thank you. We will now take our next question.
Speaker Change #155: Please stand by.
Speaker Change #156: And the next question comes from the line of Jesper Ilse from Carnegie. Please go ahead, your line is now open.
Jesper Ilse: Thank you so much. A few questions from my side on the petroleum side as well. Firstly, thanks for the comments on new studies in both Combo and Type I.
Speaker Change #158: Perhaps, since you've now announced this, what is your current thoughts on also making head-to-head studies?
Speaker Change #159: versus Tier 1 to really prove differentiation and better tolerability versus Tier 1. That's my first question. Second question, just a follow-up on your comments about keeping 50% rights to US.
Speaker Change #160: So I understand that you want to stay involved in development, but can you please explain why it's It's good for a big pharma partner to have you on board on commercialization as well because I guess they can already do that quite quite good given their current sales force and focus
Speaker Change #161: And also on that note, have you had any initial feedback from partners on those demands for 50% U.S. rights?
Speaker Change #162: So I just wonder if it could mean that a partner potentially will avoid a partnership, as I guess a long-term value creation for a partner would be lower if they give away, if you can say that, 50% of U.S. rights.
Christian: And just a last question, will that also be the demand for our partnership programs such as the PicoType? Thank you so much.
Speaker Change #164: Thanks for the questions, Jesper.
Speaker Change #165: On head-to-head studies, that is something we will consider in the future and not something we have in the plans right now. Normally, you do these studies when you know the dose that you are moving into phase 3 with as well.
Speaker Change #166: But of course, we see huge potential not only in patients with type 2 diabetes, where you can see there's already data out there suggesting that amylin is potentially can be more effective than the GFP1s.
Speaker Change #166: but also just on exploring the tolerability profile between being a losing weight on a tier 1 versus an amylin, but here it's actually good to know the dose that you anticipate to utilize in phase 3 before you do those studies.
Speaker Change #167: on the partnership discussions, I think it will be...
Speaker Change #168: partners that we're discussing with will ultimately have to answer by themselves why they could think it would be attractive to share commercial rights with us.
Speaker Change #168: We feel we are sitting with a very unique opportunity here. We think we have one of the strongest opportunities within a space which is
Speaker Change #168: you can say just emerging the obesity space and we think we are in a very strong position to negotiate, deal with, focus on long-term value creation for seed and farmer and in our minds that
Speaker Change #168: includes having commercial rights in the major markets. Otherwise, you lose your strategic impact and also you compromise on the long-term value creation. I will of course not comment on, you can say, conversations we have with these partners. That would be premature. But that is how we enter these discussions.
Speaker Change #168: I feel these will be fruitful as we progress them. On your last question on the...
Speaker Change #168: Daffy Glutide if we will have the same conversations. Our focus right now from a partner perspective is on protein side but of course when discussing that we will at one point also discuss Daffy. But I again have to remind everyone that we still need to see probably the most important data that comes out later in this quarter.
Speaker Change #169: So before we have those data, we will not comment on the pattern structure that we anticipate for this molecule. But I understand your questions, but it's too early to address them.
Speaker Change #170: Thank you.
David Goodside: Thanks so much.
Speaker Change #172: Thank you.
Speaker Change #172: As there are no further questions, I would like to hand back to Adam Steensberg for any closing remarks.
Speaker Change #173: Thanks for watching, and don't forget to like, share, and subscribe to our channel.
Speaker Change #174: 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.
Speaker Change #175: This concludes today's conference call. Thank you for participating. You may now disconnect.
Speaker Change #176: Dr. Charles Mabbutt.