Full Year 2023 Zealand Pharma A/S Earnings Call
Operator: www.globalonenessproject.org Good day, and thank you for standing by. Welcome to the Zealand Pharma results for full year 2023 webcast. At this time, all participants are in a listen-only mode.
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Good day and thank you for standing by welcome to the Zealand pharma results for full year 2023 webcast.
At this time all participants are in a listen only mode. After.
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Please be advised that today's conference is being recorded I would now like to hand, the conference over to your speaker today on a krasowski VP of Investor Relations. Please go ahead.
Anna Krassowska: Thank you, operator. Welcome, and thank you for joining us today to discuss Zeeland's results for the full year of 2023. With me today are the following members of Zeeland's management team: Adam Steensberg, President and Chief Executive Officer, Henrietta Winniker, Chief Financial Officer, and David Kendall, Chief Medical Officer.
Thank you operator, welcome and thank you for joining us today to discuss <unk> results for the full year of 2023 with me today are the following members of <unk> management team out of exchange bass, President and Chief Executive Officer, Henrietta Vinegar, Chief Financial Officer, and David Kendall Chief Medical Officer.
Anna Krassowska: You can also find the related company announcement and annual report on our website at zealandpharma.com. As described on slide two, I caution listeners that we will be making forward-looking statements that are subject to risks and uncertainty. Moving to slide three, I will turn the call over to Adam Steensberg, President and CEO. Adam?
You can also find the related company announcements and annual reports on our website at Zealand pharma Dot com.
Scribed on slide two our caution listeners that we will be making forward looking statements that are subject to risks and uncertainties.
Moving to slide three I will turn the call over to Adam <unk>, President and CEO Adam.
Adam Steensberg: Thank you, Anna, and thanks to everyone for joining us today. 2023 was an extraordinary year for Zealand. I'm very proud of our team's performance to deliver significant progress across our obesity and rare disease aspects, while building a strengthened financial position. In obesity, we reported positive phase 1 results for progenitide that support our conviction for amylin potential as a monotherapy and an alternative to tier-1-based therapy. With dabiglutide, we have a truly differentiated GFP1-containing molecule, and we are very excited about the trials evaluating its potential to address not only obesity but also low-grade inflammation associated with metabolic disease. Our partner, Boehringer, reported positive Phase II results for Cervalutide in obesity and advanced the molecule into a global Phase III program. And yesterday's top-line results, in mass, provide evidence of clear differentiation that potentially positions Servutotide to become a leading GLP-1-containing weight-loss medication. And finally, with two NDA submissions. We progress our rare disease products into the regulatory phase towards patients who need them. Moving to slide four.
Thank you Anna and thanks for everyone for joining today.
2023 was an extraordinary year preceding and I'm very proud of our team's performance to deliver significant progress across our <unk> and <unk> assets.
By building a strengthened financial position.
In obesity, we reported positive phase one results for protein inside that support our convention for eminent potential as a monotherapy and in alternative so thank you everyone.
<unk> based therapies.
With direct side, we have a truly differentiated you everyone containing molecule and we are very excited about the trials evaluating its potential to address not only obesity, but also low grade inflammation associated with Mr. Pollack diseases.
Our partner pairing our reported phase II results for several exciting obesity and advanced the molecule into a global phase III program in.
In Yesterdays topline results in mass provide evidence of clear differentiation that potentially position <unk> to become a leading tier one containing weight loss medication.
And finally with two NDA submissions we.
We progressed, our rare disease products.
Into the regulatory phase two worst patients who need them.
Moving to slide four.
Adam Steensberg: Zealand is well positioned to achieve significant milestones in 2024. We look forward to important clinical results for both of our wholly owned and differentiated obesity assets, which we anticipate will position us to expand our efforts and advance into substantial Phase IIb trials. We will work closely with the FDA during the NDA review of our two rare disease assets, dasigluagon for congenital hyperinsulinism and glipaglutide for short-vowel syndrome. For these assets, we also expect to progress our partnership discussions further.
<unk> is well positioned to achieve significant milestones in 2024.
We look forward to important clinical results for both of our wholly owned and differentiated obesity assets that we anticipate will position us to expand our efforts in advance into substantial phase <unk> trials.
We will work closely with the FDA during the NDA review of our two rare disease assets that she grew up on and congenital hyperinsulinism and could paclitaxel and short bowel syndrome.
For these assets, we also expect to progress our partnership discussions further.
Adam Steensberg: This year, we also expect two of our preclinical programs targeting inflammation to move into first in human trials. Moving to slide five, I will now turn over the call to our CMO, David Kendall, to discuss our R&D pipeline.
This year, we also expect.
Two of our preclinical programs targeting inflammation to move into first in human trials.
Moving to slide five I will now turn over the call to our CFO, David Kendall to discuss our R&D pipeline David.
Thank you Adam.
Today I'd like to focus my remarks on the continued progress of our obesity programs and also provide an update on the regulatory progress with our rare disease assets.
David Kendall: Thank you, Adam. Today, I'd like to focus my remarks on the continued progress of our obesity programs and also provide an update on the regulatory progress with our rare disease. Turning to slide 6.
Turning to slide six and beginning with patrolling tied our long acting amylin analogue. Many of you are aware that we presented data demonstrating a mean weight loss of more than 5% and healthy lean and overweight people. After weekly doses at both 0.6 and $1 two milligrams administered.
David Kendall: And beginning with petrolentide, our long-acting amylin analog, many of you are aware that we presented data demonstrating a mean weight loss of more than 5% in healthy lean and overweight people after weekly doses at both 0.6 and 1.2 mg administered for six weeks, data presented in full at Obesity Week 2023. We are both excited by the opportunity that our amylin analog represents and are very encouraged by the significant weight loss observed, which we believe is on par with the results reported in the initial short-term studies of GLP-1-based therapy. Importantly, we also believe that the side effect profile and tolerability of petrolontide offer the opportunity for a considerable improvement as compared to the adverse event profiles reported with Inkritsen or GLP-1-based therapy Furthermore, non-clinical data support that amylin agonists like petrolontide may offer the potential for preservation of lean mass and, as such, a higher quality weight loss as compared to increased weight loss.
For six weeks data presented in full at obesity week 2023.
We are both excited by the opportunities that are amylin analogue represents and are very encouraged by the significant weight loss observed, which we believe is on par with the results reported in the initial short term studies of <unk> based therapies.
Importantly, we also believe that the side effect profile and Tolerability of petroleum side offer the opportunity for a considerable improvement as compared to the adverse event profiles reported with acreage in our <unk>.
<unk> one based treatments.
In addition, Amazon Agonism provides a unique alternative mechanism for achieving weight loss and those with overweight and obesity by reducing food intake restoring leptons sensitivity and inducing satiety, which is a mechanism distinct from the appetite suppression observed with <unk> based therapies.
Furthermore, non clinical data support that amylin agonists like patrolling Todd may offer the potential for preservation of lean mass and as such a higher quality weight loss as compared to <unk> 10 based treatments in.
In addition, both our own and clinical observations with other Amazon analogs have demonstrated improvements in cardiovascular risk factors, such as C. Reactive protein lipids blood pressure and heart rate supporting a potential for cardiovascular protection from this class of therapy.
This profile supports our conviction for developing patrolling tied as monotherapy to achieve and maintain weight loss and thus provide an alternative to GOP one based therapies with the potential for improved tolerability preservation of lean body mass and improvements in cardiovascular risk.
The next key readout for our <unk> program will be the topline results from the 16 week multiple ascending dose trial exploring significantly higher doses of patrolling tied using a dose titration scheme with.
With data anticipated later in the first half of 2024.
We expect these results will further inform our plans for a large phase II B trial planned for initiation in the second half of 2024.
David Kendall: In addition, both our own and clinical observations with other amylin analogs have demonstrated improvements in cardiovascular risk factors, such as C-reactive protein, lipids, blood pressure, and heart rate, supporting a potential for cardiovascular protection from this class of therapy. This profile supports our conviction for developing petrelentide as monotherapy to achieve and maintain weight loss and thus provide an alternative to GLP-1-based therapy, with the potential for improved tolerability, preservation of lean body mass, and improvements in cardiovascular risk. The next key readout for our petrolontide program will be the top line results from the 16-week multiple ascending dose trial exploring significantly higher doses of petrolontide using dose titration, with data anticipated later in the first half of 2024. We expect these results will further inform our plans for a large Phase 2b trial planned for initiation in the second half. Turning to slide seven.
Turning to slide seven.
And turning our attention to <unk>, our first in class and only in class dual <unk>, one <unk> two receptor agonist.
We await data readouts from two clinical trials to be reported in 2024.
In the first half of 2024, we anticipate top line results from the investigator led dream trial.
<unk> not only the potential of this therapy to provide significant weight reduction, but also assessing <unk> potential to address both the low grade inflammation associated with metabolic disease that drives organ damage and achieved improvements in gut barrier function, which may play an important role in the management of those with Obi.
<unk> related metabolic diseases.
In the second half of 2024, we also look forward to top line results from the 13 week dose titration trial evaluating higher doses of <unk> and are currently being explored and dream and the previously reported phase one multiple ascending dose trial in which a mean relative reduction in body weight of four.
3% was observed after weekly dosing over four weeks.
We Furthermore, anticipate that these results will inform annually to the initiation of a large phase <unk> trial planned for startup in the first half of 2025.
Turning now to slide eight and the <unk> program, the glucagon <unk> dual agonist being developed by Beringer Ingelheim.
David Kendall: And turning our attention to dapiglutide, our first-in-class and only-in-class dual GLP-1 and GLP-2 receptor agonist. We await data readouts from two clinical trials to be reported in 2024. In the first half of 2024, we anticipate top-line results from the investigator-led DREAM trial, evaluating not only the potential of this therapy to provide significant weight reduction but also assessing dapaglutide's potential to address both the low-grade inflammation associated with metabolic disease that drives organ damage and achieve improvements in gut barrier function, which may play an important role in the management of those with obesity-related metabolic disease. In the second half of 2024, we also look forward to top-line results from the 13-week dose titration trial, evaluating higher doses of dapiglutide than are currently being explored in DREAM and the previously reported Phase 1 Multiple Ascending Dose trial, in which a mean relative reduction in body weight of 4.3% was observed after weekly dosing over four weeks.
As was reported earlier this week ended prior scientific Congresses service <unk> has demonstrated efficacy in treating obesity and now has demonstrated a positive effect in individuals with metabolic dysfunction associated Seattle hepatitis or Nash.
We are particularly excited with the recent reported topline results from the phase II trial in match, which demonstrated that 83% of participants treated with <unk> showed a biopsy proven.
Biopsy proven improvement in liver disease due to match stages F. One F. Three after 48 weeks of treatment when compared to placebo.
Importantly, there were also significant improvements in all secondary endpoints and the significant improvements in measures of fibrosis, a key secondary endpoint in this trial.
These exciting and important results provide evidence for clear differentiation of services tied amongst current GOP, one containing weight loss medications and we look forward to detailed results of this match study, which will be presented at an upcoming medical Congress.
Now turning to slide nine and to offer an update on our rare disease programs.
For now the glucagon and congenital hyperinsulinism, we've had productive and informative interactions with regulatory authorities and now have greater clarity on the path forward for these regulatory submissions.
This information puts us on track for Resubmission of the NDA part one or original one for up to three weeks of treatment the <unk>.
Resubmission follows the complete response letter issued by the FDA in December last year related to the deficiencies identified in our third party manufacturing facilities that are not specific to <unk> glucagon.
We look forward to responding to and resubmitting the information to the FDA before the end of the first half of 2024.
David Kendall: We furthermore anticipate that these results will inform and lead to the initiation of a large Phase 2B trial planned for startup in the first half of 2025. Turning now to slide 8 in the Cervo-Dutide program, the glucagon-GLP-1 dual agonist being developed by Behringer-Ingelheim. As reported earlier this week and at prior scientific congresses, cervidutide has demonstrated efficacy in treating obesity and now has demonstrated a positive effect in individuals with metabolic dysfunction associated steatohepatitis, or MAP.
In addition, we anticipate completing and submitting part two of the NDA for the use of <unk> glucagon and CACI beyond the three weeks of treatment also in the first half of 2024.
Our plan is in place to submit the additional analyses requested by the FDA from existing continuous glucose monitoring datasets that were included as secondary outcome measures in the phase III program.
These additional data will support the use of <unk> glucagon beyond the three weeks of treatment something the vast majority of children with CACI will require.
We believe that Aussie glucagon, if approved can be an important and effective treatment option for this rare and devastating diseases. This program represents a significant opportunity for Zealand to address a major unmet medical need for these children and their families.
David Kendall: We are particularly excited with the recent reported top-line results from the Phase 2 trial in MASH, which demonstrated that 83% of participants treated with Cervidutide showed a biopsy-proven improvement in liver disease due to MASH, stages F1 to F3, after 48 weeks of treatment when compared to placebo. Importantly, there were also significant improvements in all secondary endpoints and significant improvements in measures of fibrosis, a key secondary endpoint in These exciting and important results provide evidence for clear differentiation of Cervidutide amongst current GLP-1-containing weight-loss medications, and we look forward to detailed results of this MASH study, which will be presented at an upcoming MedicalCon.
We plan to make does it glucagon available to U S health care professionals and patients as soon as possible after regulatory approval and expect to continue to engage with potential partners for future commercialization.
Turning to slide 10, and <unk>, our long acting <unk> that we believe has the potential to be the best in class therapy for the treatment of adult patients with short bowel syndrome, who are dependent on parenteral support.
The NDA for <unk> was submitted in December 2023, and now has been accepted for a full review.
We anticipate notification of a <unk> date in the coming weeks.
And with that I would now like to turn the call over to our Chief Financial Officer Henrietta benefit to review our financial results for the full year 2023 Henrietta.
Thanks, David and Hello, everyone.
Move to slide 11, and the income statement.
Revenue for the full year 2023 was $343 million DKK.
This was mainly driven by a $30 million milestone payment from Boehringer ingelheim, as well as 10 million U S dollar milestone from Sanofi.
David Kendall: Now turning to slide nine and to offer an update on our rare disease program. For daviglucagon and congenital hyperinsulinism, we have had productive and informative interactions with regulatory authorities, and now we have greater clarity on the path forward for these regulatory submissions. This information puts us on track for resubmission of the NDA Part 1, or Original 1, for up to three weeks of treatment. The resubmission follows the complete response letter issued by the FDA in December last year related to deficiencies identified at a third-party manufacturing facility that are not specific to dosing glucagon.
Operating expenses for the full year of 2023 896 million DKK compared to 941 million DKK in the same period of 2022.
The decrease was driven by lower sales and marketing expenses as well as Noah admin expenses due to the cost reduction efforts following the restructuring announced in March 2022.
This was partly offset by higher R&D expenses in fact, 76% of OPEC plus allocated to R&D activities in 2023, driven by the progression of the late stage <unk> assets towards submission and significant investments in the advancement of our wholly owned <unk> programs.
We expanding our workforce by approximately 30% instruments of 23 to support these efforts.
Net financial items for 2023 resulted in a loss of 137 million DKK driven by the final repayment and termination of the loan with Oberland capital in May 2023.
Let's move to slide 12, and the cash position.
In 2023, we have taken significant action to strengthen our balance sheet.
In April we raised $1 5 billion DKK.
David Kendall: We look forward to responding to and resubmitting the information to the FDA before the end of the first half of 2024. In addition, we anticipate completing and submitting part two of the NDA for the use of dozyglucagon in CHI beyond three weeks, also in the first half of 2024. Our plan is in place to submit the additional analyses requested by the FDA from existing continuous glucose monitoring data sets that were included as secondary outcome measures in the Phase 3 program. These additional data will support the use of doxyglucagon beyond three weeks of treatment, something the vast majority of children with CHI will require.
Cash proceeds from a direct placement of new shares.
In may we settle and repay the debt facility with Oberland capital.
Also in May we established a 350 million DKK evolving credit facility.
In December we obtained a $90 million year debt facility with the European investment Bank.
And finally early January 2020, Paul.
<unk>, one <unk> 5 billion DKK <unk> proceeds from our private placement of new shares.
As a result of these actions we now have a cash position of approximately Nathalie fault fund 1 billion DKK.
Let's say I'm very satisfied that our financial position, which now takes our runway into 2027.
This solid foundation allow us to expense our investment in our wholly owned new PCC programs to ensure we have the right speed and quality and the advancements of these assets as we conclude phase one and initiate phase II.
At the same time it will continue to invest in progressing our rare disease program product candidates further regulatory phase modeling casing the partnership discussion.
And this takes me to slide 13, and our financial guidance.
In 2020, full we will increase our investment and it guides our net operating expenses up between one one to $1 2 billion DKK.
David Kendall: We believe that dozyglucagon, if approved, can be an important and effective treatment option for this rare and devastating disease. This program represents a significant opportunity for Zealand to address a major unmet medical need for these children and their families. We plan to make doziglucagon available to U.S. healthcare professionals and patients as soon as possible after regulatory approval and expect to continue to engage with potential partners for future commercialization. Turning to slide 10, englopaglutide, our long-acting GLP-2 that we believe has the potential to be the best in-class therapy for the treatment of adult patients with short bowel syndrome who are dependent on parenteral support. The NDA for glopaglutide was submitted in December 2023 and has now been accepted for full review.
We do not provide guidance on revenue anticipated from mixed system and potential new license and publishing agreements due to the uncertainty related to the timing as well as the size of such revenue.
Let's move on to slide 14, and our ESG strategy.
Beyond the clinical and financial progress we made in 2023, we also refined our ESG strategy and initiated preparation for the CSI requirements.
SG&A, we are committed to change and live with next generation peptide therapeutics and we do recognize the importance of overwriting of responsible and sustainable business as we grow and expand out.
Therefore, we have identified three pillars made in sustainability, which are affected by our activities.
First pillar is our patients.
We leverage innovation to advance the health and wellbeing of patients.
Our work is to develop patient centric treatment.
All severe unmet medical needs, which is why the vast majority of our resources resources are allocated to this.
Second pillar is our people.
We strive to foster and engaging enriching and inclusive workplace for our people, which you measure engagement scores and turnover rates.
Both of these measures came out very positively in 2023 with an engagement score of eight eight on a 10 point scale.
The third pillar is our operations.
We take responsibility for our impact of our operations and focus on minimizing and mitigating our climate impact while having proper controls in place to avoid adverse events.
For each pillar, we have or will set clear goals and ambitions to ensure the sealant continue continuously.
Henrietta Winniker: We anticipate notification of a PDUFA date in the coming week. And with that, I would now like to turn the call over to our Chief Financial Officer, Henrietta Venneke, to review our financial results for the full year 2021.
Responsibly and sustainably.
And with that we will move to slide 15, and I will turn the call back to Adam.
Thank you Henry.
Looking ahead.
I expect an exciting next 12 months with several key events and catalysts across our computing areas.
And our PCT, we expect top line results from the 16 week clinical trial with our amylin analogue petroleum side later in the first half. We expect these results will further inform our plans for a large phase III <unk> trial planned for initiation in the second half of the year.
Henrietta Winniker: Thanks, David. And hello, everyone. Let's move to slide 11 and the income statement. Revenue for the full year of 2023 was 343 million DKK. This was mainly driven by a 30 million euro milestone payment from Borenger Ingelheim as well as a 10 million US dollar milestone from Sanofi. Operating expenses for the full year of 2023 were 896 million DKK compared to 941 million DKK in the same period of 20
A debit to Todd we expect topline results from the investigator led phase II trial in the first half followed by top line results from the 13 week trial in the second half of 2024.
In rare diseases, NDA submissions allow for potential regulatory approvals in 2024.
And in chronic inflammation, we expect two preclinical programs to advance into the clinic this year.
So in summary, I hope.
Very much forward to a phenomenal 2024 that has the potential to elevate <unk> into a new league.
We are progressing our product candidates in obesity and rare diseases with quality and speed.
Backed by a solid balance sheet and our engaged experienced an extra <unk> employees, who are committed to deliver throughout the year.
And with that I will now turn over the course of the operator for questions.
Henrietta Winniker: The decrease was driven by lower sales and marketing expenses, as well as lower admin expenses, due to the cost reduction efforts following the restructuring announced in March 2022. However, this was partly offset by higher R&D expenses. In fact, 76% of OPEX was allocated to R&D activities in 2023, driven by the progression of late-stage rare disease assets towards submission and significant investments in the advancement of our wholly owned obesity program. We expanded our workforce by approximately 30% in 2023 to support these efforts. Net financial items for 2023 resulted in a loss of $137 million DKK, driven by the final repayment and termination of the loan with Oberlin Capital in May 2023.
Thank you as a reminder to ask a question you will need to press star one on one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one on one again, please standby, while we compile the Q&A queue.
Our first question comes from the line of Raj Sharma from Goldman Sachs. Please go ahead. Your line is open.
Hi, Thanks for taking my question just.
First one just on the Nash trial yesterday.
And I realize that kind of we'll see the data at a medical conference, but I was just wondering if there are any axillary trend points, which look at fibrosis improvement with no worsening of Nash.
And then secondly, just on petrol and Todd just wondering if you could give us some color on how you're thinking about the bar for efficacy at 16 weeks in the context of some competitor data that we've seen this morning. Thank you.
Thanks for those questions.
So first on the mass data on.
<unk> data it really is.
Got to release. These further insights into these data at a scientific conference in the types that we can unfortunately, not provide more flavor on the data, but we look very much forward to bring that Shang. These data later in the first half and beyond.
Henrietta Winniker: Let's move to slide 12 and the catch position. In 2023, we have taken significant action to strengthen our balance sheet. In April, we raised 1.5 billion DKK in progress proceeds from a direct placement of new shares. In May, we settled and repaid the debt facility with Oberlin Capital.
As I think it's clear from also press releases extremely excited with the.
With the top line results that has been released and believe that that looks extremely promising here.
<unk> inside our amylin analog maybe I'll just start here and then hand over to David.
As you mentioned, we expect to have 16 week data coming out in this.
First half of the year.
<unk>.
I think it's incredibly important to understand that what we are developing to training.
<unk> is an alternative to the <unk> so for US, it's really about passing the baton to wait till it's to weight loss in patients.
Looking forward, it's not like we are competing with the tier one costs. So our bias is really relating to.
Henrietta Winniker: Also in May, we established a 350 million DKK evolving credit facility. In December, we obtained a €90 million debt facility with the European Investment Bank. And finally, in early January 2024, we raised 1.45 billion DKK in gross proceeds from a private placement of new shares. As a result of these actions, we now have a cash position of approximately 4.1 billion DKK. I must say I'm very satisfied with our financial position, which now takes our runway into 2027. This solid foundation allows us to expand our investment in our wholly owned obesity programs to ensure we have the right speed and quality in the advancement of these assets as we conclude Phase 1 and initiate Phase 2B. At the same time, we will continue to invest in progressing our rare disease program product candidates through the regulatory phase while engaging in partnership discussions.
Achieving geared to one like weight loss than we would be more than happy and if you look into some of the early studies that is in the range of 7% to 9% weight loss.
And that for me would be definitely enough to define <unk> as a potential future winner in this space.
<unk> is an alternative for those patients who cannot tolerate it yet the one I would like to try something else.
The data that just came out this morning.
<unk> IP, we have honestly not at the time to look into the details of those data, but I would expect them to look similar to other tier two anti IP containing molecules.
And the same.
Concepts at David any any additions to the SCS ill just add some flavor to Adam's comment for petroleum side.
I think the long acting and we think more potent <unk> agonist.
At least in the short term trials 12 to 16 weeks I would anticipate that high single digit weight reduction.
Having seen in the six week.
Low dose PARP one of the trial previously reported achieving in excess of 5% I think that for us would give us a clear indication.
That it meets the threshold that Adam described obviously, both for patrolling tied in other <unk> agonists.
Extended treatment.
Beyond 24 to 36 weeks will be what is necessary to get the clearest read on both the dose response to this therapy.
Henrietta Winniker: And this takes me to slide 13 and our financial guidance. In 2024, we will increase our investment and be guided for net operating expenses of between 1.1 to 1.2 billion DKK. We do not provide guidance on revenue anticipated from the existence and potential new license and partnership agreements due to the uncertainty related to the timing as well as the size of such revenues. Let's move on to slide 14 on our ESG strategy.
Give us insights into.
Whether we achieve weight loss that as Adam says, we anticipate to be on par with GOP ones I think Theres, one historic reference which is older studies with high dose Pramlintide now a shorter acting agent, which as you may recall achieved nearly 10% weight reduction in the phase II study.
Henrietta Winniker: Beyond the clinical and financial progress we made in 2023, we also refined our ESG strategy and initiated preparation for the CSRD requirements. At Zealand, we are committed to changing lives with next-generation peptide therapeutics, and we do recognize the importance of operating a responsible and sustainable business as we grow and expand our pipeline. Therefore, we have identified three pillars of sustainability which are affected by our activities.
<unk>.
So I think without trying to predict trial results are those of the a range of responses. That's in a 16 week trial, we would be looking for to fit with the pattern that we would anticipate for this drug.
Brian Thank you very much.
Thank you we will now move onto our next question.
Okay.
Our next question comes from the line of Lucy Codrington from Jefferies. Please go ahead. Your line is open.
Thank you for taking my questions.
I appreciate that.
Limited information you can give on the <unk>.
Henrietta Winniker: The first pillar is our patients. We leverage innovation to advance the health and well-being of patients. Our work is to develop patient-centric treatment that solves severe unmet medical needs, which is why the vast majority of our resources are allocated to this. The second pillar is our people.
If you could remind us of the rationale for including the F. One patients within this trial and I guess any idea.
Is that the proportion of the Athlon patient was in the trial.
And.
I appreciate you and we may need to wait for this.
The detailed data, but is it fair to say that.
Henrietta Winniker: We strive to foster an engaging, enriching, and inclusive workplace for our people, which we measure through engagement scores and turnover. Both of these measures came out very positively in 2023, with an engagement score of 8.8 on a 10 point scale. The third pillar is our operations. We take responsibility for our impact on our operations and focus on minimizing and mitigating our climate impact while having proper controls in place to avoid adverse events.
The Nash.
<unk>.
Is.
Maybe.
Potentially easier endpoint.
The Nash resolution.
And any reason to expect that the Nash resolution endpoint would be.
Materially worse than what we've seen with the likes of Tis appetite, which reported on Nash resolution as it is.
Phase two Nash and treatment.
And then on the amylin understood on what we're looking for in terms of efficacy. It seems to me that Tolerability here is perhaps even more important.
And I guess.
Or do we want to see or mild adverse events and it comes from Gi or will some moderate and then Becky.
Henrietta Winniker: For each pillar, we have well-set clear goals and ambitions to ensure that Zealand continues to act responsibly and sustainably. And with that, we will move to slide 15, and I will turn the call back to Adam. Thank you, Henry. Looking ahead, I expect an exciting next 12 months with several key events and catalysts across our therapeutic areas. In obesity, we expect top-line results from the 16-week clinical trial with our amylin analog petroleum type later in the first half. We expect these results will further inform our plans for a large phase 2B trial planned for initiation in the second half of the year. For dabiglutide, we expect top-line results from the investigator-led Phase 2 trial in the first half of 2021, followed by top-line results from the 13-week trial in the second half of 2021.
Okay as long as we're not seeing significantly severe events under discontinuation.
Thank you.
Thanks Lucy.
Provide some color first and then maybe David you can add in.
For the for the trial results with <unk>, we can really not provide more flavor on the data onto their presented at a scientific conference. It was really off of our patent up of airline to do this you are correct that.
Patients with F. One to phase three.
Three years, including in this study I think it's important to understand that all studies.
You cannot you should be always be careful when you compare across trials. There were also other differences for instance, <unk> did not have BMI requirements into the <unk> study, which would actually be required into the foremost I do so so that there are differences I think what excites us a lot as this is the first molecule that is reported statistical.
<unk> effects on fibrosis and Trust me others have tried to achieve that as well. So we are exceeding.
Exceed I mean extremely excited about that outcome and then I would say once we have that.
Fluent data disclosures at upcoming scientific conferences that I think is the appropriate time to discuss the differences in more detail.
Adam Steensberg: In rare diseases, NDA submissions allow for potential regulatory approvals in 2024. And in chronic inflammation, we expect two preclinical programs to advance into the clinic this year. So, in summary, I look very much forward to a phenomenal 2024 that has the potential to elevate New Zealand into a new league.
For the upcoming data with protruding tight.
I think youre right to the extent that the side effect profiles look benign when we look at our early data and beyond that just the fact that it is a different mode of action that works and satiety and not just on on suppressing appetite. It has the muscle wasting potential of preventing at that and then other <unk>.
I think it's the totality of data that will be important process as you move forward, but clearly we expect to CMO tolerable profile compared to two that you had the one cost because that was what we ship into six week study, but David maybe you want to add something here I'll make one thanks Lucy for your question on the fibrosis Quest.
Operator: We are progressing our product candidates in obesity and rare diseases with quality and speed, backed by a solid balance sheet and our engaged, experienced, and enthusiastic employees who are committed to delivering throughout the year. And with that, 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 and 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 and 1 again.
As Adam said, we will not and cannot.
Go more deeply into these data until such time as RBI colleagues present, this but I think it is important to note that while one is considered mild fibrosis fibrosis as an abnormal reaction, we do not fibrose, our liver under healthy circumstances, so reversal even of F. One for fibrosis.
Operator: Please stand by while we compile the Q&A queue. Our first question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead; your line is open.
Ken.
Be considered a significant advance as Adam said.
<unk> fibrosis has sort of been the bugaboo, maybe the Holy Grail.
Removing fat reducing inflammation.
Rajan Sharma: Hi, thanks for taking my question. The first one is just on the NASH trial yesterday. And I realize that we'll see the data at a medical conference, but I was just wondering if there are any XLRH or endpoints that look at fibrosis improvement with no worsening of NASH. And then, secondly, just on Petrolint, I'm just wondering if you could give us some color on how you think about the bar for efficacy at 16 weeks in the context of, and the competitor data Thank you for those questions.
Diminishing the ballooning Thats observed so I think you'd like you. We are excited to see the details on these data.
And get an understanding of.
The changes in fibrosis and improvements in match scores are in a sense both dependent on no worsening in fibrosis, which was included and improvements.
Which achieved statistical significance. So I think those are important points to remember as we await the full dataset.
Secondly in Tolerability again their historical data some from previous studies with <unk>, others with goodwill and tied that would support that.
GI side effects that are observed are both less intense less severe and less frequent than with GOP. One therapies would be premature to say a dream of a world with only mild adverse events, but.
Adam Steensberg: So first on the mass data, on serotonin-type data, it really is up for Boehringer to release further insights into these data at a scientific conference here in the first half. So we can unfortunately not provide more flavor on the data, but we look very much forward to Boehringer sharing these data later in the first half. And we are, as I think is also clear from the press releases, extremely excited about the top line results that have been released and believe that that server looks extremely promising here. For Petrilliantide, our amylin analog, maybe I'll just start here and then hand over to David.
Given what we've seen in the early trials I think.
Certainly a more favorable profile, both less frequent and potentially less intense.
Gi side effects could be observed.
But ultimately the data will be the teller of that tail. So we await the <unk>.
16 week data to give you a much clearer answer on that.
And maybe just a follow up I would always have been saying for some time, we really think what is needed.
In this space of weight loss and weight maintenance.
<unk> differentiated molecules, it's Mike we have to go beyond just looking at weight loss and it's about how well do you address comorbidities like.
Like mesh, which is one of the most important comorbidities and then it's of course.
Adam Steensberg: As you mentioned, we expect to have 16-week data coming out in the first half of the year. I think it's incredibly important to understand that what we are developing patriline type 4 is as an alternative to GLP-1. So for us, it's really about passing the bar for weight loss, the weight loss that patients are looking for. It's not like we are competing with the GLP-1 class.
Can you provide tools to patients who need something that is not based on a tier one.
Backbone, so I think our.
Our focus is to go beyond weight loss, you need to have enough weight loss, but the key to success for future medicines that are going to be launched that is how will they address.
Comorbidities and provide differentiation beyond weight loss.
Thank you.
Thank you we will now move on to our next question.
Our next question comes from the line of Charlie but from Morgan Stanley. Please go ahead. Your line is open.
Okay.
Charley My thought your line is open. Please go ahead.
Hi, guys can you hear me now.
Yes, Hi, Tony for Morgan Stanley. Thanks for taking my questions I guess, firstly I'd be interested to hear your thoughts on what is actually causing a fibrosis improvement I guess.
Adam Steensberg: So our bar is really relating to achieving Kierkegaard-1-like weight loss, then we would be more than happy. And if you look into some of the early studies, that was in the range of seven to 9% weight loss. And that, for me, would definitely be enough to define protein sign as a potential future winner in this space because it's an alternative for those patients who cannot tolerate DR2-1 or would like to try something else. The data that just came out this morning on DR2-1 DIP, we have honestly not had the time to look into the details of those data, but I would expect them to look similar to other DR2-1 DIP-containing molecules, as they're built on the same concept.
Do you believe is the case that all high efficacy treatments are able to achieve.
Eventually.
We are seeing that earlier with glucagon agonist given the rapid depletion of aside from the very start of the trial. What do you believe that you're doing something else special from a fibrosis perspective.
And then secondly.
I guess, just thinking about national broadly how important do you believe noninvasive biomarkers will be for the success.
<unk> tied in terms of actually being able to identify suitable patients in that sub group for the class of therapies. Thank you very much.
David Kendall: David, any additions to this? Yeah, I'll just add, thanks, Rajan, some flavor to Adam's comment about Trellantide, and I think the long-acting and, we think, more potent amylin agonists, at least in the short-term trials, 12 to 16 weeks, I would anticipate that high single-digit weight reduction, but having seen in the six-week low-dose part one of the trial previously reported, achieving in excess of Obviously, both for Trellantide and other amylin agonists, extended treatment out beyond 24 to 36 weeks will be what is necessary to get the clearest read on both the dose response to this therapy and give us insights into whether we achieve weight loss that, as Adam says, we anticipate to be on par with GLP-1s.
Thank you again, our thought China, and then maybe David can add something if I should address your first question again, we definitely expect that bring in but also provide more insights into the specific mechanism of action of this drug and the elevated now very clear that they do believe that we work on contributes to this and I think that also.
Preclinical evidence to support that.
They can work on component.
General noticed I would just say when it comes to fibrosis, we think thats much more than this than just pure weight loss of course, as we already know that benefits of weight loss. When it comes to labor health, but further specific effects of each individual molecule. That's much more to it than I personally believe that saying I have a very strong case for the involvement of kurgan onto some.
This specific pathways that should be more beneficial in fibrosis.
When it when it comes to mesh and noninvasive biomarker this versus biopsies and so on.
I would put it this way again.
If you have a weight loss medication that also achieved strong data in Nash.
For me this will be as important as if you have strong data in cardiovascular outcome studies.
If you're an obese and overweight into bto, 75% of those have naphtha, so increased level of fat in the liver and 35% of Nash <unk> Nash.
And this is just how it looks today. So that is based on data of obese individuals in the last few years.
David Kendall: I think there's one historic reference, which is older studies with high-dose Pramlantide, now a shorter acting agent, which, as you may recall, achieved nearly 10% weight reduction in phase two studies. So, I think, without trying to predict trial results, those are the range of responses that, in a 16-week trial, we would be looking for to fit with the pattern that we would anticipate for this drug.
Fast forward 10, 20 years those numbers I expect to go up significantly so when a physician will see an obese patients in the future that is a very high likelihood that such a patient will have features of Nash and they're in that situation you can say biopsies and biomarker becomes more important.
It becomes the same concept is understanding that the reason that we treat this patient who has a BS is actually to prevent.
Liver failure or liver end stage organ, just as we have data today to support use of <unk> in preventing cardiovascular disease. So I think we will when we have when you are talking about this category of drugs that also address weight loss.
Lucy Codrington: Thank you very much. Thank you. We'll now move on to our next question. Our next question comes from the line of Lucy Codrington from Jeffreys. Please go ahead; your line is open.
And provide additional health into Oregon, I think the market will be less important just as it is the case for probably cardiovascular disease, but David.
I don't know if you want to add some flavor to this yes, Charlie I'll add just a couple of things on the fibrosis front I think.
Again, we will await the presentation of the formal dataset from RBI colleagues I look forward to that as you do.
But as Adam alluded to.
Lucy Codrington: Hi, thank you for taking my questions. And I appreciate there's limited information you can give on the MASH data. But perhaps you could remind us of the rationale for including the F1 patients within this trial. And I guess any idea, if they're, what the proportion of the F1 patients were in the trial. I appreciate, again, we may need to wait for this with the detailed data, but is it fair to say that the NASH improvement may be, may be a potentially easier endpoint, I would assume, than Nash Resolution, and there is no reason to expect that the Nash Resolution endpoint would be materially worse than what we've seen with the likes of Tizeptide, which reported on NASH resolution as opposed to NASH improvement. And then on And I guess what's your bar here?
Glucagon, specifically and its effects on free fatty acid trafficking.
The ability to clear liver fat and continue to promote liberation of energy from the liver, including energy.
Stored as fat.
Likely plays an important role in reducing the overall injury that comes with fatty liver disease.
Fibrosis again as a response to injury regression of fibrosis.
<unk> suggests that the mechanism of action of <unk>.
Reduces that injury profoundly your earlier comment that just profound weight loss agents or agents that achieved significant weight loss should also be expected to reduce fibrosis has not borne out to at least in the phase II trial programs with more potent <unk> agonist.
Weight loss alone without the glucagon component has been used so I think.
These are as our colleagues have groundbreaking in terms of the.
Prevention of regression of fibrosis.
Wood.
Adam Steensberg: Do we want to see all mild adverse events when it comes to GI, or will some moderate events be okay as long as we're not seeing significantly severe events and or discontinuations? Thank you. Thanks, Lucy. I will provide some color first, and then maybe, David, you can add in. And, you know, for the trial results with Cebutatide, we can really not provide more flavor to the data until they're presented at a scientific conference. It is really up to our partner, Böhringer England, to do this.
At least mechanistically ascribe a lot of that potential to be added glucagon activity.
And then to the.
The noninvasive approaches.
I think this is a maturing science.
Use of fiber scan and other markers of hepatic injury are still.
Bill relatively in their infancy, but I would anticipate that as these assets come to market to Adam's point, the pre test or prior probability of having.
Match in.
These individual patients is so high.
Youll need convincing but I think this will certainly be a very important adjunct to use noninvasive testing biopsy. Obviously is what the agency has the regulatory authorities are looking for is the most definitive in clinical trials.
Adam Steensberg: You are correct that patients with F1 to F3 were included in this study. I think it's important to understand that all studies cannot, and you should always be careful when you compare across trials. There were also other differences.
And the future clinical reality may allow us some degrees of freedom to use these noninvasive tests.
Adam Steensberg: For instance, Berger did not have BMI requirements in their study, which were actually required in the former studies. So there are differences. I think what excites us a lot is this is the first molecule that has reported statistically significant effects on fibrosis. And trust me, others have tried to achieve that as well.
Great. Thank you very much.
Thank you.
Thank you we will now move on to our next question.
Our next question comes from the line of Jeff ill say from Carnegie. Please go ahead. Your line is open.
Thank you so much a couple of Christmas Firstly on <unk> can you just remind us what you see the face cases moving forward so whether it be a large phase III trial always the potential for an accelerated approval. A reason why I ask is just that bringing online media.
Adam Steensberg: So we are extremely excited about that outcome. And then I would say once we have the full data disclosure at upcoming scientific conferences, that I think is the appropriate time to discuss the differences in more detail. For the upcoming data with protein type, I think you are right to the extent that the side effect profiles look benign when we look at our early data. And beyond that, just the fact that it's a different mode of action, it works to promote satiety and not just suppressing appetite.
<unk> has been a bit unclear.
Indications that would be CMS that will first be launched secondly on the MLR in upcoming readout can you just remind us how you intend to announce results should we expect you to topline weight loss results, but not give any detailed safety results.
And just on that topic of slow in theory.
Amazon and <unk> be able to be combined with a tier one cips it.
<unk> always had mainly for too long I fully understand that you guys want to position it as a monotherapy, but just on the partners.
David Kendall: It has the muscle wasting potential of preventing that. And then other aspects, I think it's the totality of data that will be important for us as we move forward. But clearly, we expect to see a more tolerable profile compared to the Tier 1 class because that was what we observed in the six-week study. David, maybe you want to add something here. Yeah, I'll make one.
From our perspective, whether or not it could be combined with a few of longevity. Thank you.
Thank you and.
Again.
It's really are preparing us to also communicate on the future plan for <unk> in mesh I think they have been very clear that they are moving forward as fast as possible with this indication and as you also said.
<unk> communicated that.
It's unclear, which.
PCT match could be the first indication, which again is it just in our minds a strong testament to their commitment to this program. So of course that is a huge unmet medical need here.
David Kendall: Thanks, Lucy, for your question. On the fibrosis question, as Adam said, we will not and cannot go more deeply into these data until such time as our VI colleagues present them. But I think it is important to note that while F1 is considered mild fibrosis, fibrosis is an abnormal reaction. We do not fibrose our liver under healthy circumstances.
So they're gonna together when regulators will try to push this forward as fast as possible, while we cannot comment on the timeline, but of course, we expect to have more clarity on this throughout the year.
And so so for us it's just exciting to see these statements and I would say for eminent we will as we always do when we send out topline results provide a balanced.
Say review of the top line. So that would of course include both if you guys see some safety observations outside of PDT observations.
Yeah.
Combination its not like we don't want to combine emmeline opportunity inside with other tier ones and we also see an opportunity to do so later.
David Kendall: So reversal even of F1 fibrosis can be considered a significant advance. As Adam said, reversal of fibrosis has sort of been the bugaboo, maybe the holy grail, beyond removing fat, reducing inflammation, diminishing the ballooning that's observed. So I think, like you, we're excited to see the details on these data and get an understanding of what changes in fibrosis. And improvements in MASH scores are, in a sense, both dependent on no worsening in fibrosis, which was included, and improvements which achieve statistical significance. So I think those are important points to remember as we await the full data set. Secondly, intolerability.
We just as we have said a lot of times actually I believe that I said.
Lots of need for alternatives to the JV once that that just combination products, but having said that we will also pursue combination therapies. Once we have a good understanding of the dosing regime and we are moving into phase three with our per train title amylin analogue. It has been designed with the.
The opportunity to co formulate because its stable at the same levels as the tier one.
Once we know or at least so it is a fantastic opportunity to pursue that opportunity for those patients who need that additional amount of weight those but really.
And we asked such firm believers.
In a world five years from now the world with more people looking for alternatives than more of the same and that is again why we keep highlighting protruding.
Crown jewel in our pipeline because it is one of the most promising alternatives alternative nonincreasing weight loss agents in development.
David Kendall: Again, there are historical data, some from previous studies with pramlentide and others with cagrelentide, that would support that the GI side effects that are observed are both less intense, less severe, and less frequent than with GOP1 therapies. But it would be premature to say, you know, I dream of a world with only mild adverse events. But given what we've seen in the early trials, I think certainly a more favorable profile, both less frequent and potentially less intense GI side effects, could be observed. But ultimately, the data will be the teller of that tale. So we await the 16-week data to give you a much clearer answer on that. And maybe just to follow up, I would, as we have been saying for some time, really think what is needed in this space of weight loss and weight maintenance is differentiated molecules. We have to go beyond just looking at weight loss. It's about how well you address comorbidities like MASH, which is one of the most important comorbidities. And then it's, of course, can you provide tools to patients who need something that is not based on a tier one backbone?
Soon that will likely be a lot of tier ones tier one containing molecule was on the market.
We'll have to differentiate and how will they address different comorbidities is not just going to be about how much weight, but at that time. The world. We believe will really need alternative therapies that can help those patients who don't get the benefit from a tier one based therapy.
David.
One other comment to Adams.
Sponsor around combinations, yes for as you may recall we.
We have published preclinical data.
Looking not only at the stability of co formulation of our <unk> molecule.
<unk>.
<unk> based therapies, both some igloo tied in.
There is appetite and have shown additives and the clinical effect at least in animal models of overweight and obesity.
And that goes back again to historic parameter data, which showed additive it even with the I'll call them now first generation oral therapies like Sibutramine phentermine and so we fully expect additivity of.
<unk>, but I will reemphasize that.
Adam is spot on and our thinking is that alternatives with unique mechanisms.
<unk> with this improved tolerability profile.
It was really our primary focus.
With the opportunity to do exactly as you say to consider combinations.
Adam Steensberg: So I think our clear focus is to go beyond weight loss. We need to have enough weight loss, but then the key to success for future medicines that are going to be launched is how well they address co-morbidities and provide differentiation beyond weight loss. Thank you. Thank you. We'll now move on to our next question, which comes from the line of Charlie Mabut from Morgan Stanley. Please go ahead; your line is open. Charlie, my butcher line is open, please go ahead. Can you hear me now?
As part of the lifecycle management of this asset.
Okay. Thank you.
Thank you.
Thank you we will now move on to our next question.
Our next question comes from the line of Susan Van Fourth reason from BLK. Please go ahead. Your line is open.
Hi team. This is Suzanne Camden, Thanks for taking my questions.
Again, congrats on yesterday's data for sure. So I think we're also looking forward to the eminent data can you.
Elaborate already a bit on the <unk> that youre planning for petrol and tight.
What are your preliminary thoughts on trial design and sample size patient population endpoints et cetera and.
Charlie Mabut: Yes. Hi. Cool. This is Charlie Malbert from Morgan Stanley.
Also if you can share some color on how you are currently thinking about the timing of potentially partnering this asset.
Charlie Mabut: Thanks for taking my questions. I guess, firstly, I'd be interested to hear your thoughts on what's actually causing the fibrosis improvement. I guess it'll be interesting to know, do you believe it's a case that all high-efficacy obesity treatments are able to achieve fibrosis improvement eventually, and that we are seeing that earlier with glucagon agonists, given the rapid depletion of liver fat from the very start of the trial, or do you believe that glucagon is actually doing something else special from a fibrosis perspective? And then secondly, I guess just thinking about NASH more broadly, how important do you believe non-invasive biomarkers will be for the success of Servo-Dutide in terms of actually being able to identify suitable patients in that subgroup for the class of therapies? Thank you very much. Thank you. Again, I will start, Charlie, and then maybe David can add something.
What are the considerations on your mind. Thank you.
Thanks, Suzanne and thanks for the question.
So we cannot provide the details of the phase II design, yet and what we have.
Has committed to and also communicated it is going to be a very large phase <unk> phase <unk> study and as we also alluded to at our R&D day.
Its actually extremely important to do this right because we think we have potential best in class Amylin analogue. We think we have the potential to create a new category for weight management, which in our minds with the data we've seen thus far acknowledging it's early days looks to be a very very.
Potentially strong future category. So we wanted to do this right and that means of course, a large phase II B study not trying to cut corners.
And making sure we hit the doses right and also have the right extent of exposure before concluding on on how to progress into phase III. So for US it's important to do it right. Having said that we will also seek to to keep the momentum and then I can reassure you that we are.
Deeply engaged in preparing for this study under the anticipation of positive data readout later in the year. So.
So that's our thinking on that one with regard to patent ring.
For MLD and it is really our ambition to now start the phase <unk> study and hopefully also get to data readout. We think we can we can build.
Adam Steensberg: If I should address your first question, again, we definitely expect that Birn will also provide more insights into the specific mechanism of action of this drug. And they are already very clear that they do believe that gluagon contributes to this. And I think they have also published preclinical evidence to support the gluagon component. And as a general note, I would just say, when it comes to fibrosis, we think there's much more to this than just pure weight loss. Of course, we already know there are benefits of weight loss when it comes to liver health. But for the specific effects of each individual molecule, there's much more to it. And I personally believe that Birn will have a very strong case for the involvement of gluagon on some of the specific pathways that should be more beneficial in fibrosis.
Building a lot more value in this asset we have a very clear strategy for how to progress. This asset and then before entering phase III. It is in our minds and logical time two to two <unk> a partner.
Ship, where we have to make large investments into manufacturing and also make sure we have a true global reach.
But at that time.
Would seek to have strategic rights and stay involved in the program. We think we have a lot to contribute with and also.
I would like to contribute.
Okay.
Yes.
Okay.
Our next question Krishna.
Thank you.
We'll now move on to our next question.
Okay.
Our next question comes from the line of Julian Harrison from BP.
Please go ahead your line is open.
Hi, Congrats on the progress and thank you for taking my question.
I am curious if you could talk more about the payer supported and self pay segments of the obesity market.
Arching strategies in addressing both and if there are any specific mechanisms or target profiles that are more amenable to one over the other.
Thanks for that question Julien and I think it is it's highly relevant to consider these things.
Adam Steensberg: When it comes to mesh and non-invasive biomarkers versus biopsies, and so on. I would put it this way again: if you have a weight-loss medication that also achieves strong data in MASH, for me, this will be as important as if you have strong data in cardiovascular outcome studies. If you're an obese and overweight individual, 75% of those have NAFL, so an increased level of fat in the liver, and 35% have NASH, so some degree of NASH. And this is just how it looks today.
At least our observations is that.
Is it.
That's a deep patient engagement in these new.
Medicines, because it's a huge desire for patients to lose weight.
In future in the future environment, we do expect this to stay you can say as a very significant segment.
Patients, who are willing and can afford to pay themselves for these therapies.
So ultimately we do believe that you will of course also have more access from the payer side, because but that will need.
You can say clear data on organ protection clinical outcome data.
Adam Steensberg: So that is based on data from obese individuals in the last few years. If we fast forward 10, 20 years, those numbers, I expect, will go up significantly. So when a physician sees an obese patient in the future, there is a very high likelihood that such a patient will have features of NASH. And in that situation, you can say biopsies and biomarkers become more important. It becomes the same concept as understanding that the reason that we treat this patient who's obese is actually to prevent liver failure, a liver end-stage organ, just as we have data today to support the use of GLD1s in preventing cardiovascular disease. So I think we will, when we have, when you're talking about this category of drugs that also address weight loss, provide additional health to organs. I think these markers will be less important, just as it is the case for probably cardiovascular disease, but David, I don't know if you want to add some flavor to this.
Can you can describe the full value.
That society get from these weight towards medications, we think it's highly likely that we will see these positive clinical readouts with a number of these molecules that are in development.
Because we already know that losing weight today is associated with health benefits and by adding some of these novel modalities that we have discussed today into the bid.
Yes.
Phenomenon, and we think that will be a lot of positive clinical outcome data that will support the payer segments, but the segment of patients who will be willing to pay themselves to achieve the weight loss that they have been trying to achieve for many years without being successful we think will remain a big category.
As a society I truly believe we should be very happy with that because ultimately that should lead to better health outcomes in a more healthy population. So it is something we are very focused on it.
When we did.
These medicines and also to make sure that we make the right choices to be able to address the needs and desires from from all the stakeholders, but the ultimate goal.
Really it is to secure that we will not be hit with this tsunami of comorbidities that are associated with that.
Our PCT pandemic, we are seeing right now.
So I think it's a unique.
Self paid segment is a unique opportunity.
In this space that we really want to embrace in the future.
Yeah.
Excellent. Thank you.
Thank you.
We will now move on to our next question.
David Kendall: Yeah, Charlie, I'll add just a couple of things on the fibrosis front. I think, again, we will await the presentation of the formal data set from our BI colleagues and look forward to that, as you do. But as Adam alluded to, glucagon specifically and its effects on free fatty acid trafficking, the ability to clear liver fat and continue to promote the liberation of energy from the liver, including energy that's stored as fat, likely plays an important role in reducing the overall injury that comes with fatty liver disease.
Yeah.
Our next question comes from the line of Robin Sharma from Goldman Sachs. Please go ahead. Your line is open.
Hi, Thanks for taking my follow up questions just actually on that from a competitive perspective on the rare disease side.
Phase one trials for big tide, and graft versus host disease.
Which is expected to read out in the first half of this year. So I was just wondering to what extent not could be informative to future development plans with <unk> and also potentially.
Extending maybe informative of potential inflammation benefits with <unk> given that <unk> component. Thank you.
Thanks for that question and it is interesting that we discussed the radices acid. So little these days, but of course, we understand that and we flip.
David Kendall: Fibrosis, again, is a response to injury, and a regression of fibrosis would suggest that the mechanism of action reduces that injury profoundly. Your earlier comment that just profound weight loss agents or agents that achieve significant weight loss should also be expected to reduce fibrosis has not borne out, at least in the phase two trial programs with more potent GLP-1 agonists, where weight loss alone without the glucagon component has been used. So I think these are, as our colleagues said, groundbreaking in terms of the prevention of regression of fibrosis. I would at least mechanistically ascribe a lot of that potential to the added glucagon activity. And then to the noninvasive approaches; I think this is a maturing science, and the use of FibroScan and other markers of hepatic injury are still relatively in their infancy.
<unk> as we as David also alluded to in the prepared remarks, we really believe we have a best in class GSE. One analog that has now been accepted for review by the FDA.
And we have also been very clear to the market that we're looking for companies to commercialize it.
Not only <unk> and CSI, but also <unk> for short bowel syndrome, and I think one of the reasons is of course.
We truly believe there's more to this end we are in the future patent I would of course be wonderful. If they would also look into expanding the label with future studies in future indications. So we truly believe there is much more on this.
In <unk> than what we have seen just in the first generation <unk> that was that was launched into Sps and it would be our hope that our future patent would also look into expanding the opportunities with what we believe could become a best in class here too.
And the whole information aspect of <unk> is something that has been heavily under studied logging to give you time to see more and more data of not only the indirect effects of <unk> direct anti inflammatory effects of tier two coming out and then for <unk>. It is really for us at.
David Kendall: But I would anticipate that as these assets come to market, to Adam's point, the pre-test or prior probability of having a MASH in these individual patients is so high that you'll need convincing. But I think this will certainly be a very important adjunct to the use of noninvasive testing. Biopsy, obviously, is what the agencies and the regulatory authorities are looking for because it is the most definitive in clinical trials.
A unique opportunity with attitude tied to leverage that you had one effects on weight dosing metabolic benefits and then adding that anti inflammatory component of the tier two into the molecule in theory that should be hugely beneficial for not.
Not only cardiovascular disease, but also mesh as we discussed before and at this time and other diseases in general if you have metabolic challenged organs, you will always see inflammation alone.
David Kendall: In the future, clinical reality may allow us some degrees of freedom to use these noninvasive tests. Great, thank you very much. Thank you. Thank you. We'll now move on to our next question. Our next question comes from the line of Jesper Ilfe from Carnegie. Please go ahead, your line is open.
And we believe with <unk>, we have a unique opportunity to address that to a large extent than some of the other tier one containing molecules.
Thank you.
Thank you.
There are no further questions at this time, so I'll hand, the call back to Adam Steams backup for closing remarks.
With that we would like to thank you all for attending and for your questions. We look very much forward to future announcements and to updating and connecting in the coming weeks and months.
Jesper Ilfe: Thank you so much. There are a couple of questions. Firstly, on cervotrite mass data, can you just remind us what you think the base case is moving forward? So, will it be a large phase 3 trial, or is there potential for an accelerated approval? A reason for asking is just that the Bering-Alenheimer-Media interviews have been a bit unclear with indications of obesity or mass that will first be belong to. Secondly, on the MLN upcoming readout, can you just remind us how you intend to announce results? Do we expect you to give us top-line weight loss results but not give any detailed safety results? And just on that topic as well, in theory, would your amylin analog be able to be combined with a Tlp1-GIP as it is, or is it mainly for Tlp1?
Thank you.
This concludes today's conference call. Thank you for participating you may now disconnect speakers. Please standby.
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Adam Steensberg: I fully understand that you guys want to partition it as a monotherapy, but just from a partner perspective, whether or not it could be combined as well with Tlp1-GIP. Thank you. Thank you, Esther.
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Adam Steensberg: And again, it's really up to Berger to also communicate the future plan for servutitide in mash. I think they have been very clear that they are moving forward as fast as possible with this indication. And as you also said, communicated that it's unclear which of the obesity or MASH could be the first indication, which again is just, in our minds, a strong testament to their commitment to this program. So, of course, there's a huge unmet medical need here, and Boeing, together with regulators, will try to push this forward as fast as possible. But we cannot comment on the timeline, but, of course, we expect to have more clarity on this throughout the year. So for us, it's just exciting to see these statements.
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Adam Steensberg: And I would say for Amelin, we will, as we always do when we send out top line results, provide a balanced, you can say, review of the top line. So that would, of course, include both efficacy and some safety observations or tolerability observations, in combination. It's not like we don't want to combine amylin, our protein inside, with other DLP ones, and we also see an opportunity to do so later.
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Adam Steensberg: We, just as we have said a lot of times, actually believe that there is a much larger need for alternatives to the GFP1s that are just combination products. But having said that, we will also pursue combination therapies once we have a good understanding of the dosing regime and we are moving into phase three with our protein type or amylin analog. It has been designed with the opportunity to co-formulate because it's stable at the same pH levels as the GFP1s we know of, at least. So it is a fantastic opportunity to pursue that opportunity for those patients who need that additional amount of weight loss. But really,
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David Kendall: And we are such firm believers that in a world five years from now, the world will more often be looking for alternatives than more of the same. And that is, again, why we keep highlighting protein as the crown jewel in our pipeline because it is one of the most promising alternatives, alternative non-ingredient weight loss agents in development. Soon, there will likely be a lot of DLT1s, or DLT1-containing molecules, on the market. They will have to differentiate on how well they address different comorbidities. It's not just gonna be about how much weight, but at that time, the world, we believe, will really need alternative therapies that can help those patients who don't get the right benefit from a DLT1-based therapy. Yeah, one other comment on Adam's response around combinations, Jesper, as you may recall, we have published preclinical data looking not only at the stability of co-formulation of our petrolantide molecule with GLP-1-based therapies, both stomaglutide and terzapotide, but we have shown additivity in the clinical effect, at least in animal models, of overweight and obesity.
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David Kendall: And that goes back, again, to historic pramlantide data, which showed additivity even with the, I'll call them now, first-generation oral therapies like cebutramine and phentermine. So we fully expect additivity of petrolantide, but I will reemphasize that Adam is spot on in our thinking that alternatives with unique mechanisms, potentially with this improved tolerability profile, are really our primary focus, with the opportunity to do exactly as you say, consider combinations as part of the lifecycle management of this asset.
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Suzanne Van Voorhuizen: Very clear. Thank you. Thank you. Thank you. We'll now move on to our next question. Our next question comes from the line of Suzanne Van Voorhuizen from VLK. Please go ahead, your line is open. Hi, team. This is Suzanne from Kempen.
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Suzanne Van Voorhuizen: Thanks for taking my questions. Again, congrats on yesterday's data for Servo. I think we're also looking forward to the amylin data. Can you elaborate already a bit on the phase to be that you're planning for the petroleum diet?
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Adam Steensberg: What are your preliminary thoughts on trial design, sample size, patient population, endpoints, et cetera? And also, if you can share some color on how you are currently thinking about the timing of potentially partnering these assets, what are the considerations on your mind? Thank you. Thanks, Suzanne, and thanks for the question. But we cannot provide the details of the phase 2 design yet.
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Adam Steensberg: What we have committed to and also communicated is that it is going to be a very large phase 2b study. And as we also alluded to at our R&D day, for us, it's actually extremely important to do this right because we think we have a potential best-in-class amylin analog. We think we have the potential to create a new category for weight management, which, in our minds, with the data we have seen thus far, acknowledging its early days, looks to be a very, very strong future category. So we want to do this right, and that means, of course, a large phase 2b study, not trying to cut corners and making sure we hit the doses right and also have the right extent of exposure before concluding on how So for us, it's important to do it right.
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Adam Steensberg: Having said that, we will also seek to keep momentum, and then I can reassure you that we are deeply engaged in preparing for this study with the anticipation of positive data readout later in the year. So that is our thinking on that one. With regard to partnering, for Ameline, it is really our ambition to now start the phase 2B study and, hopefully, also get to data readout. We think we can build in a lot more value to this asset. We have a very clear strategy for how to progress this asset. And then, before entering phase 3, it is, in our minds, a logical time to initiate a partnership where we have to make large investments in manufacturing and also make sure we have a true global reach. But at that time, we would seek to have strategic rights and stay involved in the program. We think we have a lot to contribute and also would like to contribute. Yeah,
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Adam Steensberg: I hope that helps. Thanks. Thank you. We will now move on to our next question. Our next question comes from the line of Julian Harrison from BTIG. Please go ahead, your line is open.
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Julian Harrison: Hi, congrats on the progress and thank you for taking my question. I'm curious if you could talk more about the payer-supported and self-pay segments of the obesity market, your overarching strategies for addressing both, and if there are any specific mechanisms or target profiles that are more amenable to one over the other. Thanks for that question, Julian. And I think it's highly relevant to consider these things. At least, our observation is that...
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Adam Steensberg: There's such deep patient engagement in these new medicines because of the huge desire for patients to lose weight. And in the future, in the future environment, we do expect this to stay as a very significant segment of patients who are willing and can afford to pay for these therapies. So ultimately, we do believe that you will, of course, also have more access from the payer side because, but that will need clear data on organ protection and clinical outcomes so you can describe the full value that society gets from these weight-loss medications. We think it's highly likely that we will see positive clinical readouts with a number of these molecules that are in development because we already know that losing weight today is associated with health benefits.
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Adam Steensberg: And by adding some of these novel modalities that we have discussed today to this phenomenon, we think there will be a lot of positive clinical outcome data that will support the payer segment, but the segment of patients who are willing to pay themselves to achieve the weight loss that they have been trying to achieve for many years without being successful, we think will remain a big category. And as a society, I truly believe we should be very happy with that because, ultimately, that should lead to better health outcomes and a more healthy population. So it's something we are very focused on when we develop these medicines and also make sure that we make the right choices to be able to address the needs and desires of all the stakeholders. But the ultimate goal... really is to ensure that we will not be hit with this tsunami of comorbidities that are associated with the obesity pandemic we are seeing right now. So I think it's a unique opportunity in this space that we really want to embrace in the future.
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Adam Steensberg: Excellent, thank you. Thank you. We'll now move on to our next question. Our next question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead, your line is open.
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Rajan Sharma: Hi, thanks for taking my follow-up questions. Just actually, from a competitive perspective on the red Z side, we noticed that there is a Phase 1 trial for apiglutide in graft-versus-host disease, which is expected to read out in the first half of this year. So I was just wondering to what extent that could be informative, in terms of Development Plans. Glepiglutide, and also potentially... To what extent may it be informative of potential inflammation benefits with DAPI Glutide given that it also has... Thanks for that question.
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Adam Steensberg: And it is interesting that we discuss this rare disease as it's so rare these days, but, of course, we understand that. And with glipaglutide, as we, as David also alluded to in the prepared remarks, we really believe we have a best-in-class GLP-1 analog that has now been accepted for review by the FDA, and we have also been very clear to the markets that we are looking for companies to commercialize not only CHI, DASI Global CHI, but also clopacrotide for short bowel syndrome. And I think one of the reasons is that, of course, we truly believe there's more to this.
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Adam Steensberg: And with a new future partner, it would, of course, be wonderful if they would also look into expanding their label with future studies in future indications. So we truly believe there's much more to this in GLP-2 than what we have seen just in the first generation GLP-2 agate that was launched into SPS. And it would be our hope that a future partner would also look into expanding the opportunities with what we believe could become a best-in-class GLP-2. And the whole information aspect of GLP-2 is something that has been heavily understudied.
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Adam Steensberg: Luckily, we are starting to see more and more data of not only indirect effects of GLP-2 but direct anti-inflammatory effects of GLP-2 coming out. And for dabiglutide, it is really for us a unique opportunity with dapaglutide to leverage the GFD1 effects on weight loss and metabolic benefits and then add that anti-inflammatory component of GFD2 to the molecule. In theory, that should be hugely beneficial for not only cardiovascular disease but also MASH, as we discussed before, Alzheimer's, and other diseases. In general, if you have metabolically challenged organs, you will always see inflammation accompany that.
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Adam Steensberg: And we believe with dapaglutide, we have a unique opportunity to address that to a larger extent than some of the other GFD1 containing molecules. Thank you. There are no further questions at this time, so I'll hand the call back to Adam Steensberg for closing remarks. With that, we would like to thank you all for attending and for your questions. We look very much forward to future announcements and to updating and connecting with you in the coming weeks and months. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect. Speakers, please stand by. 2021 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. For more information, visit moojimedia.org.
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