Zealand Pharma A/S

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Good day and thank you for standing by. Welcome to Zealand Pharma results for third quarter 2022 conference call. At this time all participants are in listen-only mode. After the speaker presentation there will be the question and answer session. To ask a question during the session you need to press star 1 1 on your telephone keypad. You will then hear an automatic message advising your hand is raised. Please be advised that today's conference has been recorded. I would now like to hand the conference over to a speaker today, Anna Krasowska. Please go ahead.

Thank you, operator. Welcome, and thank you for joining us today to discuss Zealand's third quarter results for 2022. I'm Anna Krasowska, Vice President of Investor Relations and Corporate Communications at Zealand. With me today to review the items on slide two are the following members of Zealand's management team. Adam Stainsberg, President and Chief Executive Officer, Henrietta Venica, Chief Financial Officer, and David Kendall, Chief Medical Officer. You can also find the related company announcement and supporting information on our website at zeelandpharma.com. I would like to point out, as described on slide three, that we will be making forward-looking statements that are subject to risks and uncertainties. With that, I will turn the call over to Adam Stainsberg, President and CEO. Adam?

Thank you, Anna, and thanks for everyone for joining today. I'll begin on slide four, This has been another busy quarter for Sealand. I'm very happy with the progress we have made to deliver on the key priorities that we set in March when we announced our decision to prioritize investment in peptides research and development, which is our core strength. In September, we completed our objective of partnering our marketed product. We are very pleased to announce a global license and development partnership with Novo Nordisk, a global leader in diabetes, to commercialize Zika lock. Beyond the financial terms, there are two key elements of this agreement for us. The first is that we have a commercial partner with a global reach that has the potential to bring this product to many more patients around the world. The second is that we'll continue to contribute and support NOBU. Under the agreement, we are responsible for certain plant development, regulatory, and manufacturing activities to support approval of Segaloft outside US. As you consider further partnerships for other pipeline assets, one important element for us is our ability to continue to contribute across the value chain. We have core strength as a peptide R&D company and we have unique expertise and insight gained through our development programs. We will therefore seek to maximize the value of our assets by thoughtfully and strategically leveraging those strengths. In the last six months, our rich pipeline has delivered two positive phase three trial readouts in two separate programs aimed at changing the lives of people living with rare and severe diseases. The first was for DASIC-luorine and congenital hyperinsulinism. The results from the phase 3 trial of DASIC-luorine in infants with CHI were presented in September. We believe these results support the potential for DASIC-luorine to be a novel, effective, and well-tolerated treatment for children with this rare and severe condition. The second was for Gepaglutine, our long-acting DLT2 analog designed for subcutaneous delivery by an auto-injector in patients with short bowel syndrome. In September, we were excited to report positive top-line results from this PIVOTO phase 3 EAST-SPS-1 trial. The robust results present a tremendous milestone for senior farmers and people living with short bowel syndrome. We now look forward to engaging regulators regarding both programs as we prepare for potential submissions of new drug applications with the U.S. Food and Drug Administration. Our obesity portfolio has continued to advance. Werner Engelheim presented results from the Phase II clinical study of BI-456906, the gluagon TLC1 receptor dual agonist in people with type 2 diabetes at both ESAD and the recent obesity week. We are extremely encouraged by the early data from this program and look forward to seeing the results of the ongoing phase 2 trial in obesity expected next year. We are also pleased to note that the phase 2 trial of BI456906 in people with non-alcoholic steatohepatitis or NASH has completed enrollment in the last quarter. For our long-acting amidine analog ZPE8396, we have completed dose escalation in the phase 1A single ascending dose trial in the last quarter and expect to dose the first subjects in our phase 1B multiple ascending dose study later this month. So building on the positive momentum, we were happy to announce a raise of almost 800 million Danish kroner in October as we progress towards yet another people-to-year for C-Land Pharma. Finally, I'm excited to welcome Henriette Winnicke, our new Chief Financial Officer to C-Land. She will join us on the call today. Henriette brings broad finance and business experience from large organizations, including in healthcare, and I look very much forward working with her. Before Henriette reviews the financial results for the period, I will turn over the call to our chief medical officer, David Kendall, to discuss our pipeline. David?

Thank you very much, Adam. Turning to slide five, I would like to begin with glopaglutide, our long-acting GLP-2 analog currently being studied for the potential treatment of short bowel syndrome, or SBS. As Adam has already mentioned, in September, we were extremely pleased to release positive top-line results from the EASE-1 pivotal phase 3 trial of glopaglutide in SPS patients. As we reported in this randomized double-blind placebo-controlled study, glopaglutide treatment significantly reduced the volume of parenteral support required compared to placebo when administered to patients with SPS and intestinal failure. From baseline, the glipaglutide twice-weekly treatment resulted in both rapid and continued reductions in parenteral support, with an average reduction of 5.13 liters per week at the end of the 24 weeks of study, as compared with a reduction of 2.85 liters per week for those treated with placebo. While there was also a numeric reduction in the total parenteral support Required among patients treated with the once-weekly glopaglutide, this reduction was not statistically different as compared to placebo. Importantly, approximately one in eight patients treated with glopaglutide over the course of study were able to completely wean off parenteral support. This included patients from both the twice-weekly and once-weekly glopaglutide dose groups, as well as SPS patients with stoma and colon incontinuity. no placebo-treated patients were weaned off parenteral support. Glifaglitide was assessed to be safe and was well tolerated in the trial. The most frequent reported adverse events were injection site reactions and gastrointestinal events. In total, 102 of the 106 participating patients completed the trial, of which 96 continued into the ongoing extension trials, EASE-2 and EASE-3, where efficacy and safety will continue to be assessed in an ongoing fashion for up to 104 weeks of treatment. We anticipate interim results from EASE-2 before the end of the year and from EASE-3 in the first quarter of 2023, and we look forward to engaging with regulatory authorities as we plan for submission of our new drug application with the FDA. I would like to now turn to slide six in our second phase three program, investigating dosiglucagon treatment in patients with congenital hyperinsulinism. CHI is an ultra-rare pediatric disease in which patients suffer from recurrent and persistent hypoglycemia due to excess insulin release. We've previously announced top-line results from Part 1 of the Phase 3 trial of newborns and infants up to 12 months of age who required IV glucose for maintenance of normal glucose levels, as shown on the left panel. In Part 1 of this study, Daziglucagon treatment over 48 hours significantly reduced the requirement for IV glucose to maintain glycemia when compared to placebo. We recently presented detailed data from both Part 1 and Part 2 of this trial at the 2022 European Society for Pediatric Endocrinology meeting. In addition to the results of Part 1 and the primary endpoint just discussed, additional data from Part 2 of the study showed that Daziglucagon reduced time in hypoglycemia enabled periodic or permanent discontinuation of IV glucose infusion in a majority of patients. And overall, seven of the 12 individuals who did not require pancreatectomy were completely weaned off IV glucose at the completion of the trial. All of this shown on the right side of the slide. Daziglucagon was observed to be well-tolerated, and no serious adverse events were reported in either part of this trial. The positive findings of our second Phase III trial and these additional data deepen our understanding of dosaglucogon's potential as an innovative treatment for CHI patients who have significant unmet need managing this challenging disease. We anticipate the data from this Phase III trial, along with data from the previous Phase III trial in older children, as well as the information derived from the safety extension trial, will form the basis of an NDA for dosaglucogon in CHI. We look forward to engaging with regulatory authorities and submitting a new drug application for daziglucagon in CHI in the first half of 2023. Turning to our obesity portfolio, we are excited to continue to advance a number of novel and exciting assets. On the pipeline chart on slide seven, you can see that the most advanced of these assets is the long-acting dual-glucagon GLP-1 receptor agonist, VI456906. which is being developed in partnership with Beringer Ingelheim. Our wholly owned obesity assets in clinical studies include a first-in-class GLP-1 and GLP-2 receptor dual agonist, dapiglutide, which will be advanced into Phase II early next year, and a long-acting amylin analog, ZP8396, currently in Phase I. We recently completed dose escalation in the phase 1A single ascending dose trial, the ZP8396, with the maximum tolerated dose reached. ZP8396 delivered subcutaneously appears to be well tolerated with no unexpected side effects and demonstrates a PK profile suitable for once-weekly dosing. We have received regulatory clearance and have initiated participant screening in the phase 1B multiple ascending dose trial, and we expect the first participants to be dosed in the coming weeks. Moving to slide 8, positive clinical results from phase 2 studies of BI456906 in type 2 diabetes were reported at two recent scientific meetings. The results presented at EASD in September demonstrated that treatment with BI-456906 led to dose-dependent lowering of hemoglobin A1C by up to 1.88% at 16 weeks, while treatment with open-label semaglutide used in the same trial resulted in a reduction in A1C of 1.47%. More recent results of the weight chain observed with BI-456906 treatment in this type 2 diabetes cohort were presented over the past week at the obesity week meetings, which you can see on slide 9. In the same study, treatment with this novel glucagon GLP-1 receptor agonist for 16 weeks resulted in dose-dependent reductions in body weight of up to 9% after treatment with BI-456906. while those treated with open-label semaglutide had a 5.4% decline in body weight. In addition, there were dose-dependent reductions in waist circumference observed in those treated with the BI compound, with decreases of up to nearly 13 centimeters at 16 weeks in the highest dose group, compared with the decrease in waist circumference of 1.95 centimeters seen with placebo. Treatment with open-label semaglutide at 1 milligram led to a decrease The safety and tolerability profile were consistent with that anticipated with a GLP-1 receptor agonist, with gastrointestinal side effects being the most commonly reported. It is anticipated that slower dose escalations over a longer duration will mitigate both the frequency and severity of GI adverse events, and longer follow-up beyond 16 weeks will be needed to more formally assess the full impact on body weight. This is an exciting time for our pipeline and a strong push towards potential NDA filings and advancement of our obesity portfolio assets, and we look forward to continuing to build upon this momentum for the remainder of 2022 and into 2023. I will now turn the call over to our CFO, Henrietta Wenneke, to review the nine-month financial results. Henrietta?

Thanks, David, and hello, everybody. Great to meet you all virtually today. I am truly excited to join the Zeeland team and I look forward to working with all of you and my colleagues at Zeeland to fully leverage the value of Zeeland's rich pipeline and contribute to the strong momentum the company is building. Let's move to slide 10 and the income statement. Revenue for the first nine months was 80 million DKK, driven by the development agreement with Alexium and the new agreement with Nova Nordisk. CELAN receives an upfront payment of 25 million DKK from NOEL and is eligible to receive up to 45 million DKK in development milestones. CELAN is also eligible to receive up to 220 million DKK in sales-based milestones and royalties. The operating expenses for the period were 676 million DKK. This is slightly above last year due to progression of our research and development activities especially our light-stage critical programs. The sales and marketing expenses and the administration expenses are decreasing compared to last year following the announced restructuring. Net financial items for the period were $153 million DKK compared to $22 million DKK for the same period last year. These costs are primarily related to the loan with other loans. As a result of the announced disruption, all income and expenses related to the commercial activities of Vigo and Sigalock are accounted for at discontinued operations. Net results from discontinued operations for the first nine months in 2022 was a loss of 215 million DKK. Let's move to slide 11 and the cash position. Cash, cash equivalents, and market completion securities was approximately 1.5 billion DKK after the third quarter and the successful private placement which was done early October. The private placement of almost 5 million new shares at a price of 158 DKK per share resulted in a nice cash addition of almost 800 million DKK as Adam also mentioned. Let's turn to the financial guidance on slide 12. And let me keep this short, as this guidance is on-chain from our updated guidance issued on March 30th this year. We still expect net operating expenses in 2022 to be 1 billion DKK plus minus 10%, excluding discontinued operations. And with these brief remarks, I would like to turn the call back to Adam.

Thank you, Henriette. The third quarter has delivered several important milestones. And we believe CELAN is well positioned to continue to build momentum and leverage the value of our pipeline. So with that, I would thank all of you. And I'll now turn over the call to the operator for questions.

Thank you. Dear participants, as a reminder, to ask a question, you need to press star 11 on your telephone keypad and wait for a name to be announced. Please stand by while we'll compile the Q&A roll start. This will take a few moments. Now we're going to take our first question. And the first question comes from Joseph Stringer from Nipsom and Company. Your line is open. Please ask a question.

Hi. Thanks for taking our questions. Two from us. Wondering if you could comment on both the regulatory and also the commercial risk of, you know, a broad label for CLEFA in SPS in terms of you know, differentiation between stoma-only patients versus CIC patients. How do you see that playing out from, you know, regulatory perspective, but also commercial? Do you think that payers would need to see sort of the effect in both of those types of patients for commercial success? And then the second question is on EASE-SPS4. Can you remind us again of the goal of this trial and Is it possible that the data from this trial could be sufficient or used to expand the GLEFA SBS label to include patients without or who are not on parenteral support?

Thank you, Joseph. I will just start, and then maybe David want to add something. question on the regulatory and commercial risk regarding stoma and keep patients it's of course something that gets a lot of attention um due to the history of of both the development and of the ethics but but and then also you can say it's had a there's been a lot of discussions on these two patient groups over the years as we as they reported we have actually seen and that we have reported before we have seen robust changes with the twice weekly dosing in both patient groups, both the stoma and the kick patients. And David also mentioned here on the call that we saw patients with stoma and the kick weaning off completely. So we do think we have a strong data set to express, to address the potential benefits of the hepatotide in both patient groups. We think that Overall, they are actually quite similar. We think some of the findings from prior programs have perhaps not been over exaggerated a little bit, and at least the data set that we look at, then we feel very comfortable that we can argue for potential benefits in both staging groups. On EaseSBS4, I think that the main purpose of this product is really to address mechanistic differentiators of glipaglutide in this patient group. And of course, it will be interesting to potentially, as we develop this molecule further, also consider expanding into the SDS patient segments who are not on parenteral support. But that would not be the primary purpose of this study. But we could get additional information around the potential benefit of glibber in these patients as we allow the inclusion of such patients in the study, actually.

David, do you want to add something? Yeah. Thank you, Adam and Joseph. Thanks for the question. I think Adam has clearly described what we see that we believe the EASE-1 population, Kik and Stoma, a variety of etiologies of their shortfall is a very representative population of a group with SPS and intestinal failure obviously the study was powered primarily to demonstrate the reduction in parental support needed across the population not in specific subgroups but to Adam's point we feel we have robust data that obviously will be part of the submission to the FDA for them to consider, you know, what does this population represent and how might that be represented ultimately in a label. I learned long ago not to speculate as to what may be the regulatory response to that, but suffice it to say that both StomaKick etiologies of SBS, we feel we have very important and broad representation of the disease state. And to add to Adam's comment on expanding the label, I think we now have clear evidence from this trial we believe that this is an effective GLP-2 agonist and where it may play beyond those with documented intestinal failure like those who entered this trial. is exciting to consider, but first and foremost, our goal is to bring this forth for the intestinal failure patients and population with, again, the encouraging finding that a number of individuals on active glupaglutide treatment were able to completely discontinue that parenteral support, which we believe is a significant part of this data set. So I hope that touches on each of your questions, Joseph. Thanks.

Yeah, it's very helpful. Thank you for taking our questions.

Thank you.

Now we're going to take our next question.

And the next question comes from the line of Brian Balchan from Jefferies. Your line is open. Please ask your question.

Hi. Thanks for taking my question. Just ask the one. Just hope you can speak to the differentiation between your GLIP glue

I think we lost the connection. Operator, can you hear us?

Yes, I can hear you, and Brian is also connected to us.

Okay, we cannot hear Brian. We can still not hear Brian.

Excuse me, Brian, so I think your line is, okay, I believe Brian has been disconnected. So, dear participants, if you wish to ask a question, please press star 11 on your telephone keypad.

Dear speakers, there are no further questions at this time. Please continue.

So, can you repeat that?

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Okay. Yeah, we'll follow up on that. But I think if there are no further questions, then we will thank all the attendants for your questions. We look forward to connect. And I would also say if there are follow-up questions after this call, please feel free to reach out to us and we'll address them. My sense is that there is a technical issue with dialing in here, but please follow up directly with us afterwards.

That does conclude our conference for today. Thank you for participating. We may now all disconnect. Have a nice day.

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