Zealand Pharma A/S (ZEAL) Earnings Call Transcript & Summary

[Audio Gap] We have David Kendall, CMO of Zealand. And then we also have Charlie Haywood, who covers the stock on -- in the virtual landscape here, who will kind of come on and ask some Q&A at the end. But also at the end, feel free to raise your hand, and I can call on you for any questions. But I know that David wants to kick off with a little presentation, and then we'll do the Q&A.

Thanks, Dominic, and good morning, everyone. As Dominic said, David Kendall, I've been the Chief Medical Officer at Zealand Pharma in the past 3 years. I've been with the company now approximately 5 years and joined after short period at Amylin Pharmaceuticals. If any of you have a long memory back in San Diego days, the originators actually of both Amylin-based and GLP-1-based therapies. And the first 2 therapies approved in those respective spaces were at Amylin and then spent nearly 8 years at Eli Lilly, working in the diabetes metabolism unit there on the medical and development side. So any of you who were alert to or heard our quarterly earnings last week. This is a bit of a summary from that. But I want to start by reemphasizing Zealand and its mission. We have been a peptide discovery and development organization for the history, now 26-year history of the company, developing peptide therapeutics, much of them in the metabolism space, we are now in late-stage development with an asset in rare disease and short-bowel syndrome as well as continuous infusion version of one of our assets, dasiglucagon, which is a rescue therapy for hypoglycemia or low blood sugar in diabetes, which we've partnered and licensed out to Novo Nordisk, but long-acting infusion or the continuous infusion in development for something called congenital hyperinsulinism. I'll touch briefly on a I'd really like to focus on -- but we set out to do more than 3 years ago, which was to establish ourselves significantly in the middle of the obesity space, in part given the assets we had at, and as many of you know, we've had a partnership with Boehringer Ingelheim on a unique GLP-1 glucagon dual agonist, which I'll talk about. So as I'm always told by Adam, who's my Investor Relations, colleague here. Forward-looking statements are included First and foremost, Zealand, believe has never been in a stronger position, both financially but from the standpoint of essentially doing what we set out to do. 3-plus years ago, we set out to establish ourselves in the obesity space, particularly on the backs of petrelintide, a unique in what we consider a potential best-in-class Amylin agonist. It is a long-acting weekly injection. And that in combination now with the partnership with Roche, that compound will also be developed in combination with CT-388, which is a GLP-1/GIP dual agonist in Phase II development by Roche following their acquisition of the [ Carma ] Assets. We also have a GLP-1/GLP-2 dapiglutide which I'll talk about briefly. And many have sort of lost track of the survodutide program. Survodutide is a GLP-1 glucagon dual agonist that was invented at Zealand of it now fully licensed out for development and commercialization to Boehringer Ingelheim. So petrelintide is not all we've got. It's quite a bit of what we talk about because it is our lead program. And then the rare disease assets continue to progress despite regulatory setbacks. I spent far too much with the 2 divisions of the FDA, but we have a path forward for both straightening out and getting appropriate manufacturing clearance for our CHI program. So that file has been reviewed and the CRL returned specifically for issues with a third-party manufacturer not related specifically to dasiglucagon the clinical supply. And then glepaglutide CRL was issued late last year. So we are initiating the required additional Phase III study called EASE-5. I'll talk about that in a bit more detail. I think the news of the quarter is obviously the transformative partnership with Roche, which was finalized by the financial regulators as of last Friday and an announcement went out. So the HSR waiting period has been cleared and we see this not only as transformative for Zealand, but we hope transformative as well for Roche in expanding their foothold, which started with the [ Carma ] acquisition. And now a much stronger position across the obesity space with a truly differentiated pipeline. That deal, as many of you know, came with significant both upfronts and then development milestones, which will primarily be issued with the initiation of Phase III and then ultimately, commercial milestones. So more than $1.6 billion upfront, $250 million paid on each of the first 2 anniversary dates independent of progress. And then we are growing. Zealand, if you don't know, is an organization when we reorganized in 2022, close to 150 individuals. We are now in excess of 400 employees, but this is the pipeline of [Audio Gap] That means I'm done? Time to shut up. Building this with a very lean, very efficient discovery and development organization. About 80% of our employees are in R&D under my purview. We just hired a new CSO, well introduce you to. And then with the capital raise last summer of just north of USD 1 billion and the first part of the Roche payments for the partnership deal we are exceedingly well capitalized and actually talking to my finance colleagues on the road towards profitability, knowing that survodutide will potentially be ready for submission sometime in '26 with potential approval in '27 or '28 and then following with the other assets in this pipeline. So I've talked a bit about this, but it is our, I would say, our future set of programs, not just petrelintide, but now Roche brought to the partnership the first of what we hope could be many combinations of petrelintide with other assets. This is, of course, not the only pursuit. So in contrast to what many of you may have seen with the cagrilintide/semaglutide program from Lilly, so-called CagriSema, we have the opportunity as we assess the dose response of these assets, petrelintide and 388 separately. To look at what an optimal balance between the generally better tolerated petrelintide assets and the GLP-1-based therapy. So can you maximize petrelintide and optimize the 388 compound you see the characteristics that we like to describe across the board. Certainly, we see petrelintide as a new or the next foundational therapy in diabetes -- I'm sorry, in obesity, given that right now, the world looks like it only needs a GLP-1 because those are the therapies we have. So I jokingly say, and that's all you've got everyone looks GLP-1 deficient. And so we know that both for tolerability and for efficacy, that there will be significant room to play for those who have either previously tried and did not tolerate, chose not to take or who may be looking for what we would consider a better patient experience for tolerability, ease of administration, consistency of effect. The combo program I've talked about, and we expect to in Phase II, next year as early as the first half. Survodutide, I alluded to, and they are now fully enrolled in completing the obesity component of their Phase III program at Boehringer Ingelheim, given that they are generally private about a lot of these things. We haven't heard a lot of news, but we anticipate data from them in the first half next year. They also have the single largest program in MASH now in Phase III on the backs of data presented a year ago this month, actually, at the liver meetings in Europe, where they demonstrated what many consider to be best-in-class. Not only improvement in MASH inflammation, clearing of liver fat, but regression of the fibrosis that occurs in progressive disease. So knowing that MASH is triggered by obesity and often excess free fatty acid or at flux in the liver, that is the insult. The disease progresses due to the inflammation and scarring. We think that glucagon signal added to GLP-1 in the associated weight loss, which is really GLP-1 dual agonist like may have the potential for best-in-class MASH therapeutics, knowing that anywhere from 1/3 to 50% of who are overweight and obese have signs or evidence of liver disease. So this is not a small segment of the overweight and obese population, but call important one, that heretofore until the introduction of incretin-based therapies and now [ FGF21 ] and others, have had nothing at their disposal. And then finally, dapiglutide. It's a unique asset in that at first, we were looking to explore whether this could serve as a potential backup to our glepaglutide program in SBS, it turns out that our protein engineers built in a very effective GLP-1 component and then dialed in a relatively lesser GLP-2 component, and as we were looking at the opportunities in Phase I, we saw a significant weight loss in single ascending dose studies have now progressed through multiple ascending dose, and we will have full more detailed data printed from the 13-week exposure at lower dose here at the upcoming ADA scientific sessions in Chicago. But high dose and longer duration treatment, we will have top lines from so-called Part 2 of our Phase I study. The challenge with dapi with many other GLP-1-based therapies is this will be a relatively crowded space. There are a significant number of incretin-based therapies being developed. So we see this as an opportunity to leverage GLP-2, which is anti-inflammatory, improves the gut barrier to be applied specifically, not in a general obese population, looking to compete broadly but finding a segment potentially those with the greatest inflammatory risks, which include patients with MASH, a significant proportion of those with inflammatory bowel disease, knowing that GLP-2 restores gut integrity and health. But about 40% of those with [ Crohn's and colitis ] are overweight to robes. This is not an inconsequential problem and opportunities to potentially assess in that space as well as neuroinflammatory diseases or neurodegenetive diseases like Alzheimer's. There is a feed forward inflammatory component to that disease that is independent, we think of whatever the initial insult might be. The partnership, I think, many of you who either read or provide coverage. Thank you, Charlie. Looked at this deal and said we checked virtually every box that we set out to check, which is this is a true partnership, meaning it is co-development and co-commercialization, meaning all governance will be by consensus between the 2 organizations. There is not one big brother and one little sister or big sister and little brother. Obviously, there are things that Roche can bring that we have or will not build they assume all CapEx costs for future production of commercial supply. And they just announced this past week of the opening of a $700 million facility in North Carolina, for their obesity programs. But they -- during the competitive process that we put forth to identify a partner, we said we would do after the capital raise, we emphasize those key characteristics primary to this partnership was understanding that we could identify a partner who shared our vision for petrelintide, not just as a potential add-on as many people were thinking of the CagriSema program as sort of the symbol of where amylin agonist may go. But given its effectiveness, given what we expect to be an improved tolerability profile ultimately translating to a very different patient experience. Patients will tolerate a lot, if they only have one choice, but drug or treatment acceptability is a very different thing. If you can provide choice where the tolerality profile differs. We believe we have the opportunity to find an acceptability profile that with petrelintide can differentiate from GLP-1s. We also anticipate that GLP-1s will have a firm foothold in many respects. But there is likely to be as many people who've tried and stopped GLP-1-based therapies in 2029, 2030 as those on treatment. So that unmet need the significant proportion. And if the experience pans out and tolerability is, as we anticipate, this, will be a new option and a foundational treatment. The world may think about adding GLP-1 based therapies to petrelintide and not the other way around. And the other unique characteristic, and we just initiated Phase II in a diabetes population, when you take a GLP-1-based therapy if you look at tirzepatide/semaglutide in the setting of diabetes, those are very effective agents at controlling glucose. When you control glucose, you're taking essentially energy out of circulation and putting it into storage. So the weight loss in the diabetes population tends to be diminished compared to the nondiabetes population by as much as 5% to 8% depending on the studies you look at you say tirzepatide gives you 20% fat loss in the diabetes population that may be less than 15%. So if you do not need a profound impact on glucose where GLP-1s can play an important role, amylin is a glucose lowering agent, but much less potent. One, it does not stimulate insulin release, which is a growth hormone. Remember, insulin is for storage and it is anabolic. We believe we can maintain the same degree of weight loss in the presence of type 2 diabetes versus the absence. So this in well-controlled diabetes early glucose intolerance or prediabetes may offer the most suitable option for weight loss specifically. The tolerability profile I've talked about in the combination we've talked about. And as I said, we are in now just the fifth day of open discussions given the regulatory approval of the partnership, but we will be talking with our Roche colleagues about how do we find the sweet spot between these 2 seemingly very effective agents. The Phase I data support that both are effective, both are in Phase II, and we'll have that information by the first part of next year for both therapies and can initiate the combination program shortly thereafter. As I said, Roche emerged as an obvious choice on one, they do partnerships. Half their pipeline is in collaboration with other organizations or developers. There share division for petrelintide. This wasn't just to plug into, but to feature petrelintide as another potentially foundational therapy, as I've talked about, and it is a true co-commercialization, co-development. And so governance will be equally representative. We at Zealand don't anticipate going from 400-plus employees to 106,000, which is, I think, what Roche has today. So we'll leverage the strengths of both organizations, we hope the agility of Zealand as well. And we really do bring something that Roche, I hope, and I -- from their statements appreciate, which is the peptide discovery and development opportunities. Unmet need, looking at both the therapies in the partnership, petrelintide alone and the combination and accelerating these programs as much as possible to bring options for weight management forward. Here are the basics in addition to our capital raise last summer of just north of $1 billion, $1.65 billion upfront, $250 million is paid on the first 2 annual anniversaries regardless of progress, but those will be anniversary payments, $1.2 billion on the initiation of Phase III, so a development milestone and then $2.4 billion in sales-based milestones with 50-50 profit share in the major geographies, U.S. and the major EU European geographies. Survodutide, I've alluded to, and I won't repeat it in detail here. As I said, they've completed enrollment in their Phase III obesity. This will likely be the third incretin-based therapy introduced to the obesity market. It is unique because of the glucagon signal. Glucagon has effects potentially on energy expenditure. May be additive in terms of reducing appetite and certainly has beneficial effects on fat trafficking, which is why targeting the MASH or liver disease population makes good sense. Their Phase III program will be the single largest in MASH ever completed. And importantly, as was at least suggested in their Phase II data, can likely work across the range of liver disease severity, so-called F2, F3 and F4, the compensated and early decompensated cirrhotic patients. Dapiglutide I talked about. And as I said, we are looking at options to find the space for this unique asset. Again, it is not our anticipation. That this can or should play broadly into the space but really can leverage the anti-inflammatory effects and the targeted GLP-2 activity to improve gut barrier function. I've talked about this, and there are 2 individuals I'd like to highlight. I come from a previous career at Lilly, and we've now got another Lilly red guy in the fold at Zealand. It's not all Novo Blue from across the street literally. But Utpal Singh who I worked with during my time at Lilly comes to us, having led most recently, their entire small molecule development program but previously worked on a number of peptide-based discovery programs. He's a discovery scientists, majority of his career was spent at Lilly, working with me, Enrique Conterno, our Board member and many others, really a remarkable high-energy CSO. I have the Discovery Research Organization as part of my responsibilities but bringing in an experienced lifelong discovery research leader has really both recharged and I think we'll reenergize us for the next wave of innovation. And then Steven Smith, Steven was the Scientific Director at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, then took over the Translational Research Institute in Orlando, Florida for the past 10 or 15 years. Steven has been a leader in the obesity space and now leads on my medical team, many of the interactions, both with the thought leaders will be part of regulatory discussions and be a key player in the Roche partnership. We've exceeded 400 employees probably on our way to close to 500 by the end of this year across the organization to build out capabilities to support the partnership. But also to continue our innovation and acceleration of all of the clinical programs. So for a company of 400 to have the 5-plus clinical phase programs including then the sixth survodutide requires an organization that is hard-working, efficient, and we knew that growth would be part of this plan, if all was successful. Speaking of success, I tease our CFO, Henriette, that she's got the easiest job in biotech, right now. Unfortunately, market cap is about the same as our cash, which is not unusual, but we will be in excess of $2.6 billion in cash when the first modeling from Roche hits the books. So that said, it is not cash to just earn interest and/or equity a return on, we have targeted spend of DKK 2 billion to DKK 2.5 billion this year, which is a significant step-up from the previous year and supports all of these clinical programs from Phase I through Phase III with our rare disease assets. And in particular, we'll support what will undoubtedly be a sizable and exciting Phase III program in the petrelintide partnership. So with that, final note. The news feed and the news flow with potential catalysts on Phase II for petrelintide I would say, the downside to a 42-week study as it takes 42 weeks to execute. So you have to have some patients in terms of outcome, but we will be presenting some of the subgroup analysis by gender, by body weight. In the petrelintide Phase Ib trial in addition to some detailed data from the dapiglutide Phase I and then presenting top line results as soon as available on part 2 of the dapiglutide Phase I study. The first 2 will be American Diabetes Association Scientific meetings upcoming in later June the first half of next year or the second half of this year includes completion of the survo Phase III obesity program, initiation of a dapi Phase II program and then glepaglutide initiating our Phase III trial, the one required by the U.S. FDA for regulatory review. We have reviewed that trial protocol with the agency in a Type A meeting and have plans to proceed with the study initiation early in Q3. And the submission of the MAA for that rare disease asset. And this is a biweekly GLP-2 agonist that we believe will be the best-in-class potentially replacing teduglutide and still now far ahead of apraglutide. And then first half of next year, petrelintide, petrelintide, petrelintide both alone and in combo the Phase I data, our Phase II data from ZUPREME-1 completion of ZUPREME-2 and the initiation of the fixed-dose combination program which will take shape over the coming weeks. And then top line for survodutide as BI prepares for what we anticipate to be the next submission in this space. Not to forget, we have inflammation assets, the 1/5 of our currently active clinical programs, Kv1.3 ion channel blocker that is in Phase I in single ascending dose and top line results for that should be early next year. Final pitch for my colleague Adam who does all the work on this. We will be hosting a Capital Markets Day highlighting details on these programs, the vision in more detail outside speakers and discussion of where our next-generation research, we hope will take us. So having a very healthy balance sheet in the assets we do with the discovery success we've had I know many of you will be asking what's next. So with that, Dominic, I'll turn it to you. We've got about 5 minutes left for questions or comments.

I'll go ahead and let Charlie ask any questions he has since he's kind of tuned in from London here, and then I'll open it up to the audience. Maybe we can get 2, 3 questions in. Charlie?

Perfect. Yes. Thank you, David, for that. Can you hear me okay?

We can.

Great. Yes. I appreciate that presentation. Just a couple of very quick ones. On your sort of sweet spot combo comment the GLP-1/GIP combo. I guess, assuming we see the expected spectrum of lower weight loss, best tolerability at a lower relative GLP-1 dose up to higher weight loss, worse tolerability at the higher end of the ratios. What do you expect a final dose choice to be optimized for? And within that, do you think in your Phase II, you could actually have a range of fixed doses and could you continue that into your Phase III program?

Yes. I think, Charlie, a great question when we've talked with several about. I think we will maintain optionality. I'm speaking a bit ahead of myself with Manu and Levi and others at Roche. But for general weight loss where you were seeking 20% or more because we think each of these monotherapies will be in the upper teens, approaching 20% or more, but the proportion of patients who may need 2025 and beyond, then maximizing petrelintide and optimizing the 388 compound. However, we also are aware that there is a population, the most morbidly obese, BMI is often in excess of 40 who may require the maximum dose of each that is tolerated. So I think of this in sort of 2 schools right now, Charlie, 1 for the more general population who are looking for that upper end of weight loss to further enhance the petrelintide background with 388 and finding that sort of ideal ratio and then the big guns, which would be high doses of both, but only for the selected population who may need to lose 25% up to 30% of their body weight. Again, that's a minority of those meaning go to bariatric surgery. But that's our current thinking, Charlie and more to follow, obviously, as we get together with our Roche colleagues.

Got it. Very clear. And then on your comment that you could maintain the same degree of weight loss in the presence of diabetes for the amylin therapy. Obviously, CagriSema data, which I think somewhat disappointed the markets on that. I'm interested in your confidence there has changed at all? Or what? Why are you still so confident in that in the potential to see that?

Yes. Thanks, Charlie. I probably have as many questions as answers after the CagriSema Phase III data, partly because of study design. And I think the absence of a CagriSema alone in their diabetes redefined to, I think it is was something I had hoped for. We knew it was likely to be in there. I think that study designs there did not deconvolute the question, knowing what we know from historical data with petrelintide. We are pursuing ZUPREME-2 to at least establish that proof of principle if it is comparable to what we see in ZUPREME-1 with a similar population then we can move forward in Phase III. Obviously, we will include diabetes in the population for weight management. We have no plans at this time to pursue amylin therapies and petrelintide in particular, for diabetes treatment. So time will tell. I think the study designs from Cagri left me with more questions and answers, Charlie.

Yes, you and me both. And then final 1 for me. Clearly, you're not going to be the only 1 in the amylin space. I'm hoping to be obviously increasingly competitive. You've got a very good data set. So interested in your views across the space, different backbones, amylin calcitonin, et cetera? And then where do you think you see and remain confident in your differentiation? I guess also in the context of some fairly strong data we saw a couple of months ago?

Yes. I think we clearly still see petrelintide as a potential best-in-class based on a number of characteristics. I mean, our dose range. We firmly believe that activation of all 3 receptors in the family that have been identified calcitonin, amylin-1, amylin-3, as cagrilintide does as we do with petrolatide, and they are comparable Cagri data give us some encouragement and actually our proof of principle around safety. So I think having that safety when you activate all 3 receptors in animal models and some of the data we've at least heard alluded to by AZ and others who have amylin-specific receptor targeting. The weight loss potential is aggregated. We know in animal models not targeting the calcitonin receptors in the midbrain really puts you in a metabolically disadvantaged circumstance, rodents without calcitonin receptors in the brain, gain more weight, eat more food or metabolically disadvantage. So we firmly believe that our asset, cagrilintide, perhaps the [ guber ] molecule and I always say we said it first. We were up in front of you 3 years ago saying amylin's going to establish a new way of thinking. And now we've got 3, 4, 5 others in the space. We are not only ahead in time lines for a stand-alone program. versus the others, but I think can and likely will compete with a very consistent data set from early Phase I now we hope into Phase II. The [ guber ] data left me with some questions about dose response and the fact that only 1 cohort was released in the most recent press release. So seeing more data there will help me. But again, we are approximately 2 years ahead on time lines with an asset that I think is as good or better.

Perfect. That's it. I've already gone over, so I'll hand back. Pleasure hosting you as always.

It look like we're going to be getting kicked out of the room right now. But thank you, David. I'm sure that guys can come up and ask questions as we cut it out, but thank you all.

Happy to. Thanks, Dominic.