Cool. Well, thank you all for being here. I'm James Machin from the Morgan Stanley banking team, and delighted to have Adam from Zealand Pharma here this morning. I guess over the next 30-35 minutes, we'll dive into a number of areas across the portfolio. Maybe to kick off, can start with a quick intro to yourself, maybe a short overview on what you're doing as a business, and then we can start to get into some of the detail.
Absolutely. Pleased to be here. Zealand Pharma is a Danish-founded company. We've been 27 years in the making, and we are on a journey towards becoming a leader in metabolic health. In December last year, we kicked off our new ambition, which is called the Metabolic Frontier 2030, with an ambition of having actually five products on the market in 2030, having a pipeline of 10 clinical programs, and then also having industry-leading times from idea to clinic. We are on a very, you can say, ambitious journey towards addressing what we believe is the biggest healthcare challenge of our time. Not only the obesity pandemic we are seeing, but all the health consequences that follows obesity.
Going beyond weight loss, looking into how we can help people improving their health span, living longer with a healthy life, the way people want to live their lives, that's what motivates us, and we are on a good journey towards delivering on that.
Okay, great. No, very exciting times for yourselves and for the broader industry. You hinted at it with how the market's changing. Clearly you as really one of the leaders within amylin biology, and all the benefits that that makes, which is really cementing it as one of the leading next generation mechanisms in obesity. Can you maybe dive into a little bit more detail on why the profile of amylin is so well-suited for obesity patients, and really how it starts to meet the needs that consumers are needing in the market?
Right. We were, I guess, one of the first to clearly articulate the need to introduce medicines for patients living with obesity that they can actually tolerate. Not only tolerate during the period where they're the most motivated, meaning the first few months where you lose weight, but also once you get into the weight maintenance phase. Because living with obesity is a chronic condition for most people, meaning that if you stop taking a treatment, you will rebound in weight, and you will not get all the health benefits.
When we saw the profile of petrelintide, we already at that time knew that we had something that would be a logical first choice, but also a product that patients would likely appreciate to stay on, overcoming the issues we see with the GLP-1s today, where many patients stop within a month, and after a year, probably only 20%- 30% of patients are still on treatment, meaning we don't achieve the health outcomes. The interesting perspective when looking and thinking about the future landscape of weight management and treatment of obesity is, if I'm right here, it would not be dissimilar from what we have seen in other chronic disease areas.
If you think about type two diabetes, dyslipidemia, hypertension, when we introduced the first therapeutic opportunities for these patients, we were always targeting the most difficult to treat patient, and it was often with very cumbersome but also effective medicines. As the field then matured, you would see more tolerable, more easy to be on medicines being introduced and actually becoming the therapeutic leaders and the go-to products for most patients. You also see that physicians start to treat earlier and earlier. What we're actually starting to hear more so this year is that people say, "Why are we waiting?" Or physicians are saying, "Why do we wait with treatment until you get to the highest BMI?
Why not start to treat when you pass the 27 or approach the 30?" That is completely in line with the positioning that we are thinking about petrelintide, the amylin as a broader class, that you want to start on a medicine that gives you the weight loss that most are looking for in the most pleasant way. With petrelintide, we have a profile which has delivered double-digit weight loss with a placebo-like tolerability profile. We really think that profile is the profile that most patients would actually appreciate to be on. Only if you desire an even higher weight loss, you would start to think about combination products or getting on the more cumbersome GLP-1s.
Okay, great. I guess that profile is now really starting to emerge with your positive ZUPREME-1 data, which emerged earlier this year. Can you remind us all in a little bit more what came through from that data and then really translating that through to clearly going into the pivotal trial, the design of that, and the way that you're thinking about optimizing that route to market?
Absolutely. It was a pretty comprehensive phase II program, testing five different doses of petrelintide and also with a lot of patients in each arm, including a balanced exposure to males and females. So we have a very good understanding of how the product behave also at the different dose levels. So we are moving into phase III together with Roche now with a lot of confidence that we actually have the dose setting right, and also that we understand the profile of this double-digit weight loss and placebo-like tolerability. The focus of the program will, of course, be speed to market because we think it's important, of course, to be among the first to launch into a new category and help defining the amylin class as a first-choice therapeutic class.
One of the things that really excites me, but also where I know we may still be a little bit ahead of the curve, is this thing that if you ask patients, four out of five patients would give you a weight loss number below 20%. Most people are looking for weight loss in the teens. Very few are actually looking for weight loss above 20%. However, many companies and many working in this space has been focused on what I've addressed as the weight loss Olympics, being excited when you saw a higher weight loss number, not realizing that that is actually not what patients are looking for. Even with the current use of the GLP-1s that are available today, most often the average dose is half what is approved, meaning that patients never get to those impressive weight loss numbers because they're not interested.
At the end of the day, we need to develop medicines that fits the patients' lives, the life that patients want to live. We cannot think about managing the obesity pandemic if we require people to fit the lives of a product. It has to be a product that fits the lives of patients.
Okay, great. I guess that translates through to really, there is clearly a commercial edge that is coming with tolerability of different agents. Where do you think that will be once, roll a few years into the future, once petrelintide is on market. Really, how do you think consumers are going to start to differentiate between medicines and really make those choices?
I think we are already starting to hear the conversation that more and more people are starting to articulate that the next battle is actually not going to be who delivers a few percent more weight loss. It is going to be around who can deliver the weight loss that patients are looking for with the best tolerability profile. The one thing that could actually cause a change in perception faster than what you would normally see in other chronic disease areas is that we know that patients are so engaged in this category. I think it is around 60%-70% of all scripts, it is actually a patient-initiated conversation.
It is a patient who goes up to the doctor and say, "I would like to get on a weight loss medication, and I would like to try this product out." If we can think about a product now which delivers the weight loss that patients are looking for, but in a more pleasant way, where people can actually feel great when they are losing weight, that is a situation where we would envision that the conversations on social media would be very, very firm early on.
You could imagine a take-up that would be quite dramatic because patients are so engaged, you do not need to go through the normal channels that you normally would launch with focusing on tier one, tier two, tier three, key opinion leaders, and then you get to primary care physicians, because the patients would drive the narrative around wanting to be on a product like this.
Okay.
I would also say the other thing which excites us is that we think with petrelintide, if the profile that we have seen thus far comes true, it will also be a product which will allow patients to stay on therapy for longer. If you start to think about capturing new patients, but also having them to stay on for longer, then that's where you can actually drive up volumes and ultimately value for this category, but also in the end, truly address the obesity pandemic and all the disease that follows.
Great. No, super exciting. Super exciting. We talked a bit on mono, let's maybe think about combo as well. As a reminder, you obviously have the ZINERGI phase II trial starting as well in combo with Roche. Can you maybe speak a little bit on aims with that trial, what you're looking to demonstrate, and then translate that through, link that back to the commentary you had before of decision between mono versus combo therapy, and how you expect that will evolve over the longer term?
Absolutely. When we did the partnership with Roche, of course, it was important for us to have shared economics, not only on the petrelintide opportunity but also on the combination. So we could really, in a consolidated and shared effort, build the franchise leadership around petrelintide that we are aiming for. With the combination product, it's a unique opportunity to leverage the strength of each individual molecule. When you think about combination therapies in the future, you also have to acknowledge that these should be products that are provided to patients who can benefit from both modalities. Just as one example, even in today's market, 15% of patients don't respond to a GLP-1, so you don't want to put such a patient on a combination product.
When we envision what the combination product should do in the future, it's around providing additional weight loss or metabolic benefits for those patients who have already benefited from one of the two components that are within such a product. That's the logical positioning. That could be patients who lives with obesity and type two diabetes. It could be patients who may be coming from a very high BMI status and thus ultimately requires the deepest weight loss. Once they have started that journey, they may get onto a combination product. So it's really an opportunity to expand not only the amount of weight loss you can achieve but also perhaps how you address certain comorbidities to obesity.
Okay, great. The trial just starting to get up and running, and maybe a little bit on what the aims are on that trial, too?
Yes. It is a clear dose-finding study where we are trying to find the right balance between the GLP-1/GIP component, meaning CT-388, and then the amylin component with petrelintide. It could ultimately also be different profiles for different patient segments. But for us, it is incredibly important to get the ratios right. A little bit in line with what we have talked about with petrelintide, if you think about this market in the future, you need to have the right molecules, not just molecules. In particular, when it comes to combinations, we need to move beyond just trying to seek the highest weight loss if it comes at the compromise of tolerability. Very few would actually ever get to that in the real world. So we need to find the right balance where we also get the right amount of weight loss when you still consider tolerability.
Okay, great. A little bit more on Roche as a partner, and I guess as a reminder, this was a DKK 1.65 billion upfront partnership over DKK 5 billion in milestones, and importantly, the profit share on both the mono and the combo, as you mentioned. Can you speak a little around why Roche as a partner? What were the attributes there that really excited you as you stepped into that partnership and selected them?
It was a highly competitive process when we were partnering out petrelintide. What really excited us about Roche at that time was both Thomas and Teresa's very strong commitments when we spoke with them around how they wanted to be a top three player. They shared their plans around how they wanted to establish a strong manufacturing network and overall just where they wanted to take the company. I must say that I am extremely pleased to see that everything we discussed at that time has come true. I think people who follows LinkedIn can see how they are investing in manufacturing capacity. Also, I think they have started to be more public in their commitment to how they want to lead in this space going forward.
Among all the large pharma companies we spoke to, we just sensed the strongest commitment to actually come in and make a difference for patients in this new category, which I would still think is a new category. Remember, we are four to five years into treatment of obesity and weight loss. While a lot of people may think these treatments have been around for a long time, it is really novel. We have one category, more or less, with the GLP-1 class. We have 3%- 5% of patients being treated today in the U.S. There is so much opportunity to come in and lead if you want to do things differently.
That was what we heard from Roche, that they wanted to come in and drive innovation in this space, not only when it comes to molecules, but also how you go to market, how you secure the most effective manufacturing. That is what we see in the partnership.
Okay, great. Well, great partner. We will see how Teresa addresses it over the coming weeks as well with their respective R&D day. Let us turn to second asset within the portfolio, still on obesity versus the other areas, and clearly a different partner with Boehringer and survodutide. Can you maybe frame that as an asset, how that is distinctive from the amylin, where you are looking, where you and your partner see the greatest potential of that product?
Yeah. survodutide is a licensing agreement we made with Boehringer, so they are fully responsible for the clinical development and commercialization. So we just have high single to low double-digit royalties, which is a nice situation to be in particular because survodutide, and we just saw the first data here from their phase III program here at ADA this year. It looks to be a very strong GLP-1/glucagon molecule when you think about not only weight loss, but also metabolic health. What Boehringer showed at ADA was that while they achieved around between 16%- 17% weight loss in their phase III program, most of that weight loss was attributed to losing weight in the losing fat, getting fat out of the liver and the intestinal fat, which is normally seen as the bad fat, if you will.
It was predominantly liver and visceral fat that was lost. They also showed data that there was only 10% muscle wasting or muscle loss, which is in contrast to the 20%- 30% we have seen from other GLP-1s. I think they have a molecule here with survodutide, which is really going beyond just weight loss and addressing the metabolic health that we actually all trying to achieve with these weight losses. We are super excited, and we know Boehringer is super excited about the prospects of survodutide. As they say, you see obesity, think liver, because a lot of the metabolic disturbances you have with living with obesity starts in the liver. If you can really get fat out, that's a major event.
They will report the rest of the phase III program this year in obesity. Then they have a large program in MASH, NASH, including end-stage liver disease, that will read out in the coming years and will hopefully help further underscore the potential to actually address some of the underlying organ defects that you see with long-standing obesity. The other thing which we are pleased with the partnership is their continuous commitment to invest into the program. Earlier, I think in August, they announced that they started a phase III study in type two diabetes to really with the aim of expanding, I guess, the label universe for survodutide. Sometimes in this world of obesity treatments, we forget that the GLP-1s are still generating more revenues within type two diabetes. It's nice to see that continuous investment. They're investing in women's health.
They're investing in heart failure. They're doing additional studies to really support this product.
Okay, great. Multiple indications and really then looking to de-risk the pivotal program over the next year.
Right.
The MASH data that comes through the course of 2027?
If you look into clinicaltrials.gov, that could be one guess. They will inform the market once the data is there.
Okay, great. Let's pivot again. Let's turn to rare diseases. Clearly a number of products that you have there which are in late-stage development. Let's start on dasiglucagon. Clearly in development in congenital hyperinsulinism.
Right.
Can you frame that as an asset, the strategic value of where the product is, and how you think about that asset over the longer term, particularly with the resubmission coming up?
Right. So congenital hyperinsulinism, it is a devastating disease in neonates and small children who are born with this genetic defect where they produce too much insulin, and thus they end up with low blood sugar and really high risk of brain damage. In a lot of these children, which is still an ultra-rare indication, but for a lot of those who are diagnosed, you cannot surgically remove the affected area. So they live with these hypoglycemic events and need to be on frequent IV sugar and what have you, in order to not get into hypoglycemia. So it is really a devastating disease, and we have a phase III program now, and patients who have been on treatment for several years, demonstrating that we can ease life for these patients.
We can basically reduce the number of hypoglycemic events and allow perhaps families to sleep a little bit more through the night instead of having to wake up every two hours and feed their children. So it is a program that we will resubmit to FDA here in the second half. We hope to have it approved next year. In parallel with that, we are engaging in partnership discussions. While we do have a commercial ambition that is really focused on go-to-market with our petrelintide alongside Genentech, targeting a large consumer opportunity for the rare disease assets, our ambition is to establish a partnership with a dedicated rare disease company who can help us reach as many patients as possible, starting with the U.S., but we have a global effort on CHI as well.
Okay. Understood. Similarly with glepaglutide, your short bowel syndrome asset, can you remind us all there where that stands? I believe the second phase III trial is now ongoing.
Right.
Similar question, strategic value of the asset versus financial value as you bring this forward.
It is another rare disease asset where we have invested a lot, and we have a strong commitment to get improved therapies out to patients living with short bowel syndrome. We have just earlier in the year started the second phase III study to support regulatory approval in the U.S. based on feedback from FDA. So that is up running and recruiting. In parallel, last year, we submitted the file for potential EU approval, and we should hear back from EU this year. So for potential approval in the EU. Again, it is an asset where we want to find a partner. So once we have a little bit more progress in these aspects, it could be later this year, we will start partnership discussions and make sure that we are reaching as many patients as possible through a partner for short bowel syndrome and in particular for glepaglutide.
It is a market where today, I think with the short-acting tier one that is available is north of DKK 1 billion in sales. So it is a decent market where we think with glepaglutide, if approved, it really provides a significant improvement over current therapies, and that is it is a very easy injection, and we have also been very pleased with the clinical profile of the product that we have seen thus far. So it is another asset where you can say it is not one where we would invest in bringing it to market ourself, but we would seek a partnership, which of course, could help us expand the reach and the value of the opportunity.
Okay. Great. I will jump again. Let us go to your early, and I will come back to obesity once we wrap up. I guess earlier research efforts started to move into inflammation with a compound going into the clinic. Before we touch on that, maybe just ambitions and how you think about those earlier-stage research efforts with a bit of a broadening of the pipeline.
We are hugely ambitious on the early pipeline. We hope to have five products on the market by 2030, but we also hope to have a pipeline of 10 clinical assets, which should arrive from our research efforts. We have really stepped up our research efforts in the past few years. Just to put it into perspective, in the coming four or five years, we are going to spend five times as much on research alone as we did in the past five years. Actually, we are going to invest around $800 million into research alone. We have a very strong group in Denmark, which is where we were founded. In a few weeks' time, we are actually going to open our Cambridge, Massachusetts, research site, which will be equally sized.
We have, I would say, probably 20- 30 of the people who are going to work there already signed in. We are ready to hopefully start the first experiments quite fast. There we are going to go beyond peptides, which is where we have historically been mostly active, and into other modalities, really leveraging where we see ourselves having a competitive edge in the metabolic research. Not many companies have as much data and as deep understanding in metabolic pathways as Zealand Pharma. We will utilize that knowledge where I will collaborate with modality leaders, do more partnerships, just as we did with OTR Therapeutics last year on small molecules. We expect to do partnerships with other modality-based platform companies within the metabolic space to continue to invest.
After investments in petrelintide, it is our key second priority to invest into the pipeline to make sure we continue to innovate and have the products of the future as well.
Okay. I guess the first thing coming out of that is the Kv1.3 blocker. In going through the SAD, the MAD now starting to get going. Clearly just given the mechanism broad potential across a range of immune-mediated disorders.
Right.
How do you think about that program, taking it forward yourself versus maybe a partner in due course? Also just indication selection, as I mentioned, broad range. Where do you think the biggest potential and where do you want to take them?
It's really a super exciting asset which has this pipeline and a product potential. There's preclinical evidence for almost at least all the autoimmune diseases I can name. Of course, it's going to be important to select which one you're going for and in which kind of order. Earlier this year, we initiated a phase I-B/II-A study, a smaller study in patients living with psoriasis, just to see if we can get the first biological evidence. Now we have already seen engagement on the biological pathways we are targeting in our early exposure. So we can see we have receptor engagement. We can see we are affecting the immune pathways that we are hoping to see, but could we also pick up an early biological response in patients with psoriasis. We will soon also start another smaller study in another indication.
But ultimately, it's also a program where we envision to have it in a partnership with a more established player in the autoimmune space because it is complicated studies. Again, if we want to invest in multiple parallel programs, it's a partnership that we are looking at. So one which is a little bit outside the focus of our other early efforts, but one which could really holds a huge potential in a broad range of autoimmune diseases.
Okay, great. Let's turn then back, and you started talking on it with Metabolic Frontier 2030. You mentioned, remind us ambitions there, really how broad you are thinking on taking the business and that big vision, and then we can go to partnerships. But first of all, the vision.
Yeah. If you think about where we will be in 2030, it's of course our hope that we'll be launching our first product alongside the Roche Genentech into a very consumer-driven market. So we are investing in building what we can describe as a fully integrated presence, including commercial presence, to support such a launch. So that reflects our ambition to actually come in and play, to become a key player in the metabolic space, not only when it comes to early innovation and research and development, but also being out there addressing customers in the end. The problem that we are looking into when we think not about obesity, but all the consequences of how obese the world is becoming with all the metabolic diseases that follows, simply requires new ways of going to market.
It requires new innovation, and we are here to actually take our part in addressing that need. We think we are uniquely set. We think it's actually also a unique moment in the history of addressing these kind of metabolic diseases, because for the first time, we are in a situation where there is actually a huge alignment with what society needs and what each individual person is actually looking for. So we are getting into a situation where preventive medicine suddenly can become reality. Something people have talked a lot about, but now we are at that time where preventive medicine can become a reality as long as you develop medicines that fits into the lives of people and you find ways of getting these medicines to people so they can actually stay on them. That is what excites us as a company.
We think we are uniquely set up also with all the changes we see in the data, AI, and platforms of how you can actually ultimately reach patients. It's a unique opportunity to actually go for a market like this. Historically, it would have been almost impossible to break into primary care as a newcomer because of the size of the organization you would need. These things are changing so much, so rapidly these years, and we think it speaks to our benefit that we actually can come in and innovate and participate in getting the products to the patients.
Okay. That sounds like both with partners and internal, you had your partnership earlier this year. I guess why them as a partner? What did they bring as an organization to really fill in the vision that or help support the vision that you're bringing forward? Is this something that you're really looking for as you think about further partnerships?
I think, and this is not only with regard to obesity, but the biggest barrier to success and to innovation is if you think that what you have is what will also make you strong in the future. When you hear Teresa and Roche talk about it, they talk about innovating, doing something novel, not trying to pretend that there is a primary care sales organization that worked in the '90s that will also be beautifully set up to deliver in this space in the future. It's about innovating and doing things differently. That's what I hear when I speak to Roche and Genentech, that they are here to innovate and then a very strong commitment to lead, as both expressed by Thomas and Teresa.
That's why they're such a strong partner for us because, of course, they have a global footprint, so you can kind of tick box all those elements, but then the desire to innovate and deliver novel ways of, and driving a deep sense of wanting to make a difference for these patients and help address the metabolic consequences of where we have gone as a society is what makes them a strong partner. I think we fool ourselves if we think that what made companies successful even in the past five years is also what will make them successful in the coming five years because of the changes that we are seeing, and we are here to tap into those.
Okay. No, well, it'll be a fun next few years. Let's pull it all back together, big picture. The most important, I guess, catalyst as we go through the next 12- 18 months that we all should be looking for?
We are, of course, super excited to get the phase III program kicked off so people can sense a little bit more reality, see the progress in recruitment, and getting close to the market with petrelintide. Then we have additional data from a smaller phase II study with petrelintide in obese individuals living with type 2 diabetes that will read out later this year. We have the combo studies that is kicking off. Then for survodutide, we have further phase III data, including the CVOT study, the cardiovascular outcome study with survodutide that should read out later this year. And, of course, at one point, the MASH program, which is really what could significantly differentiate the survodutide asset compared to some of the other GLP-1s out there. Then there's the early activities, including Kv1.3.
There's the rare disease programs, EMA decision on glepaglutide, getting the CHI resubmitted to FDA potential partnerships. So that is, I would say, a very deep and rich set of news flow approaching us in not only the next three, six, nine months.
Okay, great. With that, I think we are coming up to time, so thank you for that. Thank you for being here. Hope you have a good rest of the conference, and thank you.
Thanks.