Takeda Pharmaceutical Company Limited (TAK) Earnings Call Transcript & Summary

Hi. Good afternoon. Welcome to JPMorgan Healthcare Conference. I'm Seiji Wakao, Japan pharma analyst. It's my pleasure to introduce Christophe, CEO of Takeda. Welcome him to the conference. Christophe, please go ahead.

Thank you. It's really a great pleasure to update you about Takeda's situation and outlook. I'm really excited and delighted, especially because we have good news to share. So it's a great time. So 10 years ago, I joined the company in 2014, we decided to really focus on innovation. Our mission is to discover and deliver life-transforming treatment. And for that, of course, you need scale because it's expensive to develop this treatment. And you need to have an R&D engine, which we started building, and you will see the outcome today. A few years later, we decided also to embrace digital and technology, to embrace digital and technology, and we will not talk a lot about that today, but I can tell you that it is transforming the company as we speak. We moved early. Back in 2018, we decided to move all our data to the cloud. And now in R&D, in manufacturing, in our commercial operation, in our back office, technology, digital AI is transforming the company. We work faster, better, more intelligently. So it's really important. In 3 years, 4 years, you will see a divergence between the company that embrace it and the company that didn't embrace it. It's very clear in our mind. So today, Takeda is $30 billion revenue company. More than 50% of our revenue comes from this country here from the U.S. It used to be less than 20% 10 years ago. We are -- our portfolio is comprised of a quite large portfolio of very innovative medicines. Over the year, we sold our branded generic business. We sold our OTC business, again, to focus on innovation. We are present in 80 countries. We have our global headquarter in Tokyo, with a very big presence, a big hub in Boston. And we invest about USD 5 billion per year in R&D. And we decided to focus on a few therapy areas. And we -- our research team focused on these few therapy areas. Our development team focused on these 3 therapy areas: GI and inflammation, neuroscience and oncology. So we are at a very pivotal moment Why? Because in the last 5 years, we had a lot of generic exposure. We actually lost 20% of our 2021 revenue during these 5 years. We were able to offset almost all of that through our growing portfolio of products. But we are now at the end of that cycle. And so in the last -- in the next 5 years, our generic exposure is much lower, about 1/3 actually of what we have faced in the last 5 years. We have not -- we have launched new products in the last 5 years, but they were not -- they were very innovative medicines, but not with a huge revenue potential. But we have been successful at launching this product. We are entering a phase now of very significant, very material new product launches. And this is what I will focus on today. And I talked about digital and technology, but that's something that we have prepared in the last 5 years, we'll start to really see the impact in the next 5 years. And last but not least, I'm retiring from the company in June this year. Julie Kim, who is here, will succeed me. So we are also organizing this transition. So here is my focus today. It's all about the pipeline. It's all about the new product launch. And we have now 8 late-stage assets. all of them potentially launched before the end of the decade. And they are all life transforming assets compared to standard of care. So I won't go through all of them 1 by one. I will focus on the first 3 because we had the Phase III readout for these three but it's still worthwhile to spend a bit of time on these assets. First, you can see that many of them have a breakthrough therapy status. Many of them are also orphan drug. Takeda is very strong in rare disease. We know how to help patients with rare disease. We know how to commercialize product in the rare disease space. So I'll start with the bottom right. TAK-928, TAK-921, we just added these 2 assets by doing a partnership with a Chinese company called Innovent. We are very excited about these 2 assets. There is a third one actually which is more in an early stage. So it's a very strategic partnership with Innovent. TAK-928, it's an immuno-oncology asset. It's a alpha-biased IL-2/PD-1. The alpha biased is very important because there has been other IL-2/PD-1 developed in the past, and they had some toxicity issue. We believe that because if it's focused on alpha-biased IL-2. We have a better therapeutic window. We can have this efficacy with less city and safety. So we have seen a lot of data among Chinese patients very exciting data, and we will start the Phase III development of these assets. Starting with non-small cell lung cancer, but obviously, it's an immuno-oncology asset, so it could really go into many, many indications in the future. Very, very important asset, potentially again, launch before the end of the decade. So that's a very crucial asset in our oncology pipeline. TAK-921 is a CLDN18.2 ADC. We'll focus on gastric cancer first, and then we could go into different line. It's also an asset that could enter into Phase III outside of China rapidly. So that's 2 oncology assets, which are really improving our pipeline in oncology for have followed Takeda for a while. We have not been super successful in oncology for different reasons. I mean, that's part of what we do, right? But today, we have a very different oncology pipeline between these 2. And elritercept, for example, that we are developing in MDS, starting second line could move into first-line later. We think it has a very interesting profile compared to existing therapy. We believe it could be efficacious in RS negative, for example, patients. So that's our three oncology assets in late stage. Fazirsiran is an RNA product to treat alpha antitrypsin deficiency liver disease. It's in Phase III. It's a partner with our head, and it could really transform the life of the patient with this disease. There is not much treatment available. Mezagitamab, it's a CD38 antibody. We think it has a very attractive profile, very potent profile. We have disclosed some data which is very, very exciting for IgA nephropathy and immune thrombocytopenia. So now I will focus on these 3: oveporexton, rusfertide and zasocitinib because we had the Phase III readout. We are planning to launch this asset in the next 18 months. So let's start with oveporexton. So oveporexton is our first orexin agonist that has been filed. So we just filed the product. And we expect to launch in the second semester of 2026. The Phase III readout has been, in fact, slightly beyond our expectation. In terms of the efficacy profile, all the primary endpoints, secondary endpoints were met. This is really a compound that is changing the life of the patient. And we see that and one anecdote here is that all the patients which were -- who were enrolled in the clinical trial decided to carry on after. They don't want to stop the treatment because it is really changing their life. So it is clearly a step change. It is a product that is used in 2 doses, first those are in the morning, second dose before lunch. And that's -- we have designed that to make sure that we have a pharmacokinetic profile, which mimic the natural ex profile where you peak in the middle of the day and you don't want a lot of orexin level before going to sleep. So it's really important to select the right dose but also to have very appropriate pharmacokinetic curve in order to manage well the wait period and then making sure that you don't have insomnia and people can go to sleep in the evening. So very transformative and this is an opportunity, obviously, for us to launch early. There are about let's say, 100,000 patients with narcolepsy type 1 in the U.S., half of them are diagnosed. And what I can share with you is that the level of satisfaction is very low right now. So if you interview patients, they are struggling. The use there on poly therapies. They have a lot of issues side effect. There is a very high level of unsatisfaction and it's a young population. They want to be active. So we think that we can really deliver that for them when we will launch this product. It's really transformative. At the time when we did our R&D Day back more than 1 year ago, we estimated that our peak revenue for this product could be between $1 billion to $2 billion. We think it could be higher than that, actually. Looking at the Phase III data, again, the Phase III data has been better than what we expected in terms of the number of responders and the efficacy that we have seen, the tolerability. So very, very excited with this product and with this launch. We don't think -- I mean, market access is always a challenge, but this is actually the standard of care today are relatively recent product. So we don't think -- I mean, we think we should manage market access in order to have a rapid uptake with this product. Rusfertide, the second one, also launched in the second semester of 2026. This is also a product that we filed just before the end of the year last year, before New Year. It's a hepcidin mimetic to manage polycythemia vera and again, here, the data has been very compelling. If you look at the hematocrit control, it's a type of beautiful data that you always look for when you develop new products, a very, very high level of efficacy, very strong control over time. If you look at the number of patients we don't need a phlebotomy because our control with the product, it's also very, very high. So that's a product, again, that's also a product that should completely transform the standard of care. And here, it's a market where also about half of the patients are treated, and they follow treatment path. -- about 78% of the patients are uncontrolled. So they start with phlebotomy. And then when they cannot control the disease anymore, they move to hydroxy urea. And when they do not control luxury, they move to ruxolitinib and eventually, the combined with Ropeg-interferon. And so that's really interesting because in theory, we could actually be first line. When you look at the level of efficacy that I have just shown. In theory, we should move into first line should treat all these patients. But obviously, here, we'll have to demonstrate that it's cost-effective that it is worthwhile to displace phlebotomy, but phlebotomy is very cheap because it's very old. And so we'll have to see how we enter this market and how progressively we treat the patients. But clearly, transformative compared to the current standard of care. So here, again, a very, very high potential for this product. The last one I want to really highlight is zasocitinib. So zasocitinib, we just got the Phase III readout. We have not disclosed all the data. We'll do that at an upcoming congress. It's a TYK2 inhibitor that we are developing first in psoriasis. We are also developing the product in psoriatic arthritis, and we also are in Phase IIb in IBD. And so very positive data. I will not disclose too much here because we want to, again, make that presentation in Congress. But what I can say is that we have demonstrated that the TYK2 class, if you have the right molecule at the right dose, you can really obtain a very high level of efficacy. And so for example, more than 50% of the patients reached PASI 90. About 30% of the patients reached a PASI 100, meaning clear skin. And that was -- that's not something that they can get with current overall option. And so we think that this is really something that could transform the psoriasis market in the future. So very excited about that. Again, there's been a lot of talk about the TYK2 class. The first product did not achieve this type of level of efficacy we have been able to demonstrate that you can. Again, if you have the right products with the right level of selectivity, which allows us to increase the dose and have the right dose, and this is what we have demonstrated here. So here, in terms of launch, the challenge is to change the paradigm of oral treatment. The overall segment has been stagnant for many, many years. About 16% of the patients, psoriatic patients today are treated by oral. I think the challenge for us and frankly, for another company, which has another roll, which has a comparable efficacy. The challenge is to really create an option for the patients to start when they cannot -- when the traditional therapy is steroids, topical do not work anymore for them instead of going directly to a subcu or an IV type product where they can get very strong efficacy. Here, we are creating a new option to start with an oral treatment. And we believe that we can double the size of the overall segment in the coming years. Again, we will not be alone. There is another class. There's another oral, which has comparable efficacy, which actually we welcome because it will be quite a challenge to change that paradigm and to create this oral option before moving to subcu and IV. So for zasocitinib, because of this Phase III readout, very excited to launch. At the time, we expressed a peak potential revenue between $3 billion to $6 billion in psoriasis and psoriatic arthritis, we are committed to it. We believe that with this type of data, we can achieve that. So very excited about it. So that's really the -- our agenda for the next 2 years, 3 years is to launch these 3 products. It's quite an endeavor. I mean, for a company of our size, to launch so many products at the same time. It's very, very exciting. And if you look more long term in, from 2030 onwards, our lead current product called ENTYVIO, which represent about 20% of our total revenue today will start facing biosimilars in the U.S. So for us, it's very important that with these 3 products, we are able to offset that decline, which will start in 2030. So timing-wise, it works very well. So you have oveporexton, $2 billion to $3 billion peak revenue potential; rusfertide $1 billion to $2 billion; zasocitinib, $3 billion to $6 billion. So you are talking about let's say $6 billion to $10 billion, let's say, revenue generated by these 3 products. ENTYVIO today is a $6 billion product. continue, it is growing still. But you can see that with these 3 products, we will be able to offset the decline of ENTYVIO from 2030 onwards. Now on top of these 3, we have the 5 others that I mentioned earlier, which will add to our growth potential. These 5 other products will also be launched before the end of the decade. So I think that's a very important timing. As you know, all pharmaceutical company have their cycle with patent clips. So for us, the challenge. The next challenge is from 2030 onwards with ENTYVIO, with the launch of these 3 products, we are able to manage that. And then we will have the 5 others. Hopefully, the Phase III readout will be as good as these three, and we will be able to sustain our growth in the future. That's what I wanted to share with you today. And now I'm very happy to have our Q&A, and I'm inviting my colleagues to join me. Thank you very much.

Thank you, Christophe. I will start Q&A session. From here, Milano Furuta, CFO; Julie Kim, President, U.S. business; and Teresa Bitetti, President, Global Oncology Business will be joining us. So first question is for Christophe. Christophe, this will be your final JPMorgan presentation as CEO of Takeda. What are your reflection in the past 12 years?

Well, it has been a long journey for sure. But I'm very proud, frankly, of the transformation of the company and how we were able to, one, globalize the company, but also focus on pharmaceutical and innovation. And when we think about it, when I joined the company, we were in the branded generic business, quite big. We were in the OTC business. We were in the biopharmaceutical, too. Our R&D was focusing more on follow-up and me-too product across many, many therapy paths with a focus on small molecule. And so we decided to pivot to more innovation, which I think is what is necessary today to win in the current environment. And also, we moved away from the branded generic business, and that was a good move because obviously, the branded generic business has collapsed since in many countries, and now you have like innovation and generic. And I think it was very more to exit that business. On the people side, just to -- when I joined, we had 2,000 employees in the U.S., and now we have 22,000. So we really also globalized the company. And we remain by far the leading largest company in Japan. But that's not how you win. You win by being strong globally and especially in the U.S. in that pharmaceutical space. So I think that has been a huge transformation, and we were able to do that by keeping our values and our culture very strong. So that's also something I am proud of. And of course, internal succession, which is not easy to achieve. And I'm very, very proud. I'm glad that Julie is succeeding.

Okay. Next question is for Julie. What do you see as key focus area as you prepare for the CEO role?

Well, you just heard from Christophe the fantastic results that we had in our Phase IIIs last year. So absolutely top priority is now launching these 3 assets successfully and hopefully, the ones that come behind it, too. So 100%, 150% focused on making sure we can successfully launch these new medicines.

Please raise your hand if you have a question, and we wait for microphone. Okay. So I'd like to discuss about new products. You presented strong data for oveporexton, rusfertide, and zasocitinib. Could you provide more detail on the expected launch up and the pace of revenue up for each of these assets; zaso, rusfertide and oveporexton?

Are you talking data on launch plan?

Launch plan.

Launch plan, yes. So as I mentioned, I think there are different markets different characteristics. I mean, the products are all innovative, but you have very different situations. So let's start with zaso. Zaso, it's a very competitive market, very mature, a lot of competition, obviously. So first, you need to make sure you have an entry ticket in this market, you need to have the right level of investment. You need to have the right market access strategy, which, of course, is easier when you have compelling data in terms of efficacy and safety, which we have. But that's a very competitive market. It's a market share game here. And I think we need -- we have a strong presence in the U.S. We can do it, but it's probably the most of the 3. It's the most competitive and, let's say, expensive launch, for sure. So that's why it was absolutely critical for us to have the right level of efficacy because you cannot succeed in a market like that if your product is not highly competitive. We think it is. So again, here, it's all about the overall segment and convincing prescription prescribers, physicians and patients that they should try an oral before potentially going to an IV and subcu. And I think that's very, very critical. Again, there will be -- at the moment, we see 2 overall product with this level of efficacy and safety. It's very fine actually. Because the challenge again is to convince that overall is an option before going to an out. So that's really where the competition is. Rusfertide, Teresa can talk about it because he will be the one launching the product.

Yes. No, no. I mean rusfertide, it's a very exciting product in the area of polycythemia vera. In today's world, it's really phlebotomies is where patients start. It is a very crude tool in many ways, and it comes with significant burden on the patient in terms of going into the clinic. It's a rather painful procedure. And it is only done, I would say, intermittently. And so the key thing with polycythemia vera is to get that hematocrit level below 45%. And so in between phlebotomies, you know that there's a fairly high level of volatility in that. And the beautiful thing that we have seen in the data with rusfertide is that you have rapid, durable and consistent control. So a big opportunity for patients to the one thing that we've seen with this data, too, is that it can be done as a single agent or can be used in combination. So today, patients will typically start on phlebotomies. And then from there, they will add on hydroxyurea and then they'll add on other things as they move through the treatment flow. And so it's an exciting asset. We're looking at really a prevalence market. So it's not as though there's a lot of incidents coming in every year, but patients tend to stay on the treatment that they're given. And so the opportunity here for us is to make sure that we educate and that patients begin to understand the benefit that this will bring them. It has also been very clear from the feedback we're getting that physicians clearly see the innovative benefit of what this drug is going to bring to the market.

And then oveporexton will be a slam dunk because I think that there is so much unmet medical need and satisfaction among patients that they will try. And then after that, there's a need to choose the right dose, but also they can adapt when they take the second dose, is it a bit later, a bit earlier in order to, again, measure pharmacokinetics and manage their efficacy, but also side effects as well, tolerability. Because the main side effect we see in the data is insomnia, and that's quite -- you can understand easily. So I think that would be the challenge is to help them and help the physician to tailor a little bit the treatment so that they can have the maximum efficacy. And I think based on the data we have seen in the Phase III, it would completely transform their life. And it's like immediate. You don't have to wait for 1 week. I mean it's like this, it's like a switch. I think it will be very, very impressive.

Okay. Any questions on the floor?

Very nice, wonderful to see the evolution and the growth of Takeda. My question is a bit more about your oncology pipeline. A couple of questions there. Number one, what is it about your IL-2 PD-1 bispecific that you believe that can provide a differentiation my not just use IL-2 plus a PD-1? Why do we need to bispecific? That's question number one. Question number two, thinking about your ADCs, why did Takeda look at a low DAR, if I understand correctly, these are DAR-4 syndecans and when the majority of the field is going towards a higher DAR. So those would be the 2 questions about your emerging oncology portfolio. And perhaps do you think there's a possibility for a combination of targeting with IO and ADCs?

So for the first question, perhaps Andy can explain the alpha-biased IL-2/PD-1. The alpha-biased is the most important differentiation here. And then perhaps the second question, Teresa.

So thank you very much. And it's just almost a plant. It's such a great question for us. So firstly, there are no alpha-biased IL-2 agonist right now on the market. And so of course, one could imagine the potential for combining a PD-1 inhibitor in an alpha-biased IL-2 activator. These don't exist. I think with that said, there are potentially mechanistic benefits of linking the 2 together. So the alpha-biased IL-2 that our partners at Innovent made, there's a selectivity for effector cells in tumors is there CD25 expressing T cells that when activated will attack the tumor. IL-2 alpha is also expressed on T regulatory cells. So when activated, those will suppress an immune response. So clearly, you want to go after the former, not the latter. By having the bias in the pharmacology that helps. But the second opportunity is by linking it to a PD-1 you're carrying that molecule into the tumor because the tumor cells that express PD-L1 and so you're localizing that alpha-biased IL-2 to the tumor. So that's a distinctive antigen. it's a unique molecule, and the data as Christophe described, is just incredibly exciting.

Yes. And actually, maybe before you talk about the ADC, I'll expand a little bit on our excitement with that asset. Because, I mean, the #1 relevance, obviously, is the mechanism is really interesting, but we've got 1,200 patients that have been treated, and we have seen in those 1,200 patients, the safety profile payout as well as the efficacy. And the exciting thing commercially is that there's a large unmet need in IL refractory and given the way that this activates the immune system, there's enormous potential here to address that piece of the marketplace. And also as you move into sort of earlier lines, that safety profile allows you to combine with other agents as well. So in some ways, I think of this alpha-biased IL-2/PD-1, we certainly know IL-2 works, right, for sure, a long history there, but we don't have the toxicity, and we certainly know the PD-1s work having that combination is very powerful. And I think of this as like a pipeline of product in terms of the potential of where we could develop this agent.

And then on your second question, you're obviously quite sophisticated in this space. There are multiple different elements that define the efficacy of an antibiotic drug conjugate, one of which is what you referred to, which is a drug-to-antibody ratio. And while many ADCs have higher ratios than what is now TAK-921 or CLDN18.2 antibody coupled with a topoisomerase inhibitor. It's not really the number of toxic molecules. It's how they're placed, how well they're delivered to the tumor and how stable they are via the linker because we're really trying to balance efficacy and safety. And while many, many programs are using CLDN18.2 as a target, there's something unique about TAK-921 because of the DAR, because of the fact that we're using a topoisomerase inhibitor not a tubulin, which is very consistent with the need for patients with pancreatic gastric cancer. And third, it's an Fc that's not activated. And so the safety of this molecule, tolerability is unlike anything that's been seen in this class before. So we're very excited about both molecules, the pipeline and the product and then the more specific activity of TAK-921.

I will perhaps add because it might be interesting for you that this is a strategic partnership with Innovent. It's not just a buy or in licensing. So we are codeveloping especially the alpha Bioscience to PD-1. And so it is for us, also a way to create a partnership with 1 of the most competitive Chinese company right now. we did a holistic review of the biotech space in China, the 2,200 biotech companies in China. And we had a short list and Innovent was part of this shortage. So for us, it's 3 molecule, but more importantly, it's a partnership that could lead to potentially further collaboration. But it's a way to have if you like, a foot in the Chinese ecosystem.

Next question is for Milano-san. So as you look ahead to fiscal 2026 and beyond, investment required to support launched 3 new products. How do you balance investment in launch preparation and R&D with your margin commitments?

Yes. Thank you, Wakao-san. So yes, we have been doing a lot to manage the margin. Even under the loss of exclusivity, we have big -- we are facing in loss of exclusivity, big one in the past 2 years. Now it's bringing in the past. And in the mid long run, we believe the main driver of the margin improvement should be the top line growth with the new launches. And we do believe that we have enough assets to grow in the next 5, 10 years. Then starting from 3 new launches, this is something we do not want to a compromise. And eventually, this will be the growth driver. This will bring -- this will be the main driver of the margin improvements. And then other assets coming in, the elritercept is coming in, the mezagitamab is coming in. And also, we are adding the three exciting oncology assets. So we have to also the increase or invest in R&D. Having said that, we're going to do our best to offset this incremental investment to protect the margin. So we have to now manage this a bit transition period in terms of the LOE we had in the past 2 years and then now in the coming next growth period over the 5 years.

Any other questions? Please.

Yes. Christophe, just a curiosity. You are a leader in the short bowel syndrome market with your teduglutide. I didn't see in your future program any new solution in order to give you the possibility to keep the leadership in a market that is constantly increasing?

Yes, sure, sure. It's a great question, thank you, because it to say that we have a pipeline of product here. So oveporexton is focused on NT1, narcolepsy type 1. We have a TAK-360 which we are developing for NT2 and IH. And we have another molecule for all that type of indication. So we are fully committed to really explore all the possibilities and the possible indications linked to the orexin mechanism. For different reasons, we don't have one molecule to tackle those. We have multiple molecules, but we are moving at speed, no doubt. So TAK-360 in Phase II, right? And of course, the advantage that we have, we were not the only one is I understand we're very well in the field now because we had our share of success, failure as well in life, that's how you learn. So we think that we will be able to move very fast. And the orexin class has a huge potential. And not only in the sleep space, but potentially in the cognition space, in other areas. That's what we see right in our Phase III data, we see that we improve, of course, a sleep pattern of this patient with the cognition as well. So potentially, it could be used with many disease where you have a cognition issue, Parkinson's, Alzheimer, and all those. So I mean, this is I don't know, perhaps it will take a decade to explore all the possibilities of orexin field, right?

But then to address because I think you were also asking about SBS or short bowel syndrome medicine. We don't have further development supporting SBS. But what we see with our current product and the competitors that are on the market, this is -- we have still yet to see launch. The competitive asset as well as the generic. And this is an area where the support for the patients because of the complexity of the disease is very important. And that's not easy to do. So despite the competition that has been talked about for a while and the generic, we feel quite confident in our product in GATTEX to be able to continue to support SBS patients.

Thank you so much. It's time to close. Thank you for your presentation and the Q&A session. Thank you so much.

Thank you very much.