Takeda Pharmaceutical Company Limited (4502) Earnings Call Transcript & Summary

Sure. But maybe if I dial back up and just talk about the nature of these diseases because for those of you who are close to the space, there are probably dozens of potential indications that 1 can imagine treating with an orexin agonist. I would bucket these diseases into 2 categories: NT1 and everything else. NT1 is a clear pathophysiology. This is a loss of orexin-producing neurons in the brain. You give a molecule like AF, which is an rexinagonist back, it's almost like a neurotransmitter replacement therapy. -- for all of these other conditions, we have a much more mundane understanding of the pathophysiology because there's normal orexin levels. It's a defect in orexin signaling somewhere. . And so all of those indications are going to require a very different development programs, very different, dosing, very different scheduling, and that's something that we're working towards. And NTT is an example of that. right? So what the dose level will be, it's likely to be higher. What will be the efficacy profile? Is it going to be curative like we see with NT1, what's the durability of effect. Those are all questions that we have remain to answer. I think we feel very confident based on the data that we've seen from competitors and based from based on our own data that we've seen with prior molecules.

Yes. So of course, we need to wait the result. But I think the best expected profile of TKA 60 for NTI is maybe once daily for LTI indications I can't -- it's my assumption are quite pretty fair or we won with D2 twice steady to be acceptable at now? .

Well, I think -- I mean, again, if I always go back to the science and translating the science, if in any of these conditions where you're trying to normalize sleep wake cycle you want to match normal physiology. And normal physiology is you wake up in the morning, your Orexin levels start to rise. You have a good night sleep. Over the course of the day, you're getting more and more tired to combat that tire, your brain makes more and more recon it goes higher and higher, that keeps you awake and then you got a bad and it goes down again. And so in principle, for any of these diseases in sleep weight, you want to try to mimic that natural pattern with an oral molecule. Doing that with a once-daily dose, that's a very difficult PK profile to match firstly. And secondly, everybody is going to have their individual differences. So as Rhonda was saying, having that flexibility to dose twice a day we think is critical in the vast majority of patients. So I would expect, as with NT1 and for NT2, you're going to be better off with a twice a day dosing paradigm.

The flexibility is we got it about it. In terms of 360, I'm asking too much about 360, but -- you recently have started the T1 population study what's the rationale of you already got the approval for 4 why?

Well, so I mean, state, first and foremost, we think where AF is not just a first-in-class, but has every potential to be a best-in-class drug. We're actually running a study that we don't talk too much about in Europe right now, a Phase III study it's called a randomized withdrawal study, it will be necessary to support registration in Europe. There's an element of that study that we're adding, which is a higher -- slightly higher dose. -- in this is for as fell. So we think between what we have right now and the potential to dose a little bit higher, particularly with that second dose with the flexibility where ZAP will meet the needs of NT1 patients. right? That's what we think. We're being careful. We want to make sure that we're exhausting all possibilities is already a very small NT1 study in 360, just in case, keep our options open at this point.

Got it. It's a bit too early to discuss about the pricing to our T22 to me assume that mostly the same pricing, same on cost to entity the population to with NT1. I don't think so. But so could you if you have any more color on the pricing dynamics .

I love answering pricing on like Phase 2 look, it could probably be different where the market is, where the competition is, what the data looks like. All of those factors go into pricing. I think it's still too early to tell, but yes, could it be different? Yes. .

Okay. Got it. Moving to -- congratulations for that are being accepted by the FDA for our filing. Just the confirmation, the PD data is much starting, right? .

Yes. Yes. .

So in mid-March, so you can launch it within your fiscal EIMs in March. So we didn't current ongoing fiscal year. .

Correct.

Of course, the pricing is, you cannot talk -- I know that. But yes, IQOS is already on the market and the pet quite well. So maybe competitive pricing, can we expect like that? .

You know the pricing of icotine. We know that access is critical for this launch too, like every launch, but this 1 even more. So in order to gain access, we will be competitively priced in order to do that. So .

I remember that rises Phase III data quite quick, both in efficacy and safety as well. So yes, -- in the past, investors coming with showed some concern of the stick to is some similarity to JAK inhibitors in terms of the model on, but the safety profile will quite different, I understand. But there are still some discussions on the way the investor psoriasis future up to be up with label would make some restrictions of the use some safety warning like that. So what can we fairly expect your safety profile or profile in the level going forward. Of course, it's too early, but what's the large guidance going forward.

Maybe I'll take it first, and then I'll let you talk about maybe the label and how highly selective. We are -- and you said it, I just want to reinforce -- this is a great efficacy story. I think, too, even if we were talking 6 months ago, it would be different. Like we have now turned over so many data cards with this molecule, and it just keeps getting better. And you're right. When we talk to HCP, when you talk to people out there, they want a drug that works, they want a drug that works fast, and that it continues to work. And when you look at the data, it's rapid, it's durable. And lastly, I want to talk about is the convenience piece because I do think it matters. And with that profile, I think it's a very strong 1 to have that will take to payers because we know the access fees. But it starts there. And I I'm excited about this molecule. You could talk about the label and the safety. Now on the safety side, we have to kind of do our job around educating. We've had a few of these education sessions. People are flocking to learn more, and they're excited about it, too. But we are -- and I'll let you speak to the selectivity and the label.

I mean just to accident what Ron just said, there's we are a TYK2 inhibitor. There's no activity on JAK. The challenge that we face is that TYK2s and JAK1 23 are part of the same family of kinases. And the first molecule that went to market had -- didn't have the efficacy profile that we did and actually was not a selective molecule. And so there's baggage and there's a perception issue that Ron is going to have to work through. We don't -- we haven't seen any safety issues that suggest anything related to Jack. So it would be like you said, we have to work with the FDA now along the review period and ultimately, towards the label, it will be very surprising if there is any monitoring related to Jack in this label. I think the key is going to be what Rhonda saying is overcoming these perception issues. .

Great. So I think you already have got the 1-year safety data of psoriasis studies in hand maybe you may have submitted the 1-year data to FDA as well. Is that fair to achieve that?

Yes. So as part of -- 1 of the reasons that we didn't submit the file to FDA when we finished the 2 Phase III studies is that we had to generate a larger safety base of patients exposed on ASO for a year. We've now completed a full dedicated safety study. Actually, there's great efficacy in that study that we'll present at a future congress. But we now have a very compendium of safety data. And again, no JAK-related safety effects.

On the EV was that's a 1-year data as well? Or you have not seen any.

That's right. Exactly right. Nothing that's new from the safety profile that we've presented.

So the next Investa interest beyond those risks. So IBD, you CD indications. Maybe the stress would be starting at the QD party. The I know that you have not disclosed those things precisely apart the IBD, UC CD decade -- but could you share some more color on the those increased orating UCC. And based on the accumulated safety evidence of psoriasis company can we assume that we should -- or can I think I do not so much concern about that. Safety providing higher dosage, i.e., in IBD indications. .

Yes. So maybe just again, dialing up. So I would say 3 buckets of indications for as psoriasis, psoriatic arthritis, great psoriasis data arthritis Phase III data coming out next year. IBD, I'll come back to that. And then we have 2 additional autoimmune inflammatory indications, vertiligo and HS -- those are both Phase II studies. There's a lot of rationale for why we should see efficacy. There's a lot of interest in vitiligo in particular. So we'll be very excited to see the results of those 2 studies next year. Now IBD is what you asked. And you were talking earlier about how there's some skepticism around the mechanism. And maybe I'll offer my thoughts and why I'm enthusiastic -- there are 3 levels of evidence that suggests that a TYK2 inhibitor should be effective in IBD, UC Crohn's. One is that the cytokine inhibitors, like IL-23 inhibitors and others all signal through TYK2, and we know that they're highly efficacious. -- to animal model data and the perhaps the most compelling human genetics. 1500 people of Caucasian decent walk around with reductions in 2 activities. And they get very few of them get Crohn's disease. They are protected from Crohn's disease, slightly less so, but also ulcerative colitis. We think part of the challenge with the mechanism and part of the reason these perception issues exist is that there have been 2 failed studies with TYK2 inhibitors. We believe that there are 2 reasons for that. One is the dose in at least 1 of the studies, we don't think that the exposures were high enough to what is necessary in IBD. And then the second, we think is experimental design and operationalization of the study. Regards, our trials are ongoing. They'll read out this year. We're starting at the 30-milligram QD dose, which is the psoriasis, psoriatic arthritis dose, and we're going up to a dose that's significantly higher than that. My level of confidence is very high for Crohn's, slightly less for UC based on the genetic data. I think the big question will be competitiveness. That's something we'll have to wait and see. And of course, your question about extrapolating safety. If we go at the 30-milligram dose, I think there's a lot of safety extrapolation. If we go at a higher dose, there's some, but obviously, we'll have to generate that safety database. .

And so you said also by the end of this year ended this fiscal year to be sure -- so maybe after the capital market today SP1 Definitely after the both.

Well the UC study is going a little bit faster than the Crohn's disease study. So we'll likely have data from that study first we'll disclose data. There are a variety of reasons for doing that, not just -- not just Takeda positioning, but in terms of how you run the studies, we'll disclose data from both together.

In maybe January, March.

At the end of the fiscal year. Okay. .

And so in terms of the market potential, -- so in Sias, you already 2 years ago, have said $3 billion to $6 billion. I have that -- but in terms of the IBD, you see CD indications what can we fairly expect the potential peak sales of our as .

I'll take that one, but you're not going to like the answer. Right now, we don't have peak sales yet for the IBD, like you said, distributed $6 billion. is for PSO and PSA. I think we did back a couple of years ago, '24. We're not changing those. I think we feel really good about where we are with DAS in that space. But too early to give you a number on the peak sales of IBD. I think we need to see some of this data too. .

Can we expect the Capital Market Day is some update on IBD potential DC -- and entity to big sales potential as well. .

I think we need to see the data first. But yes, I don't want to commit then you'll see that in December, but if it's ready, then we'll do it, but I can't commit to that right now.

Okay. Got it. sorry, so only 1 minute left. So I ask too much about the 2 franchises. But -- so briefly, Innovent product. I think -- so 26 to 27 million or first half '27 is a year of launch of the 3 key products for us. But after the launch of the date in March, after that, so yes. I was -- I'm a bit worried about the lack of the data readouts of our pipelines, but innovate products to maybe it too well. Could you give me -- give us the time line of the data readout of Innovent products other you highlighted compounds in definitely in '27. .

Yes. Well, so we'll have a lot -- I mean it will be a steady flow of data readouts. So next year, you have our arthritis end of this year. We talked about 279 IBD. Next year, you'll have 279azocitinib in HS and vitiligo. We have a molecule that we haven't talked much about, which is at Zima, which we're studying in acute ischemic stroke Phase II study. It's very exciting. We'll have data from that program next year. For the Innovent programs, we'll have continual data coming out from China, particularly for TAK-928 and TAK-921. And then the following year, we'll have oritasatpob, mesagitimab of zersiran. So there's a really steady stroke, not just these 3 launches. -- a pipeline that can sustain behind it.

Great. So many, many many, many --

It will be fun. .

So the great effect on point to come yes. Okay. Thank you very much. So now time is up. Thank you very much. .

Thank you.