Takeda Pharmaceutical Company - Earnings Call - Q1 2026

Transcript

Christopher David O'Reilly (Head of Investor Relations)

Hi, my name's O'Reilly. Thank you for this opportunity. I would like to explain about the language setting to begin with. Please find the language selection button at the bottom of your Zoom window. If you wish to listen in Japanese, please select the Japanese channel. If English, please choose the English channel. If you want to listen to the original, please turn it off.

Operator (participant)

For those of you who wish to listen to this call in English, please select English in the Zoom language select button.

本日のコールでは米国の1995年。

Christopher David O'Reilly (Head of Investor Relations)

Before starting, I'd like to remind everyone that we'll be discussing forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those discussed today. Factors that could cause our actual results to differ materially are discussed in our most recent Form 20-F and in our other SEC filings.

Now, 本日のコールでは国際会計基準に準拠。

Please also refer to the important notice on page 2 of the presentation regarding forward-looking statements, our non-IFRS financial measures, which will also be discussed during this call. Definitions of our non-IFRS measures and reconciliations with our comparable IFRS financial results are included in the appendix to the presentation. Now, we would like to begin. The presentation will be given by Christophe Weber, President and CEO; Milano Furuta, Chief Financial Officer; and Andrew Plump, R&D President. This will be followed by a Q&A session. Let us begin.

Operator (participant)

Christophe, over to you, please.

Christophe Weber (President and CEO)

Thank you, Chris, and thank you, everyone, for joining us today. Our fiscal year 2025 first quarter results reflect the significant impact of Vyvanse's generic erosion on revenue and corporate profit, which we had anticipated. We actually expect this impact to moderate in future quarters, and fiscal year 2025 will be the last year of significant impact from Vyvanse's erosion. There is no change to our outlook for the full year. Milano will discuss our financial results in detail in his presentation. Fiscal year 2025 is a pivotal year for Takeda, not least because of our rapidly progressing late-stage pipeline. I'm very pleased with our pipeline progress so far and excited about the future. As you know, earlier this month, we announced positive results from two pivotal phase three double-blind placebo-controlled studies of Oveporexant. Both studies met all primary and secondary endpoints at each of the doses we studied.

We are very encouraged by these results and what they could mean for people living with narcolepsy type 1. Later on this call, Andy will walk you through the top-line results and what you can expect next with Oveporexant on our Orexin franchise, as well as other pipeline achievements since Q4. Before we dive deeper into our pipeline strategy, I will pass over to Milano to review our financial results. Milano.

Milano Furuta (CFO)

Thank you, Christophe. Hello, everyone. This is Milano Furuta speaking. Let's go to slide 5, which summarizes our Q1 financial results. As we had anticipated, Q1 is highly likely to be the quarter most impacted by loss of exclusivity because of the strong finance performance in Q1 fiscal year 2024. This created a high comparative baseline for growth rates in Q1, but we expect this to moderate over the rest of the fiscal year. Revenue in Q1 this year was just over JPY 1.1 trillion, a decrease of 8.4%. Or -3.7% at constant exchange rates or CER. Core operating profit, COP, was JPY 321.8 billion, a year-on-year decrease of 15.8% at actual effects or 11.9% at CER. Reported operating profit was JPY 184.6 billion, which grew 11%. Core EPS and reported EPS were JPY 151 and JPY 79, respectively.

Cash flow was strong this quarter, with adjusted free cash flow of JPY 190.1 billion. Slide 6 shows our growth and launch products, which represents 50% of revenue. In Q1, they grew 5% at CER. We see that's a little bit slow start, but we anticipated a higher growth rate in subsequent quarters. In GI, Entyvio growth was 4.9% at CER, partially reflecting intensified competition in the IBD market. We do see an increasing number of active EntyvioPEN patients in the U.S., growing approximately 30% since the last quarter. Awareness, prescription, and satisfaction levels for EntyvioPEN are high, and our focus is to reduce complexity along the reimbursement and authorization pathway. As access for the PEN expands, we expect a higher growth rate for Entyvio in the coming quarters. In rare diseases, Takhzyro continues to grow as a market leader in HAE prophylaxis.

In our PDT portfolio, there was some phasing impact in our Q1 results. This is quite common in PDT, where we often see fluctuations on a quarter-to-quarter basis. We expect both Ig and Albumin to grow by single digit for the full year. In oncology, Frizane continues to expand as we roll out global launches. In vaccines, Qdenga was impacted by the timing of drug shipment as well as transactional effects, mainly the euro appreciation against the Brazilian real. Qdenga volume is increasing, and we still expect to deliver strong growth for the full year. Slide 7 shows the year-on-year revenue performance for the total company. Although our growth and launch products are expanding, we had a significant impact this quarter from Vyvanse generic erosion. Last year, there was a strong rebound in Vyvanse revenue in Q1. Mainly due to generic supply constraints in the U.S.

and the growth ex U.S. ahead of loss of exclusivity. This resulted in a high year-on-year comparator for Q1 this year. We saw the generic supply situation in the U.S. improved from Q2 last year and the generic launches in Canada, Germany, and Brazil last summer. This means we expect less headwind from Vyvanse from next quarter onwards. Vyvanse was a main driver of our revenue decline of 3.7% at CER, in addition to some impact from Medicare Part D redesign. FX was also a headwind this quarter due to appreciation of the Japanese yen against major currencies. Slide 8 shows the year-on-year bridge for core operating profit. You can see that the LOE of a high margin in Vyvanse was a main reason for the year-on-year decline of 12% at CER.

This was partially offset by operational efficiencies from the enterprise-wide efficiency program we initiated last year, in particular in R&D spend. Next, reported operating profit increased by 11% versus prior year, mainly due to lower impairment and restructuring expenses. Slide 10 is our latest debt maturity ladder. In June and July this year, we executed two leverage-neutral bond issuances, one in Japanese yen and the other in US dollars, to pay off the short-term funding we raised to prepare syndicated loans in March 2025. We had to prepare these loans to streamline our upcoming maturity profile in terms of both duration and currency mix. Of note, these new US dollar bonds generated significant demand, more than four times the $2.4 billion that we finally issued. This enabled us to secure favorable terms.

In addition to these refinancings, we also repaid debt that matured in Q1 this year, including an $800 million US dollar bond. Over the next three years, our average annual maturity is now approximately JPY 220 billion, which we believe is manageable considering our cash flow outlook. Slide 11 shows our full-year outlook for FY2025, which is unchanged since May. As we have explained today, Q1 was significantly impacted by Vyvanse generic erosion, but this was within our expectation, and we are not changing our management guidance. Finally, a word on tariffs. Our FY2025 outlook does not reflect the potential impact of tariffs, and in general, we believe that we are well positioned to manage the potential impact at this time. This slide is the same as we showed at Q4, and I would like to emphasize again that the value of our imports into the U.S.

is approximately 8%-10% of our U.S. revenue, and the vast majority of this comes from Europe. The tariff rate, let's say 15%, would be applied to this number once it becomes effective. Thank you, and I'll now hand over to Andy for updates on the pipeline.

Andrew Plump (President, R&D)

Thank you very much, Milano. Hello to everyone on today's call. I'm very excited to begin with the impactful update we have on Oveporexant. Narcolepsy type 1 is a neurologic disorder caused by the loss of Orexin-producing neurons in the brain. It is characterized by daytime symptoms like excessive daytime sleepiness, cataplexy, cognitive effects such as lack of sustained attention, and nighttime symptoms like sleep paralysis and disrupted nighttime sleep, which all have a substantial impact on patients' ability to function as well as quality of life. As we communicated earlier this month, both phase three studies met all primary and all secondary endpoints, demonstrating statistically significant and clinically meaningful improvements at week 12 across all symptoms at both BID doses. These doses were chosen to provide flexibility for physicians and patients to manage daytime and nighttime symptoms.

The p-value you see on this slide of less than 0.001 does not do justice to the statistical significance of the trial. Often, results had many more zeros before the one. Oveporexant is on track to be the first in class and potentially best in class Orexin-2 receptor agonist that treats the underlying Orexin deficiency and has the potential to establish a new standard of care in NT1. In two phase three trials, Oveporexant demonstrated the ability to normalize the majority of treated patients across almost all NT1 symptoms. Improvements in excessive daytime sleepiness were measured using the Maintenance of Wakefulness Test and the Epworth Sleepiness Scale. MWT is a test used for regulatory purposes where patients are kept in a dark room and asked to stay awake for four 40-minute sessions.

It is best accompanied with subjective endpoints like the Epworth Sleepiness Scale that describes how well patients respond to treatment. Most of the patients on Oveporexant achieved normal ranges for both the MWT and the Epworth Sleepiness Scale. Cataplexy is a very important endpoint for patients and regulators. We were thrilled to see that it was so significantly improved across all doses as measured by weekly cataplexy rate questionnaires. Cognitive benefits like sustained attention were recorded using the Psychomotor Vigilance Test. Finally, the benefits to patient satisfaction and quality of life were recorded using surveys like the Short Form 36 that includes measures of fatigue and measures of holistic function like the Narcolepsy Severity Scale for clinical trials that measures the effects on disrupted nighttime sleep, among other symptoms. Nighttime symptoms are also measured subjectively with the use of sleep diaries.

Importantly, all objective measurements were associated with subjective improvements of daily function. Oveporexant was generally well tolerated with a safety profile consistent with past studies. No serious treatment-related adverse effects were reported. The most common adverse effects were insomnia, urinary urgency, and frequency. As with the phase 2B experience, the majority of urinary events and insomnia decreased over time in both severity and frequency. More than 95% of participants who completed the studies enrolled in the long-term extension. We believe these data and the high enrollment in the long-term extension study are strong indicators of the transformational benefit Oveporexant can deliver across the symptoms that impact NT1 patients. We look forward to sharing multiple oral presentations starting at World Sleep, with more to follow at future medical conferences. Takeda will host an investor call on September 8, 2025, from World Sleep in Singapore.

Based on these strong phase three data, we plan to file for US approval in NT1 later this year, with regional filings to occur simultaneously or shortly thereafter. We believe these outstanding phase three results have the potential to establish Oveporexant as a new standard of care for patients with NT1. Next slide, please. The phase three results in NT1 are exciting, and this is just the beginning. We will continue to gather information in the long-term extension to see how patients fare over longer periods of time. As previously reported, sustained effects beyond six months have been observed, with many of the patients being treated for more than two years now. We believe the long-term extension data from the phase three and phase 2B trials will enhance our deep understanding of Orexin biology and allow us to optimize treatment for patients in need of this lifetime therapy.

Our Orexin franchise is making rapid progress beyond Oveporexant. The next generation Orexin-2 receptor agonist, TAC360, is in phase 2 development for narcolepsy type two and Idiopathic Hypersomnia. These results are expected to read out at the end of this fiscal year or early in fiscal year 2026. Of course, we continue to work in our laboratories on the discovery and development of additional tailored Orexin agonists that have the potential to address vast unmet needs in diseases where Orexin plays a role. We expect a new next-generation Orexin agonist to enter the clinic later this year as we accelerate development of our multi-asset Orexin pipeline. Next slide, please. Pipeline momentum in fiscal year 2025 is off to a great start. We now have outstanding results from two phase three programs in hand.

The phase three VERIFY study of Rusfertide, a first-in-class synthetic hepcidin mimetic in development to treat polycythemia vera, was presented at the American Society of Clinical Oncology plenary session. The plenary session is where data with the potential to transform medical practice is typically highlighted. The discussion at the plenary session, an ASCO-appointed expert emphasized that, "The study result is practice-changing," and recommended that Rusfertide should become part of the standard of care for patients. In our GI squared therapeutic area, we initiated a phase three head-to-head trial comparing Zazositinib versus Deucravacitinib that is designed to clearly differentiate Zazositinib in psoriasis. We also initiated a phase three trial for Eritrosept in second line, anemia-associated myelodysplastic syndrome. This is the beginning of a broad late-stage Eritrosept development program for which we will have more to say in the future.

There are several regional approvals this quarter, including European approval of Ezetras as part of an additional chemotherapy regimen in frontline Hodgkin lymphoma. Our plasma-derived therapies continue to broaden indications and enter new markets. HYCUVIA was approved in CIDP and multifocal motor neuropathy in Japan. GammaGuard ERC, a new formulation with low IgA antibodies, was approved for the U.S. and European markets. In addition, HIHUB and HIHUB Duo, two new devices designed to streamline the administration of HYCUVIA, were approved in the U.S. Looking forward to the rest of the fiscal year, and if you could move to the next slide, please, 2025 is indeed a pivotal year for our late-stage pipeline. I have already highlighted the next steps for Oveporexant.

For Rusfertide, we are targeting a medical conference in the second half of the fiscal year to share our 52-week data update that will include durability of response and additional safety. We plan to file an NDA in the U.S. for Rusfertide and polycythemia vera in the second half of fiscal year 2025. Later this year, we will have top-line data for Zazositinib in two pivotal phase three psoriasis trials, Latitude 3001 and 3002. Looking further into the future, next slide, please. The six programs in our late-stage pipeline have the potential to deliver transformative benefits to patients while contributing to Takeda's long-term growth. Zazositinib, our oral allosteric TYK2 inhibitor, continues to add expansion opportunities and will start a phase 2 study in hidradenitis suppurativa, or HS, within the next year. HS is a chronic, recurrent, and debilitating inflammatory skin condition. The global prevalence is estimated to be around 2%.

There are limited approved treatment options available, and people living with HS continue to experience high disease burden. We believe there is a significant need for a durable and effective advanced systemic therapy. Going forward, we will maintain our strong focus on late-stage development activities with a continued emphasis, where possible, on acceleration. These efforts will support our ambition to file up to five additional indications from our late-stage programs through fiscal year 2029. Thank you very much, and I'll now turn it back to Chris for Q&A.

Christopher David O'Reilly (Head of Investor Relations)

We have Christopher, Milano, Andy, and U.S. Business Unit President, Julie Kim, as well to answer your questions. If you wish to ask a question, please let us know with the raise-a-hand button on Zoom. If you're participating in the Japanese channel, please ask your question in Japanese. If you're participating in the English channel, please ask your question in English.

If you're listening in the live audio, you can ask the question in either of the two languages. Please keep your questions to a maximum of two. Please ask all the questions together. First question, Morgan Stanley, Muraoka-san, please. Unmute yourself and ask your question.

Muraoka-san (Investment Banking Analyst)

Thank you. This is Muraoka, Morgan Stanley. About the sales of individual products, looking at that interview, IG, Vyvanse, Qdenga, they were relatively weak. I think your message was they're okay, but in the second quarter. For those four products that I just mentioned, do you expect recovery? That's my first question. The second question is. Orexin. After 861360, I think you have another molecule coming into the pipeline. What is the additional benefit? What kind of clinical advantage can we expect for this new molecule that will be added to the pipeline? Thank you.

Christopher David O'Reilly (Head of Investor Relations)

First question was about IG, Entyvio, Vyvanse, and what was the fourth one?

Muraoka-san (Investment Banking Analyst)

Qdenga. Qdenga.

Christopher David O'Reilly (Head of Investor Relations)

Okay, thank you. Thank you very much.

Operator (participant)

The first question about some of the products that were a little bit weaker in Q1, so IG, Entyvio, Vyvanse, Qdenga in particular, how are these looking to perform in the rest of the year? Perhaps I'll ask Christophe to begin that answer and then Julie to add detail as required. The second question was for any additional data that we can or any additional direction we can provide on the next additional Orexin agonist coming through into the pipeline later this year. I'd like to ask Andy to comment on that, please. Thank you.

Andrew Plump (President, R&D)

Thank you, Chris. It's very clear that in our mind, the first quarter is quite soft and does not reflect the underlying dynamics of our product.

This is why we have not changed our guidance for the year. We believe that this first quarter does not reflect the dynamic of the product. In the case of Entyvio, the pen continues to accelerate. We are not at full market access yet in the U.S. That means that we are losing some prescription and therefore some switch opportunity from IV to sub-Q. We are progressing in terms of market access and will reach the maximum and the optimal stage during this year. We continue to accelerate the pen and the feedback we are getting on the pen is very strong. Julie can explain further. On Vyvanse, Milano has explained that the Q1 is extremely impactful in terms of growth rate because of a year-on-year comparison. We also know that eventually we will reach a plateau.

That's why we believe that this year is the last year of significant impact of Vyvanse generic exposure. You will see a waning impact during the year, especially because there was a very significant generic penetration at the end of last year. The immunoglobulins, there is always some quarter-by-quarter growth rate change, but we remain committed to the forecast that we gave in Q4, which is mid-single digit overall PDT franchise growth, high single digit for IG. You see we are slightly lower. I mean, remember that when it comes to immunoglobulin, the demand is greater than supply. It's all about. Allocation, and we have a very competitive portfolio right now with new indication. Qdenga is actually the same. The demand is greater than supply. We are ramping up our supply. It is all about shipment and allocating our dose to where we have greater demand.

We are very much convinced that Qdenga will continue to grow in the future. This is why overall we believe that we will deliver our guidance, which is broadly flat in revenue, for example, for the year.

Murakosan, this is Andy. Maybe I can dial up and provide some context regarding our approach to Orexin and our broader Orexin franchise. We think of diseases that could potentially be managed through Orexin agonism in three buckets. There is Orexin deficiency, which is NT1. There are other rare diseases that are characterized by normal Orexin levels like NT1 and idiopathic hypersomnia.

Then there is a large array of more common diseases that have symptoms like disruptions in sleep-wake cycles, like other neuropsychiatric symptoms that we believe modulation of the Orexin pathway could be beneficial in. It is clear that TAK-861 is not just a first-in-class for type 1 narcolepsy, but a potential best-in-class with potentially very little room for additional differentiation. For TAK-360, as I have mentioned, we are still learning a lot about TAK-360, and we have two ongoing phase 2B programs in type 2 narcolepsy and idiopathic hypersomnia, so rare diseases that are characterized by Orexin deficiency. We will have another molecule coming into the clinic later this year, and we continue to build additional molecules that have differentiated pharmacology that we can use to begin to explore benefits in more common disorders.

The way I would think about Orexin is that with 861, we are really just scratching the tip of the iceberg. ありがとうございます。すいません、その。最後のファーマコロジー、違うステージっていうのは一般的な。

Muraoka-san (Investment Banking Analyst)

Product that is different in pharmacology, is that for more general diseases, more common diseases? Is that the correct understanding?

Andrew Plump (President, R&D)

That is our intent at this point. I mean, we have to also recognize that there is still an immense amount to learn about this pathway after type 1 narcolepsy. We have the level of experience that we have in type 1 narcolepsy with these phase three results and with the extension from our phase 2B study where we have patients now up to have been on therapy for up to two years is quite extensive. There's still very little known about this pathway outside of type 1 narcolepsy.

Our intent is to win and own this pathway with multiple molecules and explore the vast potential of this disease in both rare and common disorders.

ありがとうございます。

Muraoka-san (Investment Banking Analyst)

Thank you very much.

はい、ありがとうございました。それでは次のご質問は。

Christopher David O'Reilly (Head of Investor Relations)

Thank you. Next question is Yamaguchi-san from Citi, please.

Hidemaru Yamaguchi (Equity Research Analyst and Managing Director)

Can you hear me?

Andrew Plump (President, R&D)

Yes, we hear you.

Hidemaru Yamaguchi (Equity Research Analyst and Managing Director)

Thank you. So thank you very much for taking my questions. This is Yamaguchi from Citi Group. I have two questions. The first question regarding a competitive landscape of narcolepsy. Recently, Alkermes put up top-line release on the Orexins, and they seem to be missing cataplexy portion of the data. And you talk about, Andy-san was talking about the cataplexy importance. You don't need to talk about competition, but can you elaborate how this is important and how this is going to be differentiated from your products and Alkermes' products? That's the first question. Second question is more broad questions.

Christophe was talking about some general investment strategy for the US, which does not really contain new things, but it was like a $30 billion in total. And globally speaking, a global major company like your company is trying to put up some investment to the US market for the future. Especially on the manufacturing side. Do you have any kind of a new plan how to accelerate those investments in the US, or can you make any kind of comment on what's the new sort of a business model that US companies, including your companies, are looking for in the US, like a DTC, trying to control the cost structure? That's an open question, the second one. Thank you.

Milano Furuta (CFO)

Thank you, Yamaguchi-san. The first question on our thoughts on evolving data in the narcolepsy landscape, I'd like to ask Andy to comment on that.

The second question on investment in the US, or how our business may evolve given the changing landscape in the US, I'd like to ask Christophe to comment on that, please.

Andrew Plump (President, R&D)

Thanks, Chris, and thanks for the question, Yamaguchi-san. As I mentioned, we believe that TAK-861, Oveporexton, is not just first-in-class, but a potentially best-in-class agent. We've seen benefits across all symptoms using both objective and subjective measures. In many cases, these benefits normalize these patients across all, many, or some of the symptoms of narcolepsy type 1, including cataplexy. Cataplexy is a somewhat variable measurement. We were very pleased to see that our results in cataplexy are quite significant and very meaningful for patients. We look forward to presenting those data at World Sleep next month. It is hard to comment on the competitive landscape because we have not seen data. We will see data rolling out in sleep.

I think suffice it to say, we really believe with the time advantage that we have and with the data that we will present next month, that Oveporexton is a highly competitive agent in this class.

Christophe Weber (President and CEO)

Thank you. Andy and Yamaguchi-san, regarding our investment, first, I would like to remind everyone that we are highly invested in the U.S. For example, if you look at our manufacturing network, the country where we have the biggest manufacturing presence in terms of number of sites and number of products we manufacture, number of colleagues that are involved, is by far the U.S. That is why we are extremely balanced, and we will continue to invest in this manufacturing network in the U.S. That is also why our exposure to tariff is limited, as Milano explained. Strategically, we continue to take into consideration many parameters when we decide a new investment.

Of course, we are very much aware of geopolitical considerations and other considerations so that will drive our investment decision in the future. I want to really reinforce the fact that we are extremely invested in the U.S. on the manufacturing side. Obviously, also on the R&D side, we do the majority of our research and development activities in the U.S. That, we think, is important for our long-term strategy and strategic situation because we also do the majority of our revenue, the biggest part of our revenue in the U.S. When it comes to the DTC, I will ask Julie to comment on the direct-to-consumer model. If Julie, you could give your perspective about that, that would be great.

Julie Kim (President, U.S. Business Unit)

Yes, thank you, Christophe.

In terms of the direct-to-consumer model that you have heard about in the news, this is an opportunity for the pharmaceutical companies to be able to offer their medicines on a platform, cutting out the middlemen in the U.S. This would allow us to go direct as the platform indicates. This would provide lower pricing directly to patients without necessarily impacting the pharmaceutical companies negatively. Because, as you are probably aware, on average, across the industry, roughly 50 cents of the dollar goes to other players in the value chain. The manufacturers currently receive on average $0.50 on the dollar. Being able to offer a significant discount on the list price through these platforms does give patients a direct benefit. It is also good from the manufacturer's standpoint as well.

Hidemaru Yamaguchi (Equity Research Analyst and Managing Director)

Julie, can you comment?

Still, just to manage expectation, our portfolio of product is not an easy one to apply DTC. Can you comment on that?

Sure. The key aspect of the DTC platforms that I should have mentioned is that this is cash paying for the patients. This is primarily more retail medicines. The current products like insulin are offered in this type of platform, as well as GLP-1, for example. Our portfolio is not necessarily this type of retail medicine, but we will look at opportunities for products such as Trintellix on this platform.

Thank you.

Operator (participant)

Thank you, Yamaguchi-san. Moving to the next question then. Next question, I'd like to call on Stephen Barker from Jefferies, please.

Steve Barker (Equity Analyst)

Yes, Steve Barker from Jefferies. Thanks for taking my questions. My first question is related to spending.

You are forecasting full-year SG&A flat year-on-year and a small increase in R&D, but both SG&A and R&D were both down substantially in the quarter. I was wondering if you'd comment on that and the outlook for spending. The second question is related to Erexin. As per the slide, you are looking for the new compound, which is scheduled to enter development this year. You're looking at indications like sleep-wake, respiration, metabolism. Sleep-wake, I think that's something related with Alzheimer's, respiration. Should we be thinking sleep-wake is, yeah, Alzheimer's, respiration, sleep apnea, perhaps, and then metabolism. Is that something? If you could comment on how Erexin might affect metabolism and if it could actually be useful in treating obesity. I'd like to comment on that too, please. Thank you.

Operator (participant)

Thank you, Steve, for your question.

The first question on trends of spending Q1 versus the full-year outlook, I'd like to ask Milano to comment on that. The second, on the new compounds in Erexin, looking at sleep-wake disorders. What potential exists in these areas, particularly obesity is an area of interest. I'd like to ask Andy to comment on that, please.

Milano Furuta (CFO)

Hi, Steve. Thank you for the question. Let me answer to the about SG&A first. This is mostly this decline compared to year-on-year in the last quarter one is for SG&A, it's more like FX. If you compare the constant exchange rate, it should be mostly flat. That's SG&A. So it's in line with the full-year forecast. For R&D, we do the invest for the pipeline developments. And still, we anticipate the R&D investment is ramping up. For example, now we start head study with Nadukra in July.

Alterrecept, also in July, we started the trial. For 360, also we started the trial in April. So we are ramping up all the activities. But still, it's a good thing is we also see the savings from the efficiency program we initiated last year. And then we are also keeping the very tight management of the head count, the cost, both sides. So that we see also the benefit from the older savings efforts. So that's how the Q1, the numbers, eventually landed. But eventually, we are still keeping the full-year forecast management guidance for both SG&A and R&D.

Steve Barker (Equity Analyst)

Thank you.

Andrew Plump (President, R&D)

Stephen, on your question regarding the breadth of potential of Erexin agonists across indications, I'll go back to the earlier comment that we're really just starting to scratch the surface of the potential of this biology.

We know now definitively that agonism of the Erexin 2 receptor and type 1 narcolepsy can have profound benefits and be administered in a way that's tolerable for patients. So now we're starting to imagine and develop molecules that have an array of pharmacology that will allow us to explore opportunities in other rare disorders like type 2 narcolepsy, like idiopathic hypersomnia, and then begin to explore opportunities in other disorders that are characterized by either sleep-wake cycle disruption because there's an obvious link there. Respiration, we've already shown and we've published with TAC-925, our IV molecule, that there are unique properties of this pathway in respiration. And based on extensive scientific literature and the expression patterns of the Erexin receptors and the hypothalamus, we believe that there are potential opportunities in metabolism. I don't want to get too far out ahead of ourselves.

Our goal is to develop the array of molecules that will allow us to explore this breadth of indications and to go from there. Understood. Thank you. Thank you, Steve.

Operator (participant)

Okay, moving on to the next question, I'd like to call on TD Cowan, Michael Nedelcovych. Please go ahead and ask your question.

Michael Nedelcovych (Director, Equity Research)

Hi, thank you for the questions. I have two. My first is on Entyvio. You've noted in the past that transitioning patients from Part B to Part D coverage has been a hurdle to adoption of the pen. Why should we expect that dynamic to fall away in the coming quarters? On the same topic, a competitor, IL-23, will likely soon offer subcutaneous induction and maintenance. How do you think that might change the competitive landscape, especially considering that the Entyvio pen seems to be helping to ward off competition? That's my first question on Entyvio.

My second question is on Zazositinib. In the head-to-head trial versus Ducravacitinib, can you remind us if it's powered for superiority? In that trial, if Zazositinib only shows non-inferiority, how would that affect your $3 billion-$6 billion peak sales ambition in psoriasis? Thank you.

Operator (participant)

Thank you, Mike. The first question on Entyvio, coverage and competition landscape, I'd like to ask Julie to comment on that. The second question on the head-to-head, is it powered for superiority? Andy, if you could take that one, please.

Julie Kim (President, U.S. Business Unit)

Hi, Michael. Thank you for the question. When you look at the dynamics in the U.S. around pen access, you are right. There have been challenges in terms of making the switch. We're working through the quality, I'll call it the quality of the access at the local level.

Sometimes this is a challenge of the coverage that's provided at the parent plan not being pulled all the way through to the local plan. Sometimes it's because of that switch from IV to pen, medical to pharmacy. Sometimes it's a system issue in helping, again, at the very local level, addressing those specific system issues. We're attacking all of these one by one. As we clear through them, we are seeing the pull-through on pen. This is why we believe that as we continue to improve the overall coverage level and that quality of the pull-through, we'll see the benefit from pen driving further growth, as we're seeing roughly 30% growth quarter over quarter on the pen. In terms of the second part of your question in regards to sub-Q induction, that is something that we are also looking at.

For right now, Entyvio still has very strong bionative starts within UC in particular. As we continue again to pull through on the access, we expect to see further growth for the pen.

Andrew Plump (President, R&D)

Michael, I'll start on Zazositinib and then hand it over to Christophe to talk about the competitive dynamics. So we're seeing great progress in our overall Zazositinib program, as I mentioned, on track to read out our two psoriasis phase three studies later this year. Our psoriatic arthritis program is going well. Two phase 2b studies in UC and Crohn's that will read out next year, starting now in HS. And then we have an additional indication, perhaps indications that we look forward to starting soon. Your question specifically on the head-to-head with Ducravacitinib, yes, this study is powered for superiority. And Christophe, I'll hand it back to you.

Christophe Weber (President and CEO)

Thank you, Andy, and thank you, Mike, for the question. Yeah, it's a head-to-head superiority because we are very confident, obviously, that the product profile will deliver this type of result. It is important because we want to demonstrate that Zazositinib is a new class of oral which changed the efficacy profile of the oral treatment. Overall, today, the oral treatment has around 16% market share, and it has not been growing. We believe that our compound, Zazositinib, perhaps also with another compound of another class in development in oral, you know what I'm talking about, will change that. We believe that that's the promise of this new oral, is to really change the importance or the contribution of oral treatment to the treatment of psoriasis. This head-to-head is important to really create a new oral standard in terms of efficacy.

Of course, we will also use the phase three result.

Michael Nedelcovych (Director, Equity Research)

Thank you.

Operator (participant)

Great. Thank you, Mike.

それでは次のご質問は。

Christopher David O'Reilly (Head of Investor Relations)

Moving on to the next question.

野村証券の。 野村セキュリティーズ、松原さん。 よろしくお願いいたします。

Please ask your question.

はい、野村証券の松原と申します。

Hiroyuki Matsubara (Analyst)

Yes, this is Matsubara. 野村セキュリティーズ,

can you hear me okay?

Christopher David O'Reilly (Head of Investor Relations)

Yes, we can hear you. お集まりいただきありがとうございます。

Hiroyuki Matsubara (Analyst)

Thank you for the presentation. 最初はまず一つ目、先ほどのコメント。 My first question is related to an earlier comment. First quarter growth. First quarter numbers doesn't necessarily represent the overall growth dynamics. If you look at the sales in the U.S., it looks quite weak. I want to understand why. That's my first question. The second question is about Takhzyro. Again, Takhzyro is weak in the United States. What is the reason behind this? Also, Ionis, donidalorsen is going to be launched very soon. This is going to be a competition for new patients. Should we have some concern for this product in the future?

Operator (participant)

Thank you, Matsubara-san. The first question on the U.S. revenue performance in Q1 and what some of the dynamics there are. Then the second question on Takhzyro specifically. I'd like to ask Julie to comment on those, please.

Julie Kim (President, U.S. Business Unit)

Hi, thank you, Matsubara-san, for the question. One of the things to please remember in terms of the US performance is that you're also seeing reflected in these numbers the impact of the Medicare Part D redesign across key products in our portfolio. That is part of the impact on the growth. In regards to Takhzyro in particular, Takhzyro continues to have strong performance in the US. Yes, there are new competitors coming onto the market. In terms of efficacy, there is really not a significant change in efficacy from those competitor products.

When you look at the long-term history that we have, both in terms of performance and safety, and you look at the real-world data that we've collected on Takhzyro since its launch, we are in a very strong position to defend Takhzyro in HAE. ありがとうございます。 松原さん、一言。 ですけれども。 This is Furuta speaking. I would like to add just one comment. 基本的に製品のダイナミクスについて。 In the United States, Christophe and Julie have just already mentioned the product dynamics. I don't have any additional thing to say about the overall situation. Everything that we have explained so far is US-focused, including Vyvanse. Vyvanse's impact is the biggest in the US, and this is why the US numbers, the performance, looks a little bit softer. As far as Takhzyro is concerned, demand continues to be strong, but the channel inventory is now lower. That's another factor behind the weak performance of Takhzyro.

Hiroyuki Matsubara (Analyst)

Understood. Thank you.

Christopher David O'Reilly (Head of Investor Relations)

はい、ありがとうございました。 Thank you. 次はJPモルガンです。 Next question is Wakao-san. J.P. Morgan, please.

はい。 JPモルガン、Wakaoです。

J.P. Morgan, Wakao.

Seiji Wakao (Senior Analyst)

I have a question about R&D expense. R&D expense represents only 90% progression to the full-year guidance, which seems to be slow. Is this in line with the plan, or have there been any suppression for spending? Based on the first quarter progress, do you foresee any change to your full-year R&D expense outlook? Whether TAK-861 overall extent, phase three study now completed, there also does not seem to be a factor that will drive an increase in this fiscal year. This is your first question. The second question is about MFN. You briefly mentioned the US policy, but I'd like to know more about most favored nation drug pricing policy. Are you currently in discussion with the US government on MFN? Have you received any indication of targeting pricing? That's it.

Operator (participant)

Thank you, Wakao-san. The first question on R&D expense progress towards the full-year guidance, is this in line with plan? Milano can comment on that. The second question on discussions around most favored nation. I'd like to ask Julie to comment on that, please.

Milano Furuta (CFO)

Thank you, Wakao-san. I'm going to comment on the first R&D. Spend in Q1. If you compare against last year's Q1, there are multiple effects. Sorry, I think to Steve's question previously, I explained as a kind of efficiency program as a whole, but there's a bit detailed explanation I can add. Comparing to last year, we had a few program terminations, like Sotheby's Lestat or 062. These program terminations create some space for the budget. That's one. The second, we had some pipeline financing arrangement with Blackstone. That also helps for the R&D savings.

The third one is something I mentioned previously, that we are continuing for the efficiency program efforts. We managed the overall budget. Everything is very tight. That's also creating the savings space. If you recall our explanation at the Q4, we are making all these savings, and then we will reinvest those savings for the pipeline development. That's going to happen. From July, we are starting the phase three for the Delta Recept, head-to-head study with Dukra. This will ramp up, and then we will increase. We will ramp up all these R&D operations. Eventually, all in all, we are in line with the plan.

Seiji Wakao (Senior Analyst)

Could you clarify first quarter performance? Was in line with your internal plan or below?

Milano Furuta (CFO)

Yes, we are making savings, but overall, we are in line with the plan.

Seiji Wakao (Senior Analyst)

Okay, thank you.

Julie Kim (President, U.S. Business Unit)

Thank you, Wakao-san.

In terms of MFN discussions in the U.S., there have been numerous different statements about MFN, both from the president as well as others in the administration at a high level. Details have not really been shared yet at this point. We have not been contacted directly in terms of price negotiations at this point. We are gearing up and preparing for the potential negotiation of Entyvio as part of the IRA Medicare price negotiations. Now, MFN in general, there are a basket of countries that are being considered, we think. We are assessing what the potential impact of that could be, depending on a variety of different scenarios for how MFN can be applied. We're working on our own mitigation plans for that. We're preparing, as I said, for the price negotiations as part of the IRA Medicare price negotiations.

That is a place where the MFN type of approach could be applied, but we're waiting to see further details.

Seiji Wakao (Senior Analyst)

Yeah, thank you.

ありがとうございました。

Christopher David O'Reilly (Head of Investor Relations)

Thank you very much.

それでは、お時間の都合もございますので、次のご質問を最後とさせていただきたいと思います。

Due to time limitations, the next question will be the last question.

ご質問は、ゴールドマンサックスの上田さん。

Please unmute yourself and ask your questions. ゴールドマンサックス初見の上田でございます。

Yes, this is Ueda Goldman Sachs.

こちらからオベプロックスの。 上市に向けた準備について教えていただきたいと思います。

I want to ask a question about the preparation for the launch of Oveporexton. First-in-class and best-in-class potentials were mentioned today. What about the sales team? What other preparations are underway for the launch of Oveporexton? Because you're focusing on NT1, I think diagnostics is very important. Last year, in our R&D day, you talked about the use of digital technology potentially. I want to understand how this technology is being prepared leading up to the launch. Thank you.

Operator (participant)

Thank you for the question, Ueda-san.

Andrew Plump (President, R&D)

A question on how we are preparing for the launch of Oveporexton. What are the approaches we're taking, including use of digital, etc.? I'd like to call upon Julie to answer that question, please.

Julie Kim (President, U.S. Business Unit)

Yes, thank you for the question, Ueda-san. As you can imagine, we are very excited to be preparing for the potential launch of Oveporexton for narcolepsy type 1 patients. We are gearing up in terms of our commercial structure and organization, as well as our medical team, which is already out in the field educating on Oveporexton in narcolepsy type 1. In terms of the digital support for Oveporexton, we are looking at a number of different avenues and approaches to support, particularly diagnosis in narcolepsy type 1. This is an area where we are looking to unlock the bottleneck that exists in terms of diagnosis through sleep centers.

We will share more detail once we're able to do so. This is quite an exciting opportunity for us. As I said, we're looking at multiple digital avenues to support diagnosis and the overall patient experience.

どうもありがとうございます。私から以上でございます。

Christopher David O'Reilly (Head of Investor Relations)

Thank you very much. That's all the questions I have. ありがとうございました。最後にフルタから。 Thank you. 追加のコメントがありますか。 Additional comment from Furuta-san? よろしくお願いします。 すいません、Wakao-san。ちょっとR&Dの。

Julie Kim (President, U.S. Business Unit)

Yes, Mr. Wakao. Q1 R&D spend, I just wanted to add some comment because there may have been some inaccuracies in what I said earlier. Q1, we had savings. Your question was whether this was according to our internal plan. I have to say that the savings actually were bigger than what we had planned for. R&D delivery implementation is according to plan. Saving is not impairing delivery of R&D.

We are really enjoying the benefit of the efficiency programs in the past, which means that it is possible that savings may be a little bit higher than we planned. ありがとうございました。これをもちまして、本日のウェビナーを終了させていただきます。

Christopher David O'Reilly (Head of Investor Relations)

Thank you very much. With that, we would like to conclude today's webinar. We would like to thank you all again for being a part of this program despite a very busy schedule. We appreciate your kind continued support.