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

Welcome to Takeda's ASCO IR event. We'll be discussing the rusfertide Phase III data today. This is Elizabeth from the IR team. Before we start, please ensure that you select your desired translation choice using the globe at the bottom of the screen. If you'd like Japanese, choose Japanese. If you'd like English, choose English. And if you'd like to listen to the original language, you can select off. Before starting, I'd like to remind everyone that we will be discussing forward-looking statements within the meeting -- meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those discussed today. The factors that could cause our actual results to differ materially are discussed in our recent Form 20-F and other SEC filings. Please refer to the important notice on Page 2 of the presentation. So today, we have an exciting topic of rusfertide, and joining us, we have P.K. Morrow, Head of the Oncology Therapeutic area; and Teresa Bitetti, President of Global Oncology Business Unit. And we're excited to jump in. So P.K., why don't I turn it over to you?

Thank you so much, Elizabeth. It is an honor to present practice-changing data from the VERIFY trial, a placebo-controlled trial, which evaluated the efficacy and the safety of rusfertide, a first-in-class hepcidin mimetic as an add-on therapy to standard of care therapy. As an oncologist who has treated patients with PV, I am delighted to share this data with the patients who have suffered from this disease, the caregivers who supported them, the physicians who have battled this myeloid cancer in this oncology community. Rusfertide met the prespecified primary end point in all 4 key secondary endpoints. These results were both statistically significant and clinically meaningful, including improvements in several patient-reported outcomes, addressing key symptoms that plague patients with PV such as severe, sometimes debilitating fatigue. In addition to rusfertide's positive impact on patient-reported outcomes, its safety profile was very manageable and as anticipated from earlier studies. As a result, based upon the outstanding pivotal Phase III VERIFY study, we are advancing the regulatory filing for rusfertide in the United States in the second half of fiscal year 2025 with our partner Protagonist. Next slide. Polycythemia vera is a myeloproliferative neoplasm, which is driven by a mutation in the JAK2 gene, leading to the overproduction of red blood cells. This increase in red blood cell production leads to higher blood viscosity, which can cause a cascade of complications, increasing the likelihood of thrombosis and risk of cardiovascular events. In addition, many patients with PV suffer from intolerable itching, headaches, bone pain and many other symptoms related to increased mast cell activation and hyperviscosity. As a result, the current goal of treatment is to maintain the hematocrit, which is the percent of red blood cells in the blood, less than 45% to minimize the risk of thromboembolic events. This goal was reinforced by data published in the New England Journal of Medicine, which demonstrated that uncontrolled hematocrit is associated with a 4x higher risk of death from cardiovascular causes or thrombotic events like stroke, deep venous thrombosis and pulmonary embolism. To control hematocrit levels, therapeutic phlebotomy is commonly used. However, frequent phlebotomy can be very burdensome for patients as it removes iron stores, worsening iron deficiency and exacerbating symptom burden, such as fatigue. It can also not always be counted on to adequately maintain a stable hematocrit. Next slide. Rusfertide is a synthetic peptide mimetic of hepcidin. It's a first-in-class therapy that is designed to address the overproduction of red blood cells. As shown in these images, ferroportin is a transmembrane channel that is responsible for exporting iron from the small intestine, from the liver and from the spleen into the bloodstream. Rusfertide acts like hepcidin. It binds the ferroportin, triggering internalization and degradation of this iron channel, thereby reducing iron export and lowering the production of red blood cells, which require iron. Thus, rusfertide can restore iron homeostasis and reduce red blood cell production. Its first-in-class mechanism of action is potentially transformative for PV patients, offering a rapid onset of action, sustained stabilization of hematocrit below 45% and normalization of iron homeostasis. Next slide. Rusfertide has been evaluated in 2 well-controlled clinical studies, the Phase II REVIVE and the Phase III VERIFY trials. The strength of the efficacy of rusfertide were administered on top of standard of care therapy for PV was shown to be highly consistent across multiple measures of efficacy in both studies. Next slide. In the VERIFY Part Ia trial, patients requiring frequent phlebotomies with or without stable cytoreductive therapy to control hematocrit were randomized 1:1 to receive once weekly rusfertide or placebo. Patients stayed on their concurrent therapy, whether it was phlebotomy, cytoreductive therapy or both, and they were stratified by their concurrent PV therapy. All patients completing Part Ia were then eligible to receive open-label rusfertide in Part Ib from weeks 32 to 52. Patients who then completed Part Ib were eligible to continue receiving rusfertide in Part II, which is an open label, long-term, safety assessment period. In VERIFY, all patients were required to undergo phlebotomy to have a hematocrit less than 45%. This threshold was defined to establish a uniform baseline disease burden to facilitate comparison between rusfertide and the placebo groups through week 32. Next slide. The primary endpoint was the proportion of patients achieving a clinical response, which is the absence of phlebotomy eligibility, which was defined as having a hematocrit greater than or equal to 45% and 3% or higher than baseline or a hematocrit greater than or equal to 48%. Key secondary end points, which were measured from weeks 0 to 32, included mean number of phlebotomies, proportion of patients with hematocrit less than 45% and the mean change from baseline at end of Part Ia in week 32 in the PROMIS Fatigue Short Form 8a Total T-Score and the Myelofibrosis SAF Total Symptom Score. Next slide. Baseline disease characteristics were very well balanced in terms of key subject characteristics and treatment histories between rusfertide and placebo arms. Overall, the main duration of polycythemia vera was just under 5 years before study entry. A total of 46.4% of subjects were categorized as having high-risk disease with age of greater than or equal to 60 years being the most common reason for high-risk designation. Median age was 57 years, and most patients were male. You can see the highlight, which demonstrates that the baseline phlebotomy rate in the trial population, was an average of 4 therapeutic phlebotomies. The only imbalance that was reflected in the fact that a larger proportion of patients who had required 7 or more therapeutic phlebotomies were randomized to the rusfertide arm, emphasizing the potential for the patients randomized in that arm to have a slightly higher disease burden. Next slide. At baseline, just over half of the patients receive cytoreductive therapy. Hydroxyurea was the most commonly used cytoreductive therapy and those who are on concurrent therapy, with interferons and JAK inhibitors completing this list. Next slide. The VERIFY trial met its primary end point with significantly more responders in the rusfertide arm than the placebo arm. Specifically, close to 77% of patients responded in the rusfertide arm compared to 33% in the placebo arm within this intent-to-treat population. A responder was a subject who is not phlebotomy eligible, as noted previously. Next slide. In addition, across all subgroups, as noted, including gender, race, region, PV risk with ongoing therapy at phlebotomy rate, the clinical response observed in the rusfertide arm was consistent, reinforcing the robust efficacy of rusfertide across all subgroups of polycythemia vera. Next slide. In Part Ia, there were significantly fewer phlebotomies from week 0 to week 32 in the rusfertide arm. Specifically, if you look at the right side of the slide, it has demonstrated that 73% of patients in the rusfertide arm required no phlebotomies at all during Part Ia, demonstrating the ability of rusfertide to induce durable and robust hematocrit control. Next slide. In VERIFY, all patients needed a phlebotomy to get their hematocrit below 45. So everyone in the rusfertide and placebo groups started at roughly the same hematocrit, less than 45. The placebo arm subsequently demonstrated mean increases in hematocrit from baseline, whereas the mean hematocrit in the rusfertide arm remain at or below baseline levels. As you can see from the slight lavender line in the graph, patients in the placebo group were able to achieve rapid hematocrit control without needing phlebotomy after initiating rusfertide at week 32, once again reinforcing the rapid onset of hematocrit control after rusfertide initiation. Next slide. In the setting of polycythemia vera, patients report having significant fatigue, which can be extremely debilitating. In VERIFY, we used a validated PROMIS Fatigue Short-Form 8a PRO instrument because it's a standard approach to measure how much fatigue affects patients. This short-form contains 8 questions that ask about fatigue. Data was collected every 4 weeks at the beginning of the study, followed by every 8 weeks in Part II. In VERIFY, as you can see here, there was a statistically significant improvement in the PROMIS Fatigue instrument with rusfertide versus placebo at week 32 during the end of Part Ia. This improvement is not only statistically significant, but clinically meaningful to patients, offering them the potential to take a therapy that not only helps symptom control of hematocrit but also can reduce their fatigue. Next slide. The MFSAF, or the Myelofibrosis Symptom Assessment Form, contains questions about 7 individual symptoms, including fatigue, night sweats, itching, abdominal discomfort, pain, early satiety and bone pain. The MFSAF is scored between 0 and 10. The total symptom score was scored out of 70, and the MFSAF data was collected daily. These results demonstrate that rusfertide leads to a statistically significant and clinically impactful improvement in both PROs for patients suffering from polycythemia vera. Next slide. Treatment-emergent adverse events were comparable between treatment arms with 86.3% in the placebo arm and 89% in the rusfertide arm. Most events were Grade 1 or 2, and the most common treatment-emergent adverse events in both treatment arms were infusion site reactions. All of these reactions were Grade 1 or Grade 2. Symptoms associated with PV, including fatigue, headache and itching, were also commonly reported with comparable rates in both arms. Anemia, which is known to be associated with the mechanism of action for rusfertide due to reduction of red blood cells, was seen in the rusfertide arm with a Grade of 1 or 2. And finally, serious adverse events were comparable between treatment arms and slightly lower in the rusfertide arm. There were no treatment-related serious adverse events and no Grade 5 events. Next slide. Polycythemia vera is a myeloid cancer that is also associated with increased risk of developing other cancers, particularly skin malignancies. It's not clear whether this risk is due to the etiology of the disease itself, prior therapies or a combination of factors. Given this risk, we instituted screening exams and identified 10 skin malignancies, including 1 malignant melanoma even prior to randomization. Cancer events occurred in a total of 8 patients in the trial. That included 7 patients in the placebo arm and only 1 in the rusfertide arm, reinforcing the robust safety profile of rusfertide. The patient on the rusfertide arm who experienced a nonserious event of Grade 2 squamous cell carcinoma of the skin had a prior history of cancer and prior cytoreductive therapy exposure. This patient is continuing to receive treatment with rusfertide at the time of data cutoff. There was 1 acute myocardial infarction that occurred approximately 2 to 3 weeks after treatment initiation in a patient with comorbidities, predisposing them to cardiovascular complications. This myocardial infarction was found to be unrelated to rusfertide. Next slide. In conclusion, in the Phase III VERIFY trial, rusfertide met its primary endpoint in all 4 key secondary endpoints. Rusfertide significantly improved hematocrit control, reduced the risk of thromboembolic complications and resulted in meaningful improvements in patient reported outcomes. The strength of the efficacy of rusfertide for PV is reflected not only in its ability to make statistically significant and clinically meaningful improvements in all trial endpoints but also the highly consistent results across all subgroups. Taken together, rusfertide's robust efficacy, tolerable safety profile and ability to induce rapid, predictable and sustained hematocrit control make it a meaningful and a potentially practice-changing option for patients with PV. And in fact, following today's plenary session at the American Society of Clinical Oncology Annual Meeting, the rusfertide data was reviewed and the plenary discussant and expert in myeloproliferative neoplasms proactively noted that the VERIFY study is practice changing, and she recommended that rusfertide become part of standard of care for patients. And with that, I'm delighted to transition to Teresa Bitetti, President of Oncology Business Unit.

Awesome. Thank you, P.K. Well, rusfertide is a prime example of how we're focusing our business development search on partners with promising late-stage assets that complement our research expertise and our global commercial capabilities. Rusfertide also fits nicely into our broader strategic focus on heme malignancies and specifically myeloid cancers in addition to thoracic and GI cancers. Next slide. So I want to start by talking a bit about the PV patient journey. Patients are typically diagnosed between the ages of 50 and 70, but it can occur at any age. The diagnosis happens when a blood test returns an abnormal hematocrit or after a thrombotic or cardiovascular event where high levels of hematocrit are identified, leading to a diagnosis of PV. And as a reminder, the primary treatment goal in PV is to maintain hematocrit levels below 45%. These hematocrit levels above 45% are associated with a 4x higher rate of death from cardiovascular or thrombotic events. To quickly reduce the hematocrit, PV patients typically receive phlebotomies as their first treatment within days of diagnosis. Now phlebotomy is a rather crude method, which is simply taking out the blood. And we also know that it is insufficient in maintaining a durable effect, as the patient's hematocrit levels continue to roller coaster. When phlebotomy alone becomes intolerable or too frequent, HCPs will switch to or add on hydroxyurea and/or other cytoreductive therapies. And of course, these bring additional and sometimes new side effects and safety concerns. Current therapies also come with a significant treatment burden on top of the existing symptom burden from the disease itself. Additionally, they are suboptimal in achieving rapid, consistent and durable hematocrit control. So a new treatment option that consistently controls hematocrit without requiring significant trade-offs between treatment and disease burden is needed. With rusfertide, we have the opportunity to elevate the standard of care for patients with PV by delivering a new option that is specifically designed to target hematocrit levels and keep them below 45%, which is the primary treatment goal in PV. Next slide. I'll now touch on the current PV treatment landscape and the opportunity that exists. Approximately 155,000 patients in the U.S. have been diagnosed with PV, with about 78,000 currently being treated. The unmet need remains because despite being on treatment, 3/4 of the treated population still has uncontrolled hematocrit. For these patients, rusfertide has the potential to disrupt the treatment paradigm by: first, addressing the primary treatment goal of PV, which is controlling hematocrit, so that it remains under 45%; second, providing rapid, consistent and durable hematocrit control as a monotherapy or in combination with existing agents. And third, offering patients an option that's well tolerated and has a favorable safety profile. Based on this differentiated profile, we currently estimate rusfertide has a market potential between $1 billion to $2 billion in peak sales. To realize this potential, we're focused on driving awareness of unmet needs and ensuring HCPs understand the clinical benefits of rusfertide, ensuring patients have access at launch, and leveraging the synergies and the expertise within our current heme portfolio and team. Next slide. We're confident that we're well positioned to deliver on the full potential of this important medicine, and there's many reasons why. I'll parse it into 4 buckets. The first is maintaining consistency in hematocrit levels. We saw this clearly demonstrated in the Phase III VERIFY trial, where 63% of rusfertide patients maintained hematocrit levels of less than 45% compared with just 14% on placebo plus current standard of care. The second is reducing the burden of phlebotomies. As a reminder, phlebotomies intentionally induce iron deficiency and exacerbate the underlying symptoms of PV, not to mention the hours spent in clinic and the physical toll of repeated phlebotomies. In the Phase III trial, 77% of rusfertide treated patients were no longer eligible for phlebotomy as a primary endpoint, which is a statistically and clinically meaningful difference. The third is reducing symptom burden. Patients often suffer from brain fog, weakness, itching and, most commonly, extreme fatigue. We know that patients end up spending days in bed, significantly impacting their ability to perform daily activities. And last is the fact that rusfertide can be used alone or in combination with existing therapy. Next slide. So to recap, this is a relatively large market where we know that 3/4 of the treated population have uncontrolled hematocrit. And the gold standard in PV is maintaining hematocrit below 45%. Because when it goes above, patients have a 4x higher risk of death from cardiovascular causes or thrombotic events. We have a transformative therapy here, and we're excited about the positive impact it will have for patients and about providing physicians with a truly viable option for meeting treatment goals. So we're looking forward to unlocking rusfertide's full potential and redefining the treatment paradigm in PV. So thank you.

First question will come from Shinichiro Muraoka-san from Morgan Stanley.

[Interpreted] This is Muraoka from Morgan Stanley. I will ask my question in Japanese.

Yes, please. Go ahead.

[Interpreted] First of all, about safety. So this time, you have evaluated until week 32. And after that, have you had any safety positive or negative signals? That is my first question. And my second question, by the way, about skin malignancy risk. Is there any background for that risk to have been lowered? So I would like to know about that in relation to my first one. And the second one about competition. Ionis' monthly subcutaneous, how do you see this as a mid- to long-term competition? So those 2 questions, please.

Thank you. I'll take the first 2, if that's okay. So the first question you had was related to any new safety signals following week 32. We have seen no new signals since then. And the rusfertide safety profile remains stable and consistent with our experience in both the REVIVE and particularly in the VERIFY study through Part Ia. And the second question you had was the risk of skin cancer. As you alluded to, patients with polycythemia vera have an increased risk of skin cancer. The benefit of being on the trial has been the fact that we instituted more proactive skin cancer screening. And as noted previously, we're actually able to detect skin cancers prior to patients even being randomized onto the study. We will plan to continue to recommend skin cancer screenings in order to be able to detect skin cancers early on because we know that is part of the paradigm of the disease. I'll turn it Teresa.

Yes, I'll take that. The question was around the mid- to long-term competition as well as the subcu dosing. So when we look at the competition, I'd remind you that what's exciting about rusfertide is that it is the first time in a long time that we have a new mechanism of action that is specifically designed to target hematocrit, which -- the gold standard of treatment here is maintaining control of your hematocrit below 45%. And rusfertide can do that in a rapid, consistent and durable way, and that's not something that's possible with treatment that's available today. As far as the subcu goes, it is a weekly dosing. We know from research that patients are more comfortable with the self-injection, and they actually are quite willing to make a trade-off if they don't have to leave their home for the therapy. So of course, we'll educate and train on that. But the subcu, we don't anticipate being a significant hurdle for the launch. Thank you.

Next question will come from Tony Ren at Macquarie.

Can you hear me?

Yes, we can.

Obviously, congratulations. Was at the plenary session earlier today. And the discussant, as PK said, was very, very enthusiastic. So highly recommending the regimen. So definitely, congratulations for the plenary spot -- plenary session spot. I have a question on the likely commercialization arrangement with Protagonist. I was reading their slides from February, and they mentioned that they possibly have an agreement to opt in commercialization co-promotion in the U.S. Have they indicated to you how they would like to go about commercializing it in the U.S.?

So I'll take that question. Thank you, Tony. Protagonist does have the right to opt in for a profit share as well as co-commercialization. And so -- but they don't need to exercise that option until post the NDA filing in a 7-month window. So they still have time to assess what they'd like to do.

Okay. So just looking at these 2 options, Teresa. So the first option is 14% to 29% on global net sales, right? The second one is 50-50 U.S. profit share plus 10% to 17% ex U.S. net. So what sorts of assumptions did you put in when you put these 2 options in front of them, in terms of like, say, peak sales, operating profit margin?

Yes. As we -- as -- our forecast for rusfertide is in the $1 billion to $2 billion range for peak sales. And as we've calculated that revenue range, we have looked at the market as it exists today and the fact that 75% of those patients are uncontrolled. And so our focus at launch and what would go into that revenue estimate is targeting those patients being able to be used as a monotherapy or as an add-on. We also know that physicians -- while this is a very prevalent market, physicians are hesitant sometimes to switch, and so we know that incidence is less likely. It's a smaller portion of the overall market. And so these were the factors that went into our forecast and, hence, into the profit share thinking in the contract.

Okay. Just on top of switching my last question. Where -- from which drugs do you think they will switch from hydroxyurea, Jakafi or BESREMi?

Tony, it's a good question because I think that we have utility across the entire treatment continuum. And so as what you typically see in most launches, physicians will likely use it on their most uncontrolled patients. And then once they see the benefit, they will then begin to use it in other places and in other combinations. And so I think it will be across the board where physicians will choose to try it first and then extend the use.

The nice thing is it's not instead of, but it can be in addition to, which gives great flexibility to patients and to the physicians.

Our next question comes from Citi, Hidemaru Yamaguchi.

Can you hear me?

Yes.

Yes.

So this is Yamaguchi from Citi. I have 2 questions. The first question is kind of related to Tony Ren's question, but there is a discussion at the conference that they are just add-on therapy to the current one? Or is it a monotherapy? And because the trial set to reduce the phlebotomy rather than other treatment are still ongoing. So in the future, is there any way to show that you don't need other cytoreductive drug rather than this one?

Let me take that one, if it's okay. So as you probably saw -- thank you for the question. You probably saw that around 50% of the patients actually weren't taking any concurrent therapy. They were using phlebotomy as the primary mechanism of reducing hematocrit. So we think there is -- this is a great opportunity, as you're alluding to, for us to fit that critical unmet need because it implies if you have approximately 50% or actually higher than 50% of patients not taking these therapies that they want -- they're looking for, right, a better therapy to maintain their hematocrit and keep it controlled.

Right. And the second question regarding to that, that also, today, there was a discussion about the -- how the phlebotomy itself is the burden for the patient which I understand -- which I would think about is everybody's kind of a common knowledge, but the comment was really stressing that point. So I feel like there is a kind of a gap or perception gap between doctors and the patients about the burden of phlebotomy. So is it the right way to understand? Is there some gap, you have to fill the gap through marketing or not really?

I'll take a stab at that. I mean, I think, that, right now, physicians are limited in the options that they can offer a patient. And the quickest thing they could do right now is the phlebotomy, which will control on a very short-term basis. But patients don't like it because it's at least 4 hours. It's a very painful procedure, actually. It has been harder to do. So I think that there's a willingness on the part of both physicians and patients for a new therapy like rusfertide that we know is rapid, we know it's consistent, we know it's durable and it has a tolerable safety profile, but then will make it easier for these patients to sort of have the quality of life. And as P.K. talked about, extreme fatigue is something that plagues these patients. And so when we've seen the profile with the PROMIS instrument, it really is clinically meaningful. And so I think it's really more because nothing else has been available.

Our next question comes from UBS, Fumiyoshi Sakai.

This is Sakai from UBS. Two questions. The simple one, your commercialization, $1 billion to $2 billion peak sales. You said this is estimate, but estimate is estimate. But still, you have a gap, $1 billion gap. Where this gap should come from? Is there more patient coming in for treatment, what -- you're going to find more patients in the market after you said that the patient awareness or even physicians awareness is a very important key factor to optimize this market? So that's my first question.

So I'll take that then. So the range in the forecast, the way that we have looked at this range is focusing only on uncontrolled population. So you're looking at 75% of the treated population. And we know that PV is, what we would consider, a prevalence market. So there's a large pool of patients that are there. The incidence is relatively small, incidents being the number of new patients that are identified each year. So in a prevalent patient population like this, you tend to see adoption play out over a longer time frame because physicians, in particular, in this market, where there really hasn't been new treatment, they're entrenched in the way that they treat. And so they will avoid switching until there's sort of an event or the patient is really out of control as opposed to if you had a really high incidence market where events are happening and patients are moving quickly and switching therapy. So that's another factor that we took into account. And so the longer-range adoption that could happen. And then also looking at access, the dynamics of the current market, which would have some suppression on it. And then, as well, you look at that in terms of the fact that we can be add-on and we can also be monotherapy. We're looking predominantly in the U.S. market, but we are exploring options outside of the U.S. And it is those factors and the variability in those factors that lead to that range. Thank you for the question.

Just one more question. Rusfertide seems to be a good drug, but this is no cure yet. And how long do you think the patient is going to stay on the medication after the patient likely develop the symptom, after 50, 60 years? So what's your current guesstimate for length of treatment?

Well, I agree. I don't think I have a specific estimate, but I would say that we think that this is potentially a very tolerable therapy. And because of the fact that patients are actually improving in terms of their symptomatology, they're going to be very more motivated actually to stay on this therapy. So this is what we found is that as patients are staying on this and they're feeling their fatigue improved, they're feeling these symptoms like itching, bone pain improved, and that's been documented both clinically as well as through our validated instruments, they are much more motivated to stay on this therapy. And it is a therapy that's able to be administered, as you probably heard from the discussant and now from us at home. So this is something that can be administered by themselves. So it doesn't require, unlike phlebotomy and other medications and therapies, to be -- for them to come to the hospital for in-hospital or in-clinic administration.

You're saying a reasonable length of time to the treatment.

Yes, yes. We think that this is something that they can reasonably take for a period of potentially even up to years.

All right. Just one more follow-up, right? So this is -- I mean, to add more value to the product, do you think that you're going to have the -- some sort of the Phase IV kind of trial, event prevention, patient quality of life as a kind of challenge could be possible?

We're definitely thinking through all of those elements. We welcome those thoughts. And to be frank, we've had investigators and PV experts ask us the same thing because of the fact that this is such a promising therapy.

Our next question comes from Pathology Associates, Dion Büchner.

Can you hear me?

Yes, we can.

Fantastic. I just had a quick question. I just noted the difference in the control arm versus -- the rusfertide versus the placebo in terms of thrombocytosis. Do you have any comments on that? And is it something that concerns you?

No, we don't. What we learned, or at least the investigators noted to us, is that sometimes for the patients who initially go on to rusfertide, the initial first few days to weeks may be associated with a slight increase in the platelet count. Then it actually comes back down and stabilizes. So -- and we haven't seen any clinical events related to an increase in platelets.

Dion, is that okay?

Yes.

Our next question comes from JPMorgan, Seiji Wakao.

[Interpreted] This is Wakao from JPMorgan. I have one question. As [indiscernible] is going to be used in the clinical practice, are there any additional monitoring needed? What is your assumption?

I'll start, maybe. So it will be -- we don't intend -- obviously, we'll have further discussions with the agency. But at this time, the way that we conducted this trial was very consistent with real-world practice for the most part. So we would be -- the hematologist will be monitoring per their own practice. The only element which actually the investigators noted was beneficial was the fact that we did recommend more regular skin screenings, which enabled earlier detection of skin cancers as part of the disease.

It is now 7:45 Eastern Time. We will now end the session. Thank you, everybody, for attending, and thank you for all the great questions. Thank you, and have a good night.

Thank you. [Portions of this transcript that are marked [Interpreted] were spoken by an interpreter present on the live call.]