Let me start with my question about capital allocation. In your presentation, you emphasized your long commitment to long-term growth and shareholder returns. We understand also from this that there has been no change in your capital allocation policy. However, since the amount of the Nimbus deal is larger at $4 billion, so please explain once again whether there will be any change in your capital allocation policy. I understand that your capital allocation is investment in growth drivers, deleveraging rapidly, and shareholder returns.
Thank you. Costa, do you want? Costa is our CFO.
Yes, thank you very much for the question. Absolutely, from a deleveraging, we're very encouraged with the speed of the way we've deleveraged. From the time that we completed the Shire acquisition, our net debt-to-adjusted EBITDA ratio was 5x , and as of the first half of this fiscal year, it's down to 2.6x . So the capital allocation policy around deleveraging rapidly is being achieved, and we anticipate to get down to low 2x , low to mid 2x this fiscal year. That's despite the acquisition of the $4 billion upfront for Nimbus, which, the majority is coming through, cash. So cash on hand, given the strong and abundant cash flow we've been able to deliver.
Having said that, we are very much committed to growth, investing for growth, growth drivers, in particular investing in new product launches, investing in R&D, both in-house and partnerships, investing in PDT, so we expect to see an acceleration of top-line revenue growth, and then with the abundant cash flow we're experiencing, we expect to also have more opportunities to enhance our shareholder returns in the future, so overall, the capital allocation policy is, we're still very much committed to that, but the deleveraging, we've already, we're tracking ahead of plan, and that gives us the ability to continue to invest in growth drivers.
Okay, thank you. So I take a question from audience. Any questions? Okay, so next question about the new vaccine, QDENGA. So, please comment on the current marketing and manufacturing capacity readiness. And also, you have set your peak sales at $0.7 billion-$1.6 billion. Do you think you can aim for higher sales than these peak sales, because QDENGA was approved for broad labelling, regardless of prior exposure?
Yeah, so our peak sales at the moment for QDENGA is first it's quite broad $700 million-$1.5 billion. So it's a difficult product to forecast frankly. But the label that we got with the age group from four years old above all serotypes regardless of prior exposure is it's what we were aiming for but it's the best we could get. So you know I'm very excited to launch this product. We are actually in the process of expanding our manufacturing capacity because we believe that the demand could be very strong and we will see where we get from there. You know with the vaccines it's. There is a private market but there is also a public market. So when the public will kick off and how it will happen we have to see that.
But I think we are really excited about the launch of this product.
Okay, thank you. So any questions from audience? Okay, so you have presented some update on some products. So first, you have TAK-861, the orexin. So I'd like more color on the phase I result in terms of safety or efficacy, because you decided to start phase II-B.
Yeah, so we're, of course, really excited about the fact that we have a go decision to phase II-B. And as we've said, this is our orexin agonists for narcolepsy and other related sleep-wake cycle disorders. We've accelerated 861 following the news of and discontinuation of 994. We've been running a phase I-B study, which has been a one-month study in type one narcolepsy patients, relatively few patients. And then at risk, we've been planning to start the phase II-B study, as Christophe mentioned. We understand this mechanism quite well, and we were quite enthusiastic about the profile of 861. But there were a couple of key questions that we needed to answer around safety, around dose.
We wanted to make sure that the dose was relatively low, given the potential for drug-induced liver injury that this class has demonstrated, and of course, efficacy. So we set preset criteria that were go criteria. We're not going to share those criteria today, but they're in line with the criteria that we've presented previously for 994. You know, as Christophe mentioned, we have sites activated, and we're very excited to get this phase II-B program going this year, this month. Yeah.
Okay. Could you comment on phase III design or targeting dose setting?
We will comment on it, but not today. I think what we'd like to do is we're going very quickly with this program. These data just came in on the days before Christmas. We're still synthesizing the full data set. The phase II-B study has been posted on ClinicalTrials.gov, but in upcoming events, perhaps at 3Q, and certainly over the course of this calendar year, we'll be presenting a lot more with respect to our plans for the program, the broader data set for TAK-994, which is quite significant, and then specifics for TAK-861.
Okay.
I'll also, if I may, we have an IV molecule, TAK-925, which we've been developing in-hospital indications, and we'll also be sharing with you some of the data that we're seeing there and plans for pushing forward into late-stage development for that program as well.
Okay, thank you. So, any question? No audience. Okay, so next, about our lead product, 999. So, could you comment on phase III data, and phase III design on TAK-999? So, I'd like to confirm whether the result of phase II trial were in line with your expectations.
So we're very excited about this program. We've been very excited from the beginning, from just having seen a few patients' worth of data when we put this partnership in place with Arrowhead two years ago. Arrowhead was running a phase II study, non-blinded, so we continued to see data that made us feel very compelled. So what is this program? This is a rare disease. It's actually a relatively common rare disease. There are almost 150,000 patients with alpha-1 antitrypsin deficiency. A subset of those, we don't really know what that exact number is, but it's probably somewhere between a 1/4 to a 1/3 will develop liver disease. There's no treatment for these individuals other than liver transplant.
And the cause of this liver disease is the accumulation of, of this mutant form of alpha-1 antitrypsin in the liver, these aggregates of alpha-1 antitrypsin that we know damage the liver. They cause inflammation, they cause fibrosis, and then eventually they cause cirrhosis and, without transplant, death. We were very excited by the data that we had seen prior to this phase II study, and this study confirms everything that we've seen prior, so what are those data? We see 90% or more knockdown of the expression of this mutant alpha-1 antitrypsin protein. We see 90% knockdown in the, in the presence of these, these toxic aggregates. We see reductions in liver function tests. And then in very small numbers of patients, we see very significant reductions in liver inflammation, and we even start to see trends in tiny numbers of patients in liver fibrosis, so we're really excited.
We're actually starting our phase III study. We hope to have that first patient, we have sites activated. We hope to have the first patient enrolled in this fiscal year, so by the end of March, and it's going to be a study with a two-year endpoint looking at liver fibrosis as the primary endpoint, and then, of course, a number of secondary endpoints and safety measures as well, and our hope is that between 2025 and 2027, fiscal year 2025 and 2027, we'll be ready to read out that study and to file.
Okay, thank you. So any other question? So I want to know about the outlook for 2022, 2023, and 2024. So you have commented that fiscal year 2023 will see a slight decrease in operating profit, due to the Vyvanse patent cliff. You also mentioned that from fiscal year 2024, the company will return to growth phase. Could you tell us the growth drivers for fiscal year 2024 and beyond? The Japanese market consensus is that operating profit will continue to decline fiscal year 2024 and beyond.
Yeah, so in 2023, we believe that our revenue will be flattish, because we are losing Vyvanse, which is a very significant product in the U.S. This year, we had the Velcade also declining. So 2023 is a very special year in terms of generic exposure. But our Growth & Launch products are generating incremental revenue of $ 2.5 billion every year. And so you do the math, it's balanced. So 2023 will be flattish in revenue. From 2024 onwards, our Growth & Launch products I just described, these 10 products, will continue to grow until the end of the decade. And today, they generate 38% of revenue of the company. It will rapidly increase, and very rapidly, they would generate 50% of our revenue.
So I think that's why we are confident to grow beyond 2020, after 2023, until the end of the decade. In terms of geography, our revenues repartition completely changed in the last few years. So today, 50% of our revenue comes from the U.S., about 15% from Japan. We are the leading, obviously, company in Japan, but, you know, it's only 15% of our revenue. I'm saying only because the Japanese market is the most difficult market among developed countries today. It's a declining market. The price cuts are very significant. And actually, strategically, we wanted to reduce our exposure to the Japanese market. So today, 50% of our revenue is coming from the U.S., about 15% from Japan. And then in Europe, we are growing very well, actually, in Europe.
That's a good sign because it means that we are able to gain good reimbursement in a tough market. You know, our business has been growing very well in Europe. Then one of the fastest-growing countries today is China. We are growing very rapidly in China. We developed specifically our pipeline in China in the last few years. We are now launching very rapidly new product in China, and we have been very successful getting reimbursed and being on the NRDL list as well in China. So this is our fastest-growing market today in China. We have not seen such very significant slowdown during COVID, as well. So we are very committed to grow in China.
I should mention that we are extremely committed to China, but we are not dependent on China in any way. For example, we don't have. If you look at our supply chain, we have zero dependency from China in our supply chain, for example. So in case there is a very significant geopolitical risk, we are covered on that side.
Okay, thank you. Any question? So, about PDT business. So I understand your PDT business is a very good situation. And do you have any update for us on your outlook for fiscal year 2023 or this year?
We have been very successful in our plasma collection business during COVID. I mean, we saw a significant dip when the COVID crisis started, but we rebounded very rapidly, more rapidly than our competitors for different reasons. And now we want to carry on increasing our plasma collection. We had set a goal of 65% increase in a few years back when we acquired that business, and we are on track to deliver that. And of course, that is driving ultimately our growth, you know. That's why it was so important to create this end-to-end business unit, which, when we set it up, was led by Julie before she became president of our U.S. Business.
I think Julie made a terrific job at really managing this business because, you know, this is a business that you need to very carefully manage between plasma collection, capacity, fractionation, and allocation, because this is a business where the demand is greater than supply. So you need to be very careful in the way you allocate the product so that there is no patient treatment disruption. And so I think we are very much committed to this business. It's a growing business. Another thing that we did is we created a dedicated R&D organization. Andy is managing our large R&D organization, but we have this dedicated PDT R&D organization within the Business unit, which is focusing on new indication, device innovation, and also potentially on new product NMEs, new molecules originated from plasma.
I think this is a long-term business. We need to really have a long-term view to be successful with this business. Yeah.
Okay. Any question? Nice. So, I want to know about the potential of TYK2 inhibitors, sales potential, because today's morning session, BMS commented on Sotyktu sales potential in 2030 is $4 billion+ . Can you target the same level with Sotyktu, Sotyktu, or beyond the Sotyktu?
Yeah, I'll say a few words, and then Julie perhaps could comment on, you know, how we are thinking about launching a product like that in, in the U.S. But, you know, we explained that we are going for life-transforming medicine. So either first-in-class or best-in-class or, you know, product which can really change the standard of care. We believe that this molecule has some characteristics which are very differentiated from the current launch molecule. It has much higher affinity for the TYK2 receptors. It is very specific as well. So we believe that we will be able to use higher dose, and we won't have the safety issue linked to the JAK receptor, if you like. So that's why we are extremely bullish on this product.
This will be launched in some markets where we are not in today, but we are very confident that we can manage that. Julie, if you can say a few words on that.
Sure. I guess a couple of comments to add. So when you look at the market potential of some of these disease states, whether it's psoriasis, which in about five years is predicted to be roughly a $30 billion value market, IBD, similar size, there's significant potential, especially when you have a differentiated product like Christophe just described. So we're very excited about this. And in terms of the ability to launch, when you look at what we've been able to do, for example, with the LIVTENCITY, even though that was a new disease area for us, we learned the market, and we were able to appropriately launch in a space that didn't necessarily have existing Takeda expertise, but we built the expertise and have had a very successful launch to date.
We'll take those learnings as well as what we've done in IBD to continue our presence in the IBD space. As Christophe has mentioned, we are looking at not just psoriasis, but also looking at IBD for this product TAK-279, given its potential differentiation and its specificity on TYK2. Very excited about the future potential.
Okay, thank you. So any other question?
Question?
Okay. so.
There is a question over there. Yeah.
Yeah. Oh, thank you very much.
Please.
In microphone.
Thank you so much. Very impressive presentation. Last year, Takeda's AI strategy made the news in The Wall Street Journal, and especially Takeda's philosophy to leverage AI to value the long-term values. Can you double-click on that?
Yeah, you know, we are very excited about the leverage of digital technology, AI, and we have a very significant program within the company to train our employees, educate, and really invest in this area. I mean, the speed is mind-blowing, and I think it's transforming completely the company. I would give a few examples in manufacturing. Andy can talk about what we do in R&D. Teresa and Julie, we can talk about what we do in the commercial front. In manufacturing, for example, we are looking at using data to predict future deviation. Instead of, you know, finding the deviation when they happen, we can use predictive technology to anticipate future deviation. We are using AI for quality control.
This activity of visual testing, if you have visited some sterile manufacturing product, we are still using visual testing by people to test, to look at sterile product if there are some particles that will be replaced by AI. So the majority of jobs will not be replaced by technology, but some of them will. And so it's just we believe that in the manufacturing side, we will be able to double our productivity by leveraging technology and AI, and that's the path we are in. A few examples in research?
Just very quickly because I see we're out of time. I mean, everything we're doing is, at some level, leveraging digital data. I can just give one example, which is in our clinical trial operations. So in 2022, 38% of our clinical trials had elements of decentralization. Our goal is that in two years, by 2024, the end of 2024, 100% of our trials will be leveraging decentralized technologies.
Teresa, on the commercial side.
Yeah, you know, on the commercial side right now, given the data that we have, we're able to supplement what our representatives are doing in the field by next best action using AI, taking all that data together to help them determine what exactly it is, the information that's required for each individual physician. And then, it's a continuous loop. So there's a self-learning that comes in with that data. So really, it significantly enhances new patient starts in the field.
Okay. Thank you. The time has come. Okay, so I want to wrap up. Thank you for joining us. Thank you.
Thank you, everyone.