Good morning. Good evening, everyone. This is Elizabeth Borgeson. As a part of the IR team at Takeda, I'd like to welcome you to our event where we will be discussing our new dengue vaccine, Qdenga. Before starting, I'd like to call your attention to the language or interpretation icon at the bottom of your Zoom window. For those of you who wish to listen to the call in English, please select English with this icon. Moving to slide two, I'd like to remind everyone that I will 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. The factors that could cause actual results to differ materially are discussed in our most recent Form 20-F and in our other SEC filings.
Also refer to the important notice on slide two of the presentation. We have a great presentation for you today. Without further ado, let me introduce Ramona Sequeira, President of Global Portfolio Division. Ramona, I'll hand it over to you to introduce the rest of the team.
Thank you so much, Elizabeth, and I'd like to thank you all for joining us today to discuss Qdenga. We're very excited to share more information with you about dengue fever itself, about our dengue program, and about our Qdenga launch strategy. I have a few guests joining me today. From Takeda, we have an incredibly experienced team, including Derek Wallace, who's the head of our global dengue program, and Gary Dubin, who's the head of our vaccines business unit. Both Derek and Gary bring years of experience working in clinical development in vaccines and on this program in particular. Also from Takeda, we're joined by Renata Campos. Renata is an experienced commercial leader and President of our Growth and Emerging Markets for Takeda. She's leading our launch plans in endemic markets.
To provide an external perspective, we're honored to have Professor Eng Eong Ooi from Duke and National University of Singapore Medical School. Professor Ooi is a clinician scientist, and a renowned expert with deep experience researching and treating dengue virus. He's also graciously agreed to stay with us for the Q&A. I'd like to share why Takeda has been so focused on developing a vaccine for the dengue virus. Elizabeth, if I could move one more. Thank you. In 2019, dengue was listed by the World Health Organization as one of the top 10 threats to global health, along with HIV, antimicrobial resistance, and non-communicable diseases such as diabetes, cancer, and heart disease. An estimated 40% of the world is at risk of dengue infection, and incidence rates have increased 30-fold over the past 50 years.
In 1970, there were nine countries that had experienced severe dengue epidemics. Today, the disease is endemic in over 125 countries. When a dengue outbreak sweeps through a country, often during the rainy season, we see hospital system capacity being overwhelmed in a similar way to what we saw with COVID-19, with a significant economic burden on the country as a whole, as well as on individuals and families. In addition to the threat to endemic countries, dengue is also a leading cause of fever among travelers returning to the U.S. and Europe. We've seen cases of dengue in Florida, Texas, Portugal, France, among other areas. On the next slide, Takeda has four strategic imperatives to ensure a successful global launch of Qdenga and help protect public health for millions.
Critical for us is making Qdenga available to as many people as possible who are at risk. Today, we'll share examples of work we're doing in partnership with other stakeholders to create awareness of the risks of dengue. Derek will walk you through the clinical program and the Qdenga clinical profile, which we're leveraging to build confidence with regulators, healthcare providers, and consumers. We're keenly focused on establishing rapid and broad access. I'll walk you through how access will evolve in endemic markets such as Brazil. Finally, we'll lay out how we'll maximize the potential of Qdenga through our manufacturing capacity and our well-established global footprint. Our agenda today kicks off with Professor Ooi, who'll provide insights and background on dengue. Derek Wallace will walk us through the Qdenga program. I'll cover our commercial plans to fully capture this opportunity and deliver a transformative public health impact.
We'll be joined by Gary and Renata for the Q&A. With that, I'm going to hand it over to Professor Ooi.
Thank you very much, Ramona, and thank you for this opportunity to share, you know, but about dengue and the global burden of this disease. Next slide, please, Elizabeth. This slide basically shows you where the size of the problem globally. As you can see on the map on the right-hand side, dengue is very prevalent in Central and South America and South and Southeast Asia, so it's well within the tropical belt. In Africa, you do not see many red dots, that's because many of these are misdiagnosed as malaria and treated as such. Actually, the global burden. It's estimated to be about 390 million infections a year.
About 4 billion people live within the areas of the world where dengue is actively transmitted, all year round, and especially as you heard from Ramona, during the rainy season. Because of the plans in urbanization and global warming, the projected trend is that dengue is gonna spread into the regions with subtropical climates. Because of that, by the 2080s, estimated at 6 billion people will live at risk of dengue each year. Next slide, please. What is dengue? It's on the left-hand side, I mean, if you read the textbooks and the literature, it's described as, you know, a mild flu-like illness. Those people who do have dengue will tell you that actually they wish you would die from it because it can be very painful.
If you look at the map, or this, the figure at the, on the left-hand side, you know, the muscle pain and the bone pain can be very debilitating. People do recover from dengue if with simple supportive care, except that in about 5% of the cases, they go on to develop very severe disease and potentially that's life-threatening. Why that is so is probably multifactorial, as I'll walk you through in the next slide in just a little bit.
Those with very high levels of virus in the blood, as well as some viral proteins, and in particular, the secreted NS1 protein, which is produced by the virus and is thought, at least in experimental model, to trigger all the inflammation as well as directly affecting the integrity of the blood vessel, the lining of the blood vessel. That causes the liquid component of the blood or plasma to leak out from the blood vessels and therefore compromise our ability to maintain our blood pressure. When that happens, the patient goes into shock. The next slide will show you why that this risk is affected by amongst other things, our immune experience to previous dengue virus infection.
What I mean by that can be perhaps best illustrated in these four graphs. The x-axis of these graphs are the amount of antibody in our blood, and the y-axis is the probability from left to right, probability of infection, symptomatic infection, hospitalization, and dengue hemorrhagic fever, which is the severe form of dengue. You can see on the panels A and B, the higher the antibody levels, the more likely we're gonna be protected from infection and from developing disease if we're infected. That, as you move from right to left on the x-axis, then as the antibody levels drop, then your risk of infection and symptomatic disease goes up. The risk of hospitalized dengue and risk of severe dengue is not linear.
There's actually a peak point in which the risk is actually highest. That, in practical terms, means this, that once we have been infected with one dengue virus, over time, that level of antibody that developed from the first infection will drop. When we encounter dengue virus a second time, that risk is maximum at around about two and a half-three years after the first infection. Once you pass that window, the risk drops again. This idea that is very often cited in the press and talks that, you know, the secondary dengue infection or the second infection is more likely to cause severe dengue, it's a very simplistic statement. It doesn't really capture the risk.
The risk is actually maximum only within a time period of about two and a half-three years, whereupon after that the risk would drop. Next slide, please. Besides the prior immune immunity to one of the dengue viruses, it's also important to know that dengue viruses are actually quite different. By historical reasons, they're all called dengue viruses and then named one, two, three, and four. Genetically, however, they're actually four different viruses. The, you know, the behavior, the kind of diseases they cause and all that are also different. Over the years, it's very clear that dengue one and dengue two viruses are the ones that cause the most disease. Amongst the four, dengue two is the one that's most likely to cause severe disease, particularly during a second infection.
Not all dengue viruses are the same, right? If we have to stop one virus, then dengue two is the one that we should try and tackle. Next slide, please. Because there are four viruses and because it's transmitted by mosquitoes that would breed, especially during the rainy season, then we do get dengue outbreaks, you know, especially during the rainy months. Also, you know, every three-s years, many countries experience a big spike in dengue virus, in dengue cases. When that happens, dengue cases can very quickly overwhelm healthcare resources. We've all lived through COVID. Same thing happens during dengue outbreaks. The hospitals get jammed with dengue patients and many elective medical procedures will then have to be delayed.
The cost to both the patient as well as society is very high when dengue is not properly controlled. Next slide, please. How do we control dengue, and why do we need a vaccine? I think of all the places that we've tried to control dengue, Singapore provides the best illustration or experience in terms of why we need a vaccine. There's the slide on the figure on the right-hand side of the slide is that what happens with dengue between 1966 to 2022. The red line represents the mosquito population density, right? As shown on the as indicated on the right-hand side of the raw y-axis on the right-hand side.
As you can see, in 1966, when Singapore first started surveillance on dengue, the mosquito population is extremely high. It's about 50% of all houses have Aedes mosquitoes breeding in them. During that period, dengue overtook malaria as the most common cause of death in children from a mosquito-transmitted disease. When Ministry of Health started to control the mosquito population, as you can see, the red line then dropped. As the mosquito population dropped between 1974 to about late 1980s, Singapore experienced a period without any dengue outbreak. From 1990 onwards, you can see that the blue bars now start to spike once every five-seven years or so, right? Starting from 1992-98 and all that. Despite the fact that the red line has stayed very low.
That illustrates the problem with dengue control, if you just control the mosquito. This applies to no matter what form of control we exert on trying to re-reduce the mosquito population. That as we reduce mosquito population, we also reduce dengue virus transmission and therefore, on the long term, immunity levels. Because we cannot eradicate the mosquito, then even with very small numbers, we still get outbreaks periodically. The only way we can prevent dengue, therefore, is to both control the mosquito as well as vaccinate the population so that we sustain the immunity levels as the mosquito population drop. I will leave the thought there, and I'm happy to take questions later, but I'll pass this time on to Derek to tell you more about the dengue vaccine.
Thanks very much, Eng Eong. It's a real pleasure to be here today. If we go to the first slide. Before I go into the design and the clinical profile of Qdenga, I'd like to reinforce two specificities of dengue that Eng Eong has mentioned and are really important to understand. Firstly, severe dengue, which is difficult to predict and extremely challenging for physicians to manage, is essentially a disease of vascular leakage. Fluid or plasma leaks from blood vessels into the lungs and abdomen. This is managed by trying to find a sometimes impossible balance in fluid replacement, i.e., giving enough intravenous fluid to ensure adequate volume for the circulatory system while avoiding overloading the lungs with fluid. Getting this right can prevent death in some, but not all cases of severe dengue.
One of dengue's non-structural proteins, NS1, is implicated in this vascular leakage and is highly conserved between flaviviruses. The second element of dengue pathology that I'd like to reinforce is the potential for disease enhancement. In natural infection, a secondary infection is a risk factor for severe disease. Antibodies from the first dengue infection can make severe disease more likely in a phenomenon known as antibody-dependent enhancement. This characteristic of sequential dengue infections has been a major hurdle for the development of dengue vaccines. On the next slide, with these factors in mind, we have developed a vaccine that protects against all four dengue serotypes, protects against severe disease, and has shown no evidence of disease enhancement. Qdenga is a tetravalent vaccine. It contains components of all four dengue viruses.
The principal virus is an attenuated dengue two virus. This forms the backbone for the other three serotypes in the vaccine. We have created chimeras for dengue one, three, and four by splicing the structural or premembrane and envelope genes into this dengue two backbone. The strength of this approach is that we get broad and persistent immune responses. First, Qdenga elicits neutralizing antibodies against structural proteins for all four serotypes. This reduces symptomatic dengue. Second, our vaccine induces antibodies against NS1. This directly reduces NS1-mediated vascular leakage. This mechanism could explain the excellent reduction in hospitalizations we see with Qdenga. Third, strong T and B-cell responses are generated to numerous dengue antigens. These could be contributing to the persistence of protection observed in our clinical program.
On the next slide, to test the safety and efficacy of Qdenga, we designed and executed our pivotal phase III trial following the WHO's recommendations for vaccine development for development of a dengue vaccine. This trial enrolled more than 20,000 children across eight endemic countries. Each participant received two doses of vaccine or placebo three months apart and was followed up for a total of 57 months or four and a half years after the second dose. The primary endpoint included all cases of dengue observed during the first 12 months of follow-up. Secondary efficacy endpoints were observed during 18 months, and our key secondary endpoint was reduction in hospitalization. We continued follow-up for an additional three years, making a total of four and a half years, to look at long-term safety and efficacy.
This duration is important because it refers back to the period at which a primary infection, or in this case vaccination, could potentially enhance exposure to a second infection, which as Eng Eong explained, is typically in a period around two-three years. By following up for four and a half years, we followed up beyond the period for which we might expect to see enhancement should it occur. There are two important aspects of this trial that help us to identify potential disease enhancement. Firstly, the fact that we took baseline blood samples in all participants, and that allows us to identify who was naive to dengue and who had already been exposed, and to stratify our data according to serostatus. As mentioned, we followed participants for four and a half years.
If we look at the clinical data on the next slide, we can see that we have demonstrated strong efficacy across all endpoints regardless of previous dengue exposure, and we did not identify any important safety risks. We showed an 80% reduction in symptomatic dengue at 12 months, the primary endpoint. A 90% reduction in hospitalizations at 18 months, the key secondary endpoint. Most impressively, we saw an 84% reduction in hospitalizations at four and a half years, which shows the excellent durability of protection provided by Qdenga. We can see this on the curve on the right-hand side of this slide. The solid lines are the placebo recipients, and the dotted lines the vaccinees. The orange color is seropositive participants and the blue is seronegative. We can see very clearly the reduction in hospitalizations was similar and independent of serostatus.
With respect to safety and tolerability, we did not see evidence of disease enhancement, and the vaccine was seen to be well-tolerated with the reported reactions that were most frequent being those that are common to vaccines such as injection, site pain, or headache. On the next slide, we can see the significant momentum that we are building. Our first approval was in Indonesia in August last year, followed by approval in Europe in December and Brazil earlier this month. All of these approvals have been for prevention of dengue regardless of serostatus. There is no requirement to test for prior infection before administering our vaccine. The vaccine is currently under priority review by the U.S. FDA and is also under review in a number of endemic countries that participated in the EU-M4all procedure with the EMA and WHO.
we're really excited now for continued momentum in 2023 and beyond, and I'm looking forward to handing back to Ramona to discuss the commercial opportunity for Qdenga.
Thank you so much, Derek. On the next slide, we're going to talk a bit more about our four strategic imperatives to ensure a successful launch. First, we're partnering with stakeholders to educate decision-makers and consumers on the risks of dengue that you heard about today from Professor Ooi. Second, for the first time, there's a vaccine with a strong clinical profile and a recommendation for broad use, as you heard from Derek, we want to build confidence and trust in our clinical data. Third, our goal is to make sure consumers both living in and traveling to endemic markets have access to this important vaccine. We have a tiered pricing strategy, we're working with both private and public local stakeholders to provide rapid and broad access.
Finally, it's critical we ensure launch preparedness through the work we're doing to expand our capacity and leverage our established supply networks and strong local presence across our broad global footprint. On slide 23, we're already seeing the great interest and excitement around Qdenga. In the countries where we have approval, early signs are very positive. Demand from travelers in Germany has exceeded our expectations. Both in Indonesia and Brazil, the local media coverage and desire of stakeholders to partner with Takeda have been very strong. Let me share a few examples of what we're doing around the globe. In Thailand, we're partnering with the Ministry of Health and other organizations to raise awareness of the risks of dengue through interactive digital content. A young girl named Ingma is our first artificial intelligence influencer and is a virtual representation of over 1 million dengue victims in Thailand.
Our video campaign has gone viral with over 35 million views so far. If you're interested in checking out the video, the link is in the deck. We've also partnered with top consumer brands like Kao Thailand. These campaigns are ongoing today prior to the approval of the vaccine in Thailand, showing the high unmet need that exists in dengue endemic countries. We're building trust and confidence through our partnerships, building on our strong local presence across endemic countries. In Brazil, where Qdenga was most recently approved. We've launched a collaboration with UNICEF to educate roughly 90,000 people living in underserved communities on how to reduce the risk of transmission of mosquito-borne diseases.
Finally, in travel markets such as the U.S. and the EU, we're looking at partnerships with leading travel immunization clinics to educate travelers destined for endemic countries who may not be aware of the risks of contracting dengue. Moving to slide 24. Let me now walk you through how access will work in an endemic country such as Brazil, which has a very high burden of illness for dengue. Initially, at the bottom, even in endemic markets, Qdenga will be available to consumers paying out of pocket. We refer to this as a private endemic market. This enables rapid access of the vaccine. We will further support affordability and start to broaden private access as we explore opportunities with private payers and employers who want to keep their employees safe.
We'll support initiatives with state and municipal-level governments looking at innovative financing options, value-based contracting, and more. Ultimately, the goal is to be included in the national immunization programs, which are funded by the national government and result in broad access across specific cohorts of the population. Two important nuances to note here. First, the activities to support both private and public access happen in parallel. Private access comes first and the national immunization programs come later. Second, the time it takes to activate each program will vary from country to country. For instance, in Brazil, it has historically taken 12 to 18 months before inclusion in national immunization programs, whereas in Indonesia it's historically taken several years. Moving to slide 25.
To support our access strategy, we've developed and are implementing a tiered pricing approach based on factors such as GDP and the sophistication of the healthcare system to meet the needs of individual countries. As I mentioned, when we initially launch into a country, we'll start by making the vaccine available to consumers paying out of pocket in the private market segment. In the private endemic market segment, we plan to price below the historical average price for innovative vaccines. For instance, in Indonesia, we're launching with a $40 recommended retail price compared to an average price for innovative vaccines of about $73, allowing us to penetrate more deeply into the private market by being more affordable. For the public endemic market segment, for the large government-funded programs, we aim to price at below the average cost for innovative vaccines.
Our goal is to ensure affordability for governments in endemic countries. In travel markets, which are much smaller in volume than the endemic markets, we plan to price on par with other innovative vaccines. In Germany, Qdenga is around $115 per dose, which is in line with the average price for other innovative vaccines. It's important to note that we believe implementing Qdenga public vaccination programs has the potential to create significant cost savings for individuals and at a government level. Takeda's done economic research on the burden of dengue, looking at factors such as healthcare costs, missed work, loss of tourism. We look forward to publishing this work in the coming months. On slide 26, I'll summarize how we've prepared to deliver this innovative vaccine globally. We made early investments to establish in-house end-to-end manufacturing capabilities.
We're working to expand our capacity in-house and through strategic CMO partners with a target supply of 100 million doses annually. With respect to supply chain, we're leveraging the existing distribution network that Takeda has established. The product will go from Singen in Germany to a distribution hub in Belgium, and from there will ship to each of the launch countries. We're able to leverage our local distribution networks and commercial infrastructure in our key launch markets such as Brazil and Indonesia. I think it's important to emphasize that we have deep expertise in these markets. Our Growth & Emerging Markets Business Unit has successfully launched over 150 medicines since 2019 and is growing at 14.5% in Q3 FY22.
We've hired key talent from the vaccine space, both locally and regionally, in preparation for upcoming launches. Let's move to slide 27. I'll cover our launch timelines. As you can see here, we plan to have significant global expansion through the end of this decade and into the next. We're targeting launches in over 20 countries by the middle of the decade, which accounts for 55% of the eligible at-risk population. As you've heard, we've already received approvals in Indonesia, Brazil, and the EU. We have ongoing reviews in several other countries, including the US. We'll start to initiate launches in endemic countries where approved starting in Q1 FY23.
On slide 28, today we're excited to share that we are updating our peak sales estimate to $1.6 billion-$2 billion from our original estimate of $700 million-$1.6 billion. What gives us confidence in this peak estimate is, first, we have four and a half-year data, as you heard from Derek, which demonstrated a durable reduction in hospitalizations and importantly didn't show any important safety signals. Of note, we didn't see any signs of disease enhancement. Second, we have early positive momentum and feedback from regulators so far, including the CHMP and EU-M4all opinion, recognizing Qdenga's strong clinical profile. Finally, where approved, Qdenga has received a broad label regardless of serostatus. Based on these factors, we've decided to expand our manufacturing capacity with an aim of delivering 100 million doses annually.
We believe this positions Qdenga to deliver steady revenue growth through the end of the decade and durable sales beyond that. To close out the commercial section on slide 29, in the near term, our goal is to drive early adoption. We have initial launches in key endemic and travel markets. In endemic markets, we'll establish rapid access through the private market segment and through local partnerships while we start to negotiate for national immunization programs. This will all be underpinned by our tiered pricing approach to ensure affordability for each country. In the midterm, we'll start to see acceleration of volume growth through the initiation of national immunization programs.
As I mentioned earlier, the time to initiation of national immunization programs will vary from country to country, as they start to come online, it will significantly drive up the volume, which will allow for us for economies of scale while enabling us to reduce SG&A spend and increase overall profitability. When you look long term, we expect to have durable sales beyond peak. We'll continue to expand globally into the next decade. Implementation of national immunization programs will ensure that new cohorts will continue to be vaccinated. Lastly, unlike traditional innovative pharmaceuticals, vaccines face more limited generic threats due to high barriers to entry, including in this space, with WHO guidance specifying the need for at least three-five years of longitudinal data. To close on slide 30, there's an urgent need for safe and effective dengue vaccine.
There's a significant growing global burden of dengue, with over 3.9 billion people at risk and the prevalence continuing to grow every year. Not only does dengue pose an important public health risk, it also carries significant economic burden when endemic countries have outbreaks. You've seen Qdenga's differentiated clinical profile demonstrating safety and efficacy against all serotypes and regardless of previous exposure. We saw durable results out to four and a half years with no important safety risks identified. The high unmet need, Qdenga's strong clinical profile, our manufacturing capacity, and global commercial capabilities provide us with the confidence that Qdenga will deliver steady revenue growth through the end of the decade, with peak sales of $1.6 billion-$2 billion and sustained durable revenue beyond the peak. Thank you for joining.
Now we'll hand it over to Nobi and Elizabeth to moderate the Q&A.
Yeah, go ahead and do that.
Okay. Thank you. Thanks for the question, Stacey. That's a really good one. I think, both Derek and Ramona have indicated that for the clinical trial, they've extended beyond, you know, what was required initially, which is one year after completion of vaccination to now having a five-year follow-up data. From epidemiological studies in Thailand and in Nicaragua, we know that the risk maximizes at about, you know, two and a half-three years. We've gone beyond that time. I think we're at least quite confident now that the period in which we should have seen severe dengue manifesting itself, it hadn't happened with Qdenga. I think moving forward, of course, the, you know, the uncertainty of is that, you know, what happens beyond 5 years?
When do you need to boost, if you do need to boost? I think those are certainly aspects that can be done in the post-marketing studies. I don't think we need that data to know that we can apply this vaccine and apply it effectively.
Absolutely, Stacy. I'll give you a short answer, but actually ask Derek to expand a little bit on the kind of competitive environment as well as our post-marketing studies that we're doing. You know, I will say I believe Takeda has set a bar for what regulators will expect for a vaccine in dengue. Given what we know about the disease, given the complexity of treating dengue, given the data that we generated in the time that we've watched this, we believe we've set a high bar for any any other vaccine to follow. Derek, did you wanna comment on the specific one with Merck Butantan, if you can, and then the launch some of the post-marketing work, as Stacy mentioned, that we will continue to do.
Thanks, Ramona, and thanks, Stacy, for the question. Maybe I can start with what we have with Qdenga. I mean, we've assessed this vaccine in eight different countries across four and a half years, and we've published our data, very granular data, in peer-review journals at the one-year point, 18 months, two years, three years and four and a half years now is soon to come out. It's very hard to comment on what's happening with Butantan. There's no peer-review data from their study. We're not really in a position to comment on it. I can say that, you know, one of the challenges of dengue development is getting exposure to multiple serotypes.
One of the limitations of studying a vaccine in a single country is that you're dependent on the epidemiology in that country. That was the reason we went to eight different countries across Latin America, Central America, and Asia in our program. It's a case of watching carefully what Butantan are doing and Merck. At the moment, they have a long way to go. In terms of what we are planning from a sort of ongoing data generation, the pivotal efficacy study has actually been extended by an additional two years. We're looking at the impact of a booster on safety, immunology and efficacy during that additional two-year period.
We also plan a very large scale Phase IV study, which will look at post-marketing in a post-marketing setting at effectiveness. Sort of real-world impact on dengue. Focusing on hospitalizations and also conducted in areas that have a good distribution of some of the serotypes that we saw less of in our study. We definitely need to continue to monitor safety and effectiveness in a longer term.
Thank you. That's a really great question. I think the data that Takeda has on Qdenga provides a lot of confidence because you've observed over that period where severe dengue should have manifested itself if there was going to be a risk. You're absolutely right that the medical community will always have this, you know, scar that they bear, especially in those countries that implemented the vaccination with Dengvaxia before knowing about the risk. I think that's why, you know, what Takeda has planned, what Ramona outlined, is really important, that the outreach and the education that needs to go along with the vaccine being accessible has to go hand in hand.
I think there are a lot of partners, too, around the world that are also trying to, you know, highlight the need that, you know, that actually we have solutions now that we can use to prevent dengue. We don't have to wait for the perfect vaccine, but what we have is actually good enough for us to make a big impact to both lives as well as society. I think if you look at the global data, serotype four of the four viruses, serotype four is probably the weakest of the four dengue viruses. Most of the infections are mild, very mild, compared to the other three. Of the four dengue viruses, the hardest to stop is actually dengue two.
We don't fully understand all the biology, but it looks like that's the evidence from both, you know, studying cases, looking at the data from Dengvaxia, and including the data from Butantan. Dengue two is probably the hardest to stop. I think, you know, the Takeda's data is really exciting in the sense that that's the one that it works best.
Yeah, let me just give a very high level. You know, we wanna make sure our supply chain is as de-risked as possible, so we do create some redundancy in our supply chain. It will be a combination of CMOs, our plant in Singen, and then we're looking for partnerships in other countries such as India. Gary, could you comment a little bit about how we see that staging out across our kind of supply chain? Oh, Gary, you're on mute.
Yes, thanks. Thanks for the question. When we think about our manufacturing capacity and supply strategy, there are a few important things to point out. First, the launch supply is essentially established through our current CMO. We have been working with a CMO in Germany for the last few years that has ensured that we have sufficient capacity to meet the initial launch demands. In the near term, we will be bringing our in-house end-to-end manufacturing facility online. This is the facility that Ramona mentioned in Singen, Germany. Then in the mid to long term, we'll be considering bringing online CMO partnerships in a number of countries to expand capacity.
For example, we're currently working to establish a manufacturing partner CMO in India. This will play out sequentially. In the end, the majority of the supply will still come from the Takeda manufacturing facility, but we will have some overlap dual sourcing to ensure that we can maintain supply continuity over time.
Yes. Absolutely right. In general, we will start with the private endemic markets, then we will start immediately negotiating for public, but that will take a little bit longer. In general, as you'll see over time, as our volume grows and grows and grows, you know, in some of these very large national programs, the cost will come down from what it was in the private market. It's all very nicely tied together with what Gary mentioned. As our capacity grows, our cost of goods comes down as well. it's a, it's kind of a nice scalable product, allows us to continue to build.
Renata, did you wanna comment on some of the early, you know, thoughts around Indonesia launch and, I know that you've already talked to some stakeholders around our private price and the feedback you've gotten there.
Yeah. Thank you so much, Ramona. Absolutely. We are very excited to have our two first launch across GEM. Indonesia expected to launch in Q1 2023. In Brazil, we're expecting to launch in Q2 2023. The initial feedback from medical society, doctors and stakeholders are extremely positive, specifically in Indonesia, where we are already have our price disclosed. We understand that with this pricing strategy, starting with private, we're gonna be able to differ from other innovative vaccines launched in the past, reach the middle class population in Indonesia. We receive a positive feedback, and we have a deep understanding about the potential of this market in Indonesia. In Brazil, we got recent marketing authorization approval in the beginning of the month.
It was an amazing acceptance across the society, Minister of Health, the stakeholders, and consumer in Brazil. We have a massive media coverage. To give you some numbers, more than 120 million people were impacted with the message of Qdenga launch in Brazil. We understand that there is a huge unmet need. We have a vaccine with a very strong profile in terms of efficacy and safety, and really are gonna be addressing a major public health in the high populated endemic countries across GEM. Thank you.
Hello, do you hear me?
Yes, we hear you. Go ahead.
JP Morgan, Wakao. I have two questions. one is, you have your commercial outlook for short, mid, long-term, and it was very clear. In the quantitative manner, I want to know peak sales is around 2032 to achieve $1.6 billion-$2 billion. Is that right understanding? Regarding the peak sales and the penetration into the market, can you show numbers 2025 or 2028 peak? What is the percentage of penetration that you have in the market? Can you give that kind of information?
You know, what I can tell you is that you're right about the peak sales. It will be around the end of the decade. It's difficult to predict the exact year, because it depends on how quickly some of the immunization programs move forward. But that's roughly in the right ballpark. Between now and the end of the decade, as I've mentioned, so by 2025, we expect to have launched in 20 countries, and that gets us to about 55% of the endemic population. And then we will continue to grow past that. What you can expect from a ramp. You know, the way this is launching, we're doing multiple things at the same time. One is we're launching into continuous new markets over time and over the coming years.
The second is we're penetrating into those markets through the private and then regional public and then the national public immunization systems. That's all happening in tandem. With all of that together, we expect a fairly steady ramp between now and the end of the decade. It should be fairly steady and, you know, growth between now and the end of the decade, given all of these things happening in tandem.
Thank you. That means in the beginning, short-term, sort of slow, but by 2024 or 2025 and beyond, you will accelerate significantly. Is that right?
I would say it's more steady than slow and an acceleration. Volume, yes. There will be less volume at the beginning, and then volume will accelerate towards the end of the decade, and that's when all of our extra capacity comes on board. Revenue, you can expect a more steady ramp, because the early revenue is coming from the private market, which is going to have a higher price, and from the travel markets, which will have a higher price as well.
Thank you very much. Last question, my second question. Gross margin of Qdenga. Can you give some ideas with your capacity building up and costs can be lower, you mentioned. The pricing compared to other medicines, it may be lower and live vaccine, that means the cost is a bit higher. Considering that, compared to your in-house products, gross margin would be lower than your products in-house?
With Qdenga, we expect to be accretive within a few years of launch. You know, accretive within a few years of launch to Takeda's overall margin, and then the margin of Qdenga will continue to increase as we move forward and the volume grows. You know, the other benefit of the national immunization programs, as we had mentioned earlier, is you'll also pull back a little bit towards the end of the decade on sales and marketing expenses. We expect better yields, lower COGS, less sales and marketing towards the end when we have broader national programs, more volume.
At the top margin level, is the margin level comparable to your other products? Top line.
Yeah. We're not disclosing our peak margin right now, other than to say that, we will be accretive to Takeda within a few years of launch, and the margin will continue to grow, after that.
Thank you very much. That's all.
Thank you.
Hello. This is Muraoka from Morgan Stanley. I hope you can hear my voice.
Yes, we can hear you. Please begin.
Thank you. 100 million doses of capacity, that was mentioned. Going beyond 100 million doses, capacity enhancement, is that a possibility? How likely is that possibility? If there is a likelihood that you will further enhance the capacity? What will be the specific conditions or what is happening? Can you please, maybe give me some idea?
Yes. Thank you, Muraoka-san. You know, with all of the work we've done and the assessment of how these programs will roll out, we believe 100 million is the right level of capacity to get to in a sustainable way. We'll continue to produce 100 million. The national immunization programs tend to work in cohorts. You'll see groups of the populations vaccinated at a time. As that goes on, you'll get newer people aging into some of the earlier cohorts. We believe 100 million doses is actually a good strategy for us to access the global population and keep a sustainable, durable revenue beyond beyond the peak as well. We're not planning right now going beyond 100 million doses.
I understand. Next question. When you have contracts with national governments, what are the risks? For example, in Japan, huge amount of COVID-19 vaccines were canceled. The orders were canceled in Japan. With dengue fever, is there such a risk of a massive cancellation or is that not really likely?
You know, I think to answer that, it might help, to have perhaps Derek talk a little bit about, the vaccine itself, because I think knowing about the vaccine and the durability will answer the question, about COVID. Derek, do you think that that would be the best way to address this?
I think, you know, the situation with COVID was quite specific. There was an ongoing pandemic, and a large number of vaccines with different profiles available. I think the situation that we're looking at here with dengue is, you know, it's hard to see any competitor in the near or medium term. Dengue is a massive burden, and we expect that when countries implement public programs, that they follow through on those public programs. It's a cost-effective intervention, and it's an intervention which is important at an individual level, at a family level, at a community level, and at a healthcare system level. I think the risks are quite fundamentally different to COVID, and I don't anticipate canceled orders in the public programs.
Yeah. Maybe just to build on that, as a reminder, with COVID, we had continuous variants. Certainly with the recent cancellation in Japan, it had to do with, you know, the vaccines that address certain variants and other vaccines didn't address those variants. With dengue, we've got the four serotypes. We've got a vaccine that addresses all four serotypes. The outbreaks might have different serotypes circulating at different times, but the vaccine will be the same vaccine that addresses that.
I think it's interesting to think about, you know, another flavivirus vaccine like Japanese encephalitis or yellow fever vaccine. You know, the viruses that those vaccines prevent are very stable over time. You don't see strain substitutions or changes in the confirmation of the virus that makes the vaccines less effective. We expect the same thing with dengue, which is another form of flavivirus.
If I may add to what Ramona and Derek have replied, another major difference between COVID vaccines and this dengue vaccine is that the period of observation during the clinical trial was very, very short for a COVID vaccine. There's a great uncertainty as to whether you need boosters, how frequently you need boosters, and that's why countries stockpile these vaccines without knowing the evidence. I think with Qdenga, we already have, you know, four and a half years worth of follow-up knowing that, you know, within that time that the protection is very well sustained. I think that's a major difference between the two vaccines, and that would influence how countries stockpile these vaccines.
Thank you very much. That was very clear. Just one last question. Earlier, Ramona, you mentioned that you don't disclose the margin information, but I want some kind of suggestion to help me. By 2030, let's say, Qdenga operating profit margin and gross profit margin, compared to PDT, would you say it will be higher or lower?
Maybe I'll point out the differences between PDT and vaccines. You know, when you think about PDT, one of the things we do with plasma is we have a whole BioLife organization that is involved in actually collecting the plasma. Before we even get to the manufacturing, we have an infrastructure that collects the plasma, and we have to pay the donors for the plasma. That whole piece is does not exist in vaccines. This is just more of a, we manufacture the vaccine and we distribute the vaccine. Gary, I don't know if you wanna comment on any, you know, kind of comparators, market comparators with other companies. I don't know if we can really, but in general, you'd see, it, you know, vaccines are very different from from PDT. Gary, you're on mute.
Yeah. Sorry again about that. I'm not sure I can add very much. I think that, you know, as you mentioned earlier, Ramona, we expect the margins to grow during the next decade as the cost of goods is reduced, as we increase our manufacturing capacity and build and supply the high volume public programs. You know, the margins will become accretive in a few years, continue to grow. I don't know that it's easy to
Make any comparisons with other vaccines in terms of margins, I think that's probably what we can say at this point.
Gary, I can maybe add that, you know, one of the reasons that we will get increased capacity over time is the fact that we have additional facilities. We're also improving the process. There is inherent efficiencies in how we're making the vaccine at the time as well, which also contributes to reduced cost of goods.
Thank you very much. That's all from me.
You're on mute, Ramona.
Your first question, then pass it on to, either Gary or Derek, if you'd like to answer the second piece of it. It's difficult to give a breakdown of all the different segments because they're going to be evolving in different markets at different times and over the course of the next decade. However, I will tell you that in general, about 15%-20% of the revenue will be private, and the rest will be public. That's kind of the breakdown that we would expect, in a more, you know, steady state over time. Gary or Derek, did you wanna comment on the other part of the question?
Yeah, maybe I'll start. Yeah, we expect that when the vaccines are introduced into national immunization programs, this will essentially follow the model that is used typically to introduce new vaccines for programs that have a considerable public health impact. The national immunization programs typically work through cohort-based vaccinations. For example, a given country would likely recommend the vaccine to be given to all individuals, children, or adults in a certain age range. Often, these programs have what we call catch-up vaccinations. At the beginning of the national immunization program, there's a broader range of ages that are included to try to get a certain level of population immunity. In the steady state, a more stable cohort is usually selected by the governments.
These programs tend not to be mandated programs, but programs in which the government procures vaccine, and it's offered to individuals in the recommended age range, and then it's typically up to the individuals to elect to be vaccinated.
If I could just add, I do wanna correct one thing. 15%-20%, roughly, of the market will be travel. I think I said private. We expect overall about 15%-20% of our revenue to come from the travel market versus the endemic markets. Sorry.