Daiichi Sankyo Company, Limited (4568) Earnings Call Transcript & Summary

Thank you for waiting, everybody. We'll now start Daiichi Sankyo's Oncology Business Briefing. This is Ken Asakura from Corporate Communications, and I will be the moderator today. First, about the language for this event. Presentation will be in English, and Q&A will be in both English and Japanese. Simultaneous interpretation is provided, so please click the interpretation icon at the bottom of the screen and select either English, Japanese or original audio. When original audio is selected, you will hear the original sound. English presentation slides will be shown on the Zoom screen as well as live streaming screen. Both Japanese and English presentation slides have been uploaded to IR Presentation Materials page of Investors section on our corporate website, so please view or download as needed. Our presenters for today are Mr. Ken Keller, our Global Head of Oncology business; Mr. Dan Switzer, our Head of U.S. Oncology Business Division; and Dr. Markus Kosch, our Head of EU Oncology Business Division. We'll take questions after the presentation. Dr. Sunao Manabe, our Executive Chairperson and CEO, will open the meeting, and will join for the Q&A session. Please note that this event will be recorded. With that, let's start the event. Manabe-san, please?

Hello, everyone. I am Sunao Manabe, Executive Chairperson and CEO of Daiichi Sankyo. Thank you for joining Daiichi Sankyo's Oncology Business briefing. Please go to Slide 3. Here is today's agenda. After my part, Ken Keller will provide us with an overview of our Global Oncology business, then Dan and Markus will tell us about U.S. and European Oncology Business performance, how we are establishing Daiichi Sankyo's position in Oncology and launch readiness for upcoming key events. After that, Ken will close the presentation, and we will open the floor for questions from the audience. Next slide, please. Before moving to the next agenda item, let me briefly introduce our speakers. Next slide, please. Ken Keller, our Global Head of the Oncology business, joined Daiichi Sankyo in 2014. He revamped our U.S. business structure to focus on multiple oncology launches, including ENHERTU to achieve Daiichi Sankyo's 2025 Goal and 2030 Vision. Next, please. Dan Switzer, our Head of the U.S. Oncology Business division, is celebrating his 20th anniversary with the company this year. He is responsible for the commercialization and performance of all in-line and near-term oncology assets, has launched multiple products in the company and has overseen multibillion-dollar franchises. Next please. Markus Kosch, our Head of the EU Oncology Business division, joined the company in 2021 with experience as boarded physician and over 20 years of experience in the pharmaceutical industry. He leads our European and Canadian Oncology Business overseeing 18 countries. Next please. We at Daiichi Sankyo are committed to achieving our 2025 goal of becoming a global pharma innovator with a competitive advantage in oncology and will shift -- herald further growth to realize our 2030 Vision of becoming global top 10 company in the oncology area. We will continue to challenge ourselves to bring our innovative products to more patients in need of new treatment options as quickly as possible. That concludes my remarks. Now I would like to hand it over to Ken Keller. Ken, please?

Thank you, Manabe-san. My name is Ken Keller. I've been a member of the Daiichi Sankyo team for the past 11 years. I've been part of the oncology community, bringing new important medicines to patients across the globe for over 30 years. In all those years, there has never been a time when I have seen as many near-term growth catalysts on horizon than right now here at Daiichi Sankyo in oncology. And Dan, Markus and I, we are very excited to share these details with you today. Next slide. ENHERTU, based on its DESTINY clinical development program, has transformed the treatment of multiple cancers and Daiichi Sankyo, as it has become the new standard of care in its first 4 indications in every country fully launched. Revenue will exceed $3.7 billion in 2024. Importantly, there remains further growth opportunities in these existing indications, newer approvals in HER2-positive tumor-agnostic cancers and the HER2 low, and more recently, ultralow metastatic breast cancer indications are first-in-class paradigm-changing approvals. These indications are largely untapped. Dan and Markus, who head the U.S. and Europe Oncology business, will share our growth plans in these areas. The most important message I want to share with you today is that ENHERTU is entering a catalyst-rich year with multiple new clinical trial readouts, including DESTINY-Breast09, DESTINY-Breast05 and DESTINY-Breast11. These trials move ENHERTU to an earlier disease setting where it seeks to make an even bigger impact on patient outcomes, even cures. Daiichi Sankyo has now established all the capabilities needed to now launch our second antibody-drug conjugate, DATROWAY. DATROWAY was recently approved in Japan and in the U.S. for HR-positive/HER2-negative metastatic breast cancer, and it has a PDUFA date in July for its second indication in EGFR-mutant non-small cell lung cancer, a patient segment that desperately needs new treatment options. In addition to all of these, we will see topline results for DATROWAY for triple-negative breast cancer in PD-L1 ineligible patients and the first of 3 first-line non-small cell lung cancer trials, AVANZAR. In summary, our oncology business is strong and getting stronger as we delivered continued growth with ENHERTU's older indications, accelerated growth from the newer ones and major growth inflection points as ENHERTU moves through earlier disease settings with DESTINY-Breast09, DESTINY-Breast05 and DESTINY-Breast11, which all readout this year. Next slide. ENHERTU's DESTINY clinical development program has yielded 8 breakthrough therapy designations, 6 New England Journal of Medicine publications, 19 NCCN recommendations across 10 different tumor types. These guidelines now reflect and recommend both HER2 tumor-agnostic approval and our HER2 low and ultralow metastatic breast cancer indications. In addition, key guidelines in Europe and across the globe are consistent in their positive strong recommendations for ENHERTU across all of its indications and more. Next slide. ENHERTU has now expanded to 6 indications, demonstrating major improvements in outcomes of HER2-expressing breast cancer, gastric cancer, lung cancers and others, adding in some cases, years of progression-free survival and overall survival compared to the previous standard-of-care treatments. If the trials, that I talk about next, are successful, this number will increase to 11 indications by the end of fiscal year 2026 and more than double the number of patients indicated for treatment. We are, without a doubt, entering a phase of ENHERTU's life cycle of accelerated growth potential, and we're ready to capitalize on these new opportunities. Next slide. Global net sales in fiscal 2024 Q3 were reported at JPY 143 billion. U.S. revenue was up 11.5% compared to the previous quarter and almost 40% growth year-over-year. Europe was up 10.4% compared to the previous quarter, growing over 50% year-over-year. As you can see on this slide, all regions are contributing. As newer indications advance through the individual country's access systems, we expect staggered periods of accelerated growth in each of these countries. Next slide. Today, ENHERTU is commercialized in over 60 countries. Year-over-year growth is almost 40%, has achieved #1 market share in its first 4 indications. All of them have room to further grow. With ENHERTU's more recent newer indications, ENHERTU low, ultralow and the tumor-agnostic approval in the U.S., we will continue to ramp up our revenue growth. And most importantly, ENHERTU has now helped over 130,000 patients live longer, better quality lives. Next slide. The performance that I just outlined makes ENHERTU the fastest-growing and the largest antibody drug conjugate globally as measured by revenue, almost 2x the size of the #2 ADC. Next slide. But our vision is not to have ENHERTU be the largest, most successful antibody drug conjugate ever, our vision is to harness its indisputable best-in-class efficacy and grow ENHERTU into the biggest, most successful breast cancer drug ever. Fiscal 2025 is a pivotal year because we have a number of major potentially standard of care-changing breast cancer clinical trial results reading out. I will speak to these trials in the next few slides. The theme for all of these trials is to move ENHERTU earlier in the treatment pathway and to a broader segment of patients. Next slide. So here you see that ENHERTU is destined for much, much more. These clinical trial results will all become available in the next year, delivering to the oncology community important new practice-changing data. DESTINY-Breast06 has now been approved in the United States and is currently on this month's CHMP agenda, where we anticipate a positive discussion. We have launched this indication in the U.S., and Dan Switzer will share more about the launch. DESTINY-Breast09, 11 and 5 will mature this year and next. These trials carry the opportunity to bring ENHERTU to patients earlier in the disease continuum and provide even greater benefits. Beyond breast cancer, we will see the DESTINY-Gastric04 results imminently, which is in the HER2-positive gastric cancer second-line setting. Then we will have the DESTINY-Lung04 topline results, again, consistent with the theme of moving ENHERTU earlier in the cost of treatment. And post-2026, DESTINY-Gastric05, DESTINY-Biliary Tract01 and DESTINY-Ovarian01, all will be reading out in earlier lines of treatment. Next slide. So I want to share with you a few of our thoughts on just 3 of the major registrational trial readouts this year in the breast cancer space. The first is DESTINY-Breast09. This is in the first-line HER2-positive metastatic breast cancer setting. As you can see, it's a 3-arm trial. Progression-free survival is the primary endpoint. Today, Taxol, Herceptin and Perjeta is the standard of care. And it provides 19 months of progression-free survival in its pivotal trial. Based on the efficacy we have seen with ENHERTU in this population, but the second-line setting in DESTINY-Breast03, where we provided 28.8 months of progression-free survival, we are very hopeful in what we'll see in these results. Now importantly, in the real world, attrition rates across first- to third-line therapies in this population, HER2-positive metastatic breast cancer, it shows that 29.6% of patients do not receive treatment after the first line and 34% beyond the second line. So we believe that in this setting, targeting HER2 over-amplification expression is absolutely essential. So it's important to initiate treatment with the most efficacious anti-2 therapy upfront. And the incremental population is 3,000 and 4,000 patients in the U.S. and Europe. Next slide. This is DESTINY-Breast11, which also reads out this year. This trial enrolled HER2-positive early breast cancer patients in the neoadjuvant setting. There are 3 arms in this trial. The primary endpoint is pathological complete response. The standard of care provides a pCR rate of only 56%. So there is lots of room to improve on the standard of care. Next slide. DESTINY-Breast05 is in the post-neoadjuvant patient segment. This trial selects for patients at a higher risk of disease recurrence. Patients are treated for 14 cycles. 3-year invasive disease-free survival with the current standard of care, which is T-DM, is 83%. There is a great desire from the oncology community to improve on these outcomes, and there are 8,000 patients in the U.S. and Europe. Next slide. So looking beyond ENHERTU, Daiichi Sankyo's second ADC, DATROWAY, has been approved in Japan and the U.S. for metastatic breast cancer patients. The second indication, as I mentioned earlier, will be in the EGFR-mutant non-small cell lung cancer patient segment. The PDUFA date is July of this year. These are patients who when they progress after first-line TKI therapy, they have very poor outcomes. And in this setting, DATROWAY has demonstrated over a 40% overall response rate and 7 months duration of response. Doctors are very enthusiastic about having this new option available for their patients. In the second half of the year, we expect outcomes for 2 very meaningful registration trials with DATROWAY; TROPION-Breast02 in the triple-negative breast cancer setting, and then, the first of the 3 first-line non-small cell lung cancer trials, AVANZAR. Here, DATROWAY has the opportunity to help a large number of patients. In DATROWAY's Phase I and Phase II trials, we have demonstrated synergy of Dato-DXd with IO therapy across multiple trials. And we've also shown that DATROWAY with platinum chemotherapy in a triplet regimen is also tolerable and that gives us confidence in what we'll see in the AVANZAR trial. Next slide. So in total, including the recent U.S. launch of DESTINY-Breast06 in the HER2 low and ultralow patients, Daiichi Sankyo has the potential to launch 9 new indications across ENHERTU and DATROWAY in 2025 and 2026, which increases the number of patients our medicines are indicated for threefold. I don't know of another oncology company with a catalyst riches that we have here at Daiichi Sankyo. Now I'll turn it over to Dan Switzer, who will talk you through the plans and the outlook for the U.S. Oncology business.

Thank you, Ken, and good morning, everyone. My name is Dan Switzer, and I lead the Daiichi Sankyo Oncology business for the U.S. Today, I'm going to walk you through our performance for ENHERTU in the U.S. as well as our plans for continued growth. Next slide, please. I want to start by giving you an overview of the full range of capabilities that we have in the Daiichi Sankyo US Oncology Business division. The organization has 5 core functions, all of them work together to support providers and to enhance the care that they are able to give to patients, and of course, to generate demand and ultimately deliver profit for the organization. The U.S. Oncology Business division consists of marketing, sales, market access, medical affairs and business operations, and I believe that one of the things that makes us unique is that 70% of our employees are customer-facing. All of the positions in the green text are customer-facing roles, meaning they are out in the community every day calling on oncologists and other providers. They're building awareness, educating, gaining insights, and of course, selling. And they are supported with a very strong infrastructure at the headquarters, providing strategical and operational support. Our success is a product, of course, from great science and medicine, but also of a team that works very closely together to impact prescribing utilization, and ultimately, patient care. Next slide, please. Here are our growth trends since the launch of ENHERTU in 2019. We have demonstrated significant growth since launch, strengthened by key data disclosures and FDA approvals. But perhaps most impressive is the recent growth we are seeing in the U.S. with little new data since 2022. We have achieved almost 40% growth in the current year-over-year and 11% growth in the most recent quarter-over-quarter and all of this is in advance of the launch of DESTINY-Breast06, which I anticipate will give us additional momentum. Next slide, please. This is a deeper look at the trend, and here, I'm showing the split of our business by tumor type and how that has changed over time. In the orange bars is the HER2-positive business, the dark blue is HER2 low. These 2 together make up about 85% of our total volume. What is encouraging to see is the recent expansion of our tumor-agnostic business, an approval we received earlier in 2024. And as you can see, not only is the overall revenue growing for the ENHERTU brand, but we see growth in each of the individual tumor types. Next slide, please. In spite of the success we have had and the recent upward trends, we do have significant opportunity for growth in front of us, and that opportunity is in 3 distinct areas that I'll walk through. The first is HER2-positive disease, where we have had very strong growth, about 25% year-over-year. And even though we have over a 60% market share, we still have several accounts and providers that don't use ENHERTU routinely in the second line. Instead, they use it on a case-by-case basis depending on patient characteristics. We believe, in our opinion, aligns with the NCCN guidelines, that ENHERTU should be used in every appropriate patient once she progresses on her first-line treatment. This is how many providers currently treat, and it's why we have over 60% penetration, but our mission is to make sure that more and more use ENHERTU this way by educating them on the benefits and safety of the medicine. Next, in the middle, HER2 low. Here, we have grown 30% in the past year, but the opportunity in front of us is twofold with DESTINY-Breast06. First, we are moving earlier in treatment, and we are expanding our current patient pool by including the ultralow population. This is a huge patient opportunity for us and one that will require a lot of education as all new paradigm shifts do. And lastly, the tumor-agnostic indication. This one is a true testament to the benefit of ENHERTU. The uptake here has been very strong, and the opportunity remains to significantly increase HER2 testing rates in the non-breast cancer diseases. Next slide, please. Let me start with HER2-positive metastatic breast cancer, and I'll talk about the growth opportunity in front of us. In this slide, you can see 2 groups of accounts. The light blue line represents accounts that are using ENHERTU with most of their appropriate second-line patients. The dark blue line represents slower and low adopters who are not nearly as consistent with their utilization. These slow adopters are accounts that we have identified and recently put focused effort into changing their mindset and their behavior. And since we began this initiative, we have increased their collective market share versus Kadcyla from 40% to almost 60%. There are still several accounts with ENHERTU utilization that is lower than the average. And as impressive as this medicine is there are always oncologists and accounts that require more time, more education and more effort before they change the way they treat. And they represent a great source of growth for us even as more and more accounts have increased utilization, which has fueled our recent growth trends. Next slide, please. Beyond our efforts in the field, we are supplementing this activity with advertising directed at patients, which is something unique to the U.S. market. This new campaign that we launched in October is currently live on several digital mediums as well as streaming television. The goal of this campaign is to make breast cancer patients and their caregivers aware of the potential benefits of ENHERTU and to ensure they are empowered to have informed discussions with their oncologists about ENHERTU as a treatment option. So in addition to educating doctors directly, this campaign is aimed at getting patients themselves to initiate discussions with their providers about ENHERTU. And so far, we have reached more than 150 million households at an average frequency of 4x with this ad. Next slide, please. Our next driver of growth is the DESTINY-Breast06 trial that was approved last month in the U.S. This indication is for chemotherapy-naive patients after endocrine therapy in hormone receptor-positive disease with low- or ultra-low levels of HER2 expression. In this study, ENHERTU showed a statistically significant and clinically meaningful benefit in progression-free survival versus chemotherapy. And while the OS is immature, the overall survival is trending towards an advantage for ENHERTU. We do know that at a 12-month marker, 88% of the ENHERTU arm were still alive compared to 81% in the chemotherapy arm. This indication represents a global opportunity of 18,000 patients, and it expands the eligible patient pool significantly for ENHERTU. Following this trial, ENHERTU is now the first and only targeted therapy approved to treat HER2 ultralow expressing tumors, just as it is the only agent approved in the HER2-low population. Next slide, please. There are 2 key differences between DESTINY-Breast06 and DESTINY-Breast04, which was the basis for the HER2 low approval in 2022. For DESTINY-Breast06, it is earlier. It is immediately following endocrine therapy before chemotherapy. If you recall, the DESTINY-Breast04 indication was after one line of chemotherapy. And next, it broadens the patient population to even lower levels of HER2 expression, including the ultralow patients defined as those with any membrane staining at all. With this indication, ENHERTU can now treat approximately 90% of all metastatic breast cancer patients. So the opportunity with this new approval is to go both earlier and broader. Next slide, please. And here is the historical evolution of HER2 disease that the ENHERTU program has shaped over the past few years. Up until 2022, HER2 designation was considered binary. Patients were positive or negative. HER2-positive patients made up about 15% to 20% of all metastatic breast cancer patients, and that was the total eligible pool for all HER2-targeted treatment. In 2022, with DESTINY-Breast04, ENHERTU showed a benefit in patients with lower levels of HER2 expression, and it was the first anti-HER2-targeted drug ever to do that. This new group, HER2 low, made up about 50% of the previously classified HER2-negative group, expanding the eligible population significantly for ENHERTU. And now with DESTINY-Breast06, and the data in ultralow patients, who showed the same benefit as HER2-low patients in the study, the ultralow population expands the eligible patient pool even more, and now, we can help approximately 90% of patients. Last week, ASCO-CAP, the most influential guidelines in the U.S. related to pathology, recommended that HER2 testing results now be reported as IHC 0 with no staining or IHC 0 with some staining. This is a huge step and will accelerate patient identification for the ultralow population and will speed up adoption in the U.S. And, of course, ENHERTU is the only medicine where eligibility will be determined by this distinction. It is a very unique situation and a big opportunity. Next slide, please. Of course, this new opportunity doesn't come without some challenges. Specifically, ultralow patients are not identified on pathology reports today. So patients with a HER2-negative designation should all be reevaluated to see if, in fact, they are HER2 ultralow, and therefore, eligible for ENHERTU. To do this, our strategy is twofold. First, we are calling on oncologists, educating them on DESTINY-Breast06 and encouraging them to have their pathologists reevaluate existing patients who have a HER2-negative tumor. The oncologists here really need to be the driver of retesting. Second, we are educating pathologists on the difference between HER2 negative and HER2 low and making sure they understand that there is now a clinical and actionable reason to discern these 2 patients. Ultimately, our call to action is to have existing patients with a prior biopsy have their old tissue samples reevaluated, and for new patients, to ensure that oncologists are asking to see the HER2 status as a spectrum, including ultralow and low designations. Next slide, please. As part of our educational efforts, we launched a website in 2022 called her2know.com, an educational website 4 pathologists developed in collaboration with expert pathologists to provide scientifically based evidence medicine and peer to peer led information and professional resources in support of HER2 IHC evaluation, and we have reached 25,000 pathologists globally to date. Next slide, please. The third key opportunity for growth in the U.S. is our tumor-agnostic indication, which was approved in April of last year. The uptake has been very impressive, yet we are still just beginning in terms of penetration, mostly due to the current testing rates, which I will speak more about. This approval was granted based on our DESTINY-PanTumor02 trial as well as trials in non-small cell lung cancer and colorectal cancer. You can see the objective response rates on this chart, which are quite impressive, as is the 22-month duration of therapy, and there is a huge unmet need in later lines for all of these tumor types. ENHERTU is now the only approved HER2-targeted agent approved for certain HER2-expressing solid tumors. And this opens up a patient population of 17,000 globally and 6,000 in the U.S. alone. Next slide, please. Here is how we see the opportunity. Let me orient you to this chart. The height of each bar represents the total number of patients in the U.S. with the given disease, and the shaded area at the top of the bar is the number of eligible ENHERTU patients based on IHC score of 3+. So for instance, the tallest bar, non-small cell lung cancer, has about 70,000 patients in the U.S. with that disease, about 3,000 of them have IHC scores of 3+, so our target patients here are the 3,000 patients or 4% of the non-small cell lung cancer market. You can see along the bottom the percent of each of these tumors that fall within our indication. And these numbers are one of the reasons that finding these patients is the biggest challenge. Still, when you add them up across the diseases, these 6,000 patients represent a very big opportunity for the business. And more importantly, ENHERTU represents a really great option for these patients. Next slide, please. This slide shows the testing rates for the 3 key groups of cancers, all of which around 30%. As a comparison, you can see that for breast cancer, not surprisingly, it is over 90%. The historical rates are low because prior to the ENHERTU approval, there was no treatment for HER2-expressing tumors in these diseases. So the growth opportunity here is getting the testing rates to increase and eventually hope -- eventually match what we see in breast cancer. Fortunately, the NCCN guidelines have already incorporated testing and ENHERTU as a treatment in these areas. So we have some external support and momentum as well. The good news is that when these patients are tested and identified as HER2 positive, the majority of them are already getting ENHERTU. So as we see these testing rates increase, we expect there will be a linear increase in ENHERTU utilization. Currently, we believe the tumor-agnostic indication represents about 15% of our new patients, and the demand for ENHERTU in these patients will continue to grow. Next slide, please. Similar to the HER2-low and ultralow strategy, for the tumor-agnostic business, we need to reach many different stakeholders who are all involved in patient care. Again, pathologists play a critical role as the ones performing the IHC test, but oncologists, and there are many different specialties within oncology here, are the ones ordering the tests. So our efforts continue to focus on oncologists. Feedback from the oncology community so far has been very positive about the ENHERTU data. There is a lot of enthusiasm for ENHERTU in these new types of cancer. Lastly, we have incorporated more education on our HER2Know website, and we continue to educate the entire ecosystem. This will be a critical part of our growth strategy. These were the 3 key areas of growth I wanted to highlight. Ken also spoke to the upside we have in early-stage breast cancer. So overall, in the next 2 years, we will see a doubling from our patient population, and we'll have an addressable market of about 50,000 patients. Next, I want to briefly touch on DATROWAY. Next slide, please. DATROWAY is our latest ADC to gain FDA approval. DATROWAY was approved in HR-positive/HER2-negative metastatic breast cancer based on the TROPION-Breast01 study, where it showed statistically significant and clinically meaningful progression-free survival benefit over chemotherapy with a manageable safety profile. There has been an unmet need in this population, especially in the IHC 0 or true HER2-negative patients who are ineligible for ENHERTU. Next slide, please. And from a portfolio perspective, DATROWAY fills an important area for Daiichi Sankyo's breast cancer portfolio. First, of course, with the IHC 0 population, but also, we expect to see data from our TROPION-Breast02 study soon in triple-negative breast cancer. With that indication, our portfolio will be able to help 100% of the metastatic breast cancer patients as demonstrated here. ENHERTU, of course, serving HER2-positive disease and HER2 low and ultralow for the hormone receptor-positive group and DATROWAY can benefit all hormone receptor-positive patients and after chemotherapy and endocrine therapy. And in the future, we will include triple-negative breast cancer. Lastly, we are very excited for the opportunity we have with DATROWAY in the EGFR-mutated non-small cell lung cancer patient population, which we expect in the coming months. This is a rapidly evolving area, and we think DATROWAY is a great option for about 3,200 patients who have progressed after a TKI and chemotherapy. While, of course, we have indications with ENHERTU beyond breast cancer, this indication approval for DATROWAY really rounds out our near-term portfolio and solidifies us as a key oncology leader in the U.S. And now I will turn it over to Markus Kosch to talk about Europe.

Yes. Thank you very much, Dan, and good morning also from my side to everybody. My name is Markus Kosch and I lead the Daiichi Sankyo Oncology business for Europe and Canada. I'm going to walk you through our organizational setup in Europe in special market dynamics and requirements in Europe and Canada as well as the performance for ENHERTU and the key growth opportunities moving forward. So next slide, please. Daiichi Sankyo's Oncology Business division in Europe and Canada covers the EUCAN headquarter as well as 18 markets, including Canada and Greece, the latest affiliates that were established in '23 and '24, respectively. Over the last year, the EU Oncology Business division has grown into a mature organization of now about 560 FTE with focused investments in key capabilities, including access and pricing as well as sales across those markets. And this right level of resourcing has supported and continues to support our existing business and also successfully prepare us to manage our upcoming indication expansions and asset launches. Next slide, please. Here you see our growth trends since the launch of ENHERTU in 2021. We have demonstrated significant growth since launch, and ended 2024 quarter 3 with JPY 39 billion with 10.5% sequential quarter-over-quarter growth and 53% versus Q3 in 2023. Key drivers of this growth are HER2-positive mBC, HER2low mBC at that stage, and similar to the U.S., all of this in advance of the launch of DESTINY-Breast06, which we expect to generate additional growth momentum in the near term in Europe. The next slide shows you that all our markets in the region in Europe and Canada contribute to our success. Key markets that are also important growth drivers moving forward include Germany, Italy and France, contributing more than 60% of the overall revenue, followed by Spain, Canada, U.K. and a number of other markets that actually some of them are earlier in their launch and growth trajectory. The next slide speaks to our complex access environment. With the 18 European and Canadian markets, we successfully managed a very heterogeneous and complex region. One key difference versus the U.S. is the solid chain link between regulatory approval and HTA and reimbursement decisions on a country level. We deal here with multiple regulatory pathways; EMA for Europe, MHRA for the U.K., Swissmedic and Health Canada and local pricing and reimbursement decisions in each of our 18 markets. This leads to a specific launch sequence for each asset and indication launch, slightly longer time to uptake and peak across the entire EUCAN region versus a single market such as the U.S. But also it leads to resilience across the EUCAN region and the prolonged growth trajectory driven by the sequence of country launches. The next slide shows you that we have actually managed this, I believe, very well over the last couple of years. Despite the heterogeneity and complexity that I mentioned, we have achieved more than 50 national reimbursement successes for ENHERTU across all our European markets in 4 indications, including HER2-positive mBC, HER2low mBC gastric and lung, providing patient access to ENHERTU across our EUCAN region. And it's important to mark that in all big 5, the Daiichi Sankyo market access experts and teams have led the negotiations, and they have done that in a pretty successful way. The next slide shows you that we have achieved in a number of markets record time to reimbursement for ENHERTU with, in this slide here, DESTINY-Breast03, our second-line indication. We have achieved these accelerated reimbursement timelines based on the strong capabilities and pricing and market access. And if you look at Spain example, ENHERTU was reimbursed for HER2-positive mBC second-line patients in only 5 months after EMA approval versus an average time to reimbursement for new oncology drugs in Spain of 23 months, resulting in a difference of 18 months earlier -- reimbursement earlier revenues and a deeper penetration. Similar trends hold true for other key markets, including the U.K. and France, as you see here. The next slide shows the key growth drivers, as we see it for the upcoming indication expansions. We expect to continue our strong growth trajectory with significant growth opportunities in front of us. The first key opportunity is HER2-positive mBC, where we had achieved leading naive patient shares of more than 70% in second line in key markets. However, there are still accounts and customers that don't use ENHERTU routinely in the second line, similar as Dan described for the U.S. Based on the DESTINY-Breast03 data, we believe that ENHERTU should be used in almost every patient once he or she progresses on the first-line treatment. Hence, we continue to maximize our efforts and educate on patient management of ILD in second-line mBC to really insure every eligible patients receives ENHERTU, resulting in significantly higher shares than 70% for new patients across the region. The second key opportunity area is obviously HER2low. Here, we have grown to almost 30% to 40% market share in key markets in the past year after EMA approval and local launches. So we are early in the game, but the uptake is very, very encouraging. The opportunity in front of us is twofold. We will launch ENHERTU DESTINY-Breast04 in HER2low mBC and achieve broad presentation in remaining EUCAN markets. We don't have yet reimbursement in all our European markets for this indication. And on top of that, and similar to the U.S., and what Dan described, we will launch ENHERTU DESTINY-Breast06 in Europe and Canada, and we'll move into earlier and broader treatment, including the ultralow population. Dan also mentioned the tumor-agnostic indication. The opportunity for patients also in Europe can be significant, and we are assessing the opportunity for ENHERTU tumor-agnostic indications in Europe and Canada at the appropriate time with our regulatory agencies in the region. The next slide demonstrates our key opportunity summarized in patient shares. As mentioned, and you see this on the left side here, we have achieved, in most markets, more than 70% of second-line HER2-positive mBC patients in the key markets, and we aim to grow this further and achieve even higher shares across the entire EUCAN region, including all 18 markets. Our early launch markets also show a very strong performance of 30% to 40% new patient shares in the HER2-low segment, you see that on the right side here on the slides, with the aim to launch in ENHERTU in HER2 low in the remaining EUCAN markets and to continue our growth trajectory in that segment in preparation for DESTINY-Breast06 in Europe. The next slide shows you something specific about the European region. I mentioned before the solid chain link between regulatory approval and local reimbursement decisions that leads to a specific EUCAN launch sequence for indication and asset launches across countries. Here, you can see the example for ENHERTU DESTINY-Breast03 in blue, where you see how after the EMA approval, which came a little later than in the U.S., countries driven by their reimbursement agreements and negotiations launched the assets once it was reimbursed. You see the same for DESTINY-Breast04 in the green graphs here, again, a sequence after the approval, the EMA approval, that came 6 months later than in the U.S. You can see that EUCAN is still in an earlier stage than the U.S. with expected continuous growth momentum based on the remaining DESTINY-Breast04 launches, and of course, then with a similar sequence future DESTINY-Breast06 launches after EMA approval. The next slide gives you an idea of the eligible patient opportunity in Europe. We have reduced the ENHERTU performance and also the opportunity in EUCAN, and I would like to conclude with a view on the patients. Overall, in the next 2 years, we will see a doubling of our eligible patient population, and ENHERTU will be able to help more than 37,000 patients with HER2-positive mBC, HER2-positive early breast cancer, HER2low breast cancer, gastric and lung cancer across the EU. These numbers here refer to EU4 and the U.K. So there's an upside for smaller markets that would add to these numbers. And on my last slide, I would like to close comment a little bit on DATROWAY. Dan has already highlighted the TROPION-Breast01 data and how DATROWAY will complement and grow our portfolio. In Europe, we have received a positive CHMP recommendation for TROPION-Breast01 January '25, so a couple of weeks back, and we're expecting EMA approval as an additional growth driver in 2025 soon. Importantly, DATROWAY will also complement our ENHERTU portfolio in breast cancer with an extensive and promising Phase III program for potential future expansion into lung cancer. So in summary, we are very positive that driven by the current indications and approvals by the continuing launch sequence for DB-04/DB-06. And also, DATROWAY, we have a number of growth catalysts in Europe that will enable us to grow our business and help even more patients in the years ahead. And with this, I would hand it back to Ken for concluding remarks. Thank you very much.

Next slide, please. Thank you very much, Markus and Dan. As shown on this slide, in the next 12 months, ENHERTU will be delivering major growth catalysts after major growth catalysts, substantially increasing the number of patients that this remarkable medicine can help. Next slide. ENHERTU's catalysts in '25 and '26 set the foundation for DATROWAY and the next wave of ADCs across multiple cancers. In 2025, Daiichi Sankyo transforms from being the ENHERTU company to a company known for developing and delivering standard of care-changing ADCs across multiple tumor types, time and time again. Next slide. I hope that we conveyed to you the optimism and passion we have for oncology business. We understand Daiichi Sankyo is in an enviable and unique position today to dramatically improve patient outcomes through our ADC science. Our task is to educate, motivate and even inspire the oncology community to embrace these drugs for their patients. This will lead Daiichi Sankyo to become a top 10 oncology company as measured by revenue in the next few years. Thank you very much, and now, we'll take questions.

Thank you, Ken. We'll now take questions. [Operator Instructions] The first question is from Yamaguchi-san from Citi.

This is Yamaguchi from Citi. I have a few questions, but the first one is that your comments on the U.S. raising the share on a focus account was pretty impressive. But at the same time, I'm surprised to find out there are several other doctors who are still using Kadcyla, all the data which already given. So can you give me 1 or 2 reasons why those doctors are still sticking to the Kadcyla? Is it a safety thing? Or is it just a standard of care? Or can you give me why they are sticking to it and why they stopped changing it? It's just not knowing those things, is there any reason behind it?

Yes. Dan Switzer, please answer that.

Yes. Thank you for the question. The biggest reason is that it's just hard to change habits that have been ingrained for many years. And some oncologists like the way that they treat. They are comfortable that way. They understand how Kadcyla works because they've used it for so long, and they just need additional time and effort by us to change their habits. I would say, secondarily, yes, the providers that are using it after T-DM1, some of them may have some concerns about safety because they don't have as much familiarity and some of them may want to use it after T-DM1 instead. But the good news is that over time, more and more oncologists continue to adopt ENHERTU even if it takes them a long time in the first place, and that's the growth opportunity that we have in front of us.

The second question is regarding a little bit of number of the patients, so I try to make clear. The first one is, can you give us the TB-01 patients, which was not in the slide, potential patients, if you have?

Let's see. I think, Dan, can you go to the one slide that shows all the different look in terms of ENHERTU and Dato? I believe it's slide 41, please. So when you take a look at the TB-01 opportunity, as Dan outlined, it's for the HR-positive/HER2-negative patients. However, when you look at the incredible efficacy of ENHERTU in the DB-06 trial, we expect that the majority of physicians will prefer to start with ENHERTU, right? It's just such an amazing product in terms of the overall survival that Dan mentioned and the progression-free survival. So we actually see the TB-01 being adopted more in the true HER2-null patients, the IHC 0 with no staining. And so that population is more limited compared to the opportunity that we have with DB-06.

Great. And quickly on another one. DB-09, which is the first line, the potential first-line patient should be around 20,000, but you are talking about several thousand only. But you have a footnote saying that you're trying to kind of subtract overlap with the current indication. Is that the right way to see it? Because the potential market itself on the first line should be much bigger than those numbers on DB-09.

Thank you for the question. You are correct. So what we tried to do is show the incremental population over and above DB-03. And remember, as Dan and Markus showed you, we've got nice penetration in that DB-03, which is the HER2-positive metastatic second line. And so the numbers that I quote is the incremental to DB-03.

Right. So finally, DB-06 number is also incremental or not really compared to DB04? Sorry for...

No, no. Let me make the clarification.

Yes, DB-06 number. You gave us DB-06 number, but slide says -- after DB-04.

That is correct.

Yes. Did you consider the overlap or not really?

Yes, we did.

You did. Okay. So finally, it's a kind of request for Manabe-san. You have a huge R&D day, of course, a lot of pipeline, and you have a huge commercial day, which you have a lot of things to talk about. But reality is it's kind of got together these days, R&D and the marketing is kind of the same thing on each brand. So my request for you is that why don't you have the R&D and the commercial day together, for example, Analyst Day or Capital Day rather than kind of splitting up completely because science and technology, the marketing seems to be kind of got together in oncology space.

Thank you very much, good suggestion. I would like to consider the suggestion into account.

The next question is from Muraoka-san from Morgan Stanley.

I'm Muraoka of Morgan Stanley. Let me ask the question in Japanese. DB-06, a related question, please. The past study, DB-04, et cetera, experience, after the approval, the growth has gone through one round. That timing would be about 2 -- was about 2 years for this one cycle of growth to finish. And as for DB-06, like in the initial 2 years, it would grow largely? And then, is it better for us to think that it would slow down after that? Or for the diagnosis to penetrate it, it would take long, therefore, for a longer time, the growth period would continue? What's the way of thinking about that, please?

Yes. Thank you very much for that question. We do believe that the ramp-up for DB-06 will be rate-limited to the patients being identified for that HER2-ultralow. And as Dan mentioned, one of the key things we need to do is not just ensure that the new patients are identified, and with the CAP guidelines that Dan mentioned, that will happen fast. However, in patients that have already been under treatment, we need to motivate the oncologists to ask the pathologists to go back and look at the IHC 0, whether it's staining or not. That's going to take a longer period of time. And so I expect the ramp-up to be not as steep, take a little bit longer and just get bigger and bigger and bigger over time.

[Interpreted] And next, Dato -- TB-02, and this result based upon assumption [indiscernible] ascent. If the result is similar to that, what would be the marketing strategy that you would have? So the launch will be 3 to 4 years late. And if the level of result is similar, what kind of message would you disseminate?

Well, as you mentioned, it will obviously come down to what the trial actually shows in terms of the clinical results. Based on the profile, then we'll dictate how we communicate and how we educate physicians. I do think we have a tremendous advantage in going to the oncology community, the breast cancer treating physicians with both ENHERTU and DATROWAY. As Dan mentioned, there's no other company that can actually walk into an oncology office, a breast cancer treating physician and say, "I've got 2 medicines that can help 100% of your patients." So I think the distinction is obviously the drug, but also the company, and I see great synergy there.

[Interpreted] Lastly, a short question. Today's oncology day, on the material, it was not included, but TURALIO, TGCT, for you, I understand it's a small product, but in terms of safety, a new product with a good safety profile has been approved. And TURALIO, is there any impact? And those with TURALIO was not delivered to, are you assuming a rapid treatment to prevail in those patients?

Thank you for the question. TURALIO has been available for patients with tenosynovial giant cell tumor for a number of years in the U.S. And doctors are very comfortable with the drug. So I expect that all the patients who are doing well on TURALIO today will continue to be treated. And then physicians, for the new patients, will have a choice between TURALIO and the new drug that you mentioned. There are pros and cons for both drugs, but we see that the choice will be for new patients, not existing patients. And as you know, this is a chronic disease. These patients are treated for a very, very long time.

[Interpreted] TURALIO's safety, would that reason could -- I think that there are a lot of patients that would not receive the treatment because of the safety of TURALIO?

TURALIO, as you mentioned, has -- the primary toxicity is liver toxicity. And in the United States, it requires physicians to enroll patients into a REMS program, a Risk Evaluation and Management program. I do believe that for both of these medicines, the new one you mentioned and TURALIO, patients go through multiple surgeries first. And these drugs will be used only for patients where surgery does not cure them. And so it's a later line progressive treatment. I don't believe that there is a massive pool of patients waiting to be treated. And so I think it will more be the market growing slightly and doctors making a choice for new starts between these 2 medicines.

The next question is from Hashiguchi-san from Daiwa Securities.

[Interpreted] I have a question about the Page 37. IHC testing rate is more or less as over the 30% in several cancer types you mentioned. And moving forward, how high do you think that you'll be able to raise this testing rate? And the driver of raising the testing rate, what are the factors, for example, some technological innovation of the testing or motivation for testing? Any new data motivating the people to test more? Do you have anything in mind? If any, when will they be available? I'd like to know those.

Dan, can you take that question?

Yes. Thank you for the question. The testing, we don't have a forecast for the testing rates, but there is a lot of motivation for the testing rates to increase, and we do expect them to increase significantly. The way that we will increase these testing rates comes in 2 parts. First, you mentioned the motivation, and that is an important part. We have hundreds of our colleagues educating oncologists and now pathologists on the pan-tumor studies and the tumor agnostic indication. And with the NCCN guideline update and the CAP updates, there will be more and more awareness that there is a reason to test. The rates are low because there has been historically nothing actionable to do with it. But the other, and perhaps more rapid enhancement of testing, will be with the testing companies. There are certain companies that automatically show HER2 IHC tests when a panel of tests are ordered. And when they come back, the IHC score for HER2 is included even if the oncologist didn't ask for it. We are working to get more and more companies to have the test automatically done. So between the motivation of the oncologists and the education of pathology and the testing companies, that's how we plan to increase these testing rates.

The next question is from Sakai-san from UBS.

[Foreign Language] This is Sakai from UBS. I have 2 kind of related questions. The first one, this may not be a fair question, Ken-san, but I share your optimism and passion for Daiichi Sankyo growth story. But share price recently doesn't look that way. Now what we're missing? I mean this may not be a fair question. So I'm going to say your story today really documents the nice growth story from ENHERTU; however, DATROWAY and following ADCs, we still haven't seen pathway go through. Now first things you're going to probably have to do is how you manage overlap between ENHERTU and DATROWAY. It seems to be the better the ENHERTU, less opportunity for DATROWAY, especially in the breast cancer. Is that right observation? That's my first question.

So thank you for the question and the comments. I do believe that ENHERTU's incredible efficacy, doubling progression-free survival, looking like it's making a big impact in OS, it's going to be the preferred drug for the majority of the patients that Dan Switzer outlined today. I think that's fair. I think that's what's going to happen. I do think DATROWAY is going to find a place where ENHERTU is not indicated. So that will be the TB-02, the triple negative area, and also the IHC 0 with no staining HR positive. So the right expectation is ENHERTU is going to be the dominant drug in breast cancer, but DATROWAY also will be an important supplement. The big opportunity for DATROWAY is more in the lung cancer space. The EGFR-mutant non-small cell lung cancer PDUFA date is July. Now all of these patients today are treated with a TKI, mainly osimertinib, which is sold by our alliance partner, AstraZeneca. So there's no better partnership to bring this drug to that group of patients in AstraZeneca and Daiichi Sankyo. The response rates are very impressive. And today, the other available options for that patient population after TKI are very difficult to tolerate, and so, what happens is doctors -- these patients are frail, they're sick and they're looking at DATROWAY as a really nice addition. So I think the uptake is going to be quite nice there. And then, of course, the first-line non-small cell lung cancer trials have very, very large populations, and that's where DATROWAY will really live.

Right. So we will see second half of this year after DATROWAY likely approval. So let's just keep fingers crossed. Second question is Slide 38. Now I know between -- I mean, you clearly said how you can differentiate ENHERTU and DATROWAY. But over oncology franchise, you still have to have these micro managements, especially for human resources side. Now are you saying you've got enough resources, you got enough stuff to go through all these processes with Daiichi Sankyo, excluding AstraZeneca and in the future Merck? That's my second question.

Yes. So this is Ken. And I'll start, and then, Dan, I'll turn it over to you. Today, when we're looking at this slide, we're leveraging the talents of both companies. So today, AstraZeneca, based on their portfolio beyond ENHERTU and DATROWAY, they've got a very large diagnostic educational medical affairs team and a corporate account team. So we do leverage them with a pathologist, and that's one of the beauties of this alliance. But I will say, as we look at the future, I believe Dan and Markus' team have set up very well to do things by ourselves. But it's only smart to leverage the strengths of companies that were in these alliances with. Dan?

Yes. Thank you, Ken. I agree completely. I want to emphasize the alliance is 50-50 in total, but of course, there are certain areas where one company may lead and the other company may support. Ken talked about diagnostics, and we are leveraging AstraZeneca's diagnostics team. The Daiichi Sankyo payer team, market access team in the U.S. leads in that capacity, and we have a very strong market access team. So we are using the best capabilities of the entire alliance, and Daiichi Sankyo is using this as an opportunity to enhance our capabilities for the future as well.

Can I just question the similar question in European setting? AstraZeneca, the European company, and clearly, they should have some kind of leverage. Can you elaborate a bit more?

Yes. Thank you for the question. And yes, as in the U.S., we have a partnership with equal efforts. So teams work closely together with partnered approaches in sales, in commercial and medical. Specifically, when it comes to established relationships with pathologists, clearly giving their portfolio in legacy our partners at AstraZeneca have a stronger legacy, have a stronger kizuna built with those stakeholder group. And we learn from them. We do things together. But clearly, in that part, they will -- probably when it comes to actually driving testing rates in Europe as well as a key strategy, they will probably lead and help us building our capabilities in that field.

The next question is from Tony Ren-san from Macquarie.

So my -- a couple from me. So my first question, I would like to go to DATROWAY. This is probably a question for Dan or Ken. You guys have had this drug in the U.S. market for about a month. Just want to see what are the initial clinician feedback for a few weeks that you have had it on the market? What's the initial market share, if you have already started collecting that data? This is a place with a lot of -- with a fairly wide range of therapeutic options, right, taxane, anthracycline, capecitabine and Trodelvy. Which of these are you trying to unseat or displace first?

Dan, please answer that.

Yes. Thank you for the question. It's too early for us to have a market share, and it's even too early to have a sense of the demand versus expectation, although it seems to be right on track. The early qualitative feedback is exactly as we expected. There are patients that oncologists feel are appropriate candidates for. At this stage, which is common for a new drug launch, it may be patients who have very few options, and we are also seeing and getting feedback that in the IHC 0 patients, as Ken spoke to, seems to be the best fit and the best place for an opportunity. So we will continue to update you all as we get more and more feedback and data, but mostly, I'm going on the qualitative data that we have because we're just a few weeks in.

Okay. Excellent. Yes, we definitely will await more feedback. I would like to go -- next, I would like to go to Slide #57, where basically, it appears to me that you nearly doubled the number of patients from your presentation about 10 months ago, right, in April 2024. Back then, you said 5 ADCs, over 30 indications, about 300,000 patients, now it's 700,000 patients, nearly doubling. And the number of the drugs, the number of the indications appear to have been unchanged. So I just want to see what has led to such a large dramatic increase in the number of patients.

Thank you for that question. We've built this from the bottom up. I'll answer it this way. The biggest potential in terms of helping new patients comes from ENHERTU's earlier-stage studies that's DB-11 and 5, then more than that DATROWAY's first-line non-small cell lung cancer trials have an enormous population. Those are clearly the 2 biggest. After that, R-DXd in ovarian cancer, as we anticipate data coming in, that's also a very, very significant opportunity. I'll have to go back to the previous and dissect that for you, which I'm very willing to do after this meeting.

Okay. Sure. The next one is about your 5-year plan. When you reported your third quarter results, there were some concerns amongst clients that you may or may not be able to meet the target -- revenue targets set out in a 5-year plan for fiscal year 2025. So you obviously left the target unchanged. So that's very positive. This is despite the fact that you have repositioned the DATROWAY now for a narrow set of lung cancer patients, those with refractory EGFR disease upon treatment. And then you have also had a delay due to manufacturing on HER3-DXd. So despite these delays, you left your target unchanged. So could you just explain that to us what's the thinking behind that?

Yes, this is Ken, and I'll start, which is, first, we will be doing an update in April, and so there'll be more information there. There are so many readouts this year. When we look at all the trials that we went through, that opportunity allows us to hopefully do more, especially with ENHERTU with data clearly, the first launch is going to be in a smaller population, but in April, we'll provide you full guidance.

Okay. Perfect. So talk about launches, right? So you have -- assuming you're -- for DESTINY-Breast11 and DESTINY-Breast05, assuming the interim data are positive, this is more of a regulatory question, not a commercial question, but would you be looking to file regulatory application based on these interim data? Or would you have to wait until the full study completion of these studies in 2027 and 2030 to file your application?

So for 05 and 11, this is an early-stage breast cancer. The primary endpoint is pathological complete response for one and invasive disease-free progression, both of those have been accepted by the FDA with other drugs in this setting. It's going to come down to the magnitude of benefit.

Okay. So possibly, if the magnitude of benefit is very large, you can go with and -- you can go file based on interim data.

That's correct.

The next question is from Wakao-san from JPMorgan.

This is Wakao from JPMorgan. Firstly, I'd like to know about your thought on the positioning of DB-06. In NCCN guideline, DB-06 is recommended as a recommended regimen, so Category 2A. Why it was categorized as other regimen instead of Category 1 before it? And do you think physicians will choose ENHERTU even if it is categorized as Category 2A, not 1? It is the first question.

Yes. Dan, why don't you take that?

Yes. Thank you for the question. The NCCN doesn't -- they don't share with us the rationale when they update the guidelines. So it is only to speculate. I think it goes back to something I said earlier, which is that treatments like oral chemotherapy, that have been around for a very long time, have been the standard of care and the panelists must be very comfortable with capecitabine and other systemic chemotherapies. And so their guidance is for ENHERTU to be used based on patient characteristics. That's not so much a surprise to us. ENHERTU tends to be used based on patient characteristics. But often, it is the most common patient characteristics that lead to choosing ENHERTU. So we're comfortable with it. And I think over time, we'll start to see the market evolve more and more to ENHERTU. In terms of your question, I think that what we have seen, what we have heard is that regardless of the guidelines, ENHERTU will be a very common choice for patients immediately following endocrine therapy.

And I'll just add one thing, which is Dan did mention earlier about the 12-month landmark overall survival. Overall survival is immature right now. There's only about 40% of the events, but we're already seeing a nice separation at 12 months, 7% more patients are alive on ENHERTU. So my belief is as that data matures and the OS benefit becomes very, very stable and strong, I find it hard to believe the NCCN wouldn't reflect that in the future.

Okay. Very clear. And second question about U.K., the investment. So I understand that DB-04 is not currently invested in the U.K. How should we see the investment potential of DB06?

It's -- yes, sorry. Yes, that's a very good question. And, of course, we are evaluating the options, and we will, yes, again, engage in discussions with the NHS, with the reimbursement HTA authorities there to hope, of course, to open access for patients also in the U.K. for DB-06, as we still hope in the future, and potentially DB-06 is a trigger, to consider again bringing up the DB-04 data. We have been very disappointed, as you know, that we couldn't actually find an agreement with the authorities. The U.K. is a very, very challenging environment when it comes to reimbursement. But we are hopeful that DB-06 gives us the opportunity to reopen those discussions.

And just to add, the U.K. is a complete outlier. The way their system works for metastatic disease, when you help patients live longer, there's actually a mathematical negative to that. And so we'll continue the dialogue. DB-06 is very strong, and we'll see where we go. But the U.K. is an outlier.

Yes. And look, I might add 1 sentence. You might, if you're very familiar with the U.K. system, know that the recent, yes, a couple of -- 2 years back, change in their methodology has led for all oncology drugs to make it more difficult to prove their value for these advanced diseases. The end-of-life criteria has been taken away, and there is a lot of public interest in restating this system to hopefully be more fair, let's say, in the assessment to oncology treatments for more advanced treatment. So a policy change might in the future give U.K. patients a better chance to have access to new medicines. That's my hope.

Okay. So lastly -- sorry for the detailed questions. So regarding the patient number -- target number of DB-11, so it seems there are -- the number of targeted patients you anticipate is a little higher than my expectation because in DB11, I understand, this trial, targets high-risk patients. Does this number reflect high-risk patients? If it does, what percentage of patients are estimated to be high risk?

So let's see. I'm just looking at the slide. These numbers do reflect the high-risk population within the original T-DM indication. So it's just the high-risk patients, and we're comfortable with these number estimates.

By percentage, high risk?

So if you look down, on the bottom, when you look at the different stratification, what we're looking at is about 65%, 70% of the entire T-DM1 neoadjuvant indication.

The next question is from Sogi-san from Sanford Bernstein.

So first question about the U.S., the DB-06, the -- for HER2 ultralow, the reevaluation. So this is kind of another operational question. So the -- we understood that DB-04 has been around, so the doctors are used to looking -- relooking at the HER2 status. But what we understand that is this is -- the DB-04 is HER2-low. So I think probably the data is available. So for DB-06, my understanding is this evaluation is needed for ultralow population, for the low population the data is already available as in DB-04. And for this ultralow, the diagnostics, do you require the re-biopsy or just they can look at, go back to the old, the slides and just the re-evaluation?

Yes. So absolutely, you do not need to read biopsy. These samples are kept. They just have to be retested.

I see. Great. And for Europe, I have 2 questions. So first of all, just in general, as you nicely laid out, how different each countries are in terms of their evaluation and decision on reimbursement. And based on that, probably you cannot really -- they talk about a specific strategy for specific drug, but kind of in a high level, what are the kind of general strategy in terms of sequencing of reimbursement negotiation?

Markus, please?

Yes. That's -- thank you very much for the question. As you know, there is a few countries, Germany being the most important one, where directly after EMA approval a new drug is reimbursed, and we start negotiating while the drug is available. So for a country like Germany, it's a very clear process. Within the first 12 months, you need to come to an agreement with the authorities. In most other markets, and the processes, as you said, are different country by country, we have to build dossiers, and we prepare building those dossiers, whether it's an HTA market or it's value-based pricing mechanisms or it's a budget-driven mechanism; in some countries, there's different criteria, there's different HTA assessments. We built those dossiers, and we try to submit as soon as we can after EMA approval is there. And then the sequence actually is mostly driven by the time it takes to come to an agreement. As I showed for Spain, with DB-03, we have been successfully able to secure reimbursement after only 5 months. But this could have taken, and for DB-04, as you might have heard, it took more than a year. It can take a year or 18 months. So the sequence is actually driven by the time the local system takes and needs and how many rounds of negotiation it takes to come to an agreement. And there is, of course, experiences, so some systems are slower, some are closer regulated like Germany, some take longer. And then it depends on the data, on the negotiation team. That's how the sequence is not looking always the same for each asset and dataset. Is that answering the question?

Yes, yes. Yes. And one additional question on this. Is there also the consideration of how some countries' decision influence the others?

Actually, of course, there is public prices, and there is not public prices in different markets. And, of course, the public prices are visible to all European countries. There is clearly an interest also driven by a desire for equity to find comparable reimbursement schemes for most major markets. But actually, this is not driving timing of submission or speed of negotiation, not within the European Union, where we also have, as you know, free trade and a relatively free flux of products and medicines across European member states.

And also in your presentation, you highlighted -- as one of the opportunities in Europe, you also highlighted ENHERTU's the HER2-tumor agnostic. We understand that in the U.S., there's a kind of clear -- clearly establishing a pathway to having accelerated approval for the -- for drugs such as ENHERTU based on Phase II data for tumor agnostic indication, but this is not the case in Europe. I just wanted to see how you see the path forward in Europe.

Yes. A very good question, but not an easy one as well. As you rightfully said, EMA has a slightly different approach to uncontrolled or Phase II data. We -- I -- and we at Daiichi Sankyo in Europe clearly believe and share this with our partners with AstraZeneca that the tumor-agnostic data that then shared are open, a great opportunity also for patients in Europe, and we will work with the regulatory authorities to hopefully file the path forward. Whether that looks exactly that in the FDA, that's really a matter that we need to discuss with the regulators within the alliance, but we're exploring opportunities to open this new option also to patients in Europe. And the -- actually, strategies to achieve that are similar like in the U.S. But it's too early to actually update you on when and if and how this could potentially be achieved.

The final question is from Michael Nedelcovych-san from TD Cowen.

I have 2. My first is on positioning of ENHERTU in DATROWAY in breast cancer. I know that it's very early days, but these drugs do have minor overlap in their labels. And I'm just curious if you have any insight into how physicians are using them in concert, whether it be sequencing or otherwise? And then my second question actually relates to patritumab deruxtecan, your HER3 ADC. I know it wasn't a focus of this presentation, but the early breast cancer data are very compelling, and I'm curious what your plans are to pursue that agent in breast cancer. And maybe I could layer on the question of how you might approach 3 different ADCs with the same payload in potentially overlapping indications.

Yes, this is Ken. Thank you for the question. The way we look at it, the clinical data for ENHERTU is going to make this the go-to drug for -- as Dan mentioned, we believe 90% of these breast cancer patients between DB-06 and as you look at 11 and on 5 as well, but let's stick for the metastatics, anyway that's really the overlap, ENHERTU's data is just universally looked at as being incredible. And so that's going to be the drug that physicians reach to for first for 90% of those patients. For the IHC 0 patients, DATROWAY is going to be a very important drug for those patients as well and for the triple-negative breast cancer patients. That's how I see and we see the market evolving. You are correct, the early data on our HER3-DXd ADC in breast cancer is very encouraging. We're working with our partners, Merck there, to optimize that drug as well. It's an abundance of riches to have these 3 drugs into the breast cancer space, and we hope to help as many patients as we possibly can. I think the second question was -- HER3, and so -- as the HER3 breast cancer data evolves, we will fit it in and always lead with what is best for patients.

We have run over the scheduled time, so we will now conclude Daiichi Sankyo's Oncology Business briefing. Thank you very much for joining today.