Thank you for your participation. We will now begin Daiichi Sankyo Science and Technology Day 2025. I am Asakura from Corporate Communications. You are moderator today. First, regarding languages, this briefing will be conducted in Japanese and English. Simultaneous interpretation is available. Please click the interpretation icon at the bottom of your Zoom screen and select either Japanese, English, or original audio. If you select original audio, you will hear the original audio. The Zoom screen and live stream will display the English presentation materials. The Japanese and English presentation materials are available on our corporate websites, IR Library, under the IR Presentation Materials page. Please download and view them as needed. Today's speakers are: Okuzawa, President and CEO; Takeshita, Head of Global R&D; Ken Keller, Director and Head of Global Oncology Business; Kashiwase, Head of Global Technology; and Abe, Head of Global Research.
Following the presentations, we will hold a Q&A session with all speakers. Please note that today's briefing session will be recorded. Okuzawa-san, floor is yours.
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This is Okuzawa speaking. Thank you very much for joining Daiichi Sankyo's Science and Technology Day 2025 today. We sincerely appreciate your attendance. Leveraging our greatest strength, science and technology, we have delivered numerous innovative medicines to patients. Within this effort, our oncology pipeline and product portfolio has grown significantly over the past six years through strategic alliances with AstraZeneca and Merck & Co. Enhertu has been approved for six indications, making a significant contribution to affected cancer patients, and this year we announced three positive phase III datasets for early-stage breast cancer and early-line treatment of metastatic breast cancer. For HER2-positive breast cancer first-line treatment, we obtained approval yesterday, U.S. time, for early-stage breast cancer. We are preparing to bring each of these to patients. Furthermore, we have initiated four new phase III studies to further expand the product's value.
Regarding Datroway, we have experienced various things, but following its launch early this year, it has already obtained a second indication and subsequently obtained positive data in TNBC preparations and is now underway to deliver it to patients. Moreover, we are advancing more than 10 phase III trials, anticipating substantial future expansion of the product's value. Regarding I-DXd and R-DXd, favorable efficacy and safety profiles, respectively, were confirmed in the phase II trials. We are currently engaged in discussions with the authorities to establish new treatments for cancers with high unmet needs. We are also exploring various possibilities for expanding the range of applicable cancer types. Through I-DXd and R-DXd, we aim to contribute to cancer patients in ways distinct from Enhertu and Datroway.
With respect to HER3-DXd, we are advancing clinical trials targeting solid tumors other than lung cancer, such as breast cancer, and simultaneously, we are actively pursuing biomarker discovery. Further, clinical trials for DS-3939, which we are currently developing independently, are progressing smoothly. Also, we are preparing to commence clinical trials for DS-3790, our first DXd ADC targeting hematological malignancies. Preparations are underway to commence clinical trials. Thus, the DXd ADC platform is not only driving Enhertu forward, but also numerous innovative cancer products, powerfully driving the enhancement of our corporate value. The DXd ADC platform has also obtained high praise from outside the company. In November this year, we won the Best ADC Platform Technology Award with the recognition of our DXd ADC technology as the best ADC platform capable of providing new standard treatments for cancer patients.
Moving forward, we will further leverage our science and technology to create innovations following our DXd ADC platform and aim to become a top-10 global company in the oncology field, or even more than that, by 2030. Today, we first begin with Dr. Takeshita, the Head of Global R&D, on our R&D achievements to date and future strategy. Following this, Ken Keller, Head of Global Oncology Business, will discuss the growth and outlook for our oncology business. Then, Mr. Kashiwase, Head of Global Technology, will explain our global manufacturing framework and supply chain strategy. And finally, Abe, Head of Global Research, will introduce our research domains. In the next fiscal year, we plan to announce our sixth midterm plan. We will continue to prioritize maximizing the value of DXd ADCs, and through challenging new innovations, we will strive to contribute to patients and achieve sustainable growth.
So first of all, Dr. Takeshita, please.
Thank you very much for that introduction, and it's my pleasure to go over with you our clinical development programs for Daiichi Sankyo. Next slide. I did want to emphasize here that we have four major themes from my portion of the presentation. One is that we have many DXd ADCs. We are more than just the Enhertu company. We are really becoming a DXd ADC company right now for the next few years. But in addition to the DXd ADCs, we have new concept ADCs with different characteristics than a DXd ADC that we'll go over with you, and not only that, we have a lot of interesting compounds in our pipeline that are not even ADCs, so we'll go over that with you also.
And finally, I do want to make some points that because of the strength of our internal oncology pipeline, that we can create scientifically rational combinations to include not just external combinations with external compounds, but also two internal compounds. This really is a very big advantage for us in the future. Next slide. Just to give you some additional bragging information, you can see a short list of major accomplishments for this calendar year. And it includes many, many Enhertu regulatory approvals, breakthrough designations, and as well as also regulatory approvals for Dato-DXd in lung cancer and now, of course, in breast cancer. And we are, of course, also moving ahead in other DXd ADC programs, including breakthrough designations for I-DXd and R-DXd as well. So we are really forging ahead with all of our DXd ADC programs. Next slide.
Additionally, we have published many, many papers in our DXd ADC technology and also have been featured in many articles in top journals like New England Journal of Medicine and Nature Medicine. As you just heard, we have received many awards for our technology. Next slide. Okay, so let's just go over now by indication. This, I think many of you are familiar with this, what we call a disease map. The columns represent different lines of therapy from neoadjuvant on the left column all the way to second line and later relapse refractory cancers. The rows represent various subtypes or subgroups of breast cancer. Then you can see that each box is represented by the clinical trial that we are conducting. Just to remind you that these are color-coded. The orange ones represent Enhertu clinical trials. Blue represent the Dato-DXd clinical trials.
The green represents the HER3 programs. Furthermore, the color scheme is such that the dark-colored boxes are already approved. You can see that with Enhertu, there are a lot of dark orange boxes. For this year, I would like to note that we have four additional new data that are positive phase III trials. Three are in the Enhertu category: DESTINY-Breast11, DESTINY-Breast05, and DESTINY-Breast09, and one from the Dato-DXd program, TROPION-Breast02. As you heard, DESTINY-Breast09 was just approved by the FDA earlier today, U.S. time. This one should change color from light orange to darker orange. Of course, it's an amazing set of accomplishments in just one year for this entire program. I also want to make a mention of the blue ones in star.
These are the TROPION-Breast series of Dato-DXd trials, TROPION-Breast03, 04, and 05. These are going to be a next set of trials in early-stage breast cancer in TNBC. I'm going to go over with you some early data that really points to a very strong data that predicts for, I think, what is likely to be a successful clinical trial outcome in the future. Next slide. Just to very briefly go over some of these very interesting and positive clinical trial data, DESTINY-Breast11 in neoadjuvant setting and DESTINY-Breast05 in post-neoadjuvant setting. Both of these have very positive endpoints that are not just statistically important, but also clinically meaningful data. Next slide. This is our Dato-DXd TROPION-Breast02 study. Again, this is very important data showing not just positive PFS data, but also overall survival data.
Just a side note to say that this is a very interesting clinical trial because there are additional comparisons and maybe some cross comparisons that we can make with similar ADCs. We can see that the fact that we achieved overall survival data here is very important and meaningful compared to some of the other TROP2 targeting ADCs who have studied a similar patient population that did not achieve overall survival benefit. Next slide. Now, going on to these additional ongoing studies, TB- 03, 04, and 05, we have early data from a clinical trial called BEGONIA in which Datroway is combined with durvalumab. We have some preliminary data here from the BEGONIA study, really showing us some early data, but very strong in terms of not just response rates, but durability of response.
These are very important preliminary data that gives us really good reasons to believe that our eventual phase III studies, TROPION-Breast 03, 04, and 05, will eventually report out as positive data. Next slide. Moving on to lung cancer, again, this is our disease map. And you can see that we have the EGFR mutated second line and later box filled in with TROPION-Lung 05. We have additional many trials with Datroway. Moving on to Enhertu program, as you know, we have our approval already in the HER2 mutated lung cancer in relapse refractory setting. And we are conducting early line of therapy in HER2 as well. Additionally, we have one more drug in lung cancer, and that is the I-DXd program. With the IDeate- Lung 01 clinical trial data, we were able to obtain some breakthrough therapy designation from FDA.
We are very hopeful that eventually this will lead to approval. Next slide. Moreover, it's important to note here that in small cell lung cancer, we have two drugs, not just one, but two drugs that are very active in small cell lung cancer, I-DXd that you just saw earlier in the previous slide, but also a drug called Go Ketamine. This is a DLL3 targeting T-cell engager, very different mechanism of action, but at the same time, very active in small cell lung cancer. You can really see that this is a natural place to combine these two drugs to really achieve much greater efficacy than just one drug alone. Possibly, once we generate a combination data, it may be a path forward into early line of therapy, including newly diagnosed small cell lung cancer. Next slide.
Now, in terms of the Datroway program, I do want to make a mention of this very sophisticated digital pathology predictive biomarker program that was originally pioneered by the AstraZeneca team. This is what we call TROP2 NMR. NMR stands for Normalized Membrane Ratio. This is something we used to call quantitative continuous scoring, but we have renamed it NMR. So this is what we are calling it now, and this is a fancy way to use digital images, not just regular visual examination of the staining pattern, but the computerized digital image analysis of immunohistochemistry to allow for prediction of whether or not a patient is likely to benefit from Datroway, and next slide, you'll see that indeed this is something that we can certainly do by looking at the TROP2 NMR positivity versus negativity. In this slide, this is from the TROPION- Lung 01 study.
You'll see that in a docetaxel arm, this is the gray lines, the gray solid line and gray dotted line. The overall benefit from the docetaxel is the same regardless of whether you are NMR positive or negative. On the other hand, if you look at the red colored lines, the dotted and the solid lines, you'll see that the dotted line is about the same in terms of performance as docetaxel. These are the NMR negative patients, whereas NMR positive patients have a substantially better outcome because of the ability in which the NMR was able to identify patients who are likely to benefit from Datroway. Next slide. We see a very similar trend, not just in the relapsed refractory setting, but in the early lines of therapy, the frontline setting, even when Datroway is combined with chemotherapy.
This is a very important finding because we can now incorporate this NMR into many of our frontline studies. Next slide. As many of you know, we have a lot of these frontline lung cancer studies going on, not just TROPION-Lung07 or 08, but we have the AVANZAR study. And so we also have TROPION-Lung10, TROPION-Lung12. All of these have the opportunity to have NMR incorporated into the analysis. We are very excited with this prospect of having a predictive biomarker for Datroway. Next slide. Okay. In addition, this is the gynecologic cancer disease map. You'll see again here that we have some colors colored in already. The dark orange boxes for based on the Enhertu approvals. But we also have additional clinical trials going on with Enhertu program, as well as the R-DXd ovarian cancer from REJOICE-Ovarian01. Next slide.
This is some of the data from REJOICE-Ovarian01 study, and you'll see that so far we are seeing really great efficacy. And based on this data, the FDA granted us Breakthrough Therapy Designation, so we are very hopeful that eventually, once we submit the data, this will lead to an approval. Next slide. In GU cancers, prostate cancer and bladder cancer, we also have very extensive programs, and at least in bladder cancer, we do already have an approval with Enhertu, so we have just to show that we have a lot of wide range of disease cancers besides just the lung breast cancer that you're familiar with with Enhertu programs. Next slide. Okay, new concept ADCs. Next slide. It's very important to note that ADCs are modular in nature.
It's also very important to note that our research team, you'll hear about a little bit later from Yuki Abe, has a huge amount of extensive experience in each of these modules: payload module, linker module, and antibody module. Just by combining different ways in which you can have a payload versus linker versus antibody, you can create new ADCs. Now, I think we are often asked, what is our advantage at this Daiichi Sankyo compared to other companies that have acquired ADCs from other companies, biotech companies typically? This slide illustrates our major advantage in the field of ADCs. We have extensive understanding of each of the modules and how they, when they're combined in various different ways, they create new properties and new compounds. This is our major advantage.
We have an extensive history of understanding each of these modules that make up the ADC. Next slide. Next slide. I do want to mention that in addition to our ADC programs, we have started new programs in non-ADC in oncology. This is some of the ones that are listed here. And of course, as we go further ahead, we will be able to report interesting clinical data. But just to give you some understanding of the sophistication of these programs, next slide, I'm going to go over some of these with you. DS-2243. This is a T-cell engager targeting an HLA-restricted NY-ESO-1 antibody. So NY-ESO-1, I think many of you are familiar as being a T-cell receptor target for tumors. And because this is an HLA-restricted drug, you can imagine that this is a T-cell receptor-like drug.
But it's important to note that this is not a T-cell receptor. This is an antibody. So this is a very sophisticated, very innovative way to create T-cell receptor-like properties for a monoclonal antibody. So we have this starting out in a clinical trial. And we're very excited about the scientific aspects of this program. On the right-hand side is DS-5361. This is another agent which is designed to enhance tumor immunity. This is an NMD inhibitor. This is a drug then that promotes further translation of premature termination codons that may result from frame shift mutations. So typically, when there is a premature termination codon in frame shift mutations, that messenger RNA is degraded so that that protein decoded by the frame shift mutation messenger RNA is not translated into protein.
Using this NMD inhibitor, one can force the tumor cell to translate the messenger RNA, the abnormal RNA, into a protein, resulting in an amino acid sequence within the protein that is foreign, foreign and therefore recognizable by the patient's immune system as being a foreign antigen. So this is a way to enhance immunogenicity of cancer cells. Next slide. And then we also have yet another modality in our pipeline now, a targeted protein degrader. This is something that many companies have. And I just want to let you know that we have this too. And our first one is called DS-9051. The first human patient study has started in November in solid tumors, including prostate cancer. Next slide. Okay, next slide, the scientifically rational combinations. Okay, next slide, please.
Now, what is important to note here is that based on the assets we have in our pipeline, we can create very interesting scientifically rational combinations that are based on the DXd ADC backbone. So for example, on the left-hand side, we can combine DXd ADCs with an IO agent, not just PD-1 drugs, but other ones that I just mentioned to you, and you can see the durable effect that we can see in our clinical trials. We can also promote the engagement of ADC and/or potentially synthetic lethality by combining DXd ADCs with certain drugs that target increased antigen or increased payload or increased affinity of the payload in the cells at the level of the DNA. Next slide. Okay, so we are already doing such combinations with IO agents.
You can see here, not just the PD-1 drugs, but also the very different kinds of innovative IO drugs that are available to us within our internal pipeline. Next slide. Okay, and this is all represented now in many, many of our combination clinical trials with pembrolizumab, rilvegostomig, and many other internal assets that are listed here. Next slide. Just to summarize here, from left to right, our research program is continuing to focus on both oncology and non-oncology indications, as well as to create new ADCs based on our technologies that we have in our research program. But in our clinical pipeline, we have prioritized the strength of our clinical oncology pipeline and also that emerging clinical stage non-ADC pipeline can be leveraged to create new novel combinations with existing ADCs. That's my section. And I'm going to hand it over to Ken Keller now.
Thank you very much, Ken. Next slide, please.
Today, we'll cover three topics. Number one is what we have accomplished in oncology these past five years. Number two is how we are approaching a time of unprecedented number of growth catalysts, not only for Daiichi Sankyo, but the number of near-term growth catalysts we have is among the highest in all of oncology. Number three is where we expect to be in 2030. Next slide, please. Daiichi Sankyo's oncology performance has been driven by Enhertu. In the first half of this decade, Enhertu has become the most successful antibody drug conjugate ever and the most successful new oncology drug launched in the past five years as measured by revenue. More recently, we have launched Dato-DXd, our second ADC, which is performing well.
As we enter the second half of this decade, we start from a position of strength, which will lead to even greater success in the 2026 to 2030 timeframe. In 2026, Enhertu is expected to obtain three new indications, including today's first-line HER2-positive metastatic breast cancer indication, followed by the HER2-positive neoadjuvant indication, and then the HER2-positive post-neoadjuvant indication. Dato-DXd is expected to receive its third indication, expanding into the first-line triple negative breast cancer segment. Behind Enhertu and Dato-DXd, our third and fourth DXd ADCs, I-DXd, and R-DXd have received breakthrough designation from the FDA. With our global oncology organization now fully established, coupled with our two highly productive alliances and multiple new growth catalysts, the years 2026 to 2030 are poised to be a time of unprecedented oncology growth here at Daiichi Sankyo. Next slide. Our oncology foundation is built on the strength of Enhertu.
Enhertu has attained seven indications. It has become the standard of care and achieved market share leadership in the HER2-positive second-line metastatic breast cancer indication, the HER2-low metastatic breast cancer indication, the HER2 mutant non-small cell lung cancer, and the HER2 second-line gastric cancer indication. Impressively, in every country where it has launched, it has become the market share leader and the new standard of care in less than 12 months. This performance is the result of Enhertu's exceptional clinical profile and the strength of our medical and commercial organizations and our alliances. To date, almost 200,000 patients from across 85 countries have now benefited from Enhertu. Next slide. Global net sales in quarter two fiscal 2025 totaled JPY 163.2 billion, growing 24% versus the previous quarter two. All regions are contributing to this growth, led by the United States, with more than half the total revenue.
Enhertu has made a historic mark in the community of oncology and is now poised to have an even bigger impact in 2026. Next slide. The next two years are pivotal for Enhertu as it will deliver multiple new standard of care changing data catalysts and new launches. In the metastatic breast cancer setting, as Ken Takeshita just outlined, Enhertu will move earlier in the treatment sequence with today's HER2-positive first-line metastatic breast cancer approval based on DESTINY-Breast09. DESTINY-Breast09 is the first major improvement in the outcomes in the first-line HER2-positive metastatic breast cancer space in over a decade. DESTINY-Breast09 launch will be followed by the expected approvals of DESTINY-Breast11 and DESTINY-Breast05, where Enhertu enters the early-stage breast cancer setting where cure is the goal.
Enhertu is now at the stage where the launches of these new indications will cascade country by country, providing a constant stream of new growth catalysts throughout our upcoming sixth midterm plan. Importantly, these new growth catalysts layer on top of the existing remaining untapped opportunities of Enhertu in the HER2-low metastatic breast cancer segment and especially the tumor agnostic indication in the United States, providing substantial near-term growth upside. Next slide. I'll now highlight each of our key growth opportunities in some detail, starting with the existing HER2-low metastatic breast cancer indication. The HER2-low and ultra-low indication was fully launched in the United States in Q1 of 2025, and it has become the new standard of care reaching 50% of patients in quarter two. This growth is expected to continue in the U.S. as patients and oncologists experience its substantial benefits in their own hands, as shown.
You'll see we've got many, many countries, as shown in the bottom right-hand side of the slide, that will be obtaining access and hence will be launching our HER2-low and ultra-low indication across the globe more fully in the coming year. Next slide, please. Now, I will describe the opportunity for each of the new growth catalysts I've highlighted, starting with Enhertu's HER2 first-line metastatic breast cancer indication that was obtained today. There are 24,000 patients in this indicated population across the G7 countries. Today, 30% of these patients never receive a second-line treatment, mainly because their disease advances too quickly to a point that physicians and patients decide to stop treatment. This insight underscores the urgent need to treat with the very best drug immediately. This mindset is shared by the majority of oncologists across the globe.
The remarkable benefits of Enhertu in the treatment of first-line HER2-positive metastatic breast cancer cannot be overstated. In DESTINY-Breast09, Enhertu in combination with pertuzumab reduced the risk of disease progression or death by 44% compared to the standard of care Taxol, trastuzumab, and pertuzumab. Enhertu provided over 40 months of progression-free survival, adding more than a full year free of progression compared to today's well-regarded standard of care that has been the standard of care for over a decade. Enhertu is viewed as the most efficacious drug in this setting by the overwhelming majority of oncologists. This belief, coupled with the urgency to treat with the best drug from the start and the feedback from the oncology community that we received, leaves us very confident that Enhertu will be quickly embraced by the oncology community and become the new standard of care for these patients. Next slide.
Now, adding to our growth opportunities in the HER2-low and the first-line HER2-positive metastatic breast cancer segment are these new data from ESMO Enhertu's DESTINY-Breast11, DESTINY-Breast05 in the early-stage breast cancer curative setting, and Dato-DXd's TROPION-Breast02 data in triple negative breast cancer patients. All three of these trials demonstrated statistically significant and clinically meaningful benefits over well-respected current standard of care. Based on the feedback we received from the oncology community, we are optimistic about how fast and broad these new indications will be adopted by the oncology community, and we are very confident these will all become the new standard of care. Next slide. I'll now explain the magnitude of these opportunities and share what we're hearing from the oncology community about their expectations for how these drugs will impact the treatment landscape.
In DESTINY-Breast11, Enhertu demonstrated the highest pathological complete response rate ever reported in this population. Each pathological complete response is potentially another life saved. It is well known and accepted that patients who obtain a pCR have far better overall survival than those patients who do not. In DESTINY-Breast05, Enhertu in this high-risk population reduced the risk of disease recurrence by 53% compared to the well-respected standard of care. These trials are seen as practice-changing by the majority of oncologists treating breast cancer. As you can see on the bottom right of the slide, 72% of oncologists in this syndicated survey said that these data will change how they treat breast cancer patients. That is absolutely consistent with what we've heard in all of our discussions with key opinion leaders, all of our advisory boards, and our own market research.
In the G7, there are 29,000 patients in the DESTINY-Breast11 expected indication, and there are 11,000 in DESTINY-Breast05. Enhertu adoption in these early-stage breast cancer patients brings the potential to have its greatest impact of all to potentially cure more patients. Next slide. In fiscal 2026, Enhertu has five major growth catalysts we'll be focused on. We believe Enhertu's clinical profile creates the mandate for us to make Enhertu the new standard of care for each of them. Number one is the remaining HER2-low opportunities. Number two is the new DESTINY-Breast09 HER2-positive first-line metastatic breast cancer indication. Three and four is the expected early-stage breast cancer approvals of DESTINY-Breast05 and 11. And number five is the remaining untapped opportunity for patients in the HER2-positive tumor agnostic indication in the US.
We are confident Enhertu is at the beginning of its biggest growth phase to date. Next slide. I'll now transition to an update on Dato-DXd, our second DXd ADC. Global Dato-DXd net sales have now exceeded JPY 10 billion in quarter two. In the U.S., quarter two revenue was JPY 6.6 billion, growing 113% versus the previous quarter. In Japan, Q2 revenue was JPY 3.5 billion, growing 59% compared to the previous quarter. Next slide. In the U.S., Dato-DXd is approved for HR-positive, HER2-negative metastatic breast cancer patients and EGFR-mutated non-small cell lung cancer patients. In Japan, it is the first TROP2 ADC approved for HR-positive, HER2-negative metastatic breast cancer patients. Early experiences, as reported by oncologists, have been extremely positive in both regions. Oncologists are becoming more and more comfortable and confident every time they prescribe this medicine.
These early experiences will benefit Dato-DXd greatly when it receives its expected triple-negative breast cancer indication. The clinical data in triple-negative breast cancer is viewed as best-in-class by most oncologists, and we believe it has the potential to become the new standard of care. Next slide. So let's talk a little bit about the expected triple-negative breast cancer indication. For nearly 15 years, there has been no new treatment advances in first-line metastatic triple-negative breast cancer for patients who are PD-L1 negative. Metastatic triple-negative breast cancer is the most aggressive breast cancer subtype with the fewest treatment options. Five-year survival is only 14.9%. There are 16,000 patients in the G7. One out of two patients never receive a second-line treatment. So there is a big, urgent, unmet need.
Dato-DXd's TROPION-Breast02 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival. It uniquely delivered a statistically significant improvement in overall survival. It doubled the overall response rate. We shouldn't forget that Dato-DXd provides very convenient Q3 week dosing, which is a significant advantage compared to the other TROP2 ADC in the market. Next slide. The feedback has been universally positive. The doubling of overall response rate, which is unique to Dato-DXd, coupled with the unprecedented overall survival improvement, which is unique to Dato-DXd, the impressive progression-free survival, the excellent safety profile have the oncology community eager to adopt Dato-DXd and makes us confident it will experience a rapid uptake and has potential to become the new standard of care. Next slide.
With Enhertu and Dato-DXd's current indications and expected future indications, these two ADCs can potentially improve outcomes for 100% of metastatic breast cancer patients. Our goal is to be the premier company in the eyes of the breast cancer treating oncology community. Next slide. On top of all of the anticipated launches, in 2026 and 2027, we will see the results of a number of important Dato-DXd lung cancer trials. These trials target extremely large patient populations and hold the potential to transform the treatment of lung cancer. The Dato-DXd clinical development program, depending on the success of the trials shown on this slide, has the potential to benefit an even greater number of patients than the very robust Enhertu clinical development program. Next slide. This is the full picture of where Daiichi Sankyo is going. In the past five years, we have made a successful transition into oncology.
So we start our next five years from a position of strength. Daiichi Sankyo has now reached a data-rich, growth catalyst-rich moment with four new, highly meaningful new indications expected for Enhertu and Dato-DXd in 2026. Behind these, there are numerous other new pivotal trials reading out over the next few years, as shown in this slide. This clinical development program creates a continuous stream of new launches across at least four ADCs every year through 2030. These pivotal registration trials offer the opportunity to help nearly six times as many patients live longer, better quality lives, and even bring more cures to patients across the global oncology community. Next slide. We are more confident today than ever before that our work over the next few years will cement Daiichi Sankyo's position as a true global oncology leader.
I will now hand the presentation over to our Head of Global Technology, Hiroto Kashiwase.
Thank you again.[Foreign language] Now please go to next slide. Regarding the development status and the stable supply system of the five DXd ADCs, as was already explained in the previous part, with respect to Enhertu, since its launch in 2020, demand has been increasing at a pace exceeding expectations. Our technology unit has been swiftly building a supply system to respond to this rapid increase in demand while continuing stable supply. As for Dato-DXd, it was launched this year in Japan, the U.S., and Europe, and we are building an appropriate stable supply system while monitoring market trends and development status.
In addition, for I-DXd and R-DXd, favorable clinical trial data have been accumulated, and we are currently constructing a global supply system capable of responding to the future peak demand of the entire five DXd ADCs. Please go to the next slide. Here is the supply strategy for the five DXd ADCs. Since this overlaps with last year's Science and Technology Day, details are omitted. But regarding the expansion of capacity, we are enhancing production capability through capital investment and building a global supply system. Regarding the improvement of capability, we are enhancing productivity by leveraging technological strengths, fostering and strengthening biotechnology talent, and transforming into a highly productive organization. By skillfully linking these two axes, we aim to maximize ADC supply volume and secure the necessary supply volume. Next slide, please. Here is the general manufacturing process of ADCs.
ADCs consist of multiple components such as drug linker, antibody, ADC drug substance, and ADC drug product, and each component is manufactured and managed separately. Compared to conventional small molecule drugs, the manufacturing process is more complex, and the lead time becomes very long. Therefore, in order to secure supply volume that can meet future demand, it is necessary to start manufacturing planning adjustments and preparations at an early stage. In the stable supply of ADCs, one of the most difficult points is to appropriately manage the balance between supply and inventory in line with rapidly changing demand. Next slide, please. This is a schematic representation of the manufacturing and supply routes of ADCs. Among the ADC manufacturing processes, the steps of antibody, ADC drug substance, and drug product have a large impact on quality and are recognized as critical processes.
Therefore, focusing on these three processes, we are building manufacturing systems at multiple sites of our company or CMOs, and by considering sourcing strategies and supply strategies, we combine them to secure multiple supply routes. Such a system not only secures supply capacity to respond to rapid demand increases, but also reduces supply risk since even if an unexpected trouble occurs at one manufacturing site and supplies are stopped, other supply routes can cover it. Next slide, please. Next, I will explain the policy on utilization of our facilities and CMOs. The graph on the right shows an image where the gray area indicates demand forecast, and the bar graph shows supply capacity combining our in-house and CMO manufacturing capacities.
We always compare the latest demand forecast with supply capacity, judge the necessity of capital investment or outsourcing manufacturing to CMOs, and work to ensure that supply capacity consistently exceeds demand. We also consider the balance between our in-house manufacturing and CMOs to be important. Since it takes a very long time to construct new buildings and start up production lines in-house, in the short term, we prioritize speed and effectively utilize CMOs with existing facilities to secure supply capacity. On the other hand, in the medium to long term, considering cost and stable supply, we gradually increase the proportion of our facilities, aiming to eventually build a balanced supply system between our in-house and CMO capabilities. Regarding the final manufacturing ratio between in-house and CMOs, we refrain from disclosing it.
However, from the viewpoint of BCP, utilization of CMOs is one of the important elements, and we will make comprehensive judgments based on the respective advantages and disadvantages. Next slide, please. This slide summarizes our in-house global ADC manufacturing sites. Currently, the Daiichi Sankyo Group as a whole has 13 manufacturing sites globally. Among them, in Japan, we have four sites: Onahama, Tatebayashi, Hiratsuka, and Odawara. Globally, we are building or planning ADC manufacturing systems at three sites: Pfaffenhofen in Germany, Shanghai in China, and New Albany in the U.S. Regarding specific numbers of CMOs and related information, we refrain from disclosing them. However, we are building supply systems in close collaboration with multiple CMOs, mainly in Europe and the U.S. Next slide, please. Now, I will explain the status of building supply systems for each component. First, regarding the antibodies.
Since there are a considerable number of CMOs capable of manufacturing, at present, we are effectively utilizing the speed and technology of CMOs to secure the necessary supply capacity. In the mid to long term, our policy is to strengthen in-house manufacturing and aim to build a low-cost and stable supply system. In fiscal year 2024, an antibody manufacturing facility with 15 kL scale bioreactors was completed at the Onahama plant, and preparations are underway for stable manufacturing. Next slide, please. ADC [Foreign language] Production. [ Foreign language] Twice the production capacity will be there. And also, we are currently constructing a Pfaffenhofen plant in Germany. Completion of this facility is targeted for fiscal year 2028. Next, the supply system of ADC formulations.
Regarding the drug product, considering factors such as product transportation costs, we are establishing a supply system in each region with a focus on local production for local consumption.
Domestically, the Hiratsuka plant already possesses multiple formulation lines, and we are exploring ways to increase production volume and expand our product portfolio. A new formulation line is scheduled for completion at our New Albany plant in fiscal year 2026, with plans to expand the U.S. production capacity accordingly. Furthermore, construction of new formulation lines is also being advanced at the Pfaffenhofen plant in Germany and the Shanghai plant. Next, please. Efforts are also underway to establish a one-stop production system. Right now, the various components of ADCs are manufactured at various sites globally, but consolidating key manufacturing processes at a single site is expected to reduce transportation times between manufacturing sites and enhance production flexibility, which would enable more efficient production.
Already at the Onahama plant, an integrated manufacturing system from antibody to active pharmaceutical ingredients, namely a drug substance, has already been established within the same building, enabling efficient production. Also, at the Hiratsuka plant, once the drug substance manufacturing building is completed and production commences, an integrated manufacturing system for drug substance to drug product and packaging is scheduled to be realized. Next, I should briefly outline our initiatives for developing and strengthening our biotechnology workforce. The development and stable supply of ADC product necessitates the cultivation and strengthening of bio talent possessing specialized knowledge, particularly in the manufacturing domain. As production volumes increase, the required man hours are projected to rise further, securing manufacturing personnel and accelerating their development. This has become an urgent priority. To that end, we're actively pursuing measures to cultivate and secure the necessary biotechnology personnel.
These include strengthening recruitment activities, early development and enhancement of manufacturing operators through training programs, and seamless personnel exchanges across organizational and functional boundaries. Here, taking antibodies as an example, I will now go into details about the actual training program. For antibody manufacturing personnel, we have established a training environment dedicated to operator development. We have formulated training programs utilizing these facilities, enabling the efficient development of biotech personnel. Specifically for newly assigned personnel, such as new recruits and transferees, we combine theoretical instruction, lectures, and practical training at the laboratory scale. This supports the early acquisition of the knowledge and skills required on the production floor, enabling us to develop personnel who can contribute immediately on site.
Separate from this program, each manufacturing site also conducts GMP training and OJT trainings and other educational initiatives which enable personnel to become involved in actual production as manufacturing operators within approximately six months. Further, to respond more swiftly and efficiently to tasks related to ADC development and supply, we are optimizing the organizational structure of the technology unit. And our primary production focus is shifting from small molecules to oncology and novel modalities. Approval processes have been accelerated, and because of that, the timeframe from formulation technology development to the commencement of commercial production has significantly shortened, necessitating reduced lead times. So, to address these challenges, we are determined that integrating responsibilities from clinical trials to commercial production, together with enhancing information sharing and collaboration, was essential. So, we have decided to transition from the previous structure where clinical trials and commercial production were separate to an integrated organization.
In fiscal year 2023, we integrated the Biologics Division, Pharmaceutical Technology Division, and Supply Chain Division to establish a technology unit capable of providing end-to-end support across the broad spectrum from early development to commercial production. In fiscal 2024, we reorganized functions to create a more efficient structure for advancing our ADC business by establishing six functions within the unit. Further, in fiscal 2025, we absorbed and merged the production function companies Daiichi Sankyo Propharma and Daiichi Sankyo Chemical Pharma, further strengthening collaboration in production functions. Going forward, also, we intend to continue examining and implementing optimizations to organizational functions to deliver innovations to patients worldwide as quickly and reliably as possible. Next, please. [ Foreign language] Thank you.
I am Abe, Head of the R&D Division and Head of Global Research. I will explain the research part. Next slide, please.
Our company, building on strengths in small molecule drug research and development, has long engaged in antibody drug research. Currently, under a multi-modality strategy, multi-ADC strategy, we are promoting new drug research using various approaches such as antibody drugs, including ADCs, medium molecule drug discovery, nucleic acids, gene therapy, glycan engineering, and mRNA vaccines. In the ADC platform, we have created multiple new ADC technologies, including the DXd ADC. By utilizing various modalities, we are working daily to continuously create innovative medicines that can transform standard of care across a wide range of disease areas, including cancer. Today, I will introduce some of our new drug research as part of our efforts toward the next innovation. First is ADC. I will present the direction of new ADC technology development based on the success of the DXd ADC. Second is cancer immunotherapy or immuno-oncology research.
In parallel with ADC, as a result of more than 10 years of research, we have started clinical trials of multiple assets, and I think this is the first opportunity to present them all together. Third is the combination strategy of ADC and immuno-oncology therapy. As Takeshita explained in the development part, in clinical trials, for example, the combination effect of Dato-DXd and immune checkpoint inhibitors has been observed. Our preclinical experimental data are now being validated in clinical settings. Fourth is new modalities. And finally, I will introduce the smart research laboratory and our open innovation activities in research. Next, please. Now, I will introduce DXd ADC and new concept ADC technology platforms. Next slide, please. As we have introduced several times, DXd ADC technology is considered one of the outcomes of the merger between Sankyo and Daiichi Pharmaceutical.
At Sankyo, since the 1990s, former head of R&D, Agatsuma, and others began antibody drug research. At Daiichi Pharmaceutical, at the same time, research was conducted on new drugs of topoisomerase inhibitors and drug delivery systems. With the merger in 2007, these insights were integrated, and in 2010, it developed into cross-functional activities for ADC research. At that time, I was assigned by Agatsuma as research team leader, and together with fellow researchers, created DXd ADC technology and the ADC portfolio. The strong desire to deliver excellent new drugs to patients and commitment to manufacturing and innovation are part of Daiichi Sankyo's continuing research culture. I believe this environment nurtured many research leaders and became the driving force behind the creation of Enhertu. Next slide, please. As you know, DXd ADC technology is Daiichi Sankyo's proprietary platform, and currently, clinical trials are being conducted with seven ADCs.
At the time of research, as a working hypothesis, topoisomerase inhibitors were generally not used for breast cancer. Therefore, we advanced research with the idea that delivering Daiichi Sankyo's proprietary topoisomerase inhibitor through ADC technology could become a breakthrough new agent. We also succeeded in developing technology to load eight drug linkers per antibody, and for Enhertu and Dato-DXd, which were developed ahead, we obtained approval in breast cancer. We have also launched research programs for other ADCs while formulating working hypotheses regarding which cancer types they may be effective against. For example, Dato-DXd has been approved for EGFR-mutated NSCLC, and I-DXd has demonstrated favorable clinical data in NSCLC, and R-DXd has shown promising clinical results in ovarian cancer, leading to breakthrough therapy designation. More recently, DS-3790, which targets hematologic malignancies, has advanced to the clinical stage. We are hopeful that it will also demonstrate strong efficacy in hematological cancers.
As an external evaluation of the DXd ADC technology, we have received FDA breakthrough therapy designation for a total of 13 indications to date. In recognition of the achievements demonstrated in clinical trials, as mentioned earlier by Okuzawa, we were honored this fiscal year with the Best ADC Platform Technology Award at the World ADC Awards. Next, please. Furthermore, Daiichi Sankyo's ADC technology continues to evolve across each of its components: antibody linkers and payloads, as Takeshita mentioned. Development of novel technology, antibody technologies to enhance target selection, FC engineering, and tumor specificity, and in the middle, new conjugation technologies that enable strict control of the DAR for linkers and exploration of a diverse range of payloads with mechanisms different from DXd are underway. Our strengths lie in over 15 years of ADC research and deep expertise in antibodies, linkers, and payloads.
We will continue to generate novel concept ADC technologies and lead the ADC field going forward. Next, please. As next platform candidates applying DXd ADCs, we have NPBD ADC technology using modified PBD as a payload, as well as a STING agonist ADC technology based on cancer immunology concepts. The first asset entered clinical trial stage. If clinical utility is demonstrated, we will proceed with the development of second and third assets utilizing these ADC technologies. Should further improvements be required, we will address and overcome the challenges. We are also researching additional novel concept ADC technologies, and we will introduce them as they start clinical trials. Next, please. I will explain our cancer immuno-oncology research assets and their combination strategies. Why do we invest in IO?
Immuno-oncology therapies, exemplified by immune checkpoint inhibitors, have been reported to provide durable effects in suppressing cancer recurrence, which is thought to be attributable to the immune memory. In addition, they may offer new treatment opportunities even for tumor types with low sensitivity to drugs. Furthermore, through complementary pharmacological effects, by combining IO with DXd ADCs, we would like to aim for a cure for cancer. Next, please. Through a decade of research, as I mentioned earlier, we have identified various molecules involved in cancer immune activation signals as drug targets and have generated multiple development candidates and established our proprietary IO franchise. Today's disclosure covers only part of this, but as is illustrated in this slide, we are working to activate cancer immunity against tumors through various mechanisms, including increasing novel cancer antigens, activating antigen-presenting cells, and recruiting activated T cells.
In building our IO franchise, we have adopted a multimodal strategy advancing drug discovery using the optimal modality for each target molecule. For instance, DS-5361 is a small molecule compound. DS-1103 is a monoclonal antibody. DS-3610 is a novel IO-targeting ADC, and DS-2243 is a T cell engager. As DXd ADC induces cancer cell apoptosis and serves as a trigger for tumor immunity, we anticipate that drugs within the IO franchise will offer complementary effects when used in combination with DXd ADCs, in addition to their monotherapy applications. Furthermore, there are multiple research themes at the investigational stage, and we will also introduce them when we start the clinical trials. Next, please. From within the IO franchise, I will now introduce DS-3610. DS-3610 employs a novel ADC technology concept utilizing our proprietary STING agonist as the payload.
The STING agonist is selectively delivered to the tumor tissue, activating antigen-presenting cells within the tumor microenvironment to promote T cell priming, and in non-clinical studies, we have confirmed that sustained anti-tumor effects based on immune memory and synergistic effects with multiple drugs have been confirmed. The concept involves avoiding systemic immune activation by incorporating the STING agonist into the ADC while modifying the antibody's Fc domain to suppress antibody-dependent cytokine release. We believe that this design achieves a balanced ADC with both immune activation and safety, and FIH already has started last month. Next, I will briefly introduce the progress of drug discovery research using novel modalities. Now, in the development section, Takeshita already explained this, but we have started the clinical trials for a new modality, a medium-sized protein degrader.
So while compounds that degrade target proteins have been reported by other companies aggressively, we have selected a first-in-class novel target and are advancing its development as a TPD. We also have multiple projects in preparation at the non-clinical stage and intend to collaborate between the research and development teams to cultivate this into one of our new core technology platforms. Finally, I will introduce the Smart Research Lab, which will form the next-generation research infrastructure and also the direction for open innovation. Our company has long prioritized machine learning and AI-driven drug discovery as a history. Currently, under the concept of Smart Lab, researchers themselves are undertaking initiatives to transform the drug discovery process. Essential to this effort is AI-driven drug discovery, high-quality and large-scale experimental data, and we are advancing the utilization of this data.
We think that the Smart Lab will form the foundation for AI-driven drug discovery. So for this purpose, we established the Smart Research Lab in San Diego this January. At the Smart Research Lab, robots and automated experimental equipment operate 24 hours a day, 365 days a year, with plans to generate large volumes of high-quality data. And we have selected and dispatched professional drug discovery researchers from Shinagawa and Kasai Research Institutes to the Smart Research Lab. And as one team, we are establishing the lab with talented IT engineers. We plan to start the work from next fiscal year, where the Smart Research Lab will be our first in-house drug discovery research facility in the U.S. It will also enable remote experimentation and data analysis from within Japan as well.
So I explained before as well, but molecular design using AI is already being pursued vigorously at the Shinagawa and Tokyo Research Institute. We will tackle new drug discovery through a hybrid model combining the San Diego and Tokyo efforts. Finally, I will introduce our open innovation activities at the research stage. Last year, we established research institutes in Boston and Munich, the key European and American clusters for drug discovery research as basis for external collaboration. Further, this fiscal year, we opened a new research institute in San Diego to access the drug discovery cluster on the U.S. West Coast. So Daiichi Sankyo is now advancing collaborations with external institutions in over 10 countries globally centered in our existing Tokyo, Shinagawa, and Kasai facilities. Top scientists from Shinagawa and Kasai are also dispatched to these research institutes, actively promoting joint research and sponsored research with academia and startup companies.
Further collaboration between these bases enables global information sharing and strict compliance with the regulatory requirements of each region. Regarding the focus of this research institute, we are not considering the introduction of clinical stage pipelines, but we are concentrating our early-stage research into novel biology and the discovery of new modalities. By swiftly incorporating the new science and technologies emerging daily within the Western drug discovery ecosystem and integrating them with Daiichi Sankyo's strengths and expertise, we will create new opportunities for drug discovery. Next, please. Our strength lies in the science-based technology and science culture. Our drug discovery achievements, including in Enhertu, Dato, Tarlige, Lixiana, and Effient, are underpinned by precision in manufacturing down to the finest detail. Moving forward, our researchers and employees will unite to deliver new value and superior medicines. Craftsmanship is a spirit of manufacturing deeply rooted in Japan's tradition.
So even as we globalize, we will propagate this culture, pursue science and technology that embodies Daiichi Sankyo's identity, and deliver medicines to as many patients as possible and persist in our challenge towards the lofty goal of curing diseases. Thank you.
Thank you very much. Now we'd like to move on to the Q&A. You can ask questions in either English or Japanese. If you have multiple questions, please ask a question one by one. And please limit the number of questions up to two per person. And please identify to whom you'd like to ask a question. Now, if we have a question, please use the raise-a-hand feature. The first question is Hidemaru Yamaguchi-san. Citig roup, please.
Can you hear me? This is Yamaguchi from Citi. I have two questions. First question goes to Ken Keller-san.
This time, in Science and Technology Day, you mentioned and gave us explanation about the market, especially Datroway opportunity. Details were given in your presentation. Regarding Enhertu, within one year since the launch, you had achieved a market share of over 50%. What is the trend we have seen regarding market share obtained by Datroway? And also, I believe that there will be more coming data available for Datroway. Can we expect that the same trend will be followed by Datroway like Enhertu? And also, if we have any peak expected sales number, please also let us know.
Yes, thank you for your question. The early uptake of Datroway in both Japan and the US has exceeded our expectations. It is a little bit different in both markets.
In the US, we've got about 50% of the use in the breast cancer indication and about 50% of the use in the lung cancer indication. In Japan, it is the only TROP2 approved for HR-positive HER2-negative. So a lot of it is the breast cancer indication, obviously. In terms of what we expect, we expect that the triple negative breast cancer indication for Datroway is going to be very well received. As Takeshita-san mentioned earlier, the data is truly unique. Datroway demonstrated a doubling of the overall response rate. That's unique to it. It demonstrated an improvement in overall survival. That is unique to Datroway. The safety profile was excellent as well. And I mentioned the Q3 dosing is more convenient than other options.
So we are very confident that Datroway will become the new standard of care in the first-line triple negative breast cancer space for those patients that are PD-L1, not able to receive a PD-L1 drug. The data is truly excellent. And I think all the positive experience from the two existing indications will serve it very well in terms of physicians being comfortable with it from day one. I hope that answers your question.
[Foreign language] Thank you very much. I have another question to Abe-san. In Takeshita-san's section in page 25, new ADCs, three of them were introduced. And of that, two are new DXd ADC. Another one. [Foreign language] Should I repeat the question? Well, I am, yes, now looking at page 25. May I answer? Could you repeat your question, please? Well, new ADCs, there are one, two, three, three of them.
I would like to ask you to explain what are the differences among these three and what are the specific targets of each.
Yes. And so there is the new ADC 1, 2, and also at the bottom, ADC 3. So the modified payload or the new ADCs. This is new ways of DXd ADCs. So with that new concept, it's being promoted in the research. Although I cannot disclose the details, tissue selectivity, meaning that it is more cancer-specific delivery system or within cells, more durable effect can be demonstrated. These are what we are targeting to achieve with these ADCs. Although I cannot give you more details, when it comes to the clinical trial stage, we will give you more details. And also, the third one is a new payload ADC. And that MOA is different from three ADCs that we have introduced to you.
We have started researching this new payload, and research is going well. So at the time that all those assets start clinical trials, we will give you more details. But I think highly likely, I believe that all those three programs will be able to move on to the advanced stage in clinical development. And if it's all right, can we expect that these will be entering into the clinical stage within several years?
Well, if it can, then we may say so. And all the research, development, and manufacturing units are doing our best efforts so that we'll be able to promote the implementation with a plan. Thank you very much.
Next question, please.
Daiwa Securities, Hashiguchi-san, please. Hashiguchi desu. Hashiguchi speaking. The first question is to Abe-san or Okuzawa-san. Fifth MTP 2021 announced as one of the objectives post-DXd ADC selection.
That initiative, in today's presentation, how much is that reflected? DXd ADC franchise, I like that. A large backbone or pillar, just one of that. Rather than that, with the various initiatives that you have introduced today, sustainable growth you're going to achieve, is that the understanding? Or within what you have introduced, that post-ADC modality, what is expected as a major pillar, the franchise, whether there's a possibility that that is included as well. So within what you have introduced, the weight, the difference of weight, whether there are any or not, I would like you to comment, please. So from Abe, I would like to respond.
Thank you very much for the question. Now, I personally feel that DXd ADC-like platform technology can be built. And we do have that confidence. But the IO research, taking 10 years, there are a lot of development candidates.
So not only one, but a multiple number of platforms or franchises, we will be building the pipeline, I think. And what is the pillar of that? Well. This time, I would like to refrain from clearly responding. But in our research division, we do have confidence that we could advance this forward. I would repeat, but in today's asset, we are expecting the IO asset and then protein degrader. With that, we are starting the clinical trial so that we have a research structure as well as achievement that we could lead it to the next stage. And new ADC, we are expecting four also. So I don't know whether this is an answer for you, but not only one, but we think that we'll be able to build multiple numbers of platforms.
But on the other hand, as you know, up until 2030, DXd ADC, the business, we will further expand the business. Under such circumstances, those new initiatives have been rolled out. Please understand that. That's all from me.
Thank you very much. The second question is also the question directed to Abe-san. As you mentioned earlier on page 25, new ADC 1, 2, 3. For these, the target, for instance, HER2 or TROP2, like that, the conventional DXd ADC, it's the same as that. But a further stronger efficacy safety targeted ones are included. Or the past DXd ADC, the new target that you were not able to obtain. And for those new patients, it's a kind of effort for you to provide a treatment option, which is closer to what you are aiming at as a company.
Thank you very much for your question once again.
If I say, or you might say we're doing too much, but HER2 area, the low HER2, Herceptin, Kadcyla, the standard of care, those were used as SOC for 10 years and 20 years. We're in the process of reforming it and changing it. On the other hand, the research lab so that the HER2-low's challenges could be overcome even, they are working on the drug development. And also, what we have not done, the diseases that we have not been able to provide cure, there are many such in existence. Therefore, for the new target for them or for new tumors, with that objective, we are working on developing and discovering drugs which are epoch-making. And we are working on both of those that you have mentioned. Thank you very much. Thank you.
[Foreign language] I have two questions for Takeshita-san.
Firstly, page 20, I'd like to ask about the potential incorporation of the QCS methodology into TL-07 and TL-08. We understand from our discussion that you have been discussing with FDA about the potential use of QCS to NMR in TL-07, 08. Could you provide an update on the status of those discussions and whether any conclusions have been reached? If QCS were to be incorporated, should we understand that its use would be limited to retrospective, or is there a possibility of prospective integration? In addition, I'd appreciate your perspective on whether analysis based on QCS would be considered acceptable or supportive in the context of regulatory review. This is the first question.
Yes, thank you very much for that question. So in terms of where we stand on NMR, or also known as QCS, incorporation into our lung cancer studies, we are in discussion.
And so once we have some conclusions, we will be able to report that to you. But unfortunately, not today. Perhaps in the future.
Okay. When can I hear the conclusion?
Well, I don't have a specific date for you. But as you know, we already have reported that the top-line results for TROPION-Lung07 will be available sometime in the next fiscal year. So certainly, we need to have these issues about NMR concluded sometime before we see the top-line results for TROPION-Lung07.
Thank you. Second, about Enhertu, page 11. And I'd like to ask about the development of drug for Enhertu in early line settings for the HR-positive HER2 patient population, including neoadjuvant, adjuvant, and ET. Could you share what discussion you are currently having with AstraZeneca regarding development in these settings?
Over the past years, you have indicated that you have been assessing the potential in this area. But there has been no update. Does AstraZeneca have limited interest in developing non-HER2 in these settings? Or are you considering pursuing development in this space using products other than non-HER2?
Yes. So I think your question refers to the bottom half of the slide, the hormone receptor-positive patient population. Is that correct? Yes. Okay. So now, this is a patient population that is in the adjuvant, neoadjuvant, et cetera. Much of the work is really being done through endocrine-based treatments.
And so other than some exploratory studies that we are conducting, we just need to wait to see how much progress we can make using even a drug like Enhertu that is quite active in the neoadjuvant, adjuvant space because in these earlier lines of therapy, hormone receptor-positive breast cancer is typically less sensitive to drugs like chemotherapy or even ADC, more responsive to endocrine therapy. So at the moment, what is stated here about evaluating the potential or preparing study plans is unchanged. Okay.
Thank you so much.
[Foreign language] Next question, Matsubara-san of Nomura Securities,
please. [Foreign language] Yes, I'm Matsubara of Nomura Securities. Thank you. So I think the NMD not only functions in messenger RNA quality control, but also plays a role in regulating the gene expressions.
Is there a risk that inhibiting NMD could cause off-target effects such as any intended change in gene expressions or activation of abnormal metabolic pathways?
Okay. You're asking a very interesting biological question. In a normal cell, certainly there are termination codons. These are not premature termination codons, but just regular termination codons. For reasons that are still not completely clear, the messenger RNAs with standard termination codons are unaffected by NMD inhibitors. That is to say that if you have a regular standard termination codon in your messenger RNA, that does not undergo mRNA degradation. It is these premature termination codons as a result of, for example, frame shift mutation that is specifically affected through this mechanism called mRNA degradation, which we are inhibiting with this NMD inhibitor.
What is expected is that this NMD inhibitor would not substantially affect normal cells with its own set of mRNAs with termination codons, but have a selective effect on tumor cells that have these premature termination codons.
[Foreign language] Thank you very much. That's all. [Foreign language]
Next question. Morgan Stanley MUFG Securities. Muraoka-san, please.
[Foreign language] Thank you very much. [Foreign language] Muraoka of Morgan Stanley MUFG Securities. My first question goes to Okuzawa-san. [Foreign language] Hearing your today's presentation. Daiichi Sankyo has these things. Daiichi Sankyo today. [Foreign language] You have all those assets, and you need such and such assets. I could understand it very well. But the question is about the external resources incorporation that you have been touching upon from this spring, from time to time. You do have your in-house resources, but based upon presentations made today, by when at which scale you'd like to incorporate external resources. Could you tell me those once again?
Thank you for your question, Muraoka-san. My answer is that within the sixth five-year business plan, we'd like to clarify those and we'd like to let the investors and analysts know. As the business scale expands and as we rapidly have been growing, we would like to further strengthen our path toward the future growth. As we have introduced, we have quite rich growth catalysts in-house. We are always watchful of potential external opportunities. It is going to be a new five-year business plan. Therefore, with growth driver seeds both in-house and outside, in order to effectively obtain those and make use of them, we would like to establish a management system supporting those within the new five-year business plan. Therefore, at an appropriate timing, we'd like to provide you a discussion.
Thank you very much, so it will be probably prior to the five-year business plan.
So within three months, I think my understanding is that you'll be able to give us an update by that timing.
Yes, in the next fiscal year, for sure, yes, we will explain about our new five-year business plan.
Thank you very much. Next, I would like to ask a question probably to Abe-san. Abe-san, Takeshita-san, but also probably to Abe-san regarding the new protein degrader DS-9051. It is a mid-size molecule. Is it oral or injectable? And what is the desirable administration routes? I think AstraZeneca has been working on the injectable. And target disease might be different, but the Kymera's STAT 6 showed very positive data oral administration, to my surprise. So other companies are demonstrating very positive data. What kind of differentiation is available with your DS-9051? Probably the target diseases are different, but could you tell us a little more?
Thank you for your question.
Concerning this program, please give us a little more time so that we'll be able to give you more details later on. Whether it's oral or injectable, we have been conducting research on multiple routes. Oral is considered to be better, but the injectable has its own benefits. Like every three weeks or every four weeks, a dosing may be available. Or if it's oral on a daily basis, the patient would be able to take it. Therefore, what's most important is in that targeted disease, what kind of treatment is being provided? Compared to the existing one, we should demonstrate something superior or more advantageous. Including that, we have been conducting research with different formulations or administration routes we have been researching. I myself consider and believe that this asset will become a very good drug.
Sorry, I cannot give you specific answers, but could you get what I wanted to say?
Yes, I could get the nuance very well. But just reconfirm what you said. You are a molecule. Naturally, it includes injectable, but also potentially it is possible to make it in oral, right? And especially it is a DS-9051, and it's going to be long-term administration. Therefore, naturally, in my view, I think this should be oral. Can I say that my idea is not much different from yours?
I appreciate if you think that way. In the next fiscal year, we would like to take the opportunity to introduce this. So I believe that this is going to be an excellent product. That way, we'd like to continue our research efforts. Thank you. Thank you.
Next question. Jefferies, Barker-san, please.
Stephen Barker from Jefferies.
Thanks for taking my questions. They're both for Ken Takeshita. The first question with reference to pages 9 and 10. The company obviously has a lot of history with ADCs. There's a narrative in the stock market that some other companies, which are developing a lot of ADCs of their own very rapidly, they don't have the same level of history, but the idea is that they can run clinical trials much faster, and therefore should be able to catch up and overtake Daiichi Sankyo ADCs. Would you like to comment on that, please? Thank you.
I hope you understand that we have already reported phase three clinical trial data outcome in many of these diseases and in many different types of patient segments.
For example, in breast cancer, we have all kinds of approvals now and positive data with not just Enhertu, but also with Dato, a TROP2 ADC. So I think if you, because you referred to slide 9 and 10, if you look at TROP2 data, for example, I think we are very, very competitive. And even if we compare to other TROP2 ADCs that have already reported their phase III data, we believe that we are very competitive and in many ways better set of clinical trial data, more clinically meaningful than other competing drugs. So I think that we are. I don't know. I hate to brag, but I think we're quite ahead of other competing TROP2 ADCs and other ADCs generally.
I think it's really a time element that's here, as well as the big set of clinical trial data that shows that there are, even with the same TROP2 targeting ADC, there are important, very important clinical data and safety data differences between this one, Dato-DXd versus other ones, as well as what's listed there in the middle, more convenient administration schedule. I think that's important too.
But then presumably also for new types of ADCs, your long history with this modality should give you an advantage. You should be able to come up with new ADCs ahead of the competition, I should think.
Oh, yes. So yeah, that was, I think, sorry about that. I think that was the second part of your question. And as I alluded to, these ADCs are really modular drugs.
And by creating a different combination with these three modules, you can create new ADCs with different properties. That is one of our biggest research advantages compared to other companies that are mostly buying a single ADC drug for further development. And so as you saw earlier, we are producing next-generation ADCs with different payloads. And in the future, we expect to have more ADCs with yet more different payloads or linkers or sometimes engineered antibody, the binding target. So this is really our strength here. And if you ask us what is different about our ADC program compared to others, this is one of them. This is one of our biggest differentiating factors compared to other companies.
Understood. Thank you very much.
[Foreign language]
Next question.
[Foreign language]
Sogi-san, Sanford C. Bernstein, please.
[foreign language]
Thank you very much. Two questions to Dr. Takeshita.
So first one is Datroway's TROPION-Lung15. That is slated to be read out next year. This is for second-line EGFR mutated non-small cell lung cancer. We understand that you are testing Datroway as a monotherapy as well as the combination with Tagrisso versus chemotherapy. And first of all, we believe that this is a really important study for Datroway's commercial opportunity, as well as the exciting opportunity because the TROP2 targeted ADC has shown really promising the efficacy so far. And so we believe that this combination approach with the Tagrisso is a differentiating factor for Dato-DXd comparing to Merck's Kelun's, the sac-TMT, which is currently only tested as a monotherapy. But on the other hand, there are overlap of the adverse event, the profile between Datroway and Tagrisso, notably for stomatitis and also ILD.
We'd like to understand, what do you understand this overlapping AE profile in terms of the safety risk for this combination? And would you actually think that the monotherapy is more in a base case success scenario from this trial and the combination is more the upside opportunity? Thank you.
I think ultimately it's going to be the clinical data that will tell us which is more important, the monotherapy or combination. Obviously, with the monotherapy, you could expect to see less toxicity. But with the combination, we might expect to see even additional efficacy beyond just monotherapy. But as you pointed out, there's a potential for additional safety concerns. So ultimately, I think we're going to have to see the totality of both clinical data, including efficacy and safety, to make some judgment in terms of risk-benefit, not just for regulatory agencies, but also for the prescribing physician.
Is it correct to understand that currently you don't have any supporting clinical data to understand the potential safety profile for the combination? So we are doing those clinical trials right now, yes. So we have some understanding. Okay, great. Thank you. And then there's another question regarding HER3-DXd. Okuzawa-san mentioned that you continue to explore the HER3-DXd opportunity. And we also understand the HER3, first of all, target has been of great interest among the oncology drug development. On the other hand, it's been quite elusive. And we'd like to understand that as you continue, and we understand that you are exploring the biomarker approach to achieve the better patient selection. Have you actually had any kind of initial success or where you stand in terms of understanding how to approach HER3, the patient selection strategy? Have you had any kind of the sign of the optimism?
What have you achieved with the Datroway NMR?
Y es, so as you know, with the HER3 program, there are a couple of big indications of interest: breast cancer and lung cancer. And the bulk of the early breast cancer data that we have is from our collaboration with the French group, IGR. And they have produced all kinds of very sophisticated biomarker analysis that we are working with. In addition, in lung cancer, as you know, we have a lot of experience now in doing administration of HER3-DXd in EGFR mutated patient population, as well as now extending into the non-EGFR mutated patient population. And then there, we are starting to apply the standard IHC assay, as well as some more sophisticated assays beyond just the standard immunohistochemistry.
I think there is a, here again, just like in breast cancer, there's a lot of interesting emerging data so that it is quite conceivable that there could be a biomarker-based clinical development path for HER3-DXd. I think this is one interesting avenue that we are pursuing, but we have not yet really reported it yet publicly.
Great. Thank you very much. We are looking forward to it.
Yeah.
The next question is from Tony Ren from Macquarie. Please go ahead.
Can you guys hear me? Yes. Okay. Perfect. My first question is probably to Mr. Keller. So this is about slide 44. The number of patients you guys estimated for DESTINY-Breast11 and DESTINY-Breast05 appears to have increased slightly compared to the estimates coming out of ESMO 2025 conference. Are you guys still prioritizing DESTINY-Breast11 over DB05?
And if so, could you explain to us the considerations? Is it because you hope to reduce drug exposure and therefore reduce toxicity? I believe it's four cycles versus 14 cycles, right? So much shorter drug exposure. Or is it because of the larger patient population? Or other considerations?
Thank you very much for that question. After seeing the clinical results for both of these trials, what we're hearing from the oncology community is that in HER2, in both of these settings, is highly, highly attractive. Now, as you mentioned, in DESTINY-Breast11, these are for higher-risk patients. And there is a larger number of these patients because it's neoadjuvant before surgery. But as you can see on this slide, the magnitude of benefit in terms of those patients who receive a pathological complete response is highest that it's ever been reported.
And so based on that data, and then let's go to DESTINY-Breast05. These are patients who have received neoadjuvant therapy, they've received surgery, and they still have residual disease. This study compares Enhertu to the established standard of care, Kadcyla, and the magnitude of benefit, again, is really astounding. And so I wouldn't say that we're prioritizing one over the other. As I've been speaking to the oncology community, they see it attractive in both settings. And you're 100% correct. In DESTINY-Breast11, it's only four cycles. And so the exposure is very, very limited. The safety profile is really excellent. And so what we believe is going to happen is physicians will adopt Enhertu in the neoadjuvant setting, DESTINY-Breast11.
And then for those patients that unfortunately still have residual disease after surgery, it's not going to automatically exclude those same patients from receiving Enhertu in the DB05 setting. Now, it'll get down to risk of patients. But based on the data we've seen so far, Tony, we see this drug being embraced in both settings. And so both are important to us. Does that answer your question?
Yes, it does. Yeah. Thank you very much, Mr. Keller. My next and final question is to Kashiwase-san. You mentioned a couple of times in your presentation that it takes over a year to make an antibody drug conjugate drug. Could you explain to us, is most of the time taken by making the antibody or the conjugation process or something else?
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Thank you very much for your question.
ADC for that monoclonal antibodies production starting from that conjugation step and filling and also freezing and also starting from production of monoclonal antibody up until the formulation of it. It takes that much time. As you envision, as for the production of the antibody, this is a very long step. But it is not the case that that is the longest part and is taking almost all the period. But rather, as a whole, it takes more than one year. Please understand it that way.
Okay, very good. Yeah. Thank you very much.
Last questions are from Michael Nedelcovych from TD Cowen. Please go ahead.
Hi. Thank you so much for taking my questions. I have two. My first is actually a follow-up on incorporation of the NMR biomarker into TL07 and TL08.
Is the reason for the prolonged discussion with FDA because there's some sort of debate or negotiation ongoing, or is it simply how long changing a protocol in a meaningful way takes at the agency? That's my first question. And then my second question regards use of Enhertu in the frontline HER2-positive metastatic breast cancer setting. Are you aware of any efforts ongoing, and maybe it's an investigator-initiated trial, to test Enhertu as an induction therapy in that setting as opposed to treat to progression? Thank you.
Okay. So let me take the first question. And maybe Keller, if you're aware of the medical professional. Okay. On the NMR question, this is a very complicated question. So it takes time to come up with a specific plan that we are ready to announce publicly.
Okay. Am I okay with that answer? Yes. Thank you. Appreciate that. Okay. Okay.
Okay. Then the other question.
Yeah. I'll answer the second question, and then Ken you can jump in. The concept of induction and maintenance in the first-line HER2-positive metastatic breast cancer setting, that's been around for quite some time. At the recent ESMO meeting, there was a trial presented looking at testing a new regimen in the maintenance part of that. That study was positive, and it has the oncology community interested in really how to optimize both the induction part and the maintenance part. Now, for DESTINY-Breast09, that trial was not induction maintenance. That was treatment to progression. And that's where it delivered the 40 months of progression-free survival. And so one, we do believe treating to progression with that kind of data is going to be very, very attractive.
But to specifically answer your question, yes, there are studies right now looking at optimizing in HER2 for a certain amount of time and then transitioning to a maintenance-type arm. There's at least two or three studies I know of. Those studies will take many, many years to read out. So we really won't have definitive data on what approach is better, treating to progression or doing maintenance induction for many, many years. My personal opinion is that the DESTINY-Breast09 data is so compelling that most people will treat for till progression as long as patients can tolerate it. Thank you, Michael.
Very helpful. Thank you.
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This is we would like to finish the Daiichi Sankyo Science and Technology Day 2025. Thank you so much for your attendance.