Thank you, Wakao-san. Hello colleagues. I appreciate your interest in Daiichi Sankyo, and I would like to thank JP Morgan for providing the opportunity to present today. I'm Sunao Manabe, Executive Chairperson and CEO of Daiichi Sankyo. It was a very good experience to join this conference last year, and I'm happy to be here again. Please go to page three. Today, I will begin by providing a brief overview of Daiichi Sankyo. Then I will present our ADCs focusing on ENHERTU and Datroway, and I will take you through our science and technology. Lastly, I will cover our shareholder returns. Please go to page four. Daiichi Sankyo is one of the leading Japanese pharmaceutical companies headquartered in Tokyo. For the current fiscal year ending March 31st, 2025, we expect revenue of approximately JPY 1.8 trillion and an increase of 14% from the previous fiscal year.
The forecast for operating profit, which excludes temporary income and expenses from operating income, is JPY 260 billion, reflecting a growth of 33% from the previous fiscal year. Currently, Japan represents 30% of our total revenue, while North America and Europe account for 28% and 21%, respectively. Our revenue growth outside of Japan, particularly in the U.S., is primarily driven by the strong performance of our key product, the HER2-directed ADC ENHERTU, which I will discuss in detail later. Slide five, next please. I will present our ADCs. This slide shows our innovative ADC pipeline. Our company has continuously leveraged its strong and unique research capabilities to develop innovative assets, and we are proud to present not only our DXd ADC platform, but also our second ADC platform.
There are seven characteristics that make our DXd ADCs highly competitive, such as payload optimized for ADCs, a high drug-to-antibody ratio, and a stable linker, which are all unique. Starting with ENHERTU, our DXd platform has grown significantly, and we now have seven ADCs based on DXd ADC technology. Datroway, known as Dato-DXd as our TROP2 ADC, was recently approved in Japan for breast cancer indication. We are very excited to launch our second DXd ADC. I would also like to highlight DS-9606, a PBD ADC, which is the first asset from our second ADC platform. Its phase one data was presented at ESMO 2024, marking an important milestone for this new platform. Next page, please. Page seven. On page seven, I'm proud to share that Daiichi Sankyo and AstraZeneca have been awarded the Galien Foundation 2024 Prix Galien USA Award for the best biotechnology product for ENHERTU.
The Prix Galien Award is among the global health innovation industry's most renowned honors, and is considered the industry's equivalent of the Nobel Prize. Additionally, we also received the World ADC Awards for all five leading DXd ADCs in the past five years. We are honored to receive those prestigious awards in recognition of our science and technology. Next page, please. This page shows ENHERTU's achievement over the past five years under the strategic collaboration with AstraZeneca. ENHERTU has transformed the treatment landscape by redefining standards of care and revolutionizing the HER2 classification. With the approval for HER2-positive solid tumors in the U.S. in 2024, ENHERTU now has five approved indications and has been launched in over 60 countries and regions globally. The sales have shown strong growth driven by indication expansions and rapid market penetration.
Annual product sales are expected to achieve over JPY 500 billion in fiscal year 2024. Page nine shows the product value maximization for ENHERTU. For example, DESTINY-Breast06 study demonstrated a statistically significant and clinically meaningful PFS benefit in chemo- naive, hormone receptor positive, HER2- low, and ultra-low breast cancer. We expect the regulatory decision on this indication in the U.S. by February 1st this year. We expect the regulatory decision on this indication in the U.S. by February 1st, again this year. In addition, we recently decided to develop a subcutaneous formulation of ENHERTU. We hope to develop a new formulation with a short injection time to benefit patients by reducing treatment burden. Next slide, please. This slide shows the progress of four Datroway.
We are confident that Datroway will establish a new treatment in hormone receptor positive and HER2- negative breast cancer in second- line and later based on TROPION-Breast01 outcome. Regarding the NSCLC development, we have made the decision to prioritize bringing the ADC to patients with EGFR-mutated lung cancer, among whom treatment benefits have been most pronounced in currently available data. Based on the new BLA by TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01 data, we received our 12th breakthrough therapy designation from the FDA recently. In addition, a new clinical study for biomarker-positive non-squamous NSCLC in second- line setting is planned to deliver Datroway to more patients. Next, please. On page 11, I would like to talk about the first-year achievement of our strategic collaboration with U.S. Merck. Daiichi Sankyo and U.S.
Merck entered the strategic collaboration in October 2023 to co-develop and co-commercialize HER3-DXd, I-DXd, and R-DXd globally. Recently, we announced to add MK-6070, an asset of U.S. Merck, which is DLL3- targeting T-cell engager in the combination to initially evaluate the combination with I-DXd in extensive stage small cell lung cancer. We have 15 studies across the assets under the collaboration, including those evaluating combinations with Keytruda, and nine presentations were made at major congresses. We are making a joint decision to initiate multiple new studies, and they will start in due course. The strategic collaboration offers a strong and promising start. Furthermore, we are able to allocate our resources to our next growth drivers following the five leading DXd ADCs. Next, I will take you through our science and technology. Next. Page 13 shows our breast cancer map.
You can see that there are many clinical trials going in various segments of breast cancer. Especially, multiple clinical trials for HER2-positive and triple-negative breast cancer patients in earlier lines are progressing. Next, please. Page 14 shows our lung cancer map. In order to leverage the depth of our portfolio to deliver practice-changing medicines, we will focus on the following three points. Number one is to deliver superior treatments in second- line and beyond, and differentiated combination therapies for metastatic NSCLC with DXd ADCs as foundation therapy. Number two is to leverage DXd ADC innovation to advance into biomarker-selected patients and early-stage NSCLC. And number three is to identify novel treatments for advanced small cell lung cancer to address significant unmet needs. Next, please. Page 15 shows our effort on building a digital pathology platform.
We have established a productive collaboration with AstraZeneca to explore the computational pathology for ENHERTU and Dato-DXd, and we are currently working closely with U.S. Merck on digital pathology for three partner ADCs. We are strengthening our capability to proceed with this technology for future early-stage projects. We are also evaluating digital and computational pathology for immunology and other complex biologies. Our recent progress includes establishing a high-quality AI model for fluorescent multiplex IHC and the pilot platform for clinical use. Going forward, we aim to deploy those technologies in newly generated ADCs to establish seamless integration of digital pathology all the way through commercialization. Next, please. Page 16 summarizes the future demand focused for five DXd ADCs. Our collaboration with AstraZeneca has enhanced the product value for ENHERTU and Datroway, and the collaboration with U.S. Merck realized broader clinical development opportunities in HER3-DXd, I-DXd, and R-DXd.
Such progress requires us to reevaluate the annual peak demand for five DXd ADCs, which is projected to be over 50 million vials. Its volume has increased approximately 1.5x compared to the original demand forecast in the five-year business plan. Please go to page 17. To meet the updated demand forecast, we are enhancing our supply capacity and capability. We are investing approximately JPY 600 billion in capital investment, including CMOs. As for our in-house facility, we have been executing or considering ADC capital investments for seven sites globally. Next, please. Next, I will talk about shareholder returns. Please go to page 19. By improving capital efficacy and by enhancing shareholder returns, we aim to achieve fiscal year 2025 target for ROE of 8% or more, which exceeds shareholders' equity cost.
We will enhance shareholder returns by dividend increase, taking account for profit growth, and by flexible acquisition of our own shares. Page 20 shows the latest trend of dividend increase and acquisition of our own shares. We plan to increase the dividend for three consecutive years, taking account of profit growth. In addition, we have acquired our own shares from last April through this January to enhance shareholder returns and to improve capital efficiency. By realizing dividend increase and flexible acquisition of our own stocks, we expect to achieve DOE of 8.5% or more in fiscal year 2025, which exceeds the original target. Finally, please go to page 22. By accelerating value maximization for our ADCs, I am very confident that we will achieve our 2025 goal to become a global pharma innovator with a competitive advantage in oncology.
We will continue to grow toward our 2030 vision, which is to become an innovative global healthcare company, contributing to the sustainable development of society. This is all from myself. Thank you very much for your time and attention today. Mark Rutstein, our Head of Global Oncology Clinical Development, and I am very happy to take any questions that you may have. Thank you.
Thank you, Mr. Manabe. We're moving to the Q&A session, so please raise your hand if you have a question. And I'll start from my questions. So firstly, about Datroway, Dato-DXd, AVANZAR Trial. So how do you view the probability of success for the AVANZAR Trial, which targets fast-growing NSCLC? While patient selection using QCS is expected to improve the probability of success, the result of TL01 leaves some doubt about the efficacy of Datroway, Dato-DXd itself.
As you showed in the AVANZAR trial, the combination of Dato-DXd and Imfinzi is being evaluated. I'd like to know what expectations you have for this combination therapy as you advance its development.
Yeah, thank you, Wakao-san. So again, my name is Mark Rutstein. I lead Oncology Clinical Development from Daiichi Sankyo. So we remain confident in Dato-DXd. We have eight ongoing pivotal trials. We're going to plan to do another pivotal trial in a biomarker-selected population in the second- line of non-small cell lung cancer, but now turning to think about AVANZAR. So we know that Dato-DXd is a monotherapy. This TROP2 DXd ADC has shown efficacy in the non-squamous population in TL01 study. And then we have done a retrospective exploratory analysis using patient selection with the quantitative continuous scoring TROP2 assay you mentioned. When we did retrospective analysis, we see a nice efficacy signal.
Hazard ratio for PFS 0.52. That gives us confidence. Now, this is a retrospective exploratory analysis, and so we have to now validate that QCS TROP2 assay in the AVANZAR study. But we think the presence of a potential selection strategy gives an opportunity for success of the trial. And we also have two ongoing phase 1b trials looking at the triplet combination of Dato-DXd chemotherapy and immunotherapy. And what we see there shows us that it's feasible from a safety standpoint to combine these drugs into a triplet regimen. And we also see an efficacy signal, albeit limited by small patient sample size, in the right direction at about a 75%-76% response rate.
So taken together with what we know about Dato-DXd monotherapy activity, and then this potential patient selection strategy that we're excited about, and then the clinical data we have to date with the triplet regimen, we think there's a reasonable probability of success, even if we can't give a specific probability of success.
Okay. Do you have a plan to announce some updates of TROPION-Lung04 phase 1b before the AVANZAR Trial?
Right. So as I mentioned, the TROP2 QCS assay was looked at in the monotherapy data set in TL01 in exploratory fashion. So we do have the TL04 study where we can look into the biomarker data there as well to help guide us in the TROP2 assay analysis for AVANZAR. Yes.
Okay. Thank you. Any questions?
Hello. I'm Angus Liu, Fierce Pharma reporter. Just wondering your thinking around perhaps dual-target ADC or dual-payload ADC, if Daiichi Sankyo is working, thinking, working on anything around that internally at this point.
Yeah. So thanks. So we can't comment on too much detail on the preclinical pipeline, but absolutely looking at next generations of ADCs. So looking at different structures, looking at new payloads, looking at linker technology, looking at different targets. But can't comment specifically on bi-payload or bi-specific ADCs, but more to come as we can disclose over time. We did, however, speaking of bi-specific technology, recently announce at our Science and Technology Day that we're bringing into the clinic a T-cell engaging bi-specific antibody. So we are interested in general in bi-specific technology. Yes.
Okay. Any other questions? Okay. Relating to these questions, I'd like to know your confidence on next-generation ADCs. Last year, you announced the DS-9606 data. What do you think about next-generation ADC? Do you believe Daiichi Sankyo can maintain your leading position in ADC earlier?
Yeah. I think Daiichi Sankyo has been a pioneer and a leader in ADC technology. And now there are six DXd ADCs in the clinic, six of them. And of course, we've mentioned that ENHERTU has five indications and may potentially get a sixth. And then we have we certainly have a lot more to do with DXd ADCs in terms of that platform. Now, we have announced, as you said, and we produced some early data with DS-9606, CLDN6 ADC using what we call a PBD or a pyrrolobenzodiazepine payload. There, it's early. We're still in dose selection.
We've seen activity in lung cancer, gastric cancer, and germ cell tumor. So we like what we see so far, but it's too early to, let's say, understand the full potential there yet. We are, however, working on additional, as I mentioned in response to the last question, working on additional payload and additional ADC technology. And so we'll see more to come. I think when we look at the capabilities of Daiichi Sankyo from a science and technology standpoint, I think that's a key strength. So we will continue to build out and foresee the potential of DXd, but we will bring additional constructs and pipeline forward for sustainability. And we do plan to maintain leadership. Okay.
Thank you. Please. Thank you.
So very impressive. But anything beyond ADCs? I mean, yes.
Yes. So certainly ADC technology is a focus, and it's a key area of strength.
Daiichi Sankyo is certainly interested in diversification of the pipeline. So as an example, in the clinic right now, we have a small molecule EZH1 and EZH2 inhibitor called Valametastat, which is an interesting drug, actually approved in Japan in peripheral T-cell lymphoma. But this is a drug which has potential in both solid tumor and hematologic malignancy. We also have monoclonal antibody technology we've taken into the clinic. An example is a SIRP alpha antibody that's being combined with our DXD ADCs because we've seen preclinical proof of concept for combining such monoclonal antibody with a DXD ADC. And then I'll just mention briefly again, we've now going to enter the clinic with a bi-specific T-cell engaging asset. Then in addition to that, and on Manabe's slides, we expanded our partnership with Merck for MK-6070, which is a tri-specific DLL3- targeting T-cell engaging agent.
So I think you see interest absolutely in continuing to build strength in antibody drug conjugate technology, but also in diversification as well. And I think you'll continue to see that trend in our pipeline as we go forward.
Okay. Any questions? Okay. So I'd like to know about biomarker strategies. So you mentioned that you plan to introduce DXd pathology in your collaboration with U.S. Merck. Could you provide more detail about this technology? For instance, how does it differ from QCS? What are its advantages?
Can you repeat again? How does it relate to QCS, you asked?
Yeah. So different point, QCS, so different from the QCS, probably AstraZeneca progressed QCS. But separately, Daiichi Sankyo and Merck progressed digital pathology. I'd like to know more detail on this technology.
Yes. Indeed, AstraZeneca had developed the QCS assay, which is based on a digital pathology platform and then merges that with computational pathology and artificial intelligence. We, for a while now at Daiichi Sankyo, have also been interested in digital pathology. We have digital pathology expertise and we have been discussing with our partner, Merck, on leveraging digital pathology for the assets that we collaborate on. What we'd expect to see, having learned a good deal from the QCS technology and that assay for TROP2, what you can expect to see is we'll partner with Merck to build out digital pathology strategies and potentially layer in also some computational pathology, but we'll also plan to do that with drugs that aren't partnered as well.
So we are building, and I think that was highlighted by our head of precision medicine, Dale Shuster, on our science and technology presentation. We are building our own expertise and depth in biomarker technology. And it will be in digital pathology, but it will be broader than that to look at other platforms as well.
Okay. Yeah. Thank you. Any questions? One floor. Okay. So I'd like to know about ENHERTU. Could you comment on why the development strategy for earlier treatment line in HER2-low area beyond DB06 remains unclear? What expectations should we have regarding this area?
Yeah. So ENHERTU is, as you say, under regulatory submission for DESTINY-Breast06, and Daiichi Sankyo showed that data.
And we know ENHERTU-positive breast cancer. We really now have covered all lines of therapy with our trials, right, from DESTINY- Breast 01 and very advanced HER2-positive metastatic disease, all the way to read out now in the 2025 timeframe, read out DB09 in frontline HER2-positive setting, adjuvant HER2-positive setting with DB05, and then neoadjuvant. So it would be, at this point, thinking beyond HER2-positive metastatic breast cancer. We do entertain, and we don't have plans to share now, but we do entertain looking at earlier lines of therapy in hormone receptor-positive breast cancer. And then we look at other indications as well. So last year, we announced a phase three trial. AstraZeneca, our partner, is running in biliary tract cancer. We announced recently a phase three trial in frontline gastric cancer. And we intend to bring additional trials forward.
So I think the key theme I would want to communicate is, as successful as ENHERTU has been to deliver benefit to patients and address unmet needs, we're certainly not done with the asset. And we will look in not only in additional area in breast cancer, right, but also, and particularly outside the HER2 setting, but also additional indications.
Okay. Thank you. So could you comment on anything about the TROPION-Breast01 that way?
Yeah. So TROPION-Breast01 is our phase three trial in the second- line plus setting, hormone receptor-positive, HER2-negative metastatic breast cancer. And it is in regulatory submission. And we're very close now. The PDUFA date is actually two weeks away, about. It's January 29th. And we're encouraged by the data. Of course, we can't comment specifically on the negotiations with FDA, but quite soon, we should be able to provide an update.
We think that Dato-DXd has the potential to be an important drug in advanced HER2-positive, hormone receptor-positive, HER2-negative metastatic breast cancer, particularly where patients don't express HER2, right? We call HER2 null, right, which represents about 15% of the hormone receptor-positive, HER2-negative population. Of course, Dato-DXd also is in four pivotal trials in triple-negative breast cancer. More to come.
Okay. Thank you. Any questions?
Daiichi Sankyo is developing a subcutaneous injection of ENHERTU. You mentioned that it is expected to benefit patients by reducing treatment burden. Could you elaborate on what kind of benefit can we expect from it and just beyond the dosing convenience of the patient?
Yeah. We don't have too much detail to share on the program. Our subQ program for trastuzumab deruxtecan can go into the clinic in the coming months.
And so in terms of benefits, when you think about subcutaneous therapy, I think Manabe-san alluded to infusion time, right, the time to administer the drug. If it's not parenteral, we can expect a quicker infusion time. And also, it allows the patient not to spend as much time in the infusion chair, right? It's a big difference for the patient in terms of potential quality of life and time burden for the patient, as well as for the oncology clinic as well, to the prescriber and the people administering the drug. Now, when we think about convenience to patients with a subQ regimen, we also think about, well, in terms of clinical indications, there are a wide variety of areas we could study.
But we could potentially think about settings where maybe we give a subQ trastuzumab deruxtecan along with oral therapy as an example, right, to keep patients less time in the clinic. That's just an example. So these are the types of things we think about with the potential benefits and reduced burden to patients.
Okay. Any questions? Okay. So about DS-6000, so Merck, deal, how should we interpret Merk's decision to continue clinical development for HER3-DXd? And for DS-6000, R-DXd, its decision on whether to continue development expected by October 2025, how do you assess its likelihood of continuation?
Yeah. Thank you, Wakao-san. And so, yeah, we're very excited that Merck agreed to continue the collaboration on HER3-DXd with us.
We think that's a nice vote of confidence to the drug and that Merck agrees to continue development with us and that they see the potential to address unmet needs in solid tumors. Of course, it would be a good question to pose to Merck themselves. Now, when we think of our DXd, which is our CDH6 ADC, that's now entered phase two, three study in ovarian cancer, right? So we still have to await to see what Merck will do. We're optimistic at this point because our DXd is a drug that is showing I mean, we have shown early data with about a 50% response rate in platinum-resistant ovarian cancer where patients had failed the median of four prior therapies. So we're very encouraged by what we see. We think Merck is as well.
We also see strong interest in our DXd from the oncology community given the high unmet need in advanced ovarian cancer, and then there's the opportunity to look at additional tumors beyond ovarian cancer, so we're optimistic that Merck will continue the collaboration there, but again, it would be a good question for them.
Okay. Thank you. Please.
Just a question on manufacturing maybe. Just after HER3-DXd's rejection, first of all, would you be able to share what percentage of your manufacturing is reliant on contractors versus internal? And then after HER3-DXd's rejection, is there a driving force to kind of increase the internal manufacturing percentage? And also, you're building that facility in Shanghai in China recently. Just thinking about how you're building the internal manufacturing component.
Thank you very much for your comments and questions. Of course, in the future, we may need to expand our internal capability to produce following ADCs. So far, about half of production is inside and half from CMOs. But considering the very unique of our own technology, we may expand our internal capability more in the future. Of course, we cannot produce 100% inside. Today, I cannot comment on the detail, but more than half percent inside and less than half percent, half from outside. So far, CMOs can provide us high quality. High quality is very limited. If we find good CMOs providing us high quality, that would be our future collaboration target.
Okay. Thank you. It's just about time. So we'll wrap up this Q&A session. Thank you very much for joining us. I appreciate.