Thank you, Wakao-san. My name is Sunao Manabe, CEO of Daiichi Sankyo. Hello, colleagues. Thank you for showing interest in Daiichi Sankyo. Also, I'd like to thank J.P. Morgan for giving me, us, this opportunity. It was a great experience for me to participate in last year J.P. Morgan conference; then I am very happy to be here again. Let's go to page three. Today, I'll begin by providing a brief overview of Daiichi Sankyo. Then I will present our ADCs, focusing on our five lead products, and I will take you through our latest R&D strategy. Lastly, I will cover our shareholder returns. Go to page four. Daiichi Sankyo is one of the leading Japan pharmaceutical companies, headquartered in Tokyo.
For the current fiscal year, ending March 31, 2024, we expect a revenue of approximately JPY 1.6 trillion, an increase of 21% from the previous fiscal year. The forecast for core operating profit, which excludes temporary income and expense from operating income, is JPY 155 billion, reflecting a growth of 26% from the previous fiscal year. Currently, Japan represents 37% of our total revenue, while North America and Europe account for 29% and 18% respectively. Our revenue growth outside of Japan, particularly in the US, is primarily driven by the strong performance of our key product, the HER2-directed ADC Enhertu, which I will discuss in detail later. Next, I will present our ADCs. Please go to page six.
Page six shows our proprietary DXd ADC technology, which is utilized for Enhertu and other DXd ADCs that follow Enhertu. As shown on the right part of the slide, there are seven characteristics that make our DXd ADCs competitive, including the payload, which is optimized for ADC, high drug to antibody ratio, and stable linker, which are all unique. Recent medical conferences, including ASCO, the American Society of Clinical Oncology, highlighted the focus of many oncology companies on ADC development. I believe that the competitive efficacy and safety profiles of our products, including Enhertu, have been the driver behind this trend, and we are working to enhance our DXd ADC technology further. Page seven show the current development status of our five lead DXd ADCs. We are working with AstraZeneca for the first two ADCs and with Merck for the next three ADCs.
Clinical development is progressing steadily for all five ADCs, and their value maximization is well on track. Let me briefly introduce an overview for each product. Page eight shows the revenue growth of Enhertu since its launch in the U.S. in January 2020. Revenue is growing strongly through rapid market penetration and indication expansions, and the global revenue for the current fiscal year is expected to reach JPY 433 billion, approximately 70% increase from the previous fiscal year. Enhertu is currently approved for specific indications in breast cancer, gastric cancer, and non-small cell lung cancer in the U.S. For breast cancer, Enhertu has established a strong leadership position in HER2-positive breast cancer and is making notable progress in HER2-low breast cancer, which is a new patient segment that we created and accounts for approximately half of all breast cancer cases.
In addition, we expect to obtain a filing acceptance letter in the U.S. for a new indication, tumor-agnostic therapy for patients with HER2-expressing solid tumors. Within the current fiscal year, which is by the end of March. Page nine shows the significant development progress for Dato-DXd, a TROP2-directed ADC. Dato-DXd has shown promising results in two pivotal trials. TROPION-Lung01 is a phase III study comparing Dato-DXd to the current standard of care, docetaxel, in non-small cell lung cancer patients with or without actionable genomic alterations. Dato-DXd demonstrated a statistically significant improvement in progression-free survival compared to docetaxel. The data have been shared with the FDA, and we expect to obtain a filing acceptance letter in the U.S. within the current fiscal year.
In addition, TROPION-Breast01 is a phase III study comparing Dato-DXd to investigator's choice chemotherapy in hormone receptor-positive, HER2-low or HER2-negative breast cancer patients. We aim to establish Dato-DXd as a new standard of care for TROP2 ADC in hormone receptor-positive, HER2-low breast cancer, and a new option for HER2-negative breast cancer. We plan to file this indication in the US within the current fiscal year as well. Page 10 shows an overview of our strategic collaboration with Merck for HER3-DXd, DS-7300, and DS-6000, which started in October of last year. Positive data in several tumor types, including lung and ovarian cancers, has enhanced the product value for the three products. At the same time, the competitive landscape in ADC development is becoming intense, as I mentioned earlier. Driven by three environmental changes, enhanced capacity, resources, and capabilities have become necessary to maximize our ADC portfolio.
We therefore determined that a strategic collaboration would be the best approach to deliver our innovative products to more patients, more quickly. Through the collaboration, we are working to accelerate the development and to expand the possibilities for these three ADCs. In addition, we will allocate the freed-up internal resources to our new growth drivers, following our five lead DXd ADCs. The financial terms are as shown on the bottom of this slide. Next, I will take you through our R&D strategy. Please go to page 12. Page 12 is our R&D strategy, which we call Five DXd ADCs and Next Wave. We have updated our R&D strategy from three and alpha to five DXd ADCs and Next Wave back in April last year.
In line with the strong progress of our pipeline, our main objective now is to maximize the value of these five lead ADCs. For the Enhertu and Dato-DXd, we will maximize their value together with AstraZeneca. Additionally, now we have a new collaboration with Merck for three ADCs, HER3-DXd, DS-7300, and DS-6000, as I presented earlier. Through these collaborations, we will accelerate development and expand possibilities for these five lead ADCs. Page 13 shows our expand and extend strategy to deliver our innovation to more patients. When we say expand, we aim to target earlier lines of therapy and broaden our scope beyond the lung and breast cancer. Especially in breast cancer, our clinical development plan is expanding nicely. Please see page 14 for our efforts in breast cancer. Our breast cancer program is very comprehensive.
Enhertu, shown in orange, is approved for certain patients with HER2-positive and HER2-low metastatic breast cancer. For HER2-positive breast cancer, we anticipate promising results in earlier stage of therapy, which enables Enhertu to contribute to more patients, such as first-line, adjuvant, and neoadjuvant settings. In addition, we are also awaiting the result for the first-line HER2-low setting from DESTINY-Breast06. Regarding Dato-DXd, shown in blue, positive results were acquired from TROPION-Breast01 study in hormone receptor-positive setting, as I explained previously. In addition, multiple pivotal trials for triple-negative breast cancer in first-line, adjuvant, and neoadjuvant settings are underway. Last but not least, HER3-DXd, shown in green, also showed efficacy signals in breast cancer, and we are currently evaluating the potential for HER3-DXd in breast.
The right part of slide of page 15 shows our extended strategy that will contribute to the extension of our ADC franchise, including other DXd ADCs that follow lead 5 DXd ADCs and next generation ADCs. We are interested in evaluating our existing pipeline assets to determine how they can be combined with DXd ADCs. This will provide us with an opportunity to further establish our presence in breast cancer, lung cancer, and other solid tumors. We are actively pursuing sustainable growth with these R&D strategies by striking a well-balanced approach between investment for further growth and shareholder returns. Now, shareholder returns. Please go to page 17. Page 17 shows our shareholder return policy by improving capital efficacy and by enhancing shareholder returns. We aim to achieve dividend on equity of 8% or more in fiscal year 2025, 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 18 shows the trend for our profit growth and dividend increase. As for annual dividend for fiscal year 2023, we expect an increase by 10 JPY per share from the previous fiscal year, given the profit growth driven by strong performance of Enhertu and from the strategic collaboration with Merck. We will enhance shareholder returns in line with our shareholder return policy and will maximize our shareholder value. Finally, please go to page 20. We are currently working on our five-year business plan that started in fiscal year 2021 for sustainable growth. 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 for myself. Thank you very much for your time and attention today.
Thank you, Manabe-san.
Mark Rutstein, Dr. Rutstein, our Head of Global Oncology Clinical Development, sitting there, and myself are very happy to take any question that may, that you may have. Thank you.
Thank you, Manabe-san. So, start the Q&A session, and if you have a question, please raise your hand or post a question on the web. So I start kick off my question. So could you comment on the progress of mid-term business, five-year business plan? So I'd like to know the positive side and negative side of the progress of five-year business plan, based on the business result in 2023.
Thank you, Wakao-san. Let me start from the positive side. As you know, currently, Daiichi Sankyo fifth midterm plan is running, starting from fiscal year 2021. As I explained you, our first numerical target when we started the midterm plan in fiscal year 2025 was JPY 1.6 trillion total revenue and JPY 600 billion from oncology. But based on the latest excellent performance of Enhertu and other projects, last year our latest forecast revenue in 2025 is updated from JPY 1.6 trillion to JPY 2 trillion and JPY 900 billion from the oncology business. As such, in general, our midterm plan is progressing very well. And also, other than Enhertu, Dato-DXd and the other four, including other three ADCs, the progress of the clinical trials are on track.
Also, we started a new collaboration with Merck. Thus, again, our midterm plan is progressing well. In terms of a negative part, I don't think we have a significant negative part at this moment. However, one of the issue is we would like to identify next driver, following ADCs for our future. Thank you.
Thank you. And, next about TROPION-Lung01, probably everybody is interested in it. We'd like to know, how your evaluation Dato-DXd has changed, based on the result of TROPION-Lung01.
We are very confident about the Dato-DXd's potential. Mark, would you add?
Yeah, sure. So, so based on, the data of, TROPION-Lung01, we believe that, Dato-DXd, has the potential to be an important drug for the treatment of non-squamous non-small cell lung cancer. We had a positive study in the intent to treat population. We could see the benefit was driven, in the non-squamous population. And as Manabe-san mentioned, you know, we have now filed that data package, and, we do expect filing acceptance, you know, within the fiscal year of 2023 or by March 2024. But of course, our interest in Dato-DXd is not, relegated to the second-line setting in non-small cell lung cancer, right? We have a, we have a broad frontline program.
We have two studies with Dato-DXd, with pembrolizumab, with or without chemotherapy, one in the PD-L1 less than 50% segment, one in the PD-L1 greater than 50% segment. These are studies TROPION-Lung07 and TROPION-Lung08. And we're now in the process of amending the TROPION-Lung08 study to increase the probability of technical success by capping the squamous population, because, as I mentioned, the benefit was driven by the non-squamous population in that study. But then going and looking beyond lung cancer, Manabe-san showed we have a broad program in breast cancer. We have a positive phase III trial in the hormone receptor-positive HER2-low negative setting, TROPION-Breast01, that's now filing. And then we have a very broad four pivotal trial program for Dato-DXd across all lines of therapy of triple-negative breast cancer.
And then beyond that, we have early phase signal finding studies in GU cancer, gynecologic cancer, GI cancer. So this is an important asset for us, and we remain very focused on it.
Okay. Thank you. And could you comment, more kind of on the status of the filing of, TL01? So can I assume that its progress is in line with your plan, or are there any difficulties?
Yeah, so we don't usually comment on the specifics of the filing timelines. I would say, you know, so far so good. I can just say that we have filed, and we're looking for the filing acceptance, you know, within this fiscal year of 2023. And it's hard for us to speculate, on the indication, you know, and, and the response from FDA. But we, and as I mentioned, do believe that, Dato-DXd could be a potentially practice-changing in the second-line setting of non-s, non-squamous non-small cell lung cancer. And that's all that I could really comment now on the specifics of the regulatory process.
Okay, thank you. Any questions from the audience?
Taichi Noda from T. Rowe Price. Two questions. One for Manabe-san. You've got the Merck deal, you know, achieved, and then it was great, sort of deal from my point of view. But, with the cash coming in, I don't know in yen terms, but $3-4 billion, $4-5 billion cash in front of you, you know, what is the sort of way to spend? Are you going to keep it, or you will do something with it? What's the sort of, you know, few, sort of choices you have in your mind? That's the first question. And the second question on the development programs, the what's sort of a priorities changed for HER3 and DS-6000 particularly?
I saw some potential sort of a movement in the HER3-DXd in the breast and also DS-7300, I think. Given the squamous cell lung cancer.
... didn't really go well with Dato-DXd. Maybe you can do something with DS-7300. Just could you just elaborate on the how, those three assets will be developed over time? Thank you.
To your first question, through the collaboration with Merck, our internal budget and resources can be allocated to others. Of course, through the collaboration, we can get some cash, but under current situation, Daiichi Sankyo's first priority is to invest our internal asset first. M&A and other investment would be a lower priority.
I can take that. Yeah, so your second question was related to the future development of HER3-DXd and DS-6000 and DS-7300. So indeed, HER3-DXd, the initial indication that we pursue, it's now received priority review, is in the later line of EGFR mutation-positive non-small cell lung cancer. But as we have presented previously, there's activity of HER3-DXd in really all the key segments of breast cancer. So we are considering different strategies, not able to disclose specifics, but this drug has potential in triple-negative breast cancer, hormone receptor-positive breast cancer. And so we're certainly interested in beyond just EGFR mutation-positive non-small cell lung cancer.
Now, for DS-6000, we actually have now on ClinicalTrials.gov shown the entry of DS-6000, our CDH6 ADC, into a late-stage trial of platinum-resistant ovarian cancer. So we've shown our DXd in a population of 50 platinum-resistant ovarian cancer patients who are heavily pretreated four, four lines, previous lines, was a 46% response rate. So that leads us to be very interested in this drug, not only in the platinum-resistant setting, where we've already launched a phase II/III study that's on ClinicalTrials.gov, but additionally in ovarian cancer more generally. And then you've asked about DS-7300. So this is our B7-H3 ADC. Its lead indication is small cell lung cancer, and within 2024, we will initiate pivotal trials, and that's in that setting.
And that's simply because we've seen in an early cohort of small cell lung cancer, heavily pretreated, we've seen an approximate 50% response rate. So that is why that's our lead indication. Now, beyond that, and based on the expression of B7-H3 and what we've shown publicly, the drug has shown activity in squamous non-small cell lung cancer, a small cohort, squamous esophageal cancer, and also prostate cancer. So we're gonna continue to study those areas and are considering development plans in all possible indications, including in squamous lung cancer, but more to come.
As it relates to Dato-DXd, can you update us on the use of potential Trop-2 biomarker? And to the extent you are successful in identifying a product that works, could you amend the first-line phase III trials to incorporate that?
Yeah, so thank you. So Dato-DXd, like our other DXd ADCs, is a targeted agent, so we certainly explore the possibility for a biomarker. Now, Trop-2 itself is very highly expressed in the target indications so far for Dato-DXd, that is non-small cell lung cancer and breast cancer. So, despite that high expression, we do have exploratory efforts underway, in all of our studies to look at the possibility, whether it be Trop-2 expression or some other molecular parameter or analyte that could help us predict response to Dato-DXd. But, it is exploratory, in you know, largely in the studies we're conducting. If we do find a predictive marker that we think is important, then absolutely, we would adapt our programs in such regard.
Now, I would also mention, though, that, our partner, AstraZeneca, is running a study called AVANZAR. That's with Dato-DXd, and durvalumab and carboplatin in the frontline of non-small cell lung cancer. And in that study, they're looking to validate, an assay. They're looking to validate, Trop-2 assay. So, that could be, that could be something that comes along as well, but I would rather, defer the questions to them on specifics of the, of the development of that assay.
Okay. So, relating to Dato, there are some competitors in Trop-2 area, ADC area. So could you comment on the advantage of Dato-DXd compared to the other Trop-2 ADCs?
Yes, so I mean, there are several. Well, I think there are now, like the Kelun asset, you know, which is partnered with Merck, is now in the pivotal trial setting of non-small cell lung cancer. And then, of course, there's, you know, there's Trodelvy, which is approved, you know, the asset from Gilead. And it's hard to compare the assets from a safety and efficacy standpoint because we really have no head-to-head data. But what we do know is, I mean, Dato-DXd is very active, and if we look from a cross-trial comparison, I believe we have a very competitive agent.
I think that relates to the DXd platform, where and I think Manabe-san showed that slide. I mean, there are seven key attributes of the DXd platform, and these were designed specifically to overcome limitations of previous generations of ADCs. So I would say that we think our asset is quite competitive. We think it's a leading asset. Hard to make a clear comparison head-to-head without an appropriate head-to-head data set. But also, I would refer to the fact that, you know, we are quite advanced in our program. And so we have a lot of confidence in our program.
Thank you.
So next, about Enhertu, for hormone-positive and HER2-low population, especially the strategy for the development on earlier line than DB-06 . So recently, you have presented data on DB-08 . Is it correct to assume that you are more positive about the development of earlier treatment lines than in the past?
So we're definitely interested in studying Enhertu in an earlier treatment line than DESTINY-Breast06, and DESTINY-Breast06 is in that HER2-low population where patients have not yet received chemotherapy. So we're interested in going earlier. We did present data from DESTINY-Breast08 that, as you mentioned, this is Enhertu in combination with endocrine therapy, either anastrozole or fulvestrant. I mean, what we could see is that the combinations are active and tolerable, but it was hard to really come to conclusions on efficacy, given the fact that there are approximately 20 patients per cohort with the anastrozole combination and the fulvestrant combination. So really, we would have to do more research to understand the potential of Enhertu in combination with endocrine therapy.
That being said, we are very interested, as I mentioned, in studying that earlier hormone receptor-positive HER2-low space. We're considering various options within HER2 currently, and we're just not prepared to share any specifics on those, on that program, but you'll likely see more to come from us.
Okay. Any question? Please go.
Hi, congratulations on the data.
Thank you.
Heidi Wang, OBI Pharma. Two questions. One is a small one related to the TROPION-Lung01, and, as you know, the FDA prefers to see the OS data. So I see the great PFS data, but I presume that you also have provided the OS data. And the second question is related to: I see how you lay out the entire clinical program for Enhertu, which is very impressive, including the early lines. But the question is that: How are you going to position your subsequent ADCs in the pipeline to find niche or go beyond, you know, what you're building for Enhertu into an empire? Thanks.
Yeah, so great questions. With respect to TROPION-Lung01, overall survival is a dual primary endpoint in that study, and it certainly will be of interest to the regulatory agency. But we're not commenting on our regulatory strategy and how it relates to providing OS and the timing of that, but can say that for certain, both PFS and OS will be examined by regulatory agencies. With respect to the fact that, yes, Enhertu now is being studied across various segments of breast cancer, and then we do have additional DXd ADCs, which are active, such as HER3-DXd in breast cancer. So we're looking carefully at appropriate sequence. We're trying to understand...
One of the key questions for us is to understand would resistance to Enhertu be and the DXd platform, would that be target-mediated resistance or payload-mediated resistance? And the answer to that question would help us understand how to sequence the ADCs. We also consider potentially rational combinations of ADCs, including in breast cancer. So a broad translational campaign to try to address the question you stated, because certainly, when a drug is as successful as Enhertu and is capable of meeting unmet need in a broad population of patients, we absolutely have to think what is gonna be next. And then lastly, in regard of that, we're developing multiple next-generation ADCs, where we vary the structure, we look at different targets, payloads, et cetera.
We actually do have a next-generation ADC already in the clinic, DS-9606. So, I gave a broad answer to show you that we're very interested in sequencing, combinations, and next generation. Yeah.
Thank you. So, okay, general question about ADC. So while other companies are also focusing on ADCs, so why don't you know the advantage of Daiichi Sankyo's ADC technologies?
Yeah, so I think, yeah, certainly acknowledge that, there's an intense interest in ADCs now. I mean, I think it's an exciting time in the industry, and I think in the end, that's gonna be good for patients and for oncologists, right? Because they're always looking for better treatments. I think that Daiichi Sankyo has been a pioneer and a leader in the ADC field and definitely seeks to continue to lead. We showed Manabe-san, one of Manabe-san's slides had the seven key attributes relating to payload and linker and different aspects, which have really given the DXd platform a competitive advantage. And we can see really from the growing evidence base that's there, what is capable from the DXd platform.
That is now in HER2 is approved, it has 4 clinical indications and hopefully more on the way. And you know, Dato-DXd now has the 2 positive phase III trials in lung cancer and breast cancer, respectively. HER3-DXd is now under priority review for, based on a pivotal phase II study in the third line plus EGFR mutation-positive non-small cell lung cancer. I also answered a question earlier that DS-7300 or B7-H3 ADC is now gonna enter pivotal trials in small cell lung cancer. R-DXd, our CDH6 ADC, is already in a phase II/III study in ovarian cancer. And we now have a sixth DXd-ADC, DS-3939, a Mucin 1 ADC that's in the clinic.
So there's now a comprehensive database in support of the success of this DXd platform. Now, beyond that, the same scientists that built the DXd platform, that's the basis of these five late-stage ADCs that will all soon be in pivotal trials, all five of them. Those same scientists are looking in a data-driven way, aggressively, at next generation ADCs, and what can we do beyond DXd, right? And so that is a huge focus of our company. Yeah.
Thank you. So two minutes left, and, finally, could you comment on balance between profit and R&D investment? Your company plans to enter a period of profit growth starting in fiscal 2024, which has had the number of clinical trials related to ADCs, is expected to continue to increase. How do you balance the R&D investment with profit?
Okay. In our fiscal year 2025 goal, one of them is the 40% of core operating profit before R&D expense. We have not changed that goal yet. We will keep that 40% numerical target. Of course, our profit is growing. On the other hand, our investment is also more than expected when we planned. Both are growing, then we'd like to finally keep 40% of our target.
Okay. So it's time to close. I really, I really appreciate your comment. Thank you for joining us. Thank you so much.
Thank you.