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

I'm Okuzawa. Thank you very much for attending the FY 2023 financial results presentation for Daiichi Sankyo. We have announced FY 2023 results today at 1:00 p.m. I would like to go through the presentation as per the material. Please refer to Slide 3. This is today's agenda. FY 2023 consolidated financial results, business update, R&D update, 5-year business plan update, FY 2024 forecast. As for the R&D update, the global R&D Head, Takeshita will take you through the presentation. We are going to address your questions at the end. Please refer to Slide 4. This slide shows a summary of consolidated financial results for FY 2023. Revenue increased JPY 323.2 billion or 25.3% year-on-year to JPY 1.17 billion. Cost of sales grew by JPY 65.7 billion year-on-year. SG&A rose JPY 157.2 billion, of which the profit share of DXd ADC products increased JPY 79.8 billion and other SG&A expenses rose JPY 77.5 billion. R&D expenses grew by JPY 27.6 billion. As a result, core operating income increased by JPY 72.7 billion or 59.3% year-on-year to JPY 195.3 billion. Operating income, including onetime gains and losses, increased JPY 91 billion or 75.5% to JPY 211.6 billion, and net income attributable to the parent company rose by JPY 91.1 billion or 83.8% to JPY 207 billion. As for the actual FX rate, the yen was JPY 144.62 to the dollar, a depreciation of JPY 9.14 from the previous year, JPY 156.79 to the euro. Depreciation of JPY 15.82 from the previous year. Please refer to Slide 5. From here, I will explain the factors behind the year-on-year revenue change. Revenue increased by JPY 323.2 billion year-on-year. The breakdown by business unit is as follows: For the Japan business, sales of anti-influenza agent, Inavir, anti-malignant tumor agent Enhertu, a direct oral anti-cogulant, Lixiana and pain treatment Tarlige increased. And the sales in the vaccine business, including Daichirona, COVID-19 vaccine grew to drive the sales by JPY 57.6 billion. Next, I will explain the overseas business unit. This section excludes the impact of FX rate. As for the Oncology business, sales increased by JPY 128.1 billion mainly due to the sales growth of Enhertu in the U.S. and Europe and the contribution of Vanflyta and anti [indiscernible] tumor agent launched in the U.S. and Europe in fiscal 2023. Sales of American region increased by JPY 3.2 billion, mainly due to the sales growth of Venofer and iron deficiency anemia treatment and GE injectables despite decrease in sales of Injectafer and iron deficiency anemia treatment. For the EU specialty business, sales had increased by JPY 19.7 billion, mainly due to sales growth of Lixiana and Nilemdo/Nustendi treatment for hypercholesterolemia. The ASCA business, which covers Asia and Latin America reported an increase in sales of JPY 33.1 billion, mainly due to increased sales of Enhertu, which grew mainly in Brazil. As for the upfront payment and development sales milestone related to the alliance with AstraZeneca and U.S. Merck, despite the decrease in development milestone for Enhertu, sales milestone payment for Enhertu increased. Deferred revenue of JPY 12.9 billion related to the upfront payment for the strategic alliance with U.S. Merck for DXd-83 products, including HER3-DXd was recorded at sales revenue. As a result, it increased by JPY 14.7 billion. The change in development and sales milestone for Enhertu will be discussed in more detail later in this report. FX had an overall positive impact of JPY 66.8 billion on net sales. Slide 6 shows the factors affecting the core operating profit. There is an increase of profit of JPY 72.7 billion. As explained before, the sales revenue increased JPY 323.2 billion, including the ForEx impact of JPY 66.8 billion. Now I would like to talk about the cost of sales and expenses, excluding the ForEx impact. The cost of sales increased by JPY 53.1 billion due to the increase in the sales revenue. For [ S&G ] expenses there is an increase of the profit share with AstraZeneca due to the sales revenue expansion of Enhertu. And also there is the cost increase for the preparation of Dato-DXd -- HER3-DXd and Enhertu new indications. So this increased by JPY 131.0 billion. R&D cost increased JPY 10.2 billion due to the increase in R&D investment for 5DXd ADCs. The ForEx impact affects JPY 56.2 billion. Excluding this, the core operating profit increased by JPY 62.1 billion. The Slide 7 shows the profit of this fiscal year. There is an increase of JPY 72.7 billion, including the ForEx impact. Temporary income and cost increased by JPY 18.4 billion Y-o-Y. And that temporary revenue and expenses increased by JPY 5.4 billion due to the sales of the Kyushu branch building, JPY 8.1 billion, Daiichi Sankyo Beijing transferred JPY 5.9 billion as well as the payment of the settlement from Novartis concerning the U.S. patent infringement against Plexxikon JPY 26.4 billion. For temporary cost, there is the loss of Turalio, JPY 14.2 billion. However, there is also the environmental expenses for ex Yasugawa factory, JPY 4.1 billion. So there is a decrease of the temporary cost of JPY 13 billion. Concerning the financial profit and cost, there is the increase by JPY 19.4 billion due to the improvement of the security evaluation. For corporate tax, there is an increase in the tax -- before tax profit. So there is an increase of the tax by JPY 18.6 billion. Profit at the owners of the company increased by JPY 91.5 billion to JPY 200.7 billion. Slide 8 and 9 shows the sales increase decreased by the business unit and that major product in Japan. And in Slide 5, there is the unique situation explained without the impact of ForEx. But here, there is a ForEx impact included. Now on business update, let me offer you the progress in FY 2023, progress towards Maximize 3ADCs. Please refer to Slide 12. Slide 12 shows a breakdown of Enhertu sales revenue. In FY 2023, product sales increased by JPY 188.4 billion year-on-year to JPY 395.9 billion due to the growth in the U.S. and Europe as well as other regions. For FY 2024, we forecast sales of JPY 508.4 billion, up by JPY 12.4 billion year-on-year. The sales in each country and region will be explained later. As for the development milestone, JPY 3.8 billion was recorded in FY 2023, following the approval of a second-line treatment for HER2 mutated a non-small cell lung cancer in Europe in October 2023. However, development milestone achieved in FY 2022 was JPY 12.4 billion, down JPY 14.3 billion year-on-year due to the impact of the lump-sum recognition as revenue in the previous fiscal year from the time contracts were assigned to the time milestones were achieved. In FY 2024, we expect to record JPY 9.4 billion in development milestones achieved in FY 2023, a decrease of JPY 2.9 billion year-on-year due to the impact of recording the amount equivalent to approximately 5 years from the time agreements been concluded to the time the milestones were achieved as sales revenue in the lamp sum. For the sales milestone for FY 2023, we've recorded $200 million or JPY 29.6 billion at sales revenue in one lump sum due to the achievement of $2 billion in a single year product sales in the promotion region with AstraZeneca in the fourth quarter of the current fiscal year. For FY 2024, we expect a sales milestone of JPY 387.5 million or JPY 56.2 billion to achieve single year product sales of $3.5 billion. As a result, Enhertu revenue, including upfront payments upon contracts and associated with [indiscernible] as well as development sales milestones for FY '23 was JPY 449.2 billion, an increase of JPY 190.8 billion from the previous year. For FY 2024, we forecast an increase of JPY 136.2 billion from the previous year to JPY 55.4 billion. Slide 13 onward, I use 2 slides describing the sales of Enhertu in each country and region. First, sales in the U.S. and Europe. For the United States, product sales in FY 2023 was JPY 225.5 billion or about $1.6 billion. For fiscal 2024, we are aiming for the sales of JPY 266.6 billion or more than $1.8 billion. Current indications are shown here. In April 2024, we received approval and start promotion for the indication of second-line treatment of HER2-positive solid tumors as the first anti-HER2 therapy approved across cancer types. Market share in each indication remained favorable. We maintained the market leaders' position with the share of new patients with HER2-positive breast cancer in the second-line being at approximately 60%. The market share of new patients with HER2-positive breast cancer previously treated with chemotherapy remained at about 50%, maintaining the top position. We also maintained a top position in new patients for second-line HER2-positive gastric cancer and second-line HER2 mutated NSCLC respectively. Other progress in FY 2023, including include in the NSC and guidelines for several types of cancer, including endometrial cancer and cervical cancer. Sales in Europe is also strong. Product sales in FY 2023 were JPY 101.9 billion or $704 million. In fiscal 2024, we aim the sales of JPY 152.1 billion or more than USD 1 billion. Shares of new patients in each marketed country is steadily increasing. And the share of new patients in France, Germany, Spain and Italy has expanded to the 60% level, maintaining a top position. The share of new patients with HER2 low breast cancer previously treated with chemotherapy also expanded to the 60% range in France and to approximately 50% in Germany, maintaining a leading position. In the fourth quarter, we also achieved a top position in Spain and Italy. In fiscal 2023, we obtained approval and started promotion of the drug for the second-line and beyond indications of HER2 mutated NSCLC. In addition, product was launched in Italy following Germany, France and the U.K. as well as Spain and it's showing steady growth in that country as well. Slide 14 shows the sales of Enhertu in Japan and ASCA regions. In Japan, the sales in fiscal year '23 was JPY 23.9 billion. We tried to achieve JPY 25.7 billion in 2024. The new patient share is expanding steadily in each indication, HER2-positive breast cancer, second-line treatment has 40% for the new patient share, maintaining the leading position. Chemo-treated HER2 low breast cancer has the 20% new patient share. Again, that #1 position. HER2-positive gastric cancer, third-line treatment, the share was 70%, again, #1 position. HER2 mutated NSCLC second-line treatment, the new patient share was expanded to 40% level obtaining the top position -- leading position in the fiscal year '23. HER2 mutated NSCLC second-line and after indication was approved, we started the promotion. And also in the lung cancer treatment guideline listed our product as the second-line and later HER2 mutated NSCLC as the recommended regimen. In ASCA region in fiscal year '23, the product sales was JPY 44.6 billion. We tried to achieve JPY 64 billion in fiscal year '24. ASCA region sales include the joint sales promotion revenues in China and Hong Kong, where the sales is listed for AstraZeneca. And there are other areas like Brazil and China, where the sales is growing very steadily. In fiscal year '23, in China, there was a launch with the indication of HER2-positive breast cancer, second-line treatment, and then we obtained the approval for indications for HER2 low breast cancer chemotherapy treated, and we started promotion. In Brazil, HER2-positive gastric cancer, second-line treatment and HER2-mutated NSCLC second-line treatment indication was obtained and promotion started. We would like to continue promoting that market penetration and expansion of the countries and regions where the product would be launched, and we would like to offer Enhertu to the patients who need that. Slide 15 shows the outline of the strategic alliance with U.S. Merck, concerning the joint development and joint sales promotion for HER3-DXd,I-DXd and DS-6000, 3 product development is accelerated through this collaboration, and we have expanded the new studies. And we are trying to reinforce the resource allocation for growth drivers after 5DXd ADCs. Now I would like to talk about the progress made in '23, fiscal year '23 for the existing business and product growth. Please have a look at Slide 17. Slide 17 shows the Lixiana share by the country and region. In addition to Japan, Korea and Taiwan, there is a steady growth observed in European countries, including Belgium, U.K. and Italy. As a result, the global sales in the fiscal year '23 reached JPY 287.7 billion, JPY 43.8 billion increase Y-o-Y. Slide 18 shows the change in share by the amount by yen. Lixiana has decreased share in sales due to special expansion repricing and drug price revisions. However, the sales increased steadily, and we have expanded the sales share up to 47% at the fourth quarter of fiscal year '23. And as a result, the sales revenue increased to JPY 115.6 billion, JPY 10.4 billion above the previous year than the other activities in Japan. In 2019, anticancer agent Vanflyta was launched for the indication of relapsed or refractory FLT3-ITD mutation positive acute myeloid leukemia. In May last year, we obtained an additional indication for the first-line treatment of FLT3 ITD mutation positive AML. Also in May last year, we launched a new formulation orally disintegrating tablet, OD tablet of Tarlige, a pain treatment originally launched in 2019. In December last year, we started supply of the Daichirona Omicron XBB.1.5 adopted monovalent vaccine for COVID-19, which is the first messenger RNA vaccine made in Japan. By continuing to strengthen our product portfolio, we will further enhance our contribution to the patients. As part of our enhancing transformation into a profit structure focusing on pain drug, in May last year, we concluded a share transfer agreement with Daiichi Sankyo Espha, which handles our generic drug business in Japan. The buyer is Quorum Holdings Corporation and the transfer price was JPY 25 billion. Based on the transfer agreement on October 1st last year and April 1st, we transferred 30% and 21% of our shares, respectively. Since 51% of the shares have been transferred and Daiichi Sankyo Espha is no longer a consolidated subsidiary of the company. We plan to record a gain of approximately JPY 16 billion from the transfer of shares as onetime income in the first quarter of FY '24. Although we will be in charge of distribution from FY '24 onward, for the time being, we will not record product sales of Daiichi Sankyo Espha products in our consolidated financial statements, but only revenues related to distribution operation. Slide 20 shows other initiatives in the U.S. and Europe. In the U.S., we launched anti-cancer drug Abraxane generic in May last year. And an anti-cancer drug, Vanflyta for the first-line treatment of AML in August last year in U.S. and in February in Europe. In Europe, as for Nilemdo and Nustendi, our European subsidiary, DSE and Esperion entered into an amended agreement in January this year under which the manufacturing and supply rights will be transferred from Experion to DSE. In March this year, based on the result of the CLEAR Outcomes study, we received a positive opinion from the CHMP Committee for Medical Products for human use, recommending an additional indication for cardiovascular disease risk reduction, and we expect the value of Nilumdo/Nustendi to expand in the future. Next, I would like to talk about our progress in FY '23 toward creating shared value with stakeholders. Please refer to Slide 22. Slide 22 shows the annual dividend forecast for FY '23. In FY '23, we plan to raise the annual dividend per share by JPY 20 year-on-year to JPY 50, mainly due to the strong performance of Enhertu as well as the receipt of an upfront payment in connection with the strategic alliance with Merck of the United States. We will continue to maximize shareholder value by improving capital efficiency as well as shareholder returns. Next part is the R&D update. I will now hand over to Takeshita, Global R&D Head.

Thank you very much, Okuzawa-san. This is Ken Takeshita, Head of R&D. And I'm pleased to give you an update from the R&D side. This slide is a summary of the R&D major accomplishments for fiscal year 2023. Many of you will remember that quite a while -- recently, we had been talking about maximizing 3ADCs and identifying pillars for further growth as the alpha program. However, because of the success of our DXd ADC program, we have expanded the number of ADCs from 3ADCs now to 5DXd ADCs that are listed in green here in HER2 data that you're familiar with. As well as the 3 new ones, HER3, I-DXd and DS-6000. So we now refer to our entire program as 5DXd ADCs and the next wave. And the next wave, of course, is in the light blue. This includes additional compounds and pipeline drugs in oncology as well as specialty medicine and vaccines. Next slide. So I'm going to now first focus on the progress we are making in our ADC programs. And I'm going to be going over with you some very important clinical data that we have presented over the last year or so. First is the Enhertu program, DESTINY-PanTumor02 study. This is a clinical trial in which patients with HER2-positive tumors of various types that are listed here, various gynecological cancers, bladder cancer, biliary tract cancer and pancreatic cancer were enrolled in this clinical trial. And you'll see the data here very good response rates in many of these indications. And this data set led to an FDA approval of Enhertu as the first tumor-agnostic HER2-directed therapy in unresectable or metastatic HER2-positive solid tumors in April with HER2 positivity being defined as 3 plus. And in fact, the data was so impressive that even before the approval these data DESTINY-PanTumor02 data resulted in U.S. NCCN guidelines that listed Enhertu as a treatment option for HER2-positive cancers at the IHC level of not just 3 plus, but also 2-plus in many of these cancer tyepes. Next slide. In addition, I want to report to you that Enhertu program is expanding treatment opportunities beyond Japan, U.S. and E.U. to include, especially on indication expansion in China on the basis of various clinical trials, HER2 in HER2-low base breast cancer patient population, HER2-positive gastric cancer in the third line setting and HER2-mutant non-small cell lung cancer in a second-line setting. So these are really major progress that we are making in our China programs. Next slide. Now we switch over to the Dato program. And just to give you a very brief update on the TROPION-Lung01 trial data. This data was presented previously at ESMO 2023, and we have filed this data for nonsquamous non-small cell lung cancer second plus indication in the U.S. in February 2024. And in March of 2024, we filed the same data set in Europe. So -- and we are awaiting a decision from the various regulatory agencies. And as you can see here, the PDUFA date in the U.S. is December 20, 2024. Next slide. Next, in terms of the new studies in the Dato program, I would like to describe a new study called TROPION-Lung10 study. This is a new Phase 3 study combination study of Dato plus a drug that comes from our AstraZeneca partner. This is a bispecific drug that targets both PD-L1 as well as TIGIT. And you can see that study design here is a randomized study with 3 arms. The bottom cohort being Pembrolizumab control. The second arm is the bispecific antibody only. Of course, at the very top is the combination of Dato plus the bispecific is a combination that we're most interested in. The target patient population is non-small cell lung cancer in a front-line setting previously untreated with the high PD-L1 expression. Okay. And I do want to mention to you, just at the note that on the lower right corner that the primary endpoint in this study is PFS and OS in a biomarker-defined TROP2-positive patient population. This study is slated to start in the first half of 2024. Next slide. TROPOION-Lung14 study. This is another new study in a Dato program. And this is a -- this is a Phase 3 randomized study targeting patients who have the frontline EGFR mutated locally advanced or metastatic non-squamous non-small cell lung cancer. This is a new study that started enrollment actually this month. And this is a study design with a randomized 2-arm study, the control being the Osimertinib alone, which is a standard of care currently and the experimental arm is a combination of Osimertinib plus the Dato program. And first subject in has already been achieved. And this is a very important study that allows us to keep pace with the competition in this patient population, along with the other truck directed ADCs that are being studied by other sponsors. Next slide. In the breast cancer field for the Dato program, I'm very happy to report to you that the filing for the Dato based on the TROPION-Breast01 study has been achieved for the treatment of hormonal receptor positive HER2 low or negative breast cancer in U.S., Europe, China and Japan. This is a data that I think many of you are familiar with from ESMO 2023. And you can see here now that the PDUFA date in the U.S. is listed as January 29, 2025. Next slide. Next, we are going to shift to the HER3 program and describe to you what progress we're making in the HER3 program. So based on the HER3-Lung01 study data, which was the Phase 2 single-arm study of HER3-DXd in patients with EGFR mutated relapsed non-small lung cancer. The data has been submitted and for approval and the PDUFA date on this submission is June 26, 2024, just a few months from now. I also want to mention to you that we have additional studies that are going on, the HERTHENA-Lung20 study, which is a Phase 2 randomized study, which is in progress to obtain top line results in the second half of 2024 and also the PanTumor01-HERTHENA study, which started enrollment in March of 2024. And finally, I want to make sure to mention that the NDA review from the HL01 study is progressing very smoothly. And that's, I think, is reasonable to say that we are on track to meet the PDUFA date. Next slide. In terms of what additional things we are doing in our DXd ADC program. We're very interested in combinations of our DXd ADCs with various internal assets that make sense from a scientific standpoint. And here, you see one example of a unique combination, novel, novel combination in which DXd ADC is combined with a drug called Valemetostat. Valemetostat, as you remember, is our EZH1/2 dual inhibitor. And as since the target of the drug is EZH, it is thought to be a drug that modifies a chromatin structure. And based on preclinical data, we can see very interesting synergies between Valemetostat and all of our DXd ADCs. So you can see here in this clinical trial that we're reporting to you, we have started this combination study initially starting as a Phase 1 dose escalation combination study. And eventually, we will take this combination for signal seeking in various key indications for which we have approval or about to have approval for both Enhertu and Dato. Next slide. Okay. Next slide. Okay. Now I would like to give you an update on the 2 additional DXd ADCs, the ones that are now partnered with our Merck alliance partnership. In the I-DXd program, also formerly known as DS-7300, targeting the antigen B7-H3. This is just a review of the data that we have previously presented at ESMO last year showing that this drug appears to have activity in small cell lung cancer, esophageal squamous hype lung cancer, prostate cancer as well as squamous type non-small cell lung cancer. And these are very important data. And we are very happy to report to you that we have initiated a new Phase 3 study of this drug in small cell lung cancer called the Ideate-Lung02 study in relapsed small cell lung cancer, which compares I-DXd versus physician choice. And this is scheduled to start for enrollment in the first half of fiscal year 2024. Next slide. In addition, in this I-DXd program, in addition to what I just mentioned to you about the Phase 3 study in the relapse setting, we are, of course, very interested in studying this compound in the frontline setting. And these are some combinations that we are studying now or about the study in the frontline setting in small cell lung cancer. These are, for example, a combination of I-DXd with Atezolizumab, which is really a drug that has been approved in a maintenance setting for small cell lung cancer. Okay. Next slide. Finally, we do believe that this drug, I-DXd, because of the pattern of expression of the target antigen B7-H3, which is broadly expressed in many cancer types. We have initiated a Phase 2 study targeting multiple solid tumors using this study design you are seeing here. There's a whole long list of solid tumors that are being enrolled and studied in this trial. And it is hoped that this drug, I-DXd will show activity in all of these solid tumors. Next slide. In the DS-6000 program, this is another DXd ADC, targeting the antigen KATHERINE 6. We are continuing to pursue the very promising data that we have reported already in platinum resistant ovarian cancer. And based on this data, we have initiated a new Phase 2/3 study called REJOICE-Ovarian01 study. This is for a platinum resistant ovarian cancer that started enrollment in April of 2024. And these are really based on all the very strong data that we -- that's coming from our Phase 1 study. Okay. Next slide. I do want to make sure to remember to mention that in addition to our DXd ADCs, we also have other programs going on. First one is Vanflyta program, quizartinib. It is approved now in the countries shown below based on the QuANTUM-First study for the FLT3-positive ITD-positive AML in the frontline setting. Valemetostat, also known as EZHARMIA is an EZH1/2 dual inhibitor that I mentioned to you earlier. This drug is already approved in Japan for the treatment of relapsed/refractory adult T-cell leukemia lymphoma. And now based on the new study, VALENTINE-PTCL01 study, we have submitted the data for approval in Japan for the treatment of relapsed/refractory PTCL, peripheral T-cell lymphoma. Next slide. And to complete the picture, here are additional programs that we have going and a progress update. DS-3939, this is a MUC1 directed ADC DXd ADC. DS-1471 is the anti-CD147 antibody. This is not an ADC, but a naked antibody. DS-1594, this is a Menin-MLL binding inhibitor in AML, and we have discontinued development of this program. From the vaccine program, I think you heard already that we have achieved approval in Japan with -- for the RNA-based COVID vaccine. And we have also filed for approval of a mixed measles-mumps-rubella vaccine. In the specialty medicine area, I would like to mention 3 programs. 1211, this is a TNAP inhibitor for the treatment -- for the potential treatment of pseudoxanthoma. And from a very early study, we are seeing some positive top line results on Phase 2 study. DS-7011, this is an anti-TLR7 naked antibody for the intended for the treatment of systemic lupus. And finally, DS-2325. This is a KLK5 inhibitor that's been designed to target a particular gene that is abnormal in a syndrome called Netherton syndrome, but it also has much broader potential applicability in various skin disorders. Okay. Next slide. Okay. So in terms of some news flows and upcoming conference calls for the investor community, I do want to mention that at ASCO this year, we do intend to have an Investor Relations conference call at the time and date shown on this slide. Next slide. In terms of what you can expect from a news flow standpoint, this slide lists the fiscal year news flow, including some data disclosures and publications coming at the upcoming ASCO meeting at the end of May in Chicago. And here's a list of all the Enhertu and Dato data that is anticipated to be made public at that point. We also expect a number of regulatory decisions coming in fiscal year 2024 in Enhertu program, the Dato program, the HER2 program as well as a velmetostat program. And finally, in terms of key data readouts here is a list of important data coming from the Enhertu program, Dato program as well as the HER3 program. Okay. So with this, let me turn it over to the next speaker for the 5-year business plan update.

So I want to make the 5-year business plan update. I'm Okuzawa. Please have a look at Page 46. This slide shows the target for fiscal year '25 for this midterm plan and the 4 strategic pillars to move on to the growth stage, continuous growth stage. The strategic pillar will be explained with utilizing the next 2 sides. And I would like to explain the progress made during the 3 years after 2021. First, 3ADC maximization to be realized. Concerning Enhertu during the last 3 years, there is a second-line treatment for HER2-positive breast cancer and the chemo-treated HER2 low breast cancer and NSCLC were obtained as indications. And it was obtained the indication for second-line treatment of HER2-positive solid tumor as the first lung cancer to more anti-HER2 treatment and the value of the product is expanding. And also there is an increase in the number of countries and regions where the product is approved and the market penetration is expanding and Enhertu sales has been expanded above the plan goal. And in addition to this, HER2-positive breast cancer, first-line treatment, DB-09 study and other indication expansion is moving. And Dato-DXd is used and there is a submission made for the hormone positive HER2 low breast cancer or negative breast cancer and HER3-DXd is submitted for the third-line treatment of EGFR mutated NSCLC. We may be able to provide the treatment options for the patients and we are also conducting the studies to expand the indication for earlier lines of therapy. HER3-DXd together with I-DXd and DS-6000, we have accumulated the favorable clinical study data, and we are shifting to the stage where the product value is maximizing. We have a harsh competition in ADC and development. So in order to maximize the DXd franchise, ADC franchise, we have to enhance the capacity resource and capability in order to provide the product to as many patients at an earlier stage. Earlier timing, we started the joint development with Merck through a strategic alliance and the new development plan is expanding rapidly. For the existing business and product growth, the sales of Lixiana is expanding with the higher value product. Tarlige, Venofer, Nilemdo/Nustendi cells is growing steadily, and it is contributing to the creation of the capital for the return to the shareholders and for the investment for continuous support. The transformation to new business structure is expanding steadily. There is a launch of new products such as Emgality or Ezharmia and also there is a transfer of product after the exclusivity is expired in regions and countries and Daiichi Sankyo Espha stock is transferred. In that way, we are enhancing the profitability. American Regent and Daiichi Sankyo Healthcare profit is growing steadily, and it would reach half of the consolidated core business revenue in 2024. Please have a look at Page 48. There is a growth, further development in the future growth pillars for I-DXd and DS-6000. We have accumulated the favorable clinical study data, product potential is enhanced. So we put it as a growth driver after 3ADCs. I-DXd is developed for SCLC, DS-6000 is developed for platinum resistant ovarian cancer. We are accelerating the development through the strategic alliance with Merck. And the second-generation ADC DS-9606 clinical study was started and COVID-19 messenger RNA vaccine Daichirona approval was obtained, and we realized the supply of the vaccines. There is a steady growth in the selection of the post-DXd ADC modalities. The co-creation of value with stakeholders, concerning this, there is a growth of revenue through the growth of Enhertu. There is a strategic alliance with Merck and there is a onetime lump sum payment at the time of the closure of the agreement, and we decided to increase or increase the dividend after second consecutive years. Omicron XBB0.1.5, monovalent vaccine Daichirona is supplied, and we are trying to prepare for the pandemic risk. The value chain as a whole is also working on. We are working on the value chain, environmental load reduction, and we try to make 100% renewable energy use for the electricity we are using in our business. There is the workshop with the management and all the employees, and we are trying to deepen our understanding of 3 modality of behavior, which is the core culture of Japan of Daiichi Sankyo. And we are trying to promote these activities. And we are trying to nurture on DS culture across that nationality and culture. As shown before, the 4 strategic pillars of the fifth midterm plan is making steady progress, and we are more confident to achieve the goal for the fiscal '25. Now I want to talk about the -- our expectation on the achievement of KPI for the fifth midterm plan. Please have a look at Slide 9. We expect revenue of JPY 2.1 trillion in FY 2025, up by JPY 100 billion from the JPY 2 trillion forecast as of April 2023 due to unexpected revenue in the oncology field. Although SG&A is expected to grow in line with the revenue growth, we continue to aim at 40% of core operating profit ratio before R&D expense by improving the cost of sales ratio due to changes in the product mix and by efficiently and effectively executing expenses. As the pipeline potential is steadily expanding, we will aggressively invest into R&D for sustainable growth. However, we will continue to aim for ROE of 16% or higher by balancing the cash allocation with shareholder returns. We expect the dividend on equity ratio DOE to be 8.5% and higher, up from the 8% or higher, we had expected as of April last year by improving the capital efficiency and enhancing shareholder returns. The currency rate assumption for the KPI forecast as of April '24 are JPY 145 to the dollar and JPY 155 to the euro. Please refer to Slide 50. Oncology revenue in FY '25 is expected to be more than JPY 1 trillion. The revenue forecast for Dato-DXd in FY '25 has decreased from the April 2023 level due to the revision of target patient based on the result of the TL-01 study and the revised time line of the TL-08 study. On the other hand, we expect further increase in revenue of Enhertu in the breast cancer market based on the results of DB03 and DB04 trials. Mainly due to the impact of increased revenue from the upfront payment received from the strategic alliance with U.S. Merck for HER3-DXd, I-DXd and DS-6000, we expect oncology sales revenue to exceed JPY 1 trillion in FY '25, up JPY 100 billion from our April '23 forecast. Slide 51 shows projected R&D expenses. Total R&D expenses for FY '24 and '25, altogether are expected to be about JPY 1 trillion, about JPY 150 billion, up from the estimate as of April 2023, mainly due to the start of trials of 5DXd ADCs. Compared to the forecast as of April '23, we expect a decrease in the share of development costs associated with the strategic alliance with U.S. Merck for HER3-DXd, I-DXd and DS-6000. But we will actively invest these resources in R&D for sustainable growth. And with respect to Enhertu, we aim to maximize product value by initiating new studies based on DPT-02 study result. And our 3 product development cost was decreased compared to a year ago. And we continuously make investment into the resources. For Enhertu, we aim to maximize the product value by initiating new studies based on the DPT-02 study result. DS-3930 and following DXd ADC products and the next wave of product groups, we are going to accelerate the development. And we are going to develop a next growth pillar following 5DXd ADC. In addition, Enhertu indication addition, Dato-DXd HER2-DXd launch related new evidence creation. Information dissemination and the other medical affairs activities will be expanded, and we are going to accelerate the 5DXd ADCs by expanding the R&D resources. We are going to further enhance the R&D structure, which were leading to the cost increase of R&D. Slide 52 shows the cash allocation to investment in growth and shareholder returns. The source of cash allocation during the midterm management plan period, which is the cash on hand at the beginning of the fifth midterm management plan, plus operating cash flow before deduction of R&D expenses for 5 years is expected to be approximately JPY 3.7 trillion, an increase of JPY 600 billion compared to the forecast as of April 2023, mainly due to the receipt of upfront payment for the strategic alliance with U.S. Merck. And the increased cash allocation will be used to increase R&D and CapEx for the future growth and stringent shareholder returns. We plan to allocate about JPY 1.95 trillion, an increase of JPY 150 billion from the April '23 forecast to R&D expenses, which will place priority on the Dato-ADC development. CapEx will increase by JPY 200 billion in FY '24 and '25 combined. The main application is to strengthen the production system and a large portion of this increase will be CapEx -- will be for CapEx to strengthen the DXd-Dato production system. The company will respond to the growing demand for DXd ADC, which has been fueled by the steady growth of the Enhertu business, progress in the development of Enhertu, Dato-DXd and the conclusion of a strategic alliance with U.S. Merck for HER3-DXd, I-DXd and DS-6000 as well as progress in their development. We will continue to invest in our own production facilities and in external CDMOs in a balanced manner. Regarding our own production facilities for DXd ADC, we'll also invest in Daiichi Sankyo Europe Pfaffenhofen plant and American Regents, New Albany, Ohio plant. We intend to further transition shareholder returns by increasing dividends in line with profit growth and by flexibly repurchasing own shares. The dividend forecast for FY '24 and share buyback will be explained later today. Over the past 3 years, the product value of Enhertu has greatly exceeded our original plan. Following Enhertu we plan to realize the launch of Dato-DXd and HER3-DXd in FY '24. In addition, strategic alliance with U.S. Merck will rapidly expand the development plan for HER3-DXd,I-DXd and DS-6000, which is expected to significantly enhance product value. In order to achieve our goals for fiscal '25 and realize our vision for 2030, we intend to achieve sustainable growth while maintaining a balance between investment and shareholder returns necessary for future growth. Now I would like to talk about the innovative solution provisions, and we would like to contribute to the higher enrichment of quality of life around the world. And lastly, but not least, I would like to talk about the fiscal year 2020 forecast. Please have a look at the Slide 56. In fiscal year '24, there is the sales revenue of JPY 1.750 trillion. Core operating profit will be JPY 210 billion. That sales revenue would be realized through the expansion of the cells of Enhertu, Lixiana and Tarlige. Also, there is an increase in the deferred revenue through the strategic alliance with Merck. So we would have the operating revenue of JPY 1.750 trillion, JPY 148.3 billion over the previous year. That sales cost will be reduced by the cost improvement, and there is a decrease of JPY 19.8 billion expected. For SG&A, this sales expansion of Enhertu would increase the profit share, and we would have the resource investment into the oncology business. And we try to make an investment to the DX/IT human resources as well as the strategic investment. And there is an increase of those expenses by JPY 47.7 billion. For R&D, we are focusing on 5DXd ADCs, which has a high potential, and we also make further investment in R&D so that we can make a further growth. And we would enhance the medical affairs activities to enhance the product value. And it would increase our research and development cost would increase by JPY 105.7 billion. Core operating profit would increase by JPY 14.7 billion to JPY 210 billion. Operating profit would increase by JPY 18.4 billion. 2024, fiscal 2024, we have the temporary revenue through the transfer of stock of Daiichi Sankyo Espha. However, there is no temporary cost calculated. So we would have more operating profit than core operating profit. And before tax revenue would be JPY 235 billion, minus JPY 2.2 billion over the previous year. The revenue for this year would be reduced because of the tax accounting in relation to the transfer of Daiichi Sankyo Espha. But in fiscal year '24, we don't have that effect. So there is an increase in the cost of cost related to taxation. So we would have the negative revenue of JPY 10.7 billion to JPY 190 billion. Exchange rate was calculated at JPY 145 per dollar and JPY 155 per euro. Slide 57 shows the annual dividend. As mentioned before, we are trying to increase the dividend. And fiscal year '24, we are expecting to provide the annual dividend of JPY 60. Please have a look at Slide 58. in order to improve the capital efficiency, we decided to obtain our own treasury stock. We would obtain the treasury stock up to 55 million stocks or the JPY 200 billion between the 26th of April 2024 to 15th of January 2025. All these stocks will be paid back as of the 31st of January 2025. We have an increase in the dividend and flexible acquisition of our own stocks, so that we may have a DOE of 8.5% or over, which is above our goal or our objective of 8% or higher. We are going to enhance the capital efficiency and enhance the shareholder returns. We would like to maximize the value to the shareholders. Now we would like to answer the questions.

The first question is from Citigroup Securities, Yamaguchi-san.

This is Yamaguchi speaking from Citi. My first question is related to Enhertu sales forecast for this fiscal year. Penetration is quite high. And in U.S., the deed nominal growth may slow down. However, that's within your expectation for FY 2024 PanTumor low HER2 are included. However, penetration is already high. So you're expecting the growth to be slowed down. And the B6 when is introduced, can we expect acceleration of the momentum once again?

Thank you very, Yamaguchi-san for your question. As you mentioned, that's our plan Enhertu in U.S. There has been progress in indication. But for -- it's before DB04, so we are expecting a modest progress. But in Europe and the other regions, the indication approval will be laid from U.S., but reimbursement will come in. So probably, they may catch up with the growth in U.S. or even exceed the growth of U.S. So FY 2024, we believe Enhertu will strongly grow.

The next question is on Dato-DXd. As mentioned before, the HER3 study is making a very good progress. And what about that Dato-DXd? Are there any information you can disclose to us?

That review is also concurrently ongoing. And we do have the PDUFA data that's been announced. And I do not expect that that data is going to change based on how the discussions are going.

So on the TROP2 positive study was started. TRO2 to biomarker selection, was it an issue?

In the current TL01 clinical trial, the TROP2 biomarker is, of course, of interest to the FDA, but it is not critical to the submission. On the other hand, in the new trial that we discussed earlier today, there is an important component of the TROP2 biomarker.

With regard to your outlook into R&D expense. The Merck's burden is growing, but the total R&D seems to be growing on a net basis. So the total R&D is, I think, growing excluding FX impact. So more than additional burden on Merck, I think R&D cost is increasing?

Yes. This is Ogawa speaking. FY '24, '25, total R&D expense, JPY 1 trillion, that's our forecast. And due to the weak yen impact, we have JPY 100 billion impact compared to April 2023. And then other incremental factors investment into 5ADC. This is continuing and the medical affairs function is being reinforced going to be [indiscernible]. So this is an investment into the capability. And at the same time, this is an investment to generate new evidence and also early access program. Beyond 5ADC, we have investment planned. So altogether, this is the amount of the investment plan for 2 years.

Next question Mr. Wakao of JPMorgan.

Wakao of JPMorgan. My question is the R&D development. R&D development is enhanced. And from this year, it is the phase of expansion. But through the -- you are prioritizing the R&D investment. So the profit standard or profit level is a little bit suppressed. Am I right? And you are trying to expand the profit. And the future profit level, are there any changes in the profit level you are expecting to have? And Page 51 Enhertu study is to be started. DPT02 study results will be a basis of the start of that experiment of this study.

Thank you very much, Wakao-san. Concerning the R&D cost and the profit growth shifting to the growth increase of profit growth. Enhertu growth and expansion is further possible, further expansion is possible. And also, there is the collaboration and alliance with Merck. So R&D plan is expanding greatly. And as mentioned today, 3939 or 5DXd and other internal assets are also enhanced. So we have a lot of growth opportunities within the company. That's the decision we made. And that's why we decided to continue making a positive and active investment. And the bottom line of the profit shift would be fiscal year 2025. That's something we would like you to expect. And concerning the other Enhertu study, Takeshita will answer the question.

I think the question was DESTINY-PanTumor02 study. And this is a global multicenter open-label Phase II study or Enhertu in HER2-expressing tumors. And as I mentioned earlier, it's -- the data was used to gain approval in a broadened indication of HER2-positive cancers at the 3-plus level or greater. And these data were really the basis for many additional clinical trials in the frontline setting in the various cancers that were studied in the PanTumor study, most notably the gynecological cancers. And that -- so these are really additional investments in clinical trials in the frontline setting. And of course, the -- I do want to mention that the details of these new studies will be announced to you in the future when we are ready to make the details public to you.

In relation to Takeshita-san's comment, the new study is for PanTumor. So are you initiating like several independent studies separately? Or this type of like already phase basket type of clinical trial? Is that what you're planning?

Strategy in the frontline setting. But -- so I think if you could just wait for that when we are able to make that announcement.

My second question is related to Dato-DXd overseas first line treatment and development plan TROPION-Lung08 first and then TROP2 to the one to be initiated this time. With regard to TROP2-positive, you set up the primary endpoint. And also, you have other clinical trial going on. So for the first-line setting, TROP2-positive is the main focus for your clinical development. Is that correct?

Let me try to answer your second question first. Question was about the use of the TROP2 biomarker. And the details of this particular biomarker that we are using and we're interested in. We have not disclosed that. A lot of that information comes from our partner, AstraZeneca. So we are going to wait for our partner, AstraZeneca, to be ready to disclose the details of this biomarker strategy to all of you. In terms of your first question, which was about what are the reasons for the delay that we are reporting now for TL08? What I can say to you today is that there are a multitude of reasons behind this delay. We have not really disclosed the details of the delay, but just to say here today that it is due to multiple factors.

The TROP2 biomarker is the simple truck to expression. It is not a simple expression, higher expression of TROP2 or have you identified several biomarkers? And TL08 is delayed, is it the strategic delay on your side or there are various factors and that you try to make it scheduled, but there is a delay?

Yes, the TL08 delay is not specifically linked to the biomarker that you mentioned. I think, of course, however, I do want to mention that we are very interested in understanding the biomarker as it might be applied to TL08 or even TL07, of course. But in terms of the details of biomarker, again, I ask you to please wait for announcements and public disclosure of the information on the biomarker from our partner AstraZeneca.

Next question Morgan Stanley, MUFG Securities, Muraoka-san.

I'm Muraoka of Morgan Stanley. My question is related to R&D costs and the future perspective of the R&D. In the previous presentation, you made the correction for the outlook for FY '25. So R&D would be 45 -- 450. So it would be 350. That's what you mentioned. But the figure you mentioned would be 310. when I made the simple calculation. The growth of R&D is bigger. So the core business revenue profit will be lower. But will you please -- you are going to expand the value of Dato-DXd, correct? Is that the correct understanding?

Thank you very much, Muraoka-san for your question, concerning the 5DXd ADCs potential expansion. The specific planning, we have made that specific ideas, and we have a lot of ideas to expand the value of Dato-DXd. In addition to this 5DX -- in addition to 5DXds, there are internal assets, and there are promising internal R&D assets. we have. So we would like to make an investment so that we can develop those pipelines. And after fiscal year '26 and long term and very long-term sustainable development will be assured. And that's why we made the decision, as mentioned before, and that is reflected in our forecast for the revenues.

For our reference, it is not a very good timing, but JPY 470 billion, are there any possibilities that you may not consume all those budget? And you have more than 500 employees in the U.S. So you may be able to utilize those budget. Do you think that you have a high probability of using all these budgets?

Yes, correct. That's the basic understanding. However, there is a big influence of the foreign exchange market. So it is very difficult for us to make a correct forecast how that ForEx would affect.

For DB06, I would like to confirm one thing. Ultra-low population is included in the secondary endpoint. Ultra-low even if it doesn't show good efficacy, but still you will be able to achieve the primary endpoint. So if you look at the DB06 only for ultra-low, primary -- if you can achieve primary endpoint at [IHG] low, you can still make a submission. Is that a correct understanding?

Correct. Actually, that the clinical trial is not specifically focused on ultra-low. But the Agency and of course, us in the primary endpoint, we'll be looking at the total patient population that enrolled in the clinical trial, which is far more than just the ultra-low.

Next question, so UBS Securities, Mr. Haruta.

Haruta of UBS Securities. The first question, JPY 200 billion, and there is a very big announcement. And so far, you have studied the possibilities, but this is the decision you made at this point in time what is the background behind this? Before the submission or the approval, these period, it is very difficult to purchase the treasury stock. But as a road restriction period, we would like to know the background of your purchasing your own stock?

We decided to purchase our own stock and the timing and the background behind us is the question. And the fifth midterm plan, and there is a big plan, and we are going to make investment for growth, and we have to balance it with the return to the shareholders. And in that situation Enhertu is growing very strongly above our expectations, and it becomes a pillar to support us. And also, there are other DXd ADCs who are growing. So 5DXd ADCs have been promoted through our collaboration, strong collaboration with AZ, AstraZeneca and Merck. So we would like to further support the future growth, and we can be confident in our future growth. And that's the background behind our decision made to purchase our own stock. And of course, the basic reason is that the legal conditions were satisfied.

My second question is related to TROPION-Lung01. We are waiting for OS data. But FDA received the filing for non- squamous cell cancer. And the result -- we are expecting for the result on the overall patient population. If superiority is not shown, but if superiority is shown only for non-SQ, would that still be accepted? I guess best case is to show a significant difference for total patient population as well as non-SQ. But how should we approach this?

As you may remember, in the prior data set that was disclosed already, the PFS data was positive in the overall patient population and not just the non-squamous. But with the Agency, as you know, we have set to the Agency that we are focused really on the non-squamous because that is our best dataset. But in terms of the details of how the Agency will interpret the overall survival data and how it affects our position or likelihood of an FDA approval. We're not really able to comment on that. These are confidential discussions that we are having with the regulatory agencies.

The next question BOFA Securities, Mamegano-san.

I'm Mamegano. I have one question. This is an update for the midterm plan. And this time, for DOE, 8.5% or higher, and that's the update you made. Concerning the ROE, there is no change made and you decided to purchase your own stock for JPY 200 billion. ROE is not mentioned because there is some decline from the original plan. What's the situation on ROE?

this time ROE KPI was not made -- or has not changed. Of course, there are some upside possibilities and 16% or higher. That's what we mentioned. And the guidance has not been changed a lot, and that's why we haven't made any changes. Concerning DOE including our purchase of our own stock, there wouldn't be a rapid growth of revenue or profit in the short term. However, it would be an investment for future growth, and we have a high expectation to the future growth, and we would like to try to balance it with the return to the stockholders, and that's why we changed DOE to 8.5% or higher.

Next question is from Sanford C. Bernstein, Sogi-san.

I have a couple of questions to Takeshita-san. So first of all, the question around the new study, the TROPION-Lung10, So for this one, I'd like to understand, do you -- are you getting the subpopulation analysis with TROP2 positive patients? Are we able to see the data at some point? And also on the combination partner, rilvegostomig, the bispecific for PD-1 and the TIGIT. So we understand that there are some combination studies ongoing by different companies for the combination of PD-1 or PD-L1 and TIGIT. So what is the signing rationale of making it a bispecific? What is important to have the simultaneous binding to these targets with one molecule? So that's first question.

Okay. So the first question about the TROP2 biomarker. And as I mentioned, it's something that our partner, AstraZeneca, has developed, and we haven't -- and the data has not yet been made public. So we're going to have to ask you to wait until you see the data in public, and then we can discuss further about how we are applying this biomarker to TL-010. Okay. Now in terms of the TIGIT, it's a TIGIT bispecific also to include the standard, I guess, more of a standard checkpoint PD-1. And it's because basically, it allows us to hit 2 targets with one molecule. And if you could just think of it as that, that you can do 2 things with a single drug. That will be sort of a simple way of thinking about bispecific. And it's very fortunate for us that our partner, AstaZerica, had in their pipeline a TIGIT molecule so that we can be competitive as the non-small cell lung cancer field moves into TIGIT as a very -- potentially a very important treatment modality in the treatment of lung cancer. So it's just a way -- the TIGIT bispecific is just a way to give -- allow us to hit 2 targets with one drug.

And the second question is around combination of Enhertu and also the Dato with Valemetostat. So it feels like if you look at the target indication, these studies seem to be a little bit redundant because the target cancer types have been already addressed by the monotherapy of these drugs. And so what is really the scientific rationale or the preclinical data that you see to really support this study? And also is your partner, AstraZeneca, of funding these studies?

Okay. So the scientific basis for this combination is really coming from various preclinical models in which these 2 drugs were combined. And we do see a lot of synergy between the 2 drugs. We don't yet know exactly what is the molecular mechanism for the synergy between these 2 drugs. Our current speculation is that Valemetostat being an epigenetic agent, acting on a chromatin allows easier access of Enhertu to the chromatin that the DXd payload on the inhibitor to the chromatin by the Valemetostat, allowing more of an open configuration of the chromatin so that the DXd drug can access the DNA target of the drug. So that's -- that is currently the working hypothesis for this combination. And why are we doing this combination? Let me try to answer that question. Yes, the -- yes, we are studying cancers that are already approved for -- within HER2. So with this combination, therefore, what we want to achieve is efficacy that is superior to Enhertu alone. So you can imagine that in the future, if we were to -- let's say, for example, that this combination that we're seeing here looks quite good from an efficacy standpoint, perhaps better than single agent Enhertu and Dato. And you can imagine in the future, we will be conducting a randomized Phase 3 study in which the control arm now is Enhertu or Dato depending on the indication, an experimental arm will be the combination of the DXd ADC with Valemetostat. So you can kind of see now that it is a way to, of course, improve the outcomes of patients with solid tumors. And at the same time, from an overall pipeline perspective, it allows us to offer to patients yet another drug, Valemetostat for the treatment of solid tumors, such as breast cancer, gastric cancer, lung cancer, for example.

So then -- sorry, so that's great. Then -- so Valemetostat pretty much sounds like a chemo if it is targeting the chromatin. Is that the right way to think about it?

No, it's not a chemotherapeutic agent. It's what we called an epigenetic agent. It targets a protein found in the chromatin. It's not a cytotoxication, but it acts on a particular target, a protein target that's involved in chromatin configuration.

And then final question is, is AstraZeneca funding this combination study?

Okay. Now, so this one, I don't remember this now for sure, but do you know. Yes. Okay. Yes, I think they are funding part of the study. I don't quite remember part of this -- yes. They are funding part of the study is what I'm told. But I don't quite remember...

We have already exceeded 4:30 finish time. So we would like to conclude Q&A with the analysts and investors. I do understand that some people are still keeping their hands raised, but please reach out to IR department of the company later. Thank you very much, everyone. [Statements in English on this transcript were spoken by an interpreter present on the live call.]