Daiichi Sankyo Company, Limited

Manabe speaking. Thank you very much for joining Daiichi Sankyo's Financial Results announcement meeting despite your very busy schedule today.

00 p.m. on Tuesday, April 27, Japan time, based on our presentation materials.

Please turn to Page 3.

Today, I'm going to cover FY 2020 consolidated financial results, FY 2021 forecast and business update in that order. Then Wataru Takasaki, R&D Division Head will give you R&D update and actions against COVID-19 update.

We will entertain your questions at the end.

Please turn to Page 4. This is an overview of FY 2020 consolidated results.

Revenue was JPY 962.5 billion, down JPY 19.3 billion or 2% year-on-year. Cost of sales decreased by JPY 4.9 billion.

SG&A expenses increased by JPY 30.8 billion, and R&D expenditure rose by JPY 29.9 billion compared to the previous year. As a result, operating profit reached JPY 63.8 billion down by JPY 75 billion or 54% year-on-year.

Pretax profit decreased by JPY 67 billion from the previous year to JPY 74.1 billion. Profit attributable to owners of the company was JPY 76 billion, down JPY 53.1 billion or 41.2% year-on-year.

As for the actual currency rates, the U.S. dollar was JPY 106.6 (sic) [JPY 106.06], the yen appreciated by JPY 2.69 against the dollar compared to the previous year.

The euro was JPY 123.7, the yen depreciated by JPY 2.87 against the euro.

Please turn to Page 5. From here, let me explain positive and negative factors for revenue compared to the previous year.

Revenue declined by JPY 19.3 billion year-on-year. I'd like to explain its breakdown by major business unit.

First, in our Japan business, including domestic sales and marketing, vaccines and health care business, sales increased for pain treatment, Tarlige. Anticancer agent Enhertu, which was launched in May last year, contributed.

In addition, Memantine AG and Ezetimibe AG launched in June last year also contributed. So sales of Daiichi Sankyo Espha products increased.

However, sales of Alzheimer type dementia treatment, Memary; anti-influenza agent, Inavir; direct oral anticoagulant, Lixiana; and vaccine business revenue decreased. So revenue declined by JPY 49.4 billion for Japan business as a whole.

Next, let me explain our overseas business. ForEx impact is excluded here.

Regarding Daiichi Sankyo, Inc. in the United States, sales of hypercholesterolemia and type 2 diabetes treatment, Welchol, decreased but revenue rose by JPY 16.5 billion, thanks to the contribution of Enhertu launched in January last year.

Revenue for American region in the United States decreased by JPY 6 billion as sales of Injectafer for iron deficiency anemia declined due to the impact of COVID-19, et cetera.

Revenue for Daiichi Sankyo Europe increased by JPY 13.6 billion, due to an increase in Lixiana sales and the booking of gain on sales from transferring long-listed products in June last year. As for Enhertu and Dato-DXd upfront payment, regulatory milestone related to a strategic alliance, revenue increased by JPY 6.6 billion due to the revenue recognition of Dato-DXd upfront payment and regulatory milestone from the approval of Enhertu for gastric cancer in the United States and breast cancer in Europe.

ForEx impact reduced our revenue by a total of JPY 5.3 billion.

Page 6 shows positive and negative factors for operating profit. Let me explain the profit decrease of JPY 75 billion by item.

As I explained earlier, revenue declined by JPY 19.3 billion, including the decrease of JPY 5.3 billion due to ForEx impact. Next, I will explain cost of sales and expense items by excluding ForEx impact and special items.

Cost of sales was down by JPY 15.3 billion due to the cost decrease associated with the revenue decrease.

SG&A costs were affected by the cost decrease due to the spread of COVID-19, but increased by JPY 15.4 billion due to the cost increase in Enhertu-related expenses. R&D expenditure rose by JPY 32.2 billion, because of an increase in R&D investments for the 3 ADCs as well as cost increase due to our oncology project development structure enhancement.

Costs decreased by JPY 5.2 billion in total due to ForEx impact. Special items has an impact to increase our cost by JPY 28.7 billion compared to the previous year.

I will explain the breakdown of special items later. Operating profit decreased by JPY 46.3 billion, excluding ForEx impact and special items.

Page 7 shows the breakdown of special items. In FY 2019, we booked restructuring costs in supply chain, impairment loss on intangible assets and environmental expenditures while we booked gain on sales of subsidiary and gain on sales of tangible fixed assets.

So special items had an impact to decrease the cost by JPY 13.7 billion in total. In FY 2020, we booked as SG&A cost, vaccine business loss compensation associated with the termination of vaccine business alliance with Sanofi.

So there was an impact to increase the cost by JPY 15 billion. As a result, costs rose by JPY 28.7 billion compared to the previous fiscal year.

Next, I'd like to explain positive and negative factors for our profit attributable to owners of the company. As I explained earlier, operating profit decreased by JPY 75 billion, including ForEx impact and special items.

Financial income expenses, et cetera, had an impact to increase our profit by JPY 8 billion compared to the previous year due to the recognition of financial income because of a decrease in contingent consideration of quizartinib acquisition and also due to improvement in ForEx gains and losses.

Income taxes, et cetera, fell by JPY 13.9 billion year-on-year. The tax rate in fiscal 2019 was 8.6% due to the decision to introduce the consolidation taxation system, et cetera.

But in fiscal year 2020, income taxes, et cetera, substantially decreased from the previous year into a minus figure due to the additional booking of DTA attributable to future expected taxable income increase of 3 ADCs with increasing product value. As a result, profit attributable to owners of the company reached JPY 76 billion, down JPY 53.1 billion year-on-year.

Page 9 and 10 show revenue increase or decrease in Japanese yen by major business unit and by major product. Earlier on Page 5, I explained the situation of each unit by excluding the ForEx impact.

But here, we are showing the results, including the ForEx impact.

Now I'd like to discuss FY 2021 forecast. Please look at Slide 12.

In F1 2021, we aimed for the revenue of JPY 990 billion and operating income of JPY 70 billion. The exchange rate is assumed to be JPY 105 to the dollar and JPY 120 to the euro.

From FY 2021, we are disclosing core operating profit, which excludes temporary gains and losses from operating income as an indicator of our ordinary profitability. Temporary gains and losses include gains and losses on sales of fixed assets, business restructuring, impairment losses related to tangible fixed assets, et cetera, compensation for damages and settlements as well as nonrecurring and large amounts of gains and losses.

This slide shows cost of sales, SG&A expenses and R&D expenses, excluding temporary gains and losses. Although there are negative factors such as the termination of the sales alliance for the anti-ulcer agent, Nexium, and the revision of drug prices in Japan, our revenue is expected to increase by JPY 27.5 billion due to the sales expansion of main products, such as and Enhertu, Lixiana and Tarlige.

Cost of sales is expected to decrease by JPY 17.8 billion as the cost ratio improves due to changes in the product mix.

SG&A expenses are expected to increase by JPY 15.5 billion due to an increase in profit share with AstraZeneca involved in Enhertu. R&D expenses are expected to increase by JPY 38.6 billion, with an increase in R&D investment for 3 ADCs, including the medical affairs activities.

As a result, the core operating income is expected to be JPY 70 million, a decrease of JPY 8.9 billion from the previous fiscal year. Although other revenue and expenses were recorded in FY 2020, they are not expected in FY 2021 at this time.

So the operating profit is expected to be JPY 70 billion, which is the same amount as the core operating income and is an increase by JPY 6.2 billion year-on-year.

Profit attributable to the owners of the parent company was negative in FY 2020 due to an increase in deferred tax assets caused by an increase in the expected amount of taxable income in the future, whereas since we are assuming normal levels in FY 2021, we expect the profit to be JPY 50 billion, which is a decrease of JPY 26 billion from the previous fiscal year. We anticipate that COVID-19 will continue to limit certain activities, but we expect that the impact on the operating income will be minor.

Next, I'd like to speak about our business update. Please look at Slide 14.

I will start from Enhertu. Please move to Slide 15.

This slide shows our initiatives to maximize the product value of Enhertu. Since its launch in the United States in January last year, the number of sales regions has increased, and the acquisition of new indications has been steadily progressing.

As for breast cancer, it was launched in Japan in May last year. And after obtaining regulatory approval in Europe in January of this year, it was launched in February.

In addition, it also received approval in the U.K. in February and is currently preparing for its launch.

Furthermore, regarding gastric cancer, we obtained the indication for the third-line treatment for HER2-positive gastric cancer in Japan in September last year and also obtained the indication for the second-line treatment for HER2-positive gastric cancer in the United States in January this year. We are working to maximize the product value by delivering Enhertu to as many cancer patients as possible.

The actual product sales in FY 2020 resulted in JPY 30.1 billion and it is forecasted to be JPY 69.4 billion in FY 2021.

Slide 16 shows the breakdown of the revenue of Enhertu. Enhertu sales revenue in FY 2020, which includes product sales plus a lump sum payment at the time of contract and development milestones is expected to be JPY 43.5 billion.

In FY 2021, it is expected to increase by JPY 40.6 billion from the previous fiscal year to JPY 84 billion.

In terms of product sales, we will accelerate market penetration through a strategic alliance with AstraZeneca and aim for JPY 69.4 billion in FY 2021.

Regarding the development milestone, we expect to acquire the indication for the second-line treatment for HER2 mutant lung cancer in the United States in FY 2021 for the total of JPY 4.8 billion.

I'm going to describe the initiatives for business growth in each region next. Please see Slide 18.

The initiatives to strengthen the product portfolio and maximize the product value are progressing steadily. In Japan, we launched the domestic first-in-class prophylaxis of migraine attacks, Emgality, yesterday, which has a sales alliance agreement with Eli Lilly, Japan.

In addition, the large cell B-cell lymphoma treatment product, Yescarta, for the CAR-T cell therapy introduced from Kite in the U.S. was approved in January this year, and the drug price was listed in April.

Furthermore, in December of last year, the indication of the combination therapy for tonic-clonic seizures was added to the antiepileptic drug, VIMPAT, which is one of our main products in Japan.

In Europe, we launched the hypercholesterolemia treatments, NILEMDO and NUSTENDI, licensed by Esperion in November last year. As announced in a press release today, we have signed a contract with Esperion to introduce NILEMDO and NUSTENDI at ASCA in Asia and Latin America.

Through the synergic effect with the anticoagulant Lixiana, we will further improve the regional value of ASCA. In addition, in China, Lixiana was listed on the National Reimbursement Drug list in December.

Reimbursement has started since March of this year. We will achieve sustainable growth by strengthening the profit structure centered on new drugs in each region.

The next is about Edoxaban. Please move to Slide 20.

This slide shows the transition of the shares based on the sales amount in Japan. Lixiana sales share declined in the first quarter of FY 2020 due to the drug price reduction by the special expansion repricing in April 2020.

However, the growth rate in FY 2020 was the highest in the market, and the sales as of the fourth quarter was 35%, maintaining the top share in the market.

Results of the revenue in FY 2020 was JPY 77.4 billion, which was a decrease of JPY 5.6 billion year-on-year, but the previous drug price base revenue was increased by JPY 20.2 billion year-on-year. We will continue to expand in FY 2021, and we will target for the revenue of JPY 90.4 billion.

Slide 21 shows the changes in the volume-based share in each country. In addition to Japan and South Korea, it is growing steadily in European countries such as Belgium, Spain and Germany.

As a result, global revenue for FY 2020 increased by JPY 11.9 billion year-on-year to JPY 165.9 billion. In FY 2021, we will accelerate the growth in each country and will aim for the revenue of JPY 188.4 billion.

Next is about streamlining our assets. Please see Slide 23.

We are continuously promoting the generation of cash by streamlining our assets. And generated a total of JPY 163.2 billion during the period of the 5-year business plan from FY 2016 to FY 2020.

As a general policy, we do not hold listed shares unless we find that cross-shareholding shares will contribute to the improvement of the corporate value.

During the period of the 5-year business plan, we sold 51 brands in JPY 70.5 billion. We will continue to sell the shares in order, considering the impact on the market.

We also sold real estate in sequence, generating a cumulative total of JPY 39.2 billion over 5 years. Regarding the business transfer, we generated cash of JPY 53.5 billion through the transfer of the Takatsuki factory in the long-listed product business.

I'm going to discuss the shareholder returns next. Please move to Slide 25.

We're working to further enhance shareholder returns and achieved a total return ratio of 105.6% for the cumulative total during the period of the 5-year business plan by increasing dividends and acquiring our own shares. We have decided to increase the dividend per share for FY 2020 to JPY 81, an increase of JPY 11 versus FY 2019 based on the shares before the split on October 1 last year.

Furthermore, from November last year to March this year, we acquired a total of JPY 100 billion and 29.47 million shares of our own shares. As a result, the total return ratio ended in 105.6% for a cumulative total of 5 years.

In addition, this month, we canceled 180 million own shares, excluding stock options and the number of shares to be used to restricted share-based remuneration. Going forward, we will continue to enhance shareholder returns while promoting growth investments centered on 3 ADCs and optimizing the capital structure.

The following slides are on the R&D update. I'd like to have Dr.

Takasaki to take over.

Takasaki speaking. Today, I'd like to give you our R&D update.

First, I'm going to talk about the major progress in FY 2020.

Please turn to Page 28. I'd like to use 2 pages to explain the major progress of Enhertu.

First about breast cancer. In HER2-positive breast cancer, we started 2 studies.

First, we initiated DESTINY-Breast05 study targeting high-risk, early breast cancer. This is a post neoadjuvant Phase III study in HER2-positive breast cancer patients with invasive residual disease who are at high risk of recurrence.

Secondly, we also started DESTINY-Breast07 study as a fundamental study for development in earlier treatment lines. This is a phase IB/II study targeting the first and the second-line treatment.

We are going to confirm the efficacy of Enhertu in combination with various anti-cancer agents.

In HER2 low breast cancer, we started DESTINY-Breast06 and 08 studies aiming at earlier treatment lines. DESTINY-Breast06 is a Phase III study in chemo-naive patients with progression after endocrine therapy.

DESTINY-Breast08 is a Phase Ib study to confirm the efficacy of Enhertu in combination with various cancer treatments in chemo-naive and post chemo patients.

In HER2-negative breast cancer, we newly added Enhertu cohort in AstraZeneca-led ongoing BEGONIA study, which is a Phase IB/II study for triple-negative breast cancer or TNBC in the first-line settings.

We started 5 studies, including earlier treatment lines in breast cancer, regardless of the HER2 expression level. Page 29 shows the progress of Enhertu development in tumor types other than breast cancer.

First, in gastric cancer, we initiated DESTINY-Gastric03 study as a fundamental study for development in earlier treatment lines. This is a Phase IB/II study in HER2-positive gastric cancer in the first and the second-line settings to confirm the efficacy of Enhertu in combination with various cancer treatments.

In NSCLC, DESTINY-Lung01 study is now underway with a dose of 6.4 milligram per kilo. We started DESTINY-Lung02 study for further evaluation of 5.4 milligram per kilo dose.

Also, we newly added Enhertu cohort in AstraZeneca-led ongoing HUDSON study as well. This is a Phase II study for the second-line settings and beyond.

We will confirm the efficacy of Enhertu in combination with durvalumab.

As for other cancers, we started DESTINY-CRC02 study in HER2-positive colorectal cancer in the third-line settings for further data accumulation and confirmation of the optimal dose. We also initiated 2 basket studies, DESTINY-PanTumor01 and 02 studies for further expansion of cancer types.

DESTINY-PanTumor01 study targets HER2-mutated cancers, while DESTINY-PanTumor02 study targets HER2-expressing cancers. So we started 6 studies in broad cancer types other than breast cancer, also aiming for earlier treatment lines.

Page 30 shows the major progress of Dato-DXd. In NSCLC, without actionable mutation, we started TROPION-Lung01 study for the second and the third-line settings.

This is the first pivotal study for Dato-DXd. We also started TROPION-Lung02 and 04 studies aiming for earlier treatment lines.

These are Phase I combination studies with pembrolizumab and durvalumab, respectively. Starting these studies is a significant progress for us.

In NSCLC with actionable mutation, we also started global Phase II TROPION-Lung05 study as well. We are proceeding with development not only in lung cancer, but also in HER2-negative breast cancer.

In TROPION-PanTumor01 study, we added 2 breast cancer cohorts, TNBC and HR or hormone receptor-positive breast cancer. We completed patient enrollment in the TNBC cohort.

We are planning to present the TNBC cohort data at ESMO breast in May. So we have made significant progress in the development of Dato-DXd in NSCLC and TNBC, also aiming for earlier treatment lines.

Page 31 shows the major progress of HER3-DXd. We started HERTHENA-Lung01 study, the first pivotal study for HER3-DXd, which is a significant progress for us.

This is a global Phase II registrational study for EGFR-mutated NSCLC in the third-line settings.

We also started preparation for Phase 1 study in combination with osimertinib, aiming for earlier treatment lines in the same tumor type. We're going to start this study shortly.

HER3 expression could rise as a mechanism of resistance to osimertinib, but more important efficacy is expected in the first-line settings by suppressing the resistance through the combination therapy.

In addition to NSCLC, we are developing also in CRC, we started global Phase II study in the third-line settings. So for HER3-DXd, we have made significant progress in the development of EGFR-muted NSCLC and also made progress in CRC and other cancer types.

Page 32 is a summary of major presentations on our 3 ADCs at 4 major international conferences. In FY 2020, we the number of presentations exceeded that of FY 2019, reflecting the progress of the 3 ADC development.

Please turn to Page 33. Every year, ASCO identifies areas of priority with high unmet medical needs and select drugs which have made progress in those areas as the Advance of the Year.

This year, ASCO focused on GI cancer where chemotherapies are standards of care. Enhertu DESTINY-Gastric01 and DESTINY-CRC01 study data was selected as the ASCO 2021 Advance of the Year, as the data suggested that it can be an effective drug for patients with HER2-positive metastatic gastric cancer and CRC.

We already obtained approval of the gastric cancer indication based on the DESTINY-Gastric01 study. We are also becoming more confident about development in CRC for the future as well.

Please see Slide 34. Enhertu received the Prime Minister's award at the Ninth Technology Management and Innovation Awards sponsored by the Japan Techno-Economics Society.

The following 5 points are highly recognized for the award. The first is the creation of Enhertu by utilizing the knowledge and experience of drug discovery over many years.

The second is the acceleration of R&D by building a management system that enables quick decision-making. The third is that we worked with academia and medical institutions to promptly create data that meets international regulatory approval standards.

The fourth is that by actively utilizing the new pharmaceutical jurisprudence, we sought measures to quickly deliver the product to patients. The fifth is that we have developed a manufacturing method to minimize quality risks.

We are extremely excited about this award was given in recognition of the value of Enhertu as well as the ingenuity challenges, teamwork and technological innovation of all members of the Daiichi Sankyo Group.

Slide 35 shows the major progress of the Alpha products. Regarding oncology, DS-1647, which is a virus for cancer treatment, was submitted for approval in Japan.

We started Phase I studies of 2 DXd ADC products, namely DS-6157 and DS-6000 as well as the cancer immune antibody, DS-1055.

For specialty medicine, we made submission for additional indications for atrial fibrillation in the very elderly in Lixiana and ischemic stroke in Effient. We also obtained the results of the Phase III study for central neuropathic pain with Tarlige, and the Phase I and II studies for Duchenne muscular dystrophy with DS-5141.

So we believe that the development of various modality has progressed. And that it has become a good stepping stone to build a pillar of further growth after 3 ADCs, which has been a strategic pillar of the 5-year business plan.

Slide 36 and after are related to ASCO.

Slide 37 is an update on the results of ASCO's abstract adoption. Enhertu's DESTINY-CRC01 trial and HER3-DXd's NSCLC Phase I trial have been scheduled to be oral presentations.

The results of the NSCLC cohort of Enhertu's BEGONIA and DESTINY-Gastric01 studies and the Dato-DXd Phase I study will be presented in posters.

Slide 38 is an announcement of our IR events related to ASCO. Dr.

Manabe and Dr. Takeshita, who was newly appointed as a global R&D Head, will update the data announced at ASCO and our pipelines.

We plan to hold 2 briefings for Japanese and overseas investors with the same content. It will be the first opportunity for Dr.

Takeshita to speak to you. So please look forward to it.

Slide 40 mainly describes this year's news flow, please check it later.

Slide 42 shows an update on our initiatives for COVID-19. First, the development of vaccines and therapeutic agents.

We are participating in basic research supported by AMED and are developing the messenger RNA vaccine, DS-5670 using our unique and novel nucleic acid delivery technology. Last month, we started the Phase I and II studies.

Regarding the messenger RNA vaccine, we'd like to utilize that in addition to COVID-19 to enhance our pipelines.

Regarding the Nafamostat inhalation formulation, DS-2319, which is being jointly researched and developed by the University of Tokyo, RIKEN and Nichi-Iko, we will utilize the development experience of Inavir to carry out formulation research, nonclinical research and clinical development. We conducted formulation research and nonclinical studies and started the Phase I study last month.

Next is the manufacturing and supply of vaccines. AstraZeneca's COVID-19 vaccine AZD1222 has been supplied with undiluted solution from AstraZeneca and Daiichi Sankyo Biotech started contract manufacturing from last month.

Slide 44 and beyond are appendix. We have posted a list of milestones and pipelines, so please check this one later as well.

That concludes my presentation. We're going to take your questions from here.

Let's get started.

My first question is a little detailed question. DESTINY-Breast02, 03 and 04 studies are 3 major milestone studies.

Last year, during the R&D meeting, you mentioned the timing may shift slightly before and after, but all data could be available in the July-September period. Looking at the current milestones, 02 study timeline is extended by 1 year and 04 by 2 quarters, it seems.

I'd like to ask you the reason for changing your forecast and time line. Is there any possibility of another revision in the future?

This is my first question.

Both 02 and 04 studies are event-driven studies. Because of the accuracy of our forecast we made when the number of observed events were small, we reviewed our forecast again and drew this time line based on the latest situation, which was presented to you today.

The studies themselves are making steady progress. Depending on when events will occur, the schedule can change.

We reviewed again and drew this time line. That's all from me.

02 study, in a sense, is similar to 01 study, there is a delay in the occurrence of events, resulting in the extension of the study time line by 1 year or half a year, correct?

Right.

Understood. Secondly, I'd like to ask you about FY 2021 Enhertu sales forecast, particularly in the United States.

In FY 2020, you were slightly behind the original forecast due to the impact of COVID-19 and the impact of tucatinib according to your memory. This year, you're forecasting a very good performance.

Could you please comment on the factors behind the underachievement in FY 2020 assumptions for your forecast of a good performance this year? And how to address the factors behind the shortfall in FY 2020.

It's quite difficult to forecast sales in the first year. And we presented the numbers today.

As you pointed out, the impact of COVID-19, the impact of tucatinib and reinforcing our marketing capabilities further were considered comprehensively to make this forecast we presented today.

So it's based on the forecast last year, you're assuming that these factors will be addressed, correct? The expansion of indications is also included?

Yes, that's right.

Understood. Thirdly, regarding DS-5670, you just started the clinical study recently.

We don't know what is going to happen from now. But given the situation of vaccines in Japan, you may want to hurry up in your development.

If you have an outlook for the next milestones and development data regarding DS-5670, could you share that with us?

We just started Phase I/II study last month. We cannot explain the long timeline up to approval here.

As for approval, we will have rounds of meetings with PMDA to discuss what kind of study we should design to deal with variants, for example. Depending on the spread of COVID-19 infections, where should we conduct a study.

Including such issues, we are consulting with PMDA, whenever necessary, to proceed with the plan, while we're developing our future plans, we started Phase I study. As for the timeline, we cannot disclose as of now.

First, I want to ask you about Dato-DXd Development plan on Page 30. In HER2-negative breast cancer, you newly added the hormone receptor-positive cohort.

I think this is a segment where totally development is making a lot of progress. Can I understand that you are making this decision as a result of your confidence about TNBC in the study so far?

Or should I interpret that you're still pursuing various possibilities at this stage?

We newly added 2 cohorts: TNBC and HR-positive you mentioned. We have quite positive data in TNBC.

We think we are approaching the timing to share that data with you. In total, including that portion, we're still searching for strategy at this stage.

At the bottom of this page, there is a mention that you are also aiming for earlier treatment lines. I wonder to what extent this expression is applicable just to NSCLC or also to TNBC.

Combo studies are also listed here. With which studies we will be aiming for earlier treatment lines, we need to discuss further.

In FY 2021, we will focus on NSCLC, while we also take a challenge on earlier treatment lines. That's what we mean by expression, aiming for earlier treatment lines.

So just NSCLC, for the time being, according to this question, correct?

Yes, that's what we would like to focus on this year.

Regarding TNBC, for which you said you have quite positive data right now, how do you see TNBC for FY 2021 and beyond?

Just a moment please. We are going to present the data at ESMO Breast in May.

You can check that data okay.

Okay. Understood.

One more question. Regarding Page 16, on FY 2021 forecast for Enhertu regulatory milestone payment, the last one in this table is NSCLC.

When you obtain the approval of both HER2-positive and HER2-mutant, JPY 2.6 billion payment will be made or literally, the approval of either HER2-positive or HER2-mutant will lead to JPY 2.6 billion. How do you see the probability of approval of each right now?

Can I have your comment, please?

Regarding the forecast on Page 16, the approval of either of the 2 indications will lead to this much payment.

First, about your R&D expenditure, you're forecasting JPY 266 billion for FY 2021. When you announced your new 5-year business plan, you mentioned JPY 1.5 trillion for the 5 years.

I want to ask you how R&D expenditure will increase in the next fiscal year and beyond? Can I assume that you're going to increase your R&D expenditure in accordance with your revenue?

In terms of the results, this year is going to be the bottom. In spite of an increase in R&D expenditure, you can expect revenue and also profit growth as well.

Can I understand this way?

When we announced our new 5-year business plan, we mentioned JPY 1.5 trillion for the 5 years. If you calculate simply, it's going to be JPY 300 billion each year.

When we have more development projects, R&D expenditure will also rise accordingly. We made a forecast for the 5-year period.

The amount may rise gradually from FY 2021. But if you depend on the project at that time.

So I hope you look at JPY 1.5 trillion as the total amount.

Understood. Also, regarding Dato-DXd data you're going to present at ASCO, what is the timing of the data cutoff?

And how much data can we see in terms of the sample size for 4 and 6 milligram per kilo doses? The data cutoff for the presentation at WCLC was September 2020 with the sample size of 40 subjects, if I remember correctly, how has this changed?

This is my second question.

This is going to be a late-breaking session and the abstract will be made public on the 8th of May. So I cannot answer right now.

You mentioned the sample size of 40, we will have data after the cutoff from the subjects who were enrolled. I cannot talk about the sample size today, but we are planning to present data we have been able to collect by now.

So I hope you can check that data.

Lastly, there is a delay in the timing of data becoming available from DESTINY-Breast04 study. Due to this delayed timing, the timing to start other HER2 low clinical studies may also be delayed.

Should we assume such a possibility? You're not showing your development plan for earlier treatment lines, so we don't know yet.

But due to the delay here, any possible impact on other lines? This is my last question.

As before, this is also event-driven so the forecast was slightly revised. Still, the study is making steady progress.

There's going to be no impact on other HER2 low studies in our view.

Then studies, you're assuming, will start as you have planned, correct?

Yes, you can understand that way.

Ueda from Goldman Sachs Securities. First, I'd like to ask you about your assumptions for expenses.

Regarding your assumptions for SG&A cost in this plan, expenses are going to increase mainly due to the growth of Enhertu according to your explanation. Is there any increase in reaction to the impact of COVID-19 last year?

Is there any change in the mix of the composition of SG&A cost items due to COVID-19? I can imagine a decrease in travel and entertainment costs, and more investments in the use of online, for example.

Something qualitative is fine. Could you explain the change, if any?

First, compared to the previous year, any increase in SG&A costs in reaction this fiscal year. On this matter, as you mentioned, an increase in profit sharing with AstraZeneca is the main factor behind an increase in SG&A cost.

We are not assuming any other reactionary increase in particular. As you mentioned, expenses such as travel and transportation costs decreased a lot last year due to restrictions on activities under COVID-19.

We have kept on our mind that basis to develop the SG&A cost plan for this fiscal year.

Then can I understand that the contents are changing?

The level of pre-COVID-19 ordinary spending has come down a little, but expenses are increasing along with new growth. That's why profit sharing with AstraZeneca is coming to the fore, you can understand that way.

Secondly, I'd like to ask you about your mRNA vaccine platform. For mRNA vaccine, I think it's important to continue and accumulate basic research.

Regarding Moderna's mRNA vaccine, they're making various improvements by enhancing mRNA stability, improving transcription efficiency and optimizing nanoparticles. How have you been able to develop your vaccine technology by leveraging what kind of basic research you have done internally?

What is your competitive edge? Could you tell us the background of your development and the features of your technology?

We have vaccine research laboratories. We are taking a challenge on the so-called innovative vaccines.

On top of LNP messenger RNA, we have various exploratory stage vaccine modalities, particularly in our LNP messenger RNA. In the LNP, lipid nanoparticle portion, which is very important for the delivery, what we are using is cationic with a high level of safety.

Also, we have accumulated a lot of know-how about the combination of LNP messenger RNA and its optimization. In that sense, we are very confident about this platform.

As I mentioned verbally during my presentation earlier, we are hoping to leverage this platform not only for COVID-19, but also for others as well. I think this modality will continue to expand as a core platform for Daiichi Sankyo.

Sakai from Crédit Suisse. I want to ask about just one thing.

Regarding Breast02 study, I have 2 questions. This is a third-line study, so there should be no impact from the enrollment of early cancer patients.

But due to COVID-19, the overall screening rate is declining. The enrollment of cancer patients in clinical studies may be behind overall.

Dr. Manabe responded to this question during the new business plan explanatory meeting.

But listening to Dr. Takasaki's explanation, I thought there may be some impact.

I'd like to ask again for confirmation. This is my first question.

Regarding 02 study, due to the third-line settings, progression-free survival will not be so long in the control arm, like just 5 or 6 months. I understand this is an event-driven study.

If the results are positive, the study could be stopped in my view. Data is anticipated by the second quarter of 2021, according to the disclosure in the presentation material.

But now it's going to be delayed substantially until next year. I wonder if the results are positive by comparing PFS, the study could have been stopped.

This is a hypothetical question. Is my understanding correct?

For my better understanding, please respond.

Thank you for your question. Enrollment is already over in 02 study.

So COVID-19 did not affect the speed of enrollment. I know as this is an event-driven study, the study is ongoing as patients are in good conditions.

Including an interim analysis could be one possible idea. But rather than that, we'd like to complete the study in a robust fashion until the end to perform an analysis.

That's why we are extending our timeline. 03 study is also event-driven with long PFS and OS.

So we are including an interim analysis there. But no interim analysis will be performed in 02 study with enrolled patients in good conditions.

The timeline is extended a bit, but we'd like to file a submission with robust data.

Simply put, PFS is being prolonged overall, right?

We will disclose the data in the future, so we cannot comment right now, but that's what we are predicting.

Understood. So there is no delay in the recruitment?

Correct.

This is Muraoka from Morgan Stanley. About the sales of Enhertu in the fourth quarter, it still looks weak even after the subtraction.

Japan is not increasing enough, and the U.S. is not increasing that much either in my impression.

There might be some reasons to this, but please explain the part in plain language. And in that flow, for this year, you have JPY 69.4 billion.

For example, it will stay slow between April and June, but it will increase from July through September, or there will be a solid growth in every quarter, et cetera. If you can share the image you have, that will be helpful.

It's extremely difficult to forecast. For Japan, we didn't set out forecast too high initially, but we increased it later.

After all, it didn't reach the level we set up. Since we have ILD with all patient surveillance in Japan, we have been extra careful in that regard.

For the U.S., we are seeing a certain degree of an impact to COVID-19 as well as that we haven't been able to make any prediction yet. The forecast has been falling short and has been adjusted upward and downward.

We are working to improve the prediction accuracy.

As for the U.S., I think it's $73 million during the January-March period. This fiscal year is $480 million.

Does it mean that it will present a linear growth every quarter? Or is it going to fluctuate in its growth?

What image should we have?

Since we want to improve and provide an accurate forecast, we anticipate a linear growth when we developed the forecast.

Understood. I have another question.

The question is about how this is reflected on the P&L. About AstraZeneca's vaccine vials on your P&L, where are they positioned?

And what is the impact? Well, I guess the impact is pretty small, but can you tell me what will happen hereafter?

You can think that it has almost no impact. Because of the current circumstances, we have been neglecting the profit or the sales in this initiative.

So you may consider that the impact is minimal.

Understood. And let me ask you 1 last question.

It's about Espha or about generics. In the past few weeks, it seems that there has been a sudden increase of news coverage on the regulatory authority, pressuring the company to restructure.

How do you see it now? And what do you think of it when you think of the regulatory intention?

I should have asked this question during the midterm plan, but I appreciate it if you can tell me now.

Well, since our Espha is currently focusing on authorized generics, AGs, of course, in the current situation, in terms of quality, I guess the AGs have been drawing a lot of attention. The way the company handles the situation is different from any other pure generics.

However, generally speaking, it did encounter a lot of quality issues which brought some noise in the pharmaceutical industry. We have been keeping some distance in considering the issue at this moment.

Hello, can you hear me?

It seems that we have already exhausted most of our questions, but let me ask you 1 question about DS-1062. It's about the development strategy for biomarkers for lung cancer.

If I remember correctly, you have told us that there is a possible biomarker that can screen patients responsive to DS-1062. About this issue, is there any information you can disclose at the timing of ASCO this year or WCLC in the second half of this year or at usual ESMO?

I appreciate it if you can share your current outlook, if any? That's all.

Sure. This is Takasaki, and I'll respond to this question.

Including the expression of TROP2, we are diligently considering the exploration of biomarkers. The clinical trials that are currently undergoing are conducted on an all-comer basis.

Since the tests are done thoroughly, we would like to decide on the usability of those biomarkers based on the accumulated data. In the near future, say, within this year, are we able to present an update on this matter at academic conference?

All our researchers have been working very hard. And once we get the data, we will be able to present them to you, but nothing has been decided yet.

Understood. Yes.

Yes. I have additional question.

I believe you will present the data of DS-1062 for lung cancer at ASCO and in the second half of this year. With the updates we obtained from what was presented during the conference in February this year, what progress should we expect going forward?

Yes. During the ASMO Breast in May, we will show you the data related to TNBC.

Although we are planning to show the data a few times this year, there are some conferences where we can and cannot disclose the data. For example, I believe we can present our data at ASCO and WCLC.

However, as I mentioned before, we haven't decided if we can include the data of biomarkers. You can look forward to our presentations at those conferences.

Hello, can you hear me?

I have a few questions. My first question has to do with the recent sales of Enhertu as a third-line treatment in the U.S.

It's a competitive environment with Pfizer, especially under this COVID-19 situation. When we think of the patients with an ILD risk, I hear some people say that they want to hold back from the treatment every now and then.

So we are seeing that impact. But once the results from DESTINY-Lung02 study becomes available and once we get evidence that there is a clear difference in OS compared to tucatinib, I suppose that may turn the tide.

Is that the way we should think? Could you explain the latest situation?

Yes. Tucatinib or TUKYSA has been used in the third-line breast cancer patients with brain metastases, whereas our product has been used in patients with known brain metastases.

However, if you look at the third line in total, Enhertu has the highest share of usage. As you mentioned, when additional data become available, we believe that the share will be even higher.

We now have great expectations on that.

Now here is my second question. I'd like to confirm my understanding on some updated pipeline information described in the document.

DESTINY-Breast09 is the third-line Phase III confirmatory. Is that correct?

Also, about TROPION-PanTumor01. You've listed many cancer types on the table this time, but do they have a certain level of evidence?

And are they promising to some extent? Or are they simply exploratory?

Can you explain?

Yes. The first one is Breast09.

For 09, it's for patients with HER2-positive metastatic first-line breast cancer. And the Phase III study is either on monotherapy or on combination therapy with pertuzumab in comparison with the standard of care.

So I believe your understanding is correct.

And your second question is about PanTumor?

Yes, PanTumor. The previous documents didn't have the cancer types in detail, but this time, you have PanTumor01 for colorectal cancer, bladder cancer, et cetera.

You've listed a variety of usage. I'm curious as to if you had some progress here.

Yes, it's true that we are still in an explanatory phase. Since it's just started, we will select the breast cancer type from those.

We still need to discuss if we will do all of them. But we can take a wider scope first and select the best cancer type eventually.

That's our strategy.

Okay. My third question, which is the last question is about quizartinib.

The first-line top line data will be available in Q3, but will it make it to the presentation at ASH? You might not be able to say one way or the other.

In addition to that, for recurrent and refractory AML, you received a CRL in the U.S. according to the document, you will look at the results of the first-line to consider the scoring.

By taking that into account, can we expect any major progress with quizartinib? Or is it dependent upon the results?

Can you comment on this?

To give you a short answer, it depends on the results.

Okay. But you are not dropping your hope yet, correct?

Correct. We think it depends on the results.

So you might need to wait for a while.

I'm Steven Liu from CLSA Securities. I will ask questions on behalf of Tony Ren.

Mr. Yamaguchi and Mr.Sakai have asked these questions already.

But DESTINY-Breast04 is now scheduled in Q3, and it's been extended by half a year. You also mentioned that it was extended due to the way the event schedule was made.

Did you have any specific reason to extend Breast04? That's my first question.

Nothing in particular. As I mentioned earlier, it's event-driven.

So we changed the schedule a little bit.

Okay. Now it's Page 8 of the explanatory meeting document, about the increase of DTA.

Can you tell me how this will impact the next year?

Sure. This is Okuda (sic) [Okuzawa].

I'll answer this question. FY 2020 is listed here for the recognition of this DTA, this includes the net losses carried forward in the past and in the future.

Therefore, it means that there is nothing applicable to the next year and after.

So there will be no impact on the next year, but this year's tax was reduced by the increased DTA in the previous year. Is that correct?

Yes, that's correct.

Hello, can you hear me?

Okay. I have a few questions.

My first question is about FY 2020 ending in March. Based on the results, what was the degree of impact COVID-19 brought to the sales and the profit?

Are you able to quantify the impact?

Sure. This is Okuda (sic) [Okuzawa].

I'll answer this question. As for the revenue, it's about JPY 35 billion of decrease.

On the other hand, the SG&A expenses are also decreased due to the restricted activities. So the operating profit has been hardly affected by this.

That is the general overview.

Similarly, what is your view on this year?

Okay, with regards to this year, since we had to engage with our activities in the spread of COVID-19 infection last year, we tried to employ a variety of creative ways to move forward. We have set up our sales plan and sales promotion plan by building upon this experience.

Unless there is any major changes to the situation as it has been announced to you, we believe that we will be able to achieve our business plan. Even if the environment changes and there will be a negative impact on the revenue, we will make an adjustment to the SG&A expenses again, similar to the previous year.

So there should be hardly any impact on the revenue.

Okay. Also, I have just 1 more question.

I guess someone was asking this question previously. But due to Nichi-Iko's and Kobayashi Kako's problems, I think there have been many alternative productions for generics here and there.

At Daiichi Sankyo or Daiichi Sankyo Espha, do you also see any transition to alternative productions in the area of mass production of long-listed products, for example? We have not been affected by this so far.

So there's not really anything that you will start as an alternative production, nothing along that line?

Correct. Correct.

Okay. I'm sorry, but I also have a question regarding generics in Japan.

With regards to Kobayashi Kako, which has been already mentioned in the previous questions, I believe Daiichi Sankyo Espha has a partnership with them. And it seems that they have fallen into an unbelievable situation.

Do they have any plan to reconsidering the partnership? Or will they continue the status quo?

What's their stance on their matter?

Well, there has been an impact on some part. But for reconsideration of the contract, I'd like to refrain from answering this question because there are individual circumstances.

Okay. But can you tell us what you mean by an impact on some part to the extent you are allowed to discuss?

Well, by that, I mean the sales has decreased on our end as well.

Okay. Understood.

Sorry, but I have 1 more question related to this issue. Regarding entecavir for hepatitis B, since their submission was canceled, your product has been subject to a voluntary recall due to the incomplete data in the submission documents.

I don't know what agreement you have with them, but are you going to claim any damages from them or any possibility of development to that direction?

I'd like to refrain from commenting on that matter.