Thank you for waiting. We are now ready to start Daiichi Sankyo's Enhertu Business Briefing. Please note that today's call will be recorded, and the language for today's presentation and Q&A will be English. Dr. Manabe, please go ahead.
Hello, colleagues. This is Sunao Manabe, CEO of Daiichi Sankyo. Thank you very much for joining Daiichi Sankyo's Enhertu Business Briefing during your busy end of the month time. Over the last several years, we have presented a lot of information and have many discussions with the investment community around Enhertu, previously known as DS-8201. After January 2020, when we launched Enhertu in the U.S., our presentations and discussions started to include commercial information around Enhertu. I am very happy that now we are able to help breast cancer and gastric cancer patients with Enhertu in multiple countries. Through that, we should set up an event for investors with a focus on the business side of Enhertu. Please move on to page three. This is a slide that I presented back in April of this year when we rolled out our new five-year business plan.
Our 2025 goal is to be global pharma innovator with a competitive advantage in oncology. One of our targets in 2030 to be global top 10 in oncology. Let's go to page four. This slide shows the four strategic pillars for our five-year business plan. Pillar number one is to maximize our three ADCs. We have multiple ADCs in clinical development now and expect the first three ADCs to contribute to our current five-year business plan commercially. Of course, Enhertu has already started making solid commercial contribution to our consolidated business, as I presented earlier today. Please see page five. This slide shows some image for our oncology revenue targets during the current five-year business plan. While our second ADC, Dato-DXd, as well as our third ADC, HER3-DXd, are both expected to contribute commercially before 2025.
Enhertu is the key to our commercial success. Now let's go to page six. The next four pages are the slides we presented last month after ESMO. This slide shows our current clinical development plan for Enhertu in breast cancer. We will not provide any update around clinical development today, but as you can see, we have an aggressive plan to help many more breast cancer patients with Enhertu. Next is page seven. We're already helping gastric cancer patients in Japan and the U.S. with Enhertu and planning to help more gastric cancer patients in more countries. The clinical data that we are accumulating for Enhertu in non-small cell lung cancer look quite encouraging as well. We are now refining our strategy to gain additional indication for Enhertu in NSCLC. Let's see page eight.
This slide shows our plan to help patients with other types of cancers, including colorectal cancer. The clinical data we are accumulating in this area also look very encouraging, and we will continue to work with our excellent partner, AstraZeneca, to deliver Enhertu to as many cancer patients as we can. Let's go to page 9. This slide shows data from the phase III head-to-head DESTINY-Breast03 study against T-DM1, which was featured at ESMO Presidential Symposium last month. At the pre-specified interim analysis of the study, Enhertu demonstrated a 72% reduction in risk of disease progression or death compared to T-DM1, which currently is the standard of care for HER2-positive breast cancer second-line treatment. We are very encouraged by the data. Please see page 10.
As we were working on the new five-year business plan, we felt the need for some changes around organizational structures. One of the high priority needs was to align U.S. and European oncology businesses as well as global oncology business function under one team to respond to the rapid changes we see in standard of care in the oncology market. We therefore decided to reorganize the U.S. and European business units, integrated the global oncology business functions, and created an oncology business unit. We looked at both internal and external candidates to lead this new business unit. While we looked at multiple external candidates, it was eventually clear to me that Ken Keller, who will present after me today, is the best. He was everything that we need, especially the leadership, to maximize Enhertu and the other oncology products for Daiichi Sankyo's growth.
You will recognize that once you hear his presentation. This is all from me today for today, and I will pass the baton to Ken. Ken, you're up, please.
Manabe-san, thank you very much for that kind introduction. If you can go to slide 12. First, I wanna thank you for your interest in our Daiichi Sankyo story. Today, I will share with you the progress we are making in building a leading global oncology business. The Oncology Business Unit works collectively as one team hand in hand with the rest of Daiichi Sankyo across research, development, manufacturing, and our other teams. The Oncology Business Unit's purpose is as follows. As my teammates in research and development translate our Daiichi Sankyo science into evidence, the OBU will turn that evidence into real-world practice. Our ultimate scoreboard is the number of patients we help live longer, better quality lives through our antibody-drug conjugate science and technology in our communities all across the globe. Next slide, number 13. This is our oncology business unit leadership team.
The key points to remember are this is a diverse team, it represents geographies across the globe, and it couples external experience with our top internal Daiichi Sankyo talents. What's been very satisfying is that the potential of Enhertu and our antibody-drug conjugate platform has allowed us to attract top talent from across the oncology marketplace. Moving from left to right, Dr. Mary Pinter-Schenck is our head of Global Oncology Medical Affairs. Prior to Daiichi Sankyo, Mary led the U.S. medical affairs teams at Merck Oncology and most recently Kite Pharma. Mary is also a board-certified oncologist trained at MD Anderson. Dan Switzer is the head of our U.S. Oncology Business Division. Dan has held numerous leadership roles at Daiichi Sankyo over a 17-year career.
With the importance of our AstraZeneca partnership, Naga Kamahata leads our alliance management team, and he is a top internal talent here at Daiichi Sankyo. Rich Jones leads our Global Oncology Business Strategy and Analysis team. Rich joins us from Celgene and Bristol Myers Squibb, where he held a number of key commercial leadership roles. Nadine Sprangers is our head of Market Access and Payers. Nadine led our Daiichi Sankyo European Access and Pricing Organization. We see the European pricing and access environment as most complex and a place that other parts of our organization can learn from. Dr. Marcus Koch is the head of our European Oncology Business Division. He joins us from Pfizer Oncology, where he held a number of key leadership roles, most recently heading up a large part of Pfizer's market-leading CDK4/6 programs. Kenji Shigeta is the Global Head of Oncology Marketing.
Kenji has been with Daiichi Sankyo for over 20 years. He has held global leadership roles with Edoxaban and Effient, and most recently, Kenji was the Head of Alliance Management. Next slide, number 14. The bold ambition we set forth is to significantly change the treatment landscape of breast cancer and lung cancer with other cancers to follow through our revolutionary antibody drug conjugate science and technology, and transform Daiichi Sankyo into a recognized global leader in oncology by 2025, and one of the top 10 oncology companies globally as measured by revenue by 2030.
We are very pleased with the rapid progress we have made advancing our antibody-drug conjugate science and turning it into evidence. Based on the evidence we have already generated within HER2, Dato-DXd, HER3-DXd, and DS-7300, we are confidently pursuing development plans designed to displace the current standard of care in advanced and then earlier stages of breast cancer, non-small cell lung cancer, and gastric cancer. Within HER2, we aim to become the new standard of care in the third line, then second line HER2-positive metastatic breast cancer setting. We believe we can fundamentally transform the treatment paradigm by bringing the remarkable efficacy of Enhertu to patients with high unmet needs where all existing HER2-targeted drugs have failed, specifically the large HER2-low patient segment. Our development program will eventually lead to advancing Enhertu into earlier treatment settings like the neoadjuvant setting where cure is the goal.
The first indication we're pursuing with Dato-DXd is metastatic non-small cell lung cancer patients without actionable genomic alterations. Recently, we announced that we will conduct a global phase III trial called TROPION-Lung08 that will evaluate Dato-DXd in combination with Keytruda compared to Keytruda alone in treatment-naive metastatic non-small cell lung cancer patients with PDL1 high expression without actionable genomic alterations. There is a robust lifecycle program of mono and combination trials targeting both lung cancer and breast cancer, and we look forward to sharing more about these plans in the near future. With our HER3-DXd, we have embarked on a fast-to-market strategy with EGFR-mutated metastatic non-small cell lung cancer patients who have progressed on osimertinib. Osimertinib is the standard of care, and over 250,000 patients have been treated in 2021 alone, according to AstraZeneca. Ultimately, all advanced disease patients progress.
At ESMO, very promising data from our fourth DXd ADC, DS-7300, was presented. It's important to note that each drug shown on this slide is backed by a robust lifecycle plan, including investment in multiple combinations with IO therapies and other modalities that aims to maximize patient outcomes and, importantly, deliver new business growth catalysts for years to come. All together, today we are conducting clinical trials that have the potential to deliver approximately a dozen standard-of-care-changing new indications and or new drug approvals in the next five years. In the progress we've made to date, you can see a couple of important things. Number one, the boldness of our strategy, as evidenced by the recent head-to-head trial results of DESTINY-Breast03.
Number two, the conviction we have, along with our excellent partner, AstraZeneca, for Enhertu and Dato-DXd, to maximize the benefits of these ADCs through our robust lifecycle plans. Next slide number 15. Enhertu is the foundation of our Oncology franchise. I don't think it would be possible to choose a better drug to start building the Daiichi Sankyo Oncology Business with. Both Daiichi Sankyo and our partner, AstraZeneca, see transformative potential in this medicine. Together, we aim to redefine what good and even great looks like in treating HER2-positive patients and to transform how the oncology community thinks of treating HER2 cancers. Now, our Enhertu growth strategy consists of four pillars advancing sequentially. Step one is to establish a solid foundation with the first third-line approval in HER2-positive metastatic breast cancer, which we have done successfully in Japan, the U.S., and select countries in Europe.
I'll provide you with a status report in the next few slides. Step two is to accelerate our global launches and displace Kadcyla T-DM1 as the second-line standard of care based on the DESTINY-Breast03 results and approvals. We are prepared and confident we will deliver this in record time. Step three is fast approaching as we prepare for the DESTINY-Breast04 HER2-low data in the first half of 2022. Now, based on this new indication, Enhertu will potentially transform the treatment of what today is called HER2-negative metastatic breast cancer. This is a significant opportunity. More than half of all metastatic breast cancer patients fall into the HER2-low category. Other HER2 drugs have tried, and they have all failed to benefit this population. Step four is to advance Enhertu into earlier disease settings as monotherapy and in combinations.
We believe the remarkable efficacy of Enhertu in earlier disease settings has the greatest potential to alter the course of treatment outcomes. These four Enhertu growth pillars will change the standard of care across the treatment continuum and deliver a consistent stream of growth catalysts for the next decade. Next slide number 16. Now let's move to an update on Enhertu performance launched to date. Enhertu is now approved in 37 countries. These were accelerated approvals based on the DESTINY-Breast01 single-arm trial, which showed a 60% overall response rate in heavily pretreated patients and a progression-free survival of over 19 months. Impressively, as this trial matures, the data continues to impress. At ESMO 2021, these results were updated, and we reported overall survival was well over two years at 29.1 months. The response from the oncology community has been outstanding.
Enhertu is the number one prescribed drug in the third-line HER2-positive metastatic breast cancer setting in every country where it is fully launched, and this includes the U.S., Japan, the U.K., and France. I'd like to talk about the results first in the United States. We are pleased with the commercial capabilities we've built and the competitive performance of Enhertu in the United States. Enhertu has established itself as the third-line market share leader. This market share leadership has strengthened in the past few months prior to the ESMO data release. Our latest estimate is that the third-line market share in the United States is over 40%, and we believe this increase is a result of oncologists becoming more comfortable and more confident in managing Enhertu based on their own and their colleagues' experiences.
The U.S. oncology community now expects to place 2/3 of their future third line plus, so third line and fourth line patients, on Enhertu. I just want to remind you that survey was prior to the ESMO DESTINY-Breast03 release. In Europe, Enhertu is the number one market share leader in the third-line HER2-positive metastatic breast cancer space in France and in the U.K. We have recently launched in Austria, Denmark, Finland, Norway, and Sweden, with more countries to join soon. Demand sales grew 31% in August vs July, and now there are approximately 1,000 patients that have been treated with Enhertu in Europe alone. This is a limited set of countries as access is constrained as a result of the accelerated approval being based on the single-arm DESTINY-Breast01 data.
The expected forthcoming approval in the second-line setting based on the DESTINY-Breast03 data, which compares Enhertu to T-DM1, Kadcyla, which is the gold standard of care, changes this, and we are confident Enhertu will obtain full access in all countries we operate in rapidly once approved. Next slide number 17. Now, this brings us to the recent ESMO meeting in September. I think most in the oncology community would agree that the star of the meeting was our Enhertu DESTINY-Breast03 Presidential Symposium presentation. I'll talk about that quite a bit today, but it's important to not forget that Enhertu was not the only story for Daiichi Sankyo at this meeting. We had four late-breaking presentations, including Enhertu DESTINY-Breast03 at the Presidential Symposium.
We shared important data from three of our six DXd ADCs in clinical development. Beyond DESTINY-Breast03, findings from Enhertu's DESTINY-Lung01 HER2-mutant cohort was also presented. Enhertu demonstrated an overall response rate of 55% and durable responses in this trial. This was simultaneously published in the New England Journal of Medicine. These efficacy results compare favorably to existing therapies in this difficult-to-treat population, and we will work closely with health authorities with the goal of bringing Enhertu to patients with this specific form of lung cancer. Dato-DXd, Daiichi Sankyo's second ADC, demonstrated a highly encouraging tumor response in patients with advanced non-small cell lung cancer with actionable genomic alterations. As you know, currently, there are no Trop-2 directed therapies approved for the treatment of non-small cell lung cancer. We also presented proof of concept data from DS-7300, Daiichi Sankyo's fourth ADC.
This is our B7-H3-directed ADC in patients with small cell lung cancer and metastatic castrate-resistant prostate cancer. As you can see from this slide, applying our proprietary DXd ADC technology to different targets is delivering new impressive data at an accelerating and consistent pace. This is a testament to our research and development capabilities. Next slide, number 18. Now I am pleased to share with you the impact we see the DESTINY-Breast03 trial has had and will have across the oncology community. As you know, it was the first presentation in the ESMO Presidential Symposia. As Manabe-san mentioned, this trial demonstrated that Enhertu provided a 72% reduction in the risk of disease progression or death compared to the standard of care T-DM1, which has been the standard of care across the globe for over a decade.
The median progression-free survival for Enhertu has not been reached, compared to 6.8 months for T-DM1. The investigator-assessed progression-free survival is over two years at 25 months. The confirmed overall response rate was more than double. In the Enhertu arm, it was 79.7% compared to 34.2% in the T-DM1 arm. 16.1% of patients had a complete response, which is actually higher than what is seen with the current first-line standard of care. While overall survival is not yet mature, the 12-month landmark overall survival showed a strong trend towards improved survival, with nearly all patients treated with Enhertu were alive at one year, 94.1% in the Enhertu arm compared to 85.9% in the T-DM1 arm.
Now, to understand the impact of this data, I think it's important I provide you with the right context. In the first-line HER2-positive metastatic breast cancer setting, the standard of care today is a triplet combination of Perjeta, Herceptin, and a taxane. This is based on the CLEOPATRA study, which is shown on the top left of this slide. Perjeta added to Herceptin and a taxane demonstrated an additional progression-free survival benefit of six months. Overall, progression-free survival was 18 months in the Perjeta, Herceptin, taxane arm compared to 12 months in the control arm. These data are considered groundbreaking even today, and today it remains the first-line standard of care. T-DM1, as demonstrated in the second line EMILIA study, which is shown on the bottom left, provided an additional three months progression-free survival as compared to Lapatinib and capecitabine.
Overall, 9.6 months progression-free survival with T-DM1 compared to 6.4 months. T-DM1 has been the standard of care for over a decade. Enhertu, as demonstrated in the DESTINY-Breast03 trial, provides an additional progression-free survival advantage of approximately 18 months compared to the standard of care T-DM1. Overall, Enhertu's progression-free survival has not been reached. In the investigator assessment, it is over two years. The overall response rate of 80% is twofold higher than in T-DM1. The oncology community's response to this data has been overwhelmingly enthusiastic. Oncologists have told us that to see in a second-line setting progression-free survival and an overall response rate that is better than what has been recorded in the first-line setting is unheard of. To see a hazard ratio of 0.28x is almost unimaginable. It's never been seen before in the treatment of metastatic breast cancer.
Next slide, number 19. To fully understand how impressive this DESTINY-Breast03 data is, we put it in context with not just other HER2-targeted drugs, but all meaningful drugs in the treatment of metastatic breast cancer over the last 20 years. No cherry-picking. We map these drugs along two axes, the added progression-free survival benefit over the standard of care control arm and the hazard ratio in that drug's pivotal trial. On this list and shown on this slide is all the HER2 drugs, Herceptin, Perjeta, tucatinib, neratinib, the CDK4/6 inhibitors like Ibrance and Kisqali, the PARP inhibitors. All of these drugs have made a difference in the treatment of metastatic breast cancer. They have been celebrated by the oncology community, and they represent the current standard of care. As you can see, Enhertu's DESTINY-Breast03 result is the outstanding outlier.
The magnitude of progression-free survival benefit and the hazard ratio is greater than any drug in the history of treating metastatic breast cancer. It's not close. Next slide, number 20. The news coverage we have received has been satisfying and consistently positive. I'll read just two quotes that capture the overall tone. On the top left is a quote from Fierce Pharma. "The showing is so impressive that the study authors concluded that the study, dubbed DESTINY-Breast03, will lead to a paradigm shift in the treatment of HER2-positive breast cancer." Bottom middle is a quote from Biotech Strategy Blog by Sally Church. "The last time I saw similar shock and awe or such fevered excitement in breast cancer was a decade ago, so it has been a long time coming for a new standard of care to be seen in this disease.
This is what we live for in oncology. Records and standards are meant to be broken. Next slide. Slide number 21. I can also share with you that the response from the oncology community has been equally impressive. Here are a few of the many quotes from key opinion leaders across the globe. Now, my favorite one is on the top right. "The world is brighter for women with HER2 overexpressing breast cancers." The takeaway is Enhertu is positioned to quickly become the new HER2-positive metastatic breast cancer second-line standard of care. The enthusiasm among investigators and key opinion leaders for Enhertu in earlier lines of treatment is higher than ever before. We now expect all treatment guidelines will soon be updated to reflect this change in the standard of care. In fact, the first major guideline change occurred last week. Next slide. Slide number 22.
These are the ESMO guidelines. The Annals of Oncology published on October 19th, an update to the ESMO clinical practice guidelines for the treatment of patients with metastatic breast cancer. We've highlighted on this slide the key language in the updated guidelines. I quote, "Based on the strength of these efficacy and safety data, it is reasonable to consider trastuzumab deruxtecan, Enhertu, the new standard second-line therapy in regions where this drug is available, moving T-DM1 to a later line setting." They also included Enhertu as a preferred option in patients with brain mets. Next slide. Slide number 23. Based on these data, we believe once approved, Enhertu will become the new standard of care in the second-line setting. This slide illustrates how HER2-positive metastatic breast cancer patients are treated today. This is a view of the United States landscape. It is similar across the globe.
There are a few points to highlight. First, T-DM1 is the standard of care in the second-line setting across the globe. You'll notice that the number of patients treated is reduced as patients progress. The drop off from first line to second line and second line to third line is significant and real. We see this in the DESTINY-Breast03 trial, where 15% of patients treated with T-DM1 unfortunately died at 12 months. As Enhertu moves up in lines of treatment, so does the number of patients it can potentially benefit. Next slide number 24. The next big catalyst for Enhertu after the second-line approval is Enhertu in the HER2-low space. While there are many drugs approved to treat HER2-positive breast cancer, there are no drugs approved to treat HER2-low expressing breast cancer.
As illustrated on this slide, breast cancer expresses the HER2 protein at varied levels. Only breast cancer patients with HER2 immunohistochemistry of 3+ or 2+ with FISH amplification have benefited from anti-HER2 agents. Today, breast cancer with low HER2 levels are considered HER2 negative. Enhertu's DESTINY-Breast04 trial is a phase III trial in HER2-low metastatic breast cancer patients who have received previous chemotherapy. This result will be available in Q4 of fiscal year 2021. There is a second trial, DESTINY-Breast06, in HER2-low patients previously treated with hormonal therapies. This trial is aimed to displace chemotherapy. These two trials are based on very promising data shown at the San Antonio Breast Cancer Symposium in 2018, where Enhertu demonstrated an overall response rate of 37% and a duration of response of over 10 months.
What is very important to note is that HER2-low patients can be identified with the current IHC standard of care assays, so oncologists do not need a new diagnostic to identify these patients. Next slide number 25. This HER2-low market is potentially big. After hormonal therapy and CDK4/6 inhibitors fail, current treatment is chemotherapy, which is woefully inadequate. While approximately 20% of patients are considered HER2 positive today and are candidates for HER2 therapy, approximately 55% of breast cancer patients may be characterized as HER2-low, 55%. This large patient segment has been recognized in the past by trastuzumab, and T-DM1 failed to improve outcomes, and the concept of anti-HER2 agents in this setting was put on hold or to rest. Enhertu is rechallenging this paradigm. The DESTINY-Breast04 trial results will be available in Q4 of this fiscal year. Next slide number 26.
This slide illustrates Enhertu's breast cancer program on one page. With our partner AstraZeneca, we are investing in trials that address the remaining unmet need aimed to advance Enhertu from its first approvals in the third-line setting to second-line setting, as demonstrated in the DESTINY-Breast03, to the first-line metastatic breast cancer setting, to then transform the treatment of HER2-low, previously HER2-negative patient segment, and to seek more cures in earlier disease with the DESTINY-Breast05 neoadjuvant study, as well as multiple promising combination studies like the ongoing BEGONIA study. This robust life cycle program will provide new growth catalysts for the next decade. Next slide number 27. I want to just quickly touch on Dato-DXd. It's our Trop-2 directed ADC. It has demonstrated highly encouraging tumor response in patients with advanced non-small cell lung cancer.
At ESMO, in a late-breaking mini oral presentation, we reported an overall response rate of 35% with a median duration response of 10 months. This was in non-small cell lung cancer patients with actionable genomic alterations who have received multiple previous lines of therapy. We are also conducting a global phase III trial called TROPION-Lung01 in metastatic non-small cell lung cancer patients post-IO therapy without actionable genomic alterations. We recently announced that we will conduct another global phase III trial called TROPION-Lung08 that will evaluate Dato-DXd in combination with Keytruda, compared to Keytruda alone in treatment-naive patients with PD-L1-high advanced or metastatic non-small cell lung cancer without actionable genomic alterations.
We also have a number of additional trials that have been initiated in non-small cell lung cancer and in breast cancer to evaluate Dato-DXd in either mono or in combination therapy. Next slide. Slide number 28. Our HER3 ADC has demonstrated the potential to address the broad range of resistant mechanisms in EGFR mutated non-small cell lung cancer following failure on TKI therapy. Results from the phase I trial published at ASCO earlier this year demonstrated a very impressive 39% overall response rate and eight months progression-free survival in this population. For context, salvage chemotherapy is the standard of care here, and it provides very limited efficacy. Progression-free survival is between two and three months after the failure of a TKI. Based on this, we have started the pivotal HERTHENA-Lung01 trial, which is ongoing.
We have other studies in earlier lines of EGFR mutated lung cancer in combination with osimertinib. Next slide number 29. With Dato-DXd, HER3-DXd, and in HER2, a mutated HER2 positive non-small cell lung cancer, Daiichi Sankyo has an emerging lung cancer franchise to go along with our breast cancer programs. These programs have the potential to address unmet needs across the lung cancer continuum. It also creates opportunities for commercial synergies and to further build our organizational capabilities to maximize all of these different opportunities. Next slide 30. In conclusion, we've made substantial progress in a short amount of time. The Oncology Business Unit is launched. We have an outstanding, talented, and diverse leadership team. Enhertu is now approved in 37 countries, which provides a solid foundation. Enhertu is well-positioned to become the market leader in the second-line HER2 positive metastatic breast cancer space.
We have another major growth catalyst right behind that with our HER2-low program. We have multiple drugs in breast cancer and lung cancer right behind Enhertu. Thank you very much for your time. I'll turn it back over to Manabe-san.
Would you like to start the Q&A session from now on?
We will now start the Q&A session. If you have a question, please press zero one on your phone. If you want to cancel a question, please press zero two. When the operator calls your name, please give your name and your company name and then start your question. The first question is from Hidemaru Yamaguchi at Citigroup. Please start your question.
Hi. Can you hear me?
Yes, please.
Great, thank you. This is Yamaguchi from Citigroup. I have several questions regarding the growth strategy on Enhertu. The first question is that you gave the number of the patients now on Enhertu, which is around 8,000 globally at this moment. Given the looking back the potential third line patients, which used to be called around 8,000 patients. It sounds like the penetration ratio, which based on the survey a few years ago, are already met as far as the 8,000 patients concerned.
My question is that with these 8,000 patients currently, how much do you see the penetration of this patient compared to the potential third-line patient? It doesn't mean the market sounds like it's bigger on the third line compared to what you have been seeing a few years back as far as your marketing research is concerned. That's the first question. Thank you.
Ken, would you please respond?
Yes. When we look at the third-line space, in the United States, we estimate that our market share is approximately around 40%. It's about 40%.
Yeah.
When we receive the approval for second line, the number of patients in second line is actually larger, right? Because there's no drop-off. Does that answer your question?
You're talking about 40% as share, but
Yes.
It is the same as the penetration ratio with the potential third-line patients in a sense that you can go for 2.5 times compared to your current patients in the near future on the third-line only.
If I understand your question, all third-line patients
Mm-hmm.
Most third line patients who can receive treatment, they do receive treatment today.
Yes.
We have 40% of that marketplace. What we see happening is as we get approval in the second line space-
Mm-hmm.
The number of patients there are bigger. We believe that based on the DESTINY-Breast03 data, that Enhertu will become the market leader in the second line space rather quickly.
Mm-hmm.
If we are the market leader in second line, you know.
Yeah.
The third line market share would go down.
That's right. The second question regarding on that one, sorry for that, is that, how much do you see the number of the patients on treatment bigger compared to second line vs third line?
Yeah. It's significantly bigger. I don't have those numbers on my fingers right now. When we look at it, the way we look at it is, if you look at the DESTINY-Breast03 data, at the end of 12 months, patients who receive the current standard of care, T-DM1
Right.
15% of those patients have died.
Right.
Probably more patients that are so sick, they haven't died yet, but they're so sick. The numbers are significantly bigger second line than third line.
Right.
I don't have the exact number to provide you with.
Okay. Thank you. The last question is that you don't give me a straight answer, but what is the real-world duration of the patients on the third-line at this moment? Because from the clinical trial itself, it's more than one year, could be two years as far as the duration of response is concerned. But given the number of the patients on treatment and given your sales currently, it sounds like duration of the treatment. It sounds like six months or something like that by just the pull per fee calculation. Is it the right number you are using or is it more longer or shorter? Thank you.
Six months would be not accurate. The number-
Right.
The length of therapy is in third-line longer than that.
Right.
As we mentioned back in July, our estimates were the real world duration of therapy was a little bit shorter than our estimates at the beginning, and we
Right.
Mentioned that back in July.
Right.
As we move into second line, patients are less sick, and
Right.
I fully expect that patients will stay on the drug longer than they are today in third line.
Right. Should be more than one year, is that the right way to say?
I think that's fair, yes.
Okay. Thank you.
The next question is from Naomi Kumagai, Mitsubishi UFJ Morgan Stanley Securities. Please start your question.
Can you hear me okay?
Yep.
Naomi Kumagai, Mitsubishi UFJ Morgan Stanley Securities. Question on the OBU. Can you give us an example, how does the new unit actually accelerate the development process or interaction with business partners or regulatory agencies?
Go on.
If I understood the question, how does the oncology business unit work with, for example, the research and development unit within Daiichi Sankyo? Did I understand the question correctly? The way we work right now is, Ken Takeshita is our head of research and development. Ken's team and the OBU, we work hand in hand, really from phase I all the way to phase IV programs. We have a group within our organization that works really to ensure that all of the inputs and the feedback that we get from our customers and regulators is filtered into our research and development program. We ensure that we're doing clinical trials that are designed to change the standard of care and provide us with a competitive advantage.
I hope that answers your question.
Kumagai-san.
Yeah. Can you hear me?
Yes. Yes.
Yeah. Second part of my question is also related to Oncology Business Unit. How does the oncology business in the rest of the world, especially in China, tie into the initiatives led by this new team?
Again, Ken-san.
Today, the Oncology Business Unit, solid line is the U.S. and Europe. Today, China and Japan operate separately. However, all four regions work very, very closely on all of the strategy decisions that we make. When we develop our clinical trial program, we're doing it with input from our Japan colleagues and our China colleagues to ensure that our development programs meet the needs for those regions as well. Tactically, execution, Japan and China are outside of the OBU, but in terms of strategy discussions, we all work very, very closely together.
That makes sense. Thank you so much. Thank you.
You're welcome.
The next question is from Shinichiro Muraoka at Morgan Stanley. Please start your question.
Hi. Shinichiro Muraoka. Can you hear me?
Yes, please.
Oh, great. Thank you. I have a question about the pricing in the U.S. for Enhertu. As far as I understand, the monthly cost of Enhertu is only 5% or 10% higher than Kadcyla. Maybe it will be correct. Based on the DESTINY-Breast03 readout, I think you can raise the price by, for example, 30%. My question is, do you have any plan of raising the price in the U.S. for Enhertu? If you raise, for example, huge percent like 30%, in that case, will patients or will physicians don't appreciate to use Enhertu or even though such a huge price hike, the patients are, physicians are appreciate to use Enhertu.
Could you let me know your view, please?
Yeah. Thank you for that question. We don't make comments about what we'll do with price in the future. I do appreciate your question, and I think that given these remarkable results, the value of Enhertu is going to be highly recognized in the United States. In terms of price in the future, respectfully, we don't usually provide that. If it's okay, I'll leave it at that.
Okay. Thank you. My next question is, the actual use of CDK4/6. You are first targeting how to grow will be, maybe according to page 20, slide 26, post CDK4/6 patients. Do you? I think CDK4/6 is a quite good drug. Could you let me know how, what's the ratio of CDK4/6 failures? Is it 30% or 40% or much lower than that?
Yeah. When we look at the HER2-low marketplace, today the standard of care is endocrine therapy plus CDK4/6 inhibitors. You are correct. CDK4/6 inhibitors have made a big impact in the treatment of metastatic breast cancer. Unfortunately for patients, many patients ultimately progress. In fact, the majority of patients ultimately progress on endocrine and CDK4/6 inhibitor therapy. All of those patients who progress today, for the most part, receive chemotherapy. Chemotherapy provides very modest benefits. Our first indication, which will be the DESTINY-Breast04 data, is actually post-chemotherapy. The next HER2-low data which reads out is the DESTINY-Breast06 trial, and that is to displace chemotherapy.
Our hope is that the benefits of these trials are so clear that most all patients would receive Enhertu rather than chemotherapy, because chemotherapy is simply not very effective.
What's the ratio of post CDK4/6 patients?
I don't have an exact number of what we expect our ratio to be. What I will share with you is the market is 2.5 times bigger than the HER2-positive market. You know, if our data is really outstanding, we would hope that the majority of those patients would receive our drug.
Okay. Thank you. Final question is, the DB deals with the brain metastasis data. At ESMO, you showed some information of the brain metastasis data, and it was quite positive. What's the current feedback from the physicians in terms of the brain metastasis patients? Actually, does physician choose after ESMO, your drug Enhertu or prioritize Enhertu to Tukysa plus Herceptin regimen? I'd like to know the physician's current physician update.
Yeah. Thank you for that question. Certainly the data that we shared at ESMO is providing physicians with more confidence about using Enhertu in patients with brain mets. As you're aware, Tucatinib in their clinical trial, they included patients with active brain mets. We have not included patients with active brain mets. Today, physicians are looking at patients in two different segments. A patient who has stable brain mets and is responding to treatment with, let's say, radiation therapy. For stable brain mets, Enhertu is very competitive. I'd say doctors are gaining more and more confidence there. In patients with active brain mets, since Enhertu does not have data in that population today, doctors are more reserved in choosing Enhertu.
As you know, breast cancer patients, as they go into third line and fourth line therapy, as they continue to advance, the percent of patients that develop brain mets increases. The reverse is true, too. As you go from third line to second line patients, which is where we'll go with our DESTINY-03 data, the percent of patients that actually develop brain mets there gets lower and lower. I hope that answers your question.
Okay. Yeah. Thank you. Thank you very much.
The next question is from Fumiyoshi Sakai at Credit Suisse Securities Japan. Please start your question.
Hi. Thanks for taking my questions. The first question is the overall status of the U.S. cancer patient treatment under COVID-19. In Japan, some of the patients avoided regular checkup, especially for breast cancer, the female patients obviously. Now, Roche commented at their third quarter conference that they see 90% of the daily regular treatment is now getting back to normal. What about your status in the U.S.? You obviously have just launched the Enhertu. So you may not have deeper patient population as Roche does, but I think you have kind of, let's say, the feeling how patients are now responding to the latest situation of COVID-19.
Now we are seeing the number of patients is coming down in the U.S., but not as drastic as some other countries or territory. What is the latest situation there?
Yeah. Thank you for that question. We have seen in the United States that the screening for cancer, so screening of colorectal cancer, for example, that screening number has gone down, but it is recovering. I would say it's very close to where it was pre-COVID. So that would be true for screening things like colorectal cancer or breast cancer mammographies. When we look at the care of treatment itself, today the oncology community has recovered. I don't know if it's 100%, but it's recovered close to what it was pre-COVID. What we're seeing in the United States is, for the most part, oncology care, and the whole COVID situation has improved quite a bit.
I will also add that for the patients that Enhertu is helping today, so the third-line patients and in the near future, the second-line patients, remember, those patients are already under the care of oncologists.
Mm-hmm.
I would see very little impact from COVID for that type of a patient.
Okay. That's helpful. The second question is, well, related to the DB03 data. Actually Manabe-san mentioned that, with this data, you know, Enhertu and Daiichi Sankyo with AstraZeneca picking up more interest among the physician community. I think that really is good news. What about the patient in the U.S., the patient respond to this kind of news? You know, you clearly mentioned that the patient in third-line treatment has already been treated for some time in duration. With that in, you know, with that kind of news, you're going to see more, let's say, interest coming from the second-line patient already?
You know, after you filed obviously second-line treatment, you expect the quicker or faster or bigger take-ups to begin with?
Yeah. I'll answer that question, the two parts. The breast cancer community in the United States is a very well needed community. Meaning, women who develop metastatic breast cancer especially, many, many of those women, I would say the majority, are active in the local breast cancer community, whether it be local communities or the internet community. They become very, very knowledgeable about their disease. We have heard. Now, these are, you know, anecdotal stories, but we have heard many, many stories of women advocating for Enhertu who have been on treatment for many, many years. The second part, I'll answer, which is today, but in the future we will do it more and more. We do actively educate the breast cancer consumer themselves.
For example, in the United States, we actually have a team of oncology nurses that a major part of their job is to educate the offices about Enhertu and how to manage Enhertu. They also, all of these nurses, work with the local breast cancer community to educate the breast cancer community about Enhertu. That will only increase as we move into second line and in the future, earlier lines of therapy.
Yeah. That's a good thing. The last question. AstraZeneca as a partner, I mean, this may not be a fair question, but it seems AstraZeneca is, well, you know, obviously they have such good credit or, you know, highly valued the Enhertu. But that means seems like they're taking control over Enhertu in the U.S. marketing part, and even European marketing part. How do you respond to this kind of, you know, with your comment, please?
Manabe-san, is it okay if I answer that?
Okay. We have already established a very good relationship with AstraZeneca and Daiichi Sankyo. We rely on each other. So far, we built a good relationship through JEC, Joint Executive Committee. Daiichi Sankyo sent two members, including Ken Keller-san, Ken Takeshita-san, sent to the JEC, also two members from AstraZeneca. Through that JEC, we make very fair decisions. This is my understanding. Ken Keller-san, would you please comment on? Yeah.
Yes. The only thing I'll add is, it's actually a very, very excellent partnership. When we look at decision-making in U.S. and Europe, and also the execution, it really is a 50/50 partnership. I don't feel at all that AstraZeneca is kind of doing more or leading more than Daiichi Sankyo. That's actually not true. It's really a 50/50 partnership both on the strategic and the executional level. I think in the United States, AstraZeneca is a bigger name, so I think that kind of creates a different impression. In reality, it really is a very, very good partnership.
Okay. Well, thank you very much, Keller-san. That's been more helpful. Thank you.
You're welcome. Thank you.
The next question is from Seiji Wakao at JP Morgan. Please start your question.
Hi. Hello. Can you hear me?
Yes, please.
Oh, thank you. Sorry. My mic problem. My question is about, you know, penetration speed of second line. This will be overlapping with Sakai-san's question. Let me know. Today you show the key doctors high evaluation of the DESTINY-Breast data. I believe that if Enhertu is approved for second-line settings, Enhertu sales could increase rapidly in the short term beyond the current, your company's estimation sales trend, which you show that slide five, the trends. I'd like to know your thought on the penetration speed on the second-line setting is approved, how sales performance might change. This is my first question.
Uh, inaudible, please.
Yep. I agree with your assessment. What we see happening is Enhertu quickly becoming the second-line standard of care. This will be obviously post-approval, but the magnitude of benefit is so extraordinary. The reflection that we've seen in the ESMO guidelines, which clearly state that Enhertu is now the new standard of care in the second line. I expect the NCCN guidelines in the U.S. to be updated very shortly. Given that most physicians today now have some experience with Enhertu in their own hand, I think all of those factors lead to a very successful and rapid launch in the second-line setting.
Okay. Thank you. I understand. Next question about the possibility of HER2-low adjuvant earlier line, especially about adjuvant. I'd like to know your thoughts on the possibility of adjuvant in HER2-low settings. So far, Daiichi Sankyo has not mentioned the possibility of adjuvant for HER2-low. Depending on further data, is there a possibility of a challenge here? For example, if DESTINY-Breast04 is successful, will you be targeting all patient populations as well as HER2-positive settings? Or do you have different strategies for HER2-low and HER2-positive because the competitive landscape is different? This is last question.
inaudible.
Yep. Right now our earlier disease program is the DESTINY-Breast09 study, which is. I'm sorry, that's the incorrect one. I believe it's the DESTINY-Breast05 study, which is actually looking at Enhertu vs T-DM1 in the HER2-positive, neoadjuvant setting. That's the one earlier major program that we have today. That doesn't answer your question. Your question is, are we looking at earlier in these settings in the HER2-low segment? We're actually evaluating this right now. What I can tell you is the enthusiasm from the oncology community after DESTINY-Breast03 is very high. We are working with AstraZeneca to look at these earlier programs in the HER2-low setting. We will update you on where we are sometime in the future.
Okay. Okay, I understand. It's very clear. Thank you.
You're welcome.
The next question is from Yo Mizuno at Tokio Marine Asset Management. Please start your question.
Hi, can you hear me?
Yes, please.
Yeah. Thank you very much for taking my question. Regarding HER2 breast cancer, you replace and displace chemo strategy moving forward to earlier lines. In this setting, there are many drugs, especially a partner, AstraZeneca has a wide range of molecules from PARP inhibitors and potentially ADCs. What would be trigger for you to begin combo treatment in development in not just replacing chemo, but possibly moving forward with novel combinations. Thank you.
Could you respond?
Yep. Today, one of the nice advantages of working with AstraZeneca is, as you mentioned, they've got a broad portfolio of oncology drugs, especially in the lung cancer setting. Currently, we are running a number of studies, for example, the BEGONIA study, combining Enhertu, for example, and Dato-DXd with AstraZeneca's drugs. Today we're doing proof of concept studies, based on what we see in terms of activity. We will then take that into the next advancement, you know. We're doing that today, and our hope is that some of these combinations show really exciting results.
AstraZeneca doesn't have a CDK4/6 inhibitor, but is it possible that at some time in future you'll be trying Enhertu plus CDK4/6 or possibly even Dato-DXd plus CDK4/6 in relatively near future? Thank you.
Yeah. I think you're thinking about it correctly. I mean, wherever chemotherapy has shown some modest benefits, that is an area that potentially our ADCs could provide more benefit. You know, today the combination of CDKs and chemotherapy is not standard of care. With the activity of our program, there are many different combinations that people are interested in. I don't have any comment in terms of solid plans on that, but the philosophy that undermines that statement, we completely agree with.
Yeah. Thank you. My final question is, with Enhertu, you're doing several pan-tumor studies, and we've already seen several investigator-initiated trials in minor cancers. Do you see at some time in future that Enhertu could possibly get tumor-agnostic indication?
Today we're doing a number of studies, as you mentioned, in HER2 positive lung cancer, in HER2 mutated lung cancer, which I mentioned earlier, in colorectal cancer, in gastric cancer. Those are the four major places that we're in right now, but there is many other studies in different areas. That pan-tumor question, in terms of clinical trials, we're addressing all of them, but to get a agnostic label is a more sophisticated regulatory question, which I would have to get back to you on, the possibility of doing that.
Okay. Thank you. That's all for me. Thank you.
You're welcome. Thank you.
There are no more questions. We will close the Q&A session.
Okay. Would you like to close today's conference call? Ladies and gentlemen, thank you again for your interest and participation. Goodbye.
This is the end of the call. Thank you for participating.