Thank you for waiting, everybody. We'll now start Daiichi Sankyo's ENHERTU business briefing. This is Ken Asakura from Corporate Communications, and I will be the moderator today. First, about the language for this event. We will present in Japanese and in English. Simultaneous interpretation is provided, so please click the interpretation icon at the bottom of the screen and select either English, Japanese, or off. When Off is selected, you will hear the original sound. We will show English version of the presentation slides on the Zoom screen and will show Japanese version of the slides on the live streaming screen. Both English and Japanese presentation slides have been uploaded to IR Presentation Material page of Investors section on our corporate website, so please view or download as needed.
Our presenters for today are Dr. Sunao Manabe, our President and CEO, and Mr. Ken Keller, our Head of Oncology Business Unit. Manabe-san will provide opening remarks and then Ken will present. We will take questions after the two presentations. Please note that this event will be recorded. Let's start the event. Manabe-san, please.
Manabe speaking. Thank you very much for joining Daiichi Sankyo's ENHERTU business briefing today. I'm going to talk about the positioning of oncology business in our 5-year business plan and major achievements for ENHERTU in FY 2022. Please turn to page 3. This page shows the positioning of the 5-year business plan for sustainable growth of the group. During this midterm business plan period between FY 2021 and 2025, we will achieve our FY 2025 goal to be a global pharma innovator with competitive advantage in oncology and we shift to further growth towards our 2030 vision. Page 4 shows strategic pillars for the 5-year business plan. The most important strategic pillar out of these is the first one, to maximize the 3 ADCs.
In particular, maximizing the product value of ENHERTU through a strategic alliance with AstraZeneca is the most important premise for us to achieve our FY 2025 goal in the 5-year business plan. From April, we will be in the 3rd year of the 5-year business plan. Our initiatives to maximize the product value of ENHERTU for the past 2 years are making steady progress more than we expected. We are very satisfied with the achievements by now. Page 5 shows major achievements for ENHERTU in FY 2022. We are making steady progress in maximizing the product value of ENHERTU based on approval of new indications and strong market penetration. Today, I'd like to talk about 3 major achievements in FY 2022. First, we obtained approval to transform the course of HER2-positive breast cancer second line.
DESTINY-Breast03 study showed unparalleled improvement in PFS compared to the standard of care, T-DM1, KADCYLA. Based on the study results, ENHERTU was approved for HER2-positive breast cancer second line in the United States, and we started promotion in May 2022. ENHERTU has already established leadership in HER2-positive breast cancer in the second line settings and beyond in the U.S. market. We're expanding market to other countries and regions right now. Secondly, ENHERTU is pioneering HER2-low breast cancer as a new clinically meaningful patient segment. Based on DESTINY-Breast04 study, which showed potential to transform treatment for HER2-low breast cancer patient, it was approved for HER2-low breast cancer previously treated with chemotherapy in the United States, and we started promotion in August 2022. It is known that previously untargetable HER2-low breast cancer patients account for about half of all breast cancer patients.
In other words, the number is about twice as much compared to HER2-positive breast cancer. Being able to provide a treatment option to more breast cancer patient is one of the major achievements in FY 2022. Now there is a rapid uptake for this indication, and we already achieved number one new patient share in the U.S. market. We are accelerating market expansion to other countries and regions as well. Thirdly, we are also making steady progress in our initiatives to expand leadership across other HER2 targetable tumors. In August 2022, ENHERTU was approved for HER2-mutant NSCLC second line and beyond in the United States, and we started promotion. With this, ENHERTU is approved for the third cancer type following breast cancer and gastric cancer.
We will continue to aim for approval of earlier treatment lines in these three tumor types and expand indications also to other cancer types to maximize the product value of ENHERTU. As I mentioned today, the value of ENHERTU has been substantially enhanced over the past year, we are increasingly confident about achieving our FY 2025 goal in the 5-year business plan. We will continue to take on challenges so that we can provide our product sooner to patients who need new treatment options. That's all from me. I'm now handing over to Ken Keller.
Thank you, Manabe-san. If you could go to the next slide. As Manabe-san mentioned, I am the head of our Oncology Business Unit, and today I will share with you the progress that we've made with ENHERTU, and I'll talk about the foundation that we've built that we will leverage for our next oncology launches. Next slide, please. We've made impressive progress since ENHERTU's first approval in December of 2019 and the start of the Oncology Business Unit in April of 2021. We now have an established commercial footprint in 46 countries. ENHERTU has expanded from its first indication in 3rd line, HER2-positive metastatic breast cancer, to now 4 indications. I'll show you that ENHERTU has achieved market share leadership in every indication launched in the United States and in every country where we have obtained access to for that indication.
Revenue in the calendar year 2022 exceeded $1 billion. Our momentum is accelerating, as demonstrated by the 258% year-over-year growth reported in the last quarter. Today, I'll walk you through some of those highlights and also point out a number of catalysts that we have in place to deliver continued growth in fiscal year 2023. Next slide, please. Our Oncology Business Unit, shown on this slide, works collectively as one team, hand in hand with research, development, regulatory, safety, manufacturing, and other teams across Daiichi Sankyo. Our aligned purpose is to improve the Standard of Care through our ADCs and help cancer patients live longer, better quality lives, bringing new hope and more time to patients across the globe. Our oncology leadership team is a diverse team. As you can see, it represents geographies across the globe.
It couples external experience with top internal Daiichi Sankyo talents. This team has been in place since day one of the OBU establishment. Now I'll show you that we've been able to demonstrate our ability to deliver results with excellence. Next slide, please. This is a roadmap of ENHERTU's kind of strategic plan, and you'll see it consists of four milestones that advance sequentially. Milestone number one was to establish the foundation with the first third-line approval in HER2-positive metastatic breast cancer. Milestone number two was to build market share leadership and displace KADCYLA, which had been the Standard of Care in the second line setting for over a decade. Milestone number three was to redefine the HER2 treatment landscape by having ENHERTU become the first drug to be approved to treat HER2-low metastatic breast cancer and HER2-mutant metastatic non-small cell lung cancer.
The milestone 4 was to really advance ENHERTU to the earlier disease settings, where we believe the outstanding efficacy of ENHERTU has the greatest potential to alter the course of treatment outcomes. I'll walk you through how we're tracking according to our plan. Next slide, please. Last year, 2022, was a year filled with catalyst momentum-building moments for us. ENHERTU was approved for the use in second-line HER2-positive metastatic breast cancer in both the U.S. and Europe. In the U.S., we obtained approval in May, and in Europe in July. ENHERTU was approved for use in the HER2-low metastatic breast cancer setting, post-chemotherapy in both the U.S. and Europe. First drug and only drug to obtain this indication. ENHERTU was approved in the second-line HER2-positive gastric cancer in Europe.
It was previously approved back in January 2021 in the U.S. ENHERTU was also approved for use in the HER2-mutant metastatic non-small cell lung cancer space in the United States. Impressively, ENHERTU has achieved market share leadership in every indication in every country that has obtained access. Now, the United States is the first market to obtain approval and full access. I thought it would be informative to share with you our U.S. performance. We're confident that the U.S. adoption of ENHERTU is a very good proxy for what we'll see in other countries as they gain approval and access. Let's go to the next slide, please. DESTINY-Breast03 was our pivotal trial to secure the second-line HER2-positive metastatic breast cancer approval. It was presented at ESMO in 2021, it was presented by Dr. Javier Cortés.
Unfortunately, it was a virtual meeting, we couldn't be there to see the people's reactions live. It was published in The New England Journal of Medicine in March of 2022, as I mentioned, it was approved in May of 2022. This trial demonstrated that ENHERTU delivered years versus months of progression-free survival. Progression-free survival was 4 times greater with ENHERTU than with Herceptin, it improved it by, you know, 22 months overall. Also very impressively here, we have an 80% overall response rate. You know, one of the key points that many investigators, now the entire oncology world was most impressed by, is that 21% of women here had a complete response. This is in a second-line setting.
That 21% is significantly higher of what the Standard of Care showed in the first line setting. It was really a very impressive results. Of course, incredibly important, it reduced the risk of death by 36%. I can share with you that after this presentation, the feedback from the oncology community was that ENHERTU will very quickly become the new Standard of Care. We launched this indication in May, and as the oncology community predicted, as shown on this slide on the right, ENHERTU has very quickly become the market share leader at 49% market share in fiscal Q3, which is October to December. Also the oncology community's experience with ENHERTU, it's been inspiring to observe.
I personally, and our team here, we have heard story after story after story of patients responding to ENHERTU and doing things with their family and friends that they thought was over for them. So it's just a wonderful drug to work with, and it's a privilege to bring to the oncology community. I think very importantly, while the progress has been satisfying, there are still, as shown on this slide, 50% of patients who are not receiving ENHERTU at this time. While, you know, we've done our job well, we have a lot more work to do and a lot more patients that we can help. That's really what our job is in 2023. Next slide, please.
DESTINY-Gastric01 and DESTINY-Gastric02, that was our pivotal trial to obtain the second-line HER2-positive advanced gastric cancer approval. This data was first presented in an oral presentation at ASCO in 2020, and then later on as a late breaking presentation at ESMO in 2021. It was published in The New England Journal of Medicine and approved in January of 2021 in the U.S. with breakthrough designation. This is the first and only HER2-directed treatment that has demonstrated over a year of overall survival in this patient setting. ENHERTU here demonstrated overall survival versus chemotherapy, reducing the risk of death by 41%. Three times as many patients achieved an overall response rate with ENHERTU, 51% versus 14 with standard chemotherapy.
In the July-August timeframe, as shown right on the right, ENHERTU achieved market share leadership, obtaining 46% overall market share. Similar to the second line HER2-positive metastatic breast cancer indication, we've made excellent progress, but there are many more patients that we can help in the future. Again, that's going to be our focus in the U.S. as we head into fiscal year 2023. Next slide, please. Here is our data and our market share for our HER2-low post-chemotherapy approval. This was presented at ASCO in 2022 in the plenary session. It was presented by Dr. Modi from Memorial Sloan Kettering, where we had the privilege of witnessing the first standing ovation at ASCO in over a decade. When Dr. Modi finished, the room was quiet for a few seconds. Then erupted.
I'd never seen anything like that. Just seeing the joy in the oncologists and the patient advocacy eyes, knowing that they had now a new tool to bring to their patients, was something I won't forever forget. It was published in The New England Journal in 2022, we received approval in the summer of 2022. This data, you know, really stopped people in their tracks, doubling progression-free survival, 3 times higher overall response rate, it's the first and only HER2-directed therapy to bring a significant survival advantage to these patients. Overall survival, median survival is almost 24 months for our HER2-treated patients and 17.5 months for patients receiving chemotherapy. On the right, we have our market share, you'll see that market share has grown very, very quickly.
We launched this drug, and just in 2 quarters it became the market share leader at 43%. The reaction that we saw immediately after Dr. Modi's presentation of the audience instantly understanding that the treatment of breast cancer had been transformed forever, that has now become the standard of care in the United States for HER2-low. This is, as Manabe-san mentioned, a very large patient segment. Half the patients are HER2-low today, and it is in HER2's biggest growth opportunity. Today, the oncology community, really worldwide, understands that the treatment paradigm has been transformed, and it's no longer appropriate to think of patients as HER2-positive or HER2-negative. The correct way to look at this is actually looking at HER2 expression as a spectrum.
Today, every metastatic breast cancer patient is evaluated and identified and categorized as HER2-positive, HER2-low, or HER2-zero. ENHERTU being the standard of care for second-line HER2-positive metastatic breast cancer and the HER2-low post-chemotherapy setting. The immediate reaction that physicians saw is now translating to this drug being given to thousands of patients in the United States and very soon across the world for this indication. Next slide. DL01 and 02, that was our pivotal trial for obtaining the second-line HER2-mutant metastatic or non-small cell lung cancer indication. This was originally presented at ESMO in a late-breaking session. It was published in The New England Journal of Medicine. It was approved in August of 2022 with breakthrough designation.
This is a smaller segment of patients than HER2-positive and HER2-low, but it's a group of patients that desperately needed new options and new hope. Here in ENHERTU is the first approved treatment for HER2-mutant second line non-small cell lung cancer. The majority of patients treated within ENHERTU achieves a robust response, 54% overall response rate and a 90% disease control rate. Most patients treated within ENHERTU did achieve a substantial tumor shrinkage regardless of prior therapy, many of these patients received numerous prior therapies. What you see is ENHERTU rapidly becoming the market share leader, achieving 69% share in really just one quarter.
We believe that the speed of adoption here reflects, number one, the super high med need in this patient group, and also importantly, the growing confidence that the entire oncology community feels about ENHERTU's efficacy, and very importantly, the growing comfort and confidence that the oncology community has in managing ENHERTU's side effects and toxicities. I'll talk about that in just a little bit. What you'll notice is every new indication, the speed of uptake is increasing. We believe it's because the growing understanding of what this drug means to patients, the experience doctors are having in their, with it in their own hands, and their growing confidence that, okay, they can manage these side effects and do it well. Next slide, please. Here I wanted to touch on Europe.
You'll see in the second line, metastatic breast cancer indication setting, in France and Germany, two of the biggest markets, this is where we more recently obtained full access, so it's now available to these patients. You'll see that there's been a very, very rapid uptake with France at 45% and Germany at 38%. This is tracking in terms of speed, even ahead of the original U.S. approvals and uptake. As we obtain access, as we will in the rest of Europe in 2023. We are very confident that we will see a similar very, very rapid adoption. Next slide, please. Here's a look at our global net sales. Net sales have exceeded JPY 60 billion per quarter. Overall, a 25% increase sequentially quarter-over-quarter.
That's driven by the US at 26% and a similar growth rate in Europe. What's really impressive about Europe is, again, they just got the second-line approval, and we're getting access at staggering country. We'll see that nice ramp-up as they secure access throughout calendar year 2023. In Q3, we reported a 268% year-over-year growth in that quarter. I wanna point out that while the US is the biggest contributor, followed by Europe, both Japan and our Asia region are also growing impressively. Next slide, please. On this slide, I wanted to share with you where the adoption is by indication. And what you see is that HER2-positive metastatic breast cancer is kind of the biggest segment.
The fastest-growing segment is HER2-low. As we look out into the future, we will see HER2-low catching up and surpassing the HER2-positive segment in terms of size, again, because 50% of metastatic breast cancer are HER2-low. About 20% are HER2-positive. We've already experienced significant growth in the HER2-low segment, Q3 quarter-over-quarter, about 90%. Even in the triple-negative segment and, you know, to understand how that is, you've got HER2-low patients. Those patients can be either hormone receptor positive or negative. Regardless of positive or negative, we're seeing very nice growth within HER2 in both of those patient segments. Year-to-date revenue in the HER2-low segment is $149.7 million.
Also, notably, quarter-over-quarter growth continues in the second line HER2-positive setting as well as a HER2-mutant non-small cell lung cancer setting. Next slide. I thought it would be informative to share with you some of the things that we're learning. Today, we truly are in a launch, grow, and learn cycle, and that's gonna continue for the foreseeable future. We feel it's very important that we identify and learn from the few key drivers of our momentum, so that we can immortalize those learnings and embed them into the future launches in other regions and countries. Also, to ensure that those capabilities are applied to our future antibody drug conjugate launch plans. When we evaluate the momentum that we have today, we feel it's driven by four things.
Number one, obviously, it starts with Standard of Care-changing clinical data and a few other things, and that's what I'm gonna talk about. The few other things are, Number one, having these data presented at impactful meetings. Number two, having these data published in prestigious medical journals. Number three, having the clinical data being appropriately represented in the influential oncology guidelines in both the U.S. and Europe, and doing all of this in a very quick, efficient, and timely fashion. Number two, our momentum is also driven by our commitment to educating every ENHERTU prescriber and caregiver and patient about the importance of early identification and appropriate management of ILD. This is a toxicity that we observed in our clinical program.
In preparation for the approval of ENHERTU, we educated the oncology community on what HER2-low was, and this is number 3, and what this new paradigm meant for patients, as well as raising awareness of its prevalence. That was a very important aspect. We did that even prior to launch, so that when the DESTINY-Breast04 HER2-low indication was approved, people were ready. Doctors could identify their patients quickly, thereby the adoption was quite fast. Number 4 is more future-looking. As ENHERTU's clinical trials have read out and consistently exceeded the oncology community's expectations, the confidence and excitement about the potential of our ongoing clinical programs has really been elevated.
You know, this excitement has the oncology community enthused and eager to participate in our trials, and they are very hopeful of what these trials may mean for their patients. Today, ENHERTU has a growing positive halo around it because of the clinical trial results. Because of what the oncologists are seeing with this drug in their own hands, in their own patients. This is creating even more momentum. We have a lot of wind at our back right now for all of those reasons. Next slide. What I'd like to do is now just hit on those four points and really share with you kind of what drove our momentum and specifically what we did and what we're going to attempt to duplicate in the future for all of our drugs.
Within HER2, all five pivotal trials were presented at ASCO, ESMO, or the San Antonio Breast Cancer Meeting. The majority of them in either the plenary or presidential sessions, where the entire oncology world is gathered. That's where people look for the latest and greatest information. Number 2, all of these data, all of these indications, pivotal studies, were published in the most prestigious medical journal there is, The New England Journal of Medicine. I personally cannot recall any drug where all of its indications have been published in The New England Journal of Medicine. Not to mention, you know, doing it in literally 2 and a half years. The clinical data was appropriately represented in the influential guidelines, the NCCN guidelines, the ESMO guidelines, with category 1 and 2 recommendations.
This slide is really a pictorial of the execution of our research, development, and medical affairs teams, both globally and in the regions. In addition to this, the ESMO practice guidelines were also in a very timely way, updated to include ENHERTU with very similar strong recommendations. Next slide. Here I wanna talk to you a little bit about interstitial lung disease and what we've learned and the education we did and the impact we believe it's had. In our clinical trials, the overall incidence... I missed my slide here. I'm sorry. What you see on this slide here is the growing confidence that we have that physicians have in understanding and identifying and managing ILD.
You'll see back in Q3 of 2019 was at 36% in terms of doctors rating it 6 or 7, and now that's up to 62%. You'll see in terms of managing ILD, it's also grown from 32% to 47% on a 7-point rating, and this is 6 or 7. Over time, because of the educational efforts that we've done in the field, physicians are becoming more and more confident. As a result, the adoption of ENHERTU is actually accelerating. Next slide. What you see here is something that we saw early in our clinical trial program. What this shows is that the overall incidence of ILD in our breast cancer clinical trial program was 15.5%. 70% had grade 1 or grade 2 events.
Next slide. It's really important to note that ILD and pneumonitis, it wasn't recognized early in our development program, right? It wasn't required, we weren't educating patients, in terms of the management and identification of ILD. In December of 2019, we made an adjustment, we started an educational campaign aimed at effective early identification and optimal management. The goal was to prevent high-grade ILD. What you see on this slide, and especially if you look at 2020, after implementing this education, we saw markedly lower ILD events. With this information, we duplicated this in the real world.
As I mentioned in the previous slide, the confidence that the oncology community has that they can identify patients, take the appropriate measures, and manage ILD, the confidence is growing and getting stronger, and that is one of the biggest drivers of the momentum that we have today. Next slide. Here what we have is our HER2-low adoption. For 20 years, the oncology community segmented their patients to HER2-positive or negative. HER2 has completely changed this paradigm by demonstrating standard of care changing efficacy in patients that were previously categorized as negative. Right? These patients had lower expression levels, IHC 1 and IHC 2 plus ISH negative. As I mentioned earlier, in this population in HER2, double progression-free survival and reduced the risk of death by 36%.
What we did is, through comprehensive educational efforts by our medical affairs teams. Prior to the approval of ENHERTU, we were able to help oncologists understand that HER2 expression was a spectrum. It wasn't positive or negative. They were able to really identify these HER2-low patients very, very quickly. Again, this is one of the key momentum drivers that we put into place. Next slide. In summary for 2022, it was a year of catalyst moments. We've got a lot of momentum, multiple presidential and plenary session presentations, a standing ovation, four new indications, multiple The New England Journal of Medicine publications. ENHERTU is now number one in market share in every launched indication in United States and in every launched country where we've obtained access.
Revenue surpassed $1 billion in the calendar year, we've got very nice momentum as we reported 258% year-over-year growth. We're in a very, very good position to start fiscal 2023. What I'd like to do now is share with you some of our plans. Next slide. In 2023, we will work to optimize adoption of ENHERTU in its recent new indications to change the standard of care and become number one market share in each indication across the globe. In the United States, continued growth will come from the expansion of our market leadership in the second-line setting and in the HER2-low setting, cementing our position as the new standard of care.
As I shared with you earlier, despite the rapid adoption and the progress we made, there's much more opportunity ahead of us than behind us. Our market share in the second line in the HER2-low setting is about 50% today, meaning one out of two patients are not receiving ENHERTU, the indisputably Standard of Care, at the right time, the time where they can receive optimal benefit. That's our biggest focus in the U.S. in 2023. There also remains opportunity to increase market share in the non-small cell lung cancer setting and in the metastatic gastric setting as well. Turning to Europe, accelerating growth will come from the full launch across Europe in the second line HER2-positive metastatic breast cancer setting. In 2022, most countries had not obtained full access yet.
We made excellent progress. In 2023, we expect all countries to have successfully secured access. That's gonna create tremendous growth in Europe. We will launch the ENHERTU HER2-low metastatic breast cancer indications in most countries by the end of fiscal year 2023. We will launch the HER2-mutant non-small cell lung cancer approval as well. HER2 was very recently, just last month, approved in China in the 2nd-line HER2-positive metastatic breast cancer setting, and we're working to launch this later this year. For Japan, growth will come from expansion of our 2nd-line HER2-positive metastatic breast cancer market leadership. It will come from the launch of HER2-low, wherein HER2 will quickly become the new standard of care and also the launch of HER2-mutant in continued growth in non-small cell lung cancer approval.
That's a picture of where our growth will come from in 2023. In each region, we've got very good momentum and a lot of catalysts ahead for us. Next slide. I wanted to put this slide up and share it with you just to emphasize that breast cancer is ENHERTU's number one growth opportunity. You know, it's important to recognize that ENHERTU has demonstrated indisputably to be the new standard of care for 70% of the metastatic breast cancer patients. There's no drug that has this opportunity to help as many patients. You know, this will be our growth driver in all regions in 2023, metastatic breast cancer. Next slide, please. Today, we've also got kind of our next catalyst that we're working on.
Our development program for ENHERTU, it has the potential to create more standard of care-changing opportunities. So far, what you'll see in dark orange, those are our current indications. Our future indications of trials that we're conducting today, DESTINY-Breast06, that is our second HER2-low study. This is a study that is being done to test the merits and the efficacy of ENHERTU to displace chemotherapy post-endocrine therapy. DB-04 is after chemotherapy. We expect top-line results from this study later this year. DESTINY-Breast09 is our first-line study in metastatic breast cancer, right? Here we're comparing it to the Standard of Care. We have our adjuvant and neoadjuvant studies, DESTINY-Breast05. These are the studies where cure is the goal, right?
In the metastatic setting, our hope is that we can turn months of progression-free survival into years. In DESTINY-Breast05, our hope is that the efficacy of ENHERTU can turn years into lifetimes, into cures. That's what our goal is for our ENHERTU program. Next slide. While ENHERTU is the foundation for our oncology franchise, it's also gonna create important opportunities that we can leverage across our portfolio. The synergy is greatest in the metastatic breast cancer space. As shown on this slide, our Dato-DXd ongoing trials, TROPION-Breast 01, 02, and 03. If these trials are successful, it's going to really round out our breast cancer portfolio, and Daiichi Sankyo will be among the most prominent oncology companies in helping breast cancer patients worldwide. We're conducting other trials in breast cancer with our other ADCs.
Many of them are being tested post ENHERTU, as shown in the gray area here. We've got a portfolio that we are hopeful will make Daiichi Sankyo the pre-eminent company in the breast cancer space. Next slide, please. We are also creating a similar story in lung cancer, but here, Dato-DXd is the foundational drug. ENHERTU with its metastatic non-small cell lung cancer indication and our HER3 ADC program in lung cancer, they'll synergize very, very nicely with our large Dato-DXd program in lung cancer. Then, you know, behind these drugs, we have DS-7300, which has already demonstrated very promising benefits in small cell lung cancer patients.
Very similar to the breast cancer space with Dato-DXd and ENHERTU, HER3-DXd and DS7300, our hope is to really make Daiichi Sankyo a company that can help hundreds of thousands of lung cancer patients across the globe and really be one of the companies in all of oncology. Next slide. Going back to ENHERTU, we've made excellent progress so far. We still have big opportunities with our current indications, so there's lots of growth ahead of us. Our ongoing development plan has the potential to expand ENHERTU's use in both the first line metastatic setting with DB-09 and in the earlier stage settings, neoadjuvant and adjuvant. Success in these programs, as shown on this slide, would more than triple the number of patients that we would bring new hope and more time to.
While there's tremendous growth in our current indications, if successful, we're going to help a lot of patients in the future. Next slide. To summarize, we began just a few years ago with the belief that we could transform treatment and outcomes for patients with HER2-targeted tumors and become the number-one drug of choice. We're on track to do this, and our confidence, momentum, and expectations continue to grow. As I've shared with you, we achieved third line and second line market share leadership in the HER2 breast cancer setting. We achieved market share leadership in the gastric setting. We achieved market share leadership in the HER2-low setting. We have other studies that we hope in the future to change the standard of care and even bring more cure to patients in our early stage programs.
I just wanna say there's lots of major opportunities to grow, from where we are today and in the future. I just wanna thank you very much for being on this call and listening to our Oncology Business Unit story. I look forward to answering any of your questions.
We'll now take questions from the audience. If you have questions, please click the Raise Hand icon at the bottom of the screen. I will call your name in order. When your name is called, please unmute yourself and ask your question. When you have no further questions, please lower hand and mute yourself again. Please raise hand if you have questions. First question is from Muraoka-san from Morgan Stanley. Muraoka-san, please.
Good afternoon. I am Muraoka from Morgan Stanley. I'd like to ask you questions in Japanese. Do you hear me okay? Okay. Thank you.
My first question is, and it's page 14, HER2-low penetration chart is shown on slide number 14. If I look at this, IV chemotherapy replacement has already been completed, low-hanging fruits have already been captured. That's how I read it. ENHERTU's HER2-low growth going forward, I do understand that 50% of the patients are still out there, but long duration of the use of ENHERTU can also be a good contribution to the further growth of ENHERTU. In HER2-low, Ken-san, is that the case?
You are correct, there's one nuance in the data that I'd like to share with you. When you're looking at page 14 and it says Q3 22, you see in purple there, that's the basically the Endocrine therapy. What happens sometimes today, it's not very it's not a rare or unique event. Patients will start on estrogen therapy, they usually get a second one. When they progress, doctors are really reluctant to give chemotherapy today because it's not very effective. Many times they actually give a third estrogen therapy and therapy.
After we obtain approval, if the study is positive with DB-0 6, that will show physicians that they have a better choice than the chemotherapy that they're trying to avoid and give a third and even a fourth Endocrine therapy. I think if that trial is successful, what you'll see is Endocrine therapy stopping after like the second switch and not getting a third or a fourth one. There will be growth there as well as growth in terms of length of time that people are on the drug. Does that make sense?
Thank you very much. Thank you. It's very clear. My second question, 2023. Your preparation for growth in 2023, ENHERTU portion was clearly understood. I'd like to ask you about what comes next after ENHERTU. One year later, at the end of this year, one year later from the end of this year. HER3, Dato, two product launches will be in sight perhaps. HER3, Dato launches. For those launches, what kind of preparations are you making and which areas are you paying attention to or being careful about? Ken-san, please.
Yeah, no. Thank you very much. What we will do is, we will have the top line results for TROPION-Lung01, which is Dato-DXd later this year, as well as the HER3 program. We're taking the learnings that I mentioned. They're all DXds, and so we don't know what the toxicity profile will be for them. If ILD is toxicity, we will be able to manage it. We're ready. We've learned a lot from ENHERTU, and so I think that will help us quite a bit. I think that the second key is, in today's world, information spreads very, very quickly. The oncology universe today is half in person and half virtual.
We will take our ability in terms of medical affairs to ensure that these data are presented at the right meetings. Hopefully, the data is so profound that we will have interest from prestigious journals as well. We'll work with our investigative community to make sure that we help them educate their peers very, very quickly. When I look at where we are today, there's so much synergy with what we have in ENHERTU. Our reimbursement and payer teams, you know, we've gone through that with ENHERTU. We'll simply be better for Dato-DXd and HER3. Our investigative community really is so excited. I know I mentioned about the halo of ENHERTU. I should have said it differently.
There is a halo of the DXd program, which they are very positive, and it extends to Dato and HER3 as well. I think there's just tremendous amount of synergy and, you know, with Dato-DXd especially, lung cancer will be the first indication. Down the line, it does have applications in breast cancer as I showed you, and that will just fall right into our medical affairs and commercial infrastructure. We'll apply it.
Thank you very much. One more thing. HER3, is this going to be developed by yourself? I do believe so. You have no worries of developing it on your own. Ken-san.
I think Manabe-san should. Okay.
Yes, as Ken-san has already mentioned, ENHERTU and DXd, we have been developing these with AstraZeneca. That's been co-development, and we've learned a lot throughout. Those lessons learned and also, cost-wise.
Including the two core development programs. There are a lot of expertise which can be used elsewhere. We do believe that we have enough capability to develop HER3 on our own. Thank you very much. Thank you for that.
Next question is from Wakao-san from JP Morgan. Wakao-san, please.
Wakao from JP Morgan. Thank you very much. I'd like to ask you about the EU market, HER2-low, market penetration. Page 16 in the Japanese version. Regarding the second line, there was a rapid expansion according to this page. The factors behind the rapid growth and expansion, and also for the HER2-low, can we expect a rapid expansion for HER2-low as well? From January this year, you started promotion for HER2-low. Like the second line, the situation could be similar. Maybe 2 quarters or 3 quarters later, there's going to be a rapid expansion in terms of the market penetration, in my view. What do you think? Ken-san, please.
Slide 16 is showing the second line HER2-positive metastatic breast cancer uptake. Just to clarify that. Yes, I would agree with your statement. We really do believe, based on everything that we've seen, the rapid uptake that we've seen in the U.S. for HER2-low, that will be very, very similar in Europe. You know, my experience in Europe is once the drug is approved and you get access, right? We're working on access right now. Once you obtain that access, the ramp up is every bit, if not a little accelerated compared to the U.S. We're confident in what will happen in Europe in 2023.
Thank you very much. My second question. It's towards the end, page 31. This is looking at the number of patients expected in the future in the United States, HER2-low and also metastatic breast cancer. There are two categories, metastatic breast cancer, including HER2-positive. If you think about the number of patients in the future, the target number of patients, probably HER2-low will have more patients going forward. Am I correct? Here it says early breast cancer. This early breast cancer, is this HER2-low or HER2-positive? I wouldn't know that from this chart. HER2-low looks too small for the future, looking at this chart. Can you tell me how to interpret this chart?
Okay. The HER2 population there, The HER2-low is twice as big as the HER2 positive. I'm trying to think why that's not bigger. The fact is HER2-low is twice as big as HER2 positive. Let me look at this chart. There must be something I'm not seeing here. Also, the early-stage breast cancer, that is really based on our neoadjuvant and adjuvant programs, which are just the HER2 positive patients, not HER2-low. We are doing earlier studies in the early-stage HER2-low setting. If those studies are positive and they warrant us doing pivotal studies in the early-stage HER2-low, this chart would get even bigger.
Wakao-san, did you understand that? Yes, fully. Thank you. Lastly, about your midterm business plan. Initially, Manabe-san mentioned that you are increasingly confident about the achievement of the MTP. Regarding the achievement, given the current situation, it's highly probable. You are making an upward revision for your MTP. According to your comments today, revision timing could be deferred into the future. When I ask a question in a meeting like this, you would often say you're still under consideration. According to the comments today, it may not be in the short term. Regarding the revision of your midterm business plan, any comment from you? We are discussing this right now. Regarding the current situation, as Ken-san presented, it's performing very well.
As you know, in 2025, FY JPY 1.2 billion or more for revenues, we think we may be able to make an upward revision. We are considering that possibility. After our discussions, we would like to announce. Okay. HER2-low is now in sight. It's easier for you to develop a plan. The untransparency of the plan is getting lower. I think you're close to completing this. Are you approaching the completion? I think the precision is getting higher, so please wait for a moment. Understood. Thank you very much. That's all from me.
Next question is from Yamaguchi-san from Citigroup . Yamaguchi-san, please.
Good morning. Can you hear me?
Yes, yes.
Thank you. This is Yamaguchi from Citi. First question is that you gave us some very good ramping up in the old indication in ENHERTU. At the same time, it is reaching around 50% and there are lots of shares you can take in the near future. Can you give me some reason from the marketing perspective, what is the reason for not to take shares for those things? First of all, is it lack of academic knowledge or price access, or of course, controlling the side effect ILD stuff? Can you give me which really prevent you not to take share at the moment, which you are going to, how you say, tackle in the near future? Thank you.
Thank you for the question. The dynamic in the U.S., 50% share in the second line setting. What happens in the U.S. when a doctor does not use ENHERTU in second line, just about all of those patients get it in the third line. Right? Unfortunately, there is drop off between second and third line. Right? Many not, you know, patients die. I mean, unfortunately, they die. Without a doubt, it is the best option for patients to receive it in that second line setting and not wait. Why do some physicians wait in the U.S.? Some of them are just very, very cautious and laggards. The drug's been approved for you know, a relatively short period of time.
I think those are the physicians that want to see their peers use the drug for a while, and as they see how their peers go, then they'll move it up from third line to second line. Other than the cautiousness, today, the awareness of the data is very, very high. The confidence, as I mentioned, in identifying an ILD is growing. When we look at patients who are at high risk for ILD and those kind of things, you know, we believe there's about 10% or 15% of patients that should never really receive ENHERTU, right? We're moving from that 50 to, you know, probably 80%-85% would be the top.
Really it's about cautiousness, human nature for some doctors, but there's nothing that I see that is a barrier for us continuing to grow.
Okay, thank you. Just follow up on that one. It is fair to say that the third line share used to be pretty high, but now it goes down because the value goes to the second line. Can you give me what's happening on the third line on the ENHERTU, if you know the number?
Yeah, I don't have that in front of me, but your intuition is correct. As our second line grows, the third line is dropping slightly. One way that we look at it is over the course of treatment, what % of patients receive Enhertu? In the United States it's a very, very high number.
Mm.
It's well over 80%. You know, they are getting it, but for doctors that are cautious, they're getting it later, or are some patients, as I mentioned, that shouldn't get this drug because of pre-existing conditions. That's really what's happening.
Got it. On the second question, you mentioned that the European adoption sometimes is quicker than the U.S., which a little bit surprising to me, given the slowness of some of the adoption in European market in general. Can you give me a little bit of the insight. Without the business of the EU higher, is this because everybody knows what's happening in the U.S., there's not much of information gap anymore between U.S. and Europe?
Just to clarify. You know, once approved, it does take longer in Europe to get access.
Yes.
Right? Like for example, Italy today doesn't have access to Enhertu in second line.
Right.
Approved a long time ago.
Right.
Once they get access, in my experience and most others, the Europeans adhere to the guidelines much more stringently than U.S. physicians.
Right.
US physicians, they have the freedom to treat patients kind of the way they want. They follow the guidelines more stringently. With a drug like this already in the ESMO guidelines.
Right.
right? To get access, that's why you have a quicker ramp up. I think you are correct. In this case, the history of ENHERTU and the experience of the U.S., I'm sure that is making people more confident they ever touch the drug in their own hands.
I think that the company should, to non-breast, non-gastric, non-lung.
Mm.
Actually it's going to be a tumor-agnostic treatment in the future in the sense that you don't need to talk about the organ anymore. If it's HER2, you can use it like MSI-H type of things. Do you see from the market perspectives, the future or the potential of those, the potential HER2-agnostic indication in the future?
As you just mentioned, we had a press release just a few weeks ago, AstraZeneca are a partner in ours, and we announced that the study was positive. We did go through the data. We'll be presenting that at an upcoming meeting. In that study, if I'm correct, we really looked at a number of different tumor types. We looked at biliary tract, we looked at bladder cancer, endometrial, cervical, ovarian cancer, even pancreatic cancer. I think when that data is shared with the oncology community, I think people will be impressed. What we're doing now is formulating our plans to talk to the different regulators and plan what we do with that data.
You know, HER2 expression in these tumor types, most of these or all of these are lower than what you see in breast cancer. When you look at all those patients, the unmet need is very, very high. The numbers of patients we can help is not insignificant. More to come on that one in the future.
Thank you very much. Thank you. Next question is from Hashiguchi-san from Daiwa Securities. Hashiguchi-san, please.
I am Hashiguchi from Daiwa Securities. Very nice to meet you. HER2-low breast cancer development is what I wanted to ask you about. Page 28. Right now, ET-resistant patients are at the center of the clinical program for HER2-low. As you can see, target population of the ET sensitive patients. This ET sensitive patients clinical trial phase 3, when would that start? As of now, what kind of background will target it? With what kind of administration method to developing HER2 for such patients?
Manabe would like to first answer this question. As you can see, we have those arrows. We'll be expanding our clinical programs towards these arrows. We are discussing with AstraZeneca for the clinical program. This is still under discussion right now. Once we know what we can announce, we'll be able to disclose such information.
What will be the timing of such disclosure of the information after you have a thorough discussion with AstraZeneca?
We're still under discussion right now, so when we can make that announcement, we don't know that yet. Please give us some time.
Okay, I see. Thank you.
Next question is from Amegano-san from BofA Securities. Amegano-san, please.
Hello, BofA Securities, Amegano speaking. Can you hear me?
Yes, please.
Regarding the ENHERTU penetration, you're making steady progress. I have a question to you. Regarding the duration of treatment, I'd like to ask you a question about the duration of therapy, HER2 positive and HER2-low, for each. What is the length of treatment you're assuming right now? HER2-low penetration, if I look at it, the longer the duration of therapy, more than HER2 positive, you can expect higher sales, perhaps. I'd like to know about it. Thank you very much.
Ken-san, please.
I don't have the real world data that I think you're asking for. What I can share with you though is the responses and duration of response that we reported in the clinical trials. As you know, progression-free survival in the DB03, which is the second line, is up to. It's well over two years. All right. Well over two years. We're hearing physicians say that, you know, their experience in the real world is every bit as good as the clinical trial. They're very, very happy with it. Most patients haven't been on the drug for two years yet. Right now, the responses and the duration is consistent, we believe, with the clinical trials.
In HER2-low, we would expect those patients to be on the drug for a lesser period of time compared to HER2-positive, simply based on the results of the HER2-low study. Again, real-world experience so far, we're very pleased and the doctors are very pleased. The drug is behaving in their own hands as they would expect from the clinical trials. Very, very positive about that.
Understood. Thank you very much.
Next question is from Sogi-san from Sanford C. Bernstein. Sogi-san, please.
Thank you very much. Hi. This is Miki Sogi speaking from Sanford C. Bernstein. I have two questions regarding ENHERTU and one question for HER3 -DXd. First, the ENHERTU. I understand that you guys are in the expanding the indications in HER2-positive earlier setting, namely the first line, as well as adjuvant, neoadjuvant. Also for HER2-low for chemo-naive population. I understand that, you know, that in those indications, you are expecting that ENHERTU will become the standard of care, just like, you know, you guys are seeing in the current indications. What would be the challenge to accomplish that in earlier line? Obviously, earlier lines, the efficacy, safety of the bar is higher.
Also, I think, you know, pricing might be an issue if ENHERTU should be added on top of, you know, the existing Perjeta, Herceptin chemo regimen. That's first question. Second question. Just briefly, you know, after China approval, what is your plan for NRDL negotiation and the listing timeline? For HER3-DXd, this is also a brief question, are you expecting the top-line result readout actually this month from the pivotal phase 2 study? Thank you.
Okay. To answer the first question, as you have pointed out, we are going to move to the earlier lines. We would like to get indications for the earlier lines. R&D study results, whether they turn out to be expected or not, we don't know, so there can be some risks. In terms of the pricing challenges, Ken-san, would you like to answer that question?
The pricing issues are different country by country, as you know.
Mm-hmm.
Successful in the early lines of treatment. I think that the U.S. will embrace the drug and it will be something that's available to patients very quickly. In Europe, it's country by country. You are correct. The factors that will go into the negotiations country by country in Europe are the size of the population, early-stage breast cancer gets bigger and bigger.
Mm-hmm.
Is that what our drug is on top of, or is it mono-therapy as well? As you know, every indication, in most countries, you renegotiate your price. It kind of only goes down. I do believe that with the substantial benefits that we've shown so far within HER2, you know, knock on wood, we show those kind of benefits in the earlier stage setting, and there you're talking about cure. I'm very confident we would find a way to bring this to patients, all across Europe as well. Your last question on China and the NRDL. We're working with our partners, AstraZeneca, right now, for, you know, on the second-line approval, which was just last week. You know, hopefully we can obtain that this year.
You talked about ILD management. Because of the earlier line, higher safety level will be required, perhaps. As Ken-san explained today, ILD control and management, we do have experiences, so we can address the issues, if any. First three question, this is a business update on ENHERTU, so we didn't prepare for a lot of presentations. When we have top-line readout, we will make a public announcement, and the development strategy would be developed accordingly, and then we'd like to share that with you. Thank you very much.
Next question is from Miura-san from Jefferies. Miura-san, please.
Miura from Jefferies Securities. I have 2 questions. First of all, DB06 study. In the middle of this year, the study results will become available next in the middle of the next year. The target patient population number, DB03 compared to DB04, 13,200, 8,000 more than 04, it's going to be 2.6 times more patients. Compared to this, if you look at the existing chemotherapies, after ET, PFS is around 13 months. Based on this, there can be a further extension of PFS. Regarding the market opportunities as a whole, DB04 compared to DB04, the market can be 3 times higher or bigger. Is my understanding correct?
I'm not familiar-
And-
I'm sorry. Go ahead.
Don't stop.
I'm not familiar with the exact numbers that you quoted, but your logic in terms of the number of patients being increased and patients staying on it longer, the logic and the rationale that you spoke about, I agree with that completely. The numbers, I wasn't sure exactly what, but your logic is very, very tight. That's exactly how we think about it.
Thank you very much. On top of that, on DB04 PFS, extended by 5 months compared to SoC. Likewise in DESTINY-Breast06, 5 months or more improvement can be expected for PFS? Ken-san.
I mean, every trial that we've tested in HER2 in has behaved that way for patients.
Thank you very much. My second question. The other day, Pfizer announced the acquisition of Seagen, not just as an ADC, not because it can replace chemotherapies and various tumor types, so there are a lot of opportunities. The second reason is that ADC biosimilars are difficult to be developed. It in your life cycle is the conventional one, but it can be extended usage. In that sense it's very attractive. Regarding the ADC platform, its attractiveness to view on the attraction of ADC platform. Could you comment?
Ken-san.
Oh, okay.
This is a question to Ken-san.
Okay, thank you. When I think about it and when we think about the DXd technology, as you mentioned, it's a platform technology. It's already yielded in HER2 near future. Hopefully it yields the HER3 ADC, Dato-DXd, DS-7300, DS-6000. These are all from our DXd platforms. So, you know, I think it must be one of the most attractive platforms in all of oncology. You know, what we want to do is bring these drugs to patients as fast as possible, run these clinical trials efficiently and learn so we do it faster and better for every single one of those 5.
Thank you very much. Understood. That's all from me.
Next question will be the last question. Next question will be from Tony Ren-san, from Macquarie Capital. Tony-san, please.
Hi, can you guys hear me?
Yes.
Okay. Yeah, congratulations on the very strong results. Just a couple quick ones from me. Ken mentioned the quantitative assay for measuring the continuous range of HER2 overexpression. Could you give us an update on that, where we stand? I know that Dr. Modi spoke on this in the past. Also, in your HER2-low market share, you guys are a little over 40% right now. Where do you think this can go to? Would 70% or 80% be reasonable in your estimate? The last one is, if you go to page 30 on the lung cancer development map.
It appears that you guys switched the priority, and you guys now put non-actionable genetic mutation trials ahead of the AGAs. Just wanna understand that to see if my understanding is correct. Yeah. Thank you.
Ken-san, please.
I think you mentioned something that maybe Ken Takeshita , our head of medical, talked about in the quantitative analysis. If that question was based on Ken's comments, I'm not familiar with that. Maybe we can go back to that answer the next one. When we look at the HER2 and right indication, you know, outside of patients that have some preexisting challenges that would make them not a candidate for an HER2, which is patients. You know, there's not any reason why these patients would not be better off receiving an HER2. You know, our study doubled progression-free survival versus what is really used today, the standard of care chemo. You know, I think our challenge is to just keep building confidence with doctors.
I think as those docs who are a little bit slow today, who are using it maybe third line and fourth, when they see their peers and they see the positive experience, you know, they will move forward. You know, hopefully with DB-06 we displace chemotherapy. You know, in terms of the numbers of patients, I don't think 70% is unreasonable at all. 70%-75%. Wants it higher, this is a drug to help them.
And the, uh-
Yeah.
The lung cancer actionable genetic mutation. Looks like you guys moved the non-driver mutation trials up, and you moved the actionable genetic mutation trials down. Is that correct?
Yeah. I think the illustration is causing confusion. I do apologize for that. With our Dato program, we expect the readouts for both the non-AGA, and we added a cohort of AGA patients as well. They'll read out at the same time. Nothing's changed in our thinking. I apologize for the confusion there.
Okay. Very clear. Thank you.
We have now reached our ending time, and we will now conclude Daiichi Sankyo's and HER2 Business Briefing. Thank you very much for joining today.
Thank you very much.
Thank you very much.
Thank you very much.