This is Manabe. Thank you for attending Daiichi Sankyo's R&D Day at this busy time of year-end. Today is the first R&D Day since the announcement of the five-year business plan. I'd like to talk about how we got off to the start of the five-year business plan. Please look at slide 5. This is the position of the five-year business plan for sustainable growth, which was also shown at the five-year business plan briefing session. The five-year business plan, which covers the period from FY 2021 to FY 2025, is a plan to achieve the FY 2025 target and move to the growth stage toward the realization of the 2030 vision under ESG management. Slide 6 shows the strategic pillars for the five-year business plan.
R&D capabilities are important for the first pillar, which is to maximize three ADCs, and the third pillar, which is to identify and build pillars for further growth. Regarding the first pillar of strategy to maximize three ADCs, ENHERTU and Dato-DXd will maximize the product value through a strategic alliance with AstraZeneca. HER3-DXd will be developed in-house to maximize the product value. Regarding the third pillar of the strategy to identify and build pillars for further growth, in order to achieve our sustainable growth during the period of the five-year business plan, we will identify another growth driver following the three ADCs and will aim to select a post-DXd ADC modality. Please look at slide seven. This slide is a quick summary of the major progress since last year's R&D Day.
With regard to the maximization of three ADCs, ENHERTU's market penetration and the addition of new indications are proceeding smoothly. We expect that the excellent results of the DESTINY-Breast03 study will serve as a tailwind as well. The development of three ADCs is progressing well, and in addition to ENHERTU, we have also started multiple pivotal studies of Dato-DXd and HER3-DXd. Regarding the identification of the growth driver following the three ADCs, the first clinical data of DS-7300, which is the fourth DXd ADC, will be announced at ESMO. Further development is expected for cancer types such as small cell lung cancer, esophageal cancer, and prostate cancer.
During the past year, the development of DS-5670, which is an LNP mRNA vaccine as a COVID-19 vaccine, has made great progress and is scheduled to be put into practical use next year. In addition, we have obtained approval for DELYTACT, a virus for treating cancer, and Yescarta, a CAR T-cell therapy. Toward the selection of the post-DXd ADC modality, the establishment of technologies for various modalities has gained headway, and we have accumulated the development experience and the know-how. In addition to the good performance of the three ADCs, we are beginning to see the growth driver following the three ADCs.
Furthermore, the number of options for the post-DXd ADC modality is increasing, and we believe that we have made a good start toward the realization of the five-year business plan and the 2030 vision. Please look at slide 8.
Last month, we held our first ESG briefing session. We will strive for sustainable growth through value creation with our greatest strength, science and technology as the source of our competitive advantage. Science and technology consists of human resources, corporate culture, core technologies, and so on. As for human resources, our strengths include experienced human resources who pursue cutting-edge science with connoisseurship for science and technological capabilities for refining medicines cultivated in small molecules. In addition, the tenacity of such human resources to work on new drug development with conviction, that is, their close engagement and motivation for innovation, are fostered in our free and open corporate culture. The one who leads the science part of the five-year business plan is Ken Takeshita, who joined our company this year as the global head of R&D.
In addition to his advanced scientific ability, he has balanced leadership in both research and development, has experience of growing a company that was not a mega-pharma, and has a background of being born in Japan and raised in the United States. I hired him in anticipation of his competence of bringing out the goodness of each of Japan and the U.S. With my work experience with Ken Takeshita so far, I'm convinced that I made a right choice. At our company, creating growth drivers after 2025 or 2030 is a major theme. I feel that Ken Takeshita doesn't focus solely on the three ADCs in front of us, but he's rather a leader with a mid- to long-term perspective. Further strengthening of science and technology, which is Daiichi Sankyo's strength, is indispensable for our sustainable growth.
I believe that Ken Takeshita is a leader who can achieve this. I am very much looking forward to creating drivers for our sustainable growth together with R&D unit led by Ken Takeshita. That is all for my presentation. Now I'll hand it over to Ken Takeshita.
Thank you very much, Manabe-san, for that introduction. Thank you to all of you for calling in to our R&D Day today. For today, I would like to give you an update on the progress in our R&D strategy, including where we stand in terms of our clinical trial programs for not just the three ADCs, but also the additional programs we have earlier in the pipeline, as well as a little bit about our research strategy. It'll be a very, very rich content presentation for today from a science and technology standpoint. Next slide, please. Okay, these are the topics that we'll be going through today. First, next slide, on slide number 11. This is really our vision for our R&D.
We want to contribute to the enrichment of the quality of life around the world. From us in R&D, we want to serve as a source of innovation. I think the word innovation is key here to improve the lives of patients. We want to do this globally by delivering our strengths in science and technology. This is our vision. Second, next slide. Slide number 12. These are some of the details of what we are doing from a strategic standpoint. Many of you are aware that we have a very broad program in the three ADCs that are listed here, in HER2, Dato-DXd, HER3-DXd. We also have in earlier stages the Alpha program, what we call Alpha, in oncology specialty medicine.
These three areas in the Alpha program are what we term to be rising stars and next pillars beyond the three ADCs that you see here listed. Next slide, please. Where are we with these various ADCs and other clinical-stage programs? In terms of our strategy, you will see today that we are greatly expanding the programs of three ADCs. We are now seeing very good clinical signals, early clinical signals in all our ADCs. These two ADCs, DS-7300 and DS-6000 as rising star ADCs. We're very hopeful that these are the young next generation of ADCs to develop for us. We also have some new first-in-class, best-in-class early-stage assets.
Finally, in the research program, we have a lot of modalities, scientific and technical modalities that we are using to generate new approaches to attack diseases in which the target is very well-developed. Through this, we have been able to generate second-generation ADCs beyond the initial DXd ADC program. We also have additional new concept ADCs that we'll touch on a little bit. We also have some LNP, mRNA technologies, gene therapies, et cetera. Now, supporting these clinical trial programs is something that you're not likely to see too often, but we have undergoing right now within the company, transformation of our R&D group.
This is probably not very visible if you're outside of our company, but inside, this is a major transformation to change and transform the Daiichi Sankyo R&D group into a single global R&D team that is streamlined, scalable, sustainable for our ever-expanding pipeline of clinical trial programs. Most importantly, through this unification of a single R&D team, we want to enhance our global drug development capabilities. This includes mentoring, training in things like strategic expertise as well as talent development. These are going to be the pillars or investments in our people that will lead to further able to achieve our strategies with our ADCs and our next pillars. Next slide, please.
Okay, now we're gonna go on to where we stand with our DXd ADC program. Next slide number 15. Just to give you a little bit of some news highlights.
I'm very pleased to announce to you, of course, that our HER3-DXd received the World ADC Award as the Most Promising Clinical Candidate at the World ADC San Diego. I will brag a little bit and say to you that our three ADCs have won the award three consecutive years in a row. In HER2 in 2019, Dato-DXd in 2020, and HER3 in 2021. This really reaffirms and confirms that our DXd ADC technology is well-recognized on a global level. Next slide, please. Here's a little news update again. For those of you who are not aware that we have reported our first randomized study of Enhertu against the standard of care control. In this clinical trial, Enhertu was compared directly against the old standard ADC called T-DM1.
You'll see here that I'll get to this a little bit later, that there's a dramatic difference in how ENHERTU compares to T-DM1. Highly superior with a hazard ratio of 0.28. Now ENHERTU, based on these data, is included in the ESMO clinical practice guidelines, as well as the NCCN breast cancer guidelines as the preferred second line treatment with category one recommendation. Next slide. This is our list of the DXd ADC franchise that we have publicly announced. There are seven of them, starting with ENHERTU and going all the way down to what we call DS-XXXX. The target for this is undisclosed at the moment. Just to really remind you that this ADC DXd technology has given rise to seven ADCs so far.
I will try to touch on five of these seven later today. Next slide. Okay, slide number 18. We're going to start with the ENHERTU. This is our first ADC targeting the HER2 target antigen. This is our vision. Number one at the very bottom is to transform the treatment outcomes for HER2-positive breast cancer patients. You'll see that we have already started to do that with our clinical trial program. We also want, as a second vision, to redefine the breast cancer treatment paradigm and create a new patient category. A brand-new patient category called HER2-low, which is different from the HER2-positive patient population. This HER2-low patient population is actually rather a very large patient population, and we'll tell you a little bit later how we are addressing this patient population.
As a third vision, we want to establish ENHERTU in diseases other than breast cancer, in where HER2 is expressed by the cancer cell. This includes gastric cancer, non-small cell lung cancer, and colorectal cancer. We're doing a lot of exploratory studies as well as pivotal registration studies in these diseases other than breast cancer. Next slide number 19. It's just a very condensed summary of our breast cancer program as well as the non-breast cancer program. You'll see that, we look at breast cancer world from a ENHERTU standpoint in terms of HER2 expression. We have the HER2-positive breast cancer in this middle row. This is the classic HER2-positive breast cancer patients that you are mostly familiar with.
You can see that we have a full panel of clinical trials addressing pretty much every single patient segment in this HER2-positive breast cancer patient population. As I alluded to earlier, we are trying to create a new category of patients called HER2-low breast cancer patients. Right now, we have two studies going on in this patient population, DESTINY-Breast04 and DESTINY-Breast06. I'll get to the 04 a little bit later. Way at the bottom row are the diseases beyond breast cancer, such as gastric cancer, non-small cell lung cancer, and colorectal cancer. We are generating clinical trial data that really gives us confidence that ENHERTU is more than just a breast cancer drug. Next slide.
Now in the next few slides, I'm going to go over with you the data from the DESTINY-Breast03 clinical trial, specifically a slide deck that was presented just most recently last week at the San Antonio Breast Cancer Symposium. Next slide. This is a clinical trial, it's a randomized phase II study of T-DXd, also known as ENHERTU, compared against another ADC compound called T-DM1 from another sponsor. Patient population was as listed here, relapse patients with HER2-positive breast cancer disease. It's important for this presentation to note that these patients could have had clinically stable treated brain metastases at the time of entry. There were about 80 patients out of the 544 patients enrolled who had these brain metastases. That's really the focus of this particular presentation from San Antonio. The next slide.
This is the data on the primary endpoint of progression-free survival for the entire patient population. You'll see that there's a dramatic difference with a highly superior ENHERTU data compared to the old standard ADC T-DM1. The hazard ratio is 0.28. What this really means is that the risk of progression is reduced by 72% with ENHERTU compared to T-DM1. These are incredibly dramatic improvement in the progression-free survival compared to standard control. You can see that also based on things like Median PFS of not reached versus 6.8 months and 12 months PFS rate of about 76% compared to only 34% in the control arm.
Next slide shows a breakdown of the PFS by subgroups, really showing that in every single subgroup that we have analyzed thus far, there's superiority of ENHERTU, or T-DXd, compared to T-DM1, whether it's hormonal receptor status, visceral disease, et cetera. Of note here at the bottom, patients with brain metastases also show dramatic benefit to T-DXd compared to T-DM1. Next slide. This is a similar analysis of subgroups again showing that in every single subgroup analyzed, as shown here on the left-hand side, there is superior response rate of the T-DXd compared to the control arm of T-DM1, including in patients with brain metastases. Next slide. Here we are starting now to look at the specific group of patients who had brain metastases at baseline, the 82 patients with this brain metastasis.
We can see on the left-hand side here that, when we look at progression-free survival, Kaplan-Meier curves, we maintain the superiority of ENHERTU compared to T-DM1, again with a hazard ratio of 0.25. A very similar hazard ratio to the patients who have no brain metastases, with a hazard ratio of 0.30 shown on the right-hand side of the slide. Next slide is a depiction of response rates. This is very important to see that you can achieve actually complete remission, CRs, with T-DXd in patients who have brain metastases at baseline. Of course, I think many of you are aware that there's something called the blood-brain barrier in which large molecules, such as ADCs, were thought not to penetrate the blood-brain barrier.
We can see here in this slide that the blood-brain barrier does seem to be quite open and allows drug to pass through the blood-brain barrier into the tumor bed within the brain, resulting in complete remission that we see in more than a quarter of these patients. This is really great news for patients who have brain metastases like this, the patients who enrolled in the trial. It's because, as I think many of you are aware, that patients with brain metastases have a much worse prognosis compared to those patients who do not have metastases. Okay, now we're gonna go on to other studies. Next slide. In slide number 27. This is another study that we are currently conducting, a very important one called the DESTINY-Breast04 study.
This is a study in the patient population I alluded to earlier, HER2-low breast cancer patient population. These are the patients who express a small amount of HER2, but not enough to be considered to be HER2 positive. These are patients who are IHC 1+ or patients who are IHC 2+ but ISH negative. These are the patients who are considered to be HER2-low in this clinical trial. In this study, we are comparing ENHERTU against the investigator's choice. This clinical trial has fully enrolled, and we expect to see this data sometime in quarter four, fiscal year 2021, therefore in the early part of 2022. We of course hope to report to you the results of that when we have that data. Next study.
This slide shows a brand new study that we want to alert you to. This is on slide number 28. This is called DESTINY-Breast11. This is a new study with a neoadjuvant ENHERTU monotherapy or ENHERTU followed by THP, compared to the control standard of docetaxel and cyclophosphamide followed by THP, a neoadjuvant therapy in patients with high-risk HER2-positive early-stage breast cancer. This is currently enrolling. This is a fairly large study of about 600 patients. We are very interested in the outcome of this study, which we won't have for a few years. This is our first study of ENHERTU as a neoadjuvant therapy. You can see here that we have ambitions to replace chemotherapy with a single-agent ENHERTU. Next slide.
Next slide is yet another new study that we want to alert you to. This is called DESTINY-Lung04 study. This is targeting patients who are newly diagnosed with non-small cell lung cancer, who have mutations within the HER2 gene. This is a relatively small proportion of patients with lung cancer, about 2%-3% of the patients, but they appear to be uniquely sensitive to ENHERTU. Probably because they have a mutation in the HER2 gene. Here is our clinical trial design. We are comparing ENHERTU against the current standard of pembrolizumab plus platinum plus nab-paclitaxel. This is enrolling now, and we hope to see data from this study in the near future. Slide is slide number 30.
In the next couple of slides, I want to show you, I think the summary of our ENHERTU program that we have seen before. Really just to highlight for you the new trials that we have launched. They are the ones in white with the orange border. DESTINY Breast Eleven is one of those new trials that is joining all the ongoing clinical trials. I did want to make sure to remind you that, if there is no end to the bars to the right, it means that we have not yet announced the end date for that particular trial. Next slide. Here is more of the ENHERTU program in gastric cancer and non-small cell lung cancer.
You'll see here that 104 study, the HER2-mutated lung cancer patients population in the front line setting is our new study here. Okay, next slide. Just to complete the picture on slide number 32 is the colorectal program and also to again mention to you that we have multiple tumors, multiple other indications being studied in various phases in these ongoing clinical trials. Now we're going to move on to the Dato-DXd program. Next slide. Slide number 30. Dato-DXd. This is a ADC targeting the Trop-two antigen. This is another ADC that we are developing in partnership with our partner, AstraZeneca. Our vision for this compound is listed here. We want to establish Dato-DXd as a first and best-in-class Trop-two ADC for non-small cell lung cancer.
We will introduce Dato-DXd as a key monotherapy for patients with relapsed or refractory disease. We also want to very quickly follow that with a combination with immunotherapeutic agents, checkpoint agents, the first line of defense. Second vision is to establish Dato-DXd as the TROP2 ADC of choice for patients with breast cancer. I'll go over with you some new trials that we're considering in this regard. Of course, TROP2 is expressed in many cancers besides breast cancer and lung cancer. Of course, we are very interested in exploring and delivering ADCs in other cancer indications. Okay, next slide. Slide number 34, a few slides after that is slides from a recent presentation at San Antonio Breast Cancer Symposium. This is the data on the triple-negative breast cancer results from the phase I TROPION-PanTumor01 study.
Next slide. This is a slide that shows the study design. You'll see that we have four cohorts in the study: non-small cell lung cancer, triple-negative breast cancer, hormone receptor-positive HER2-negative breast cancer, and other tumor types. For today, we're just focusing on the TNBC cohort. Next slide. You'll see that there are 44 patients in the cohort, divided among U.S. and Japan. That these are the patients who had multiple relapses, including a few patients who had brain metastases. Very important to note here that there were 13 patients who had previously been treated with ADC, including about 10 patients who had been previously treated with TROP2 ADC from another company called Trodelvy. Next slide. These are the waterfall plots of the anti-tumor responses.
You'll see that the response rate here is 34%, which is quite good. You'll see the ones in asterisk are the ones in the patients who had prior treatment with Trodelvy. You can see that even in those patients, those 10 patients, there were responses seen in 3 out of the 10 patients, approximately the same proportion as the overall response we've seen in the entire data set. Even those patients who were previously treated. Now this slide shows the anti-tumor responses among the patients who were not previously treated with either one of the ADCs. Here now we can see that the response rate jumps to 52%.
That's very interesting because of the observation that there's yet another Trop ADC out there who has reported their response rate in patients previously untreated or without any prior exposure to Topo1, IRBC, BC. At least based on a cross trial comparison, which is always not a, it's always an interesting one. The percentage of 52% is a larger number than what was previously reported in the literature. Next slide. Okay, next slide shows the spider plot again showing that there is not just responses, but the responses are durable. See that the patients shown with these dark blue lines that they have continued ongoing responses. Really quite promising based on this early follow-up data.
This is a summary of the safety data showing that we're seeing a grade 3 treatment-emergent AEs at a rate of 23%. I think it's very important and very interesting to mention that the most common AEs were nausea, vomiting, and various other. So far, no cases adjudicated as drug-related ILD in this triple-negative breast cancer patient population. Next slide. Okay, in the next few slides, I want to alert you to some new studies. TROPION-Breast01 is one study like this. This is a study of Dato-DXd in patients who are hormone receptor-positive, HER2-negative metastatic breast cancer in second or third line. We are comparing Dato-DXd versus treatment of choice. This is a 1-to-1 study design with a sample size of 700.
It's a very important study in this patient population to include the metastatic hormone receptor-positive breast cancer. Next slide. The next slide is another new one called 108 study. A very important study because this is for patients who are previously untreated but diagnosed with non-small cell lung cancer without actionable genomic alterations. Currently, our standard of care in this patient population is pembrolizumab monotherapy. Our clinical trial design is to compare that standard, pembrolizumab, versus a combination of pembrolizumab plus Dato-DXd. This is enrolling now, and it's a very exciting study, and we hope to be able to report on the findings in the near future. Okay, the next couple of slides is a summary of the entire Dato-DXd program.
Here, you can see that we have a lot of clinical trials going on within Dato-DXd, including the one in the white box. This is the 108 study that I just mentioned to you previously. Next slide. Next slide. That's slide number 45, is a rather complicated slide. This is a summary of the entire breast cancer program between ENHERTU and Dato-DXd. You can see the ENHERTU clinical trials in this kind of orange box and the Dato-DXd blue. You can see how they fit between the ENHERTU and the Dato-DXd. I hope it's apparent to you that we are trying to cover as many patient segments as possible in breast cancer between ENHERTU and Dato-DXd because we believe that both of these agents are quite active in breast cancer.
Whether it's HER2-positive patients or hormone receptor-positive patients or triple-negative breast population, including this fairly large category of this HER2-low patient population. That is a combination of some of the patients who are hormone receptor-positive and some patients which are. Next slide, on slide number 46 is yet another ADC program that we have called the HER3-DXd. This is our ADC that is not partnered with AstraZeneca. This is our own ADC that we are developing ourselves. The vision for this program, first is to establish HER3-DXd as monotherapy standard of care for EGFR mutated non-small cell lung cancer patients post the frontline EGFR TKI, such as osimertinib. Of course, we want to expand this use of this HER3-DXd in combination with EGFR TKIs, which really aligns with the...
The reason for this is that we have, as many of you are aware, we have obtained very good data with HER3-DXd in this patient population, EGFR-mutated non-small cell lung cancer. As a second part of this vision, we also want to study and introduce HER3-DXd as monotherapy or a combination treatment for HER3-expressing breast cancers. Finally, as a third part of vision, we want to expand HER3-DXd beyond the non-small cell lung cancer with EGFR mutations and also explore opportunities across other HER3-expressing tumors besides breast cancer and lung cancer. The next slide is just a very brief summary of where we stand with the HER3 program, including the ones in breast cancer and non-small cell lung cancer. Next slide.
Next slide is a really complicated diagram, I suppose, in which we try to show how the three programs fit in the world of lung cancer. You can see that we have so far three active agents in HER2, Dato-DXd, and HER3-DXd in lung cancer. This is how we have divided the patient populations with lung cancer so that we can cover all these patients with the three ADCs we have. We have non-small cell lung cancer patients divided according to whether or not they have Actionable Genomic Alterations, AGAs. For the most part, we have more of a focus on the patients with AGAs with HER3-DXd and in HER2. Let me see.
For those patients without the AGAs, you can see that there's a preponderance of TROPION studies with the Dato-DXd program. We are very, of course, very interested in learning about the outcome of many of these registration trials that we have going on at the moment. Okay, that completes the three major ADCs we have. For the next couple of slides, I'm going to go through with you what we call Rising Stars. Next slide. This is one of these Rising Stars. It's called DS-7300. This is a DXd ADC based on the original DXd ADC technology, but the target is a little bit different. The target is something called B7-H3 antigen.
This is a target that is expressed in a fairly wide range of tumors and with a preponderance of a preferential expression of B7-H3 in tumors as opposed to normal cells. The slide you're seeing here is a waterfall plot that was shown at a recent conference indicating the wide range of tumor shrinkage we are seeing in clinical trials so far. Next slide. That shows that we so far have enough data to understand that we are seeing a definite clinical signal in three tumor types so far: esophageal cancer, castration-resistant prostate cancer, and small cell lung cancer. For these three diseases, we are very actively considering what is our next clinical trial program, what are the next steps, and what are the paths to registration for DS-7300.
It doesn't mean that this is the only three histologies that we'll be studying. There are many more cancer types yet to be studied in the 7300 program. I want very much to mention that B7-H3 is widely expressed in many tumor types, and we are very excited to learn and explore what other types are known to be responsive to 7300. We'll have to wait for that. Next slide is yet another Rising Star, DS-6000. This is a ADC directed against a protein called cadherin 6, CDH6. This is expressed in various tumors, including renal cell carcinoma and also ovarian cancer. We are completing the dose escalation cohort right now. Already during the dose escalation cohort, we are seeing very good efficacy signal in both renal cell carcinoma and ovarian cancer.
These are very exciting and offers an opportunity for us to study further these two diseases, these two cancers, and hopefully that we can help some of the patients with renal cell cancer or ovarian cancer. Okay, next slide. In the next slide, at least a few slides, we're going to go through with you what we call the next pillars beyond ADCs. Next slide. This is slide number 53. When I say the next pillars, what we're talking about is what is shown on this slide in the hatched blue part at the top of the curve there. We can see that the three ADCs will support the company for the time being. They...
It's this new pillars, what's called, also called here the Alpha program, that will include not just the Rising Stars that you just saw, the two ADCs, DS-7300 and DS-6000, but also the next pillars. What does these next pillars look like? Next slide. Next slide is a summary of what these next pillars look like. I won't have enough time to go through every single one of them, but I want to highlight for you that many of these, maybe all of these, represent what I would consider to be innovations. Technology innovations, scientific innovations that we are trying to bring to address the other medical needs. For example, we spoke from left to right, we spoke already about the DS-7300, and then these DS-6000 new Rising Star ADCs.
In addition to those, we have many, many new programs. The anti-GARP antibody. This is another new immunotherapy target. This is, I believe, first in human or one of the first that, in clinical trial of immeta. The darker blue are non-cancer programs targeting diseases like pseudoxanthoma elasticum, fibrodysplasia ossificans progressiva, and systemic lupus erythematosus. These are part of our specialty medicine program in which we have developed highly targeted agents against a known pathogenic target in these diseases, and we're very hopeful to be able to help patients with these diseases. In the phase II program, we do have some new compounds, 3201, which I'll get to a little bit later, as well as, our vaccine program. This is a Japan-only internal program for COVID-19 using our own RNA vaccine and our own delivery technology.
Finally, way to the left, I mean, this is way to the right. We do have launched a new program called DELYTACT. This is a brand new drug. This is an oncolytic virus drug. I believe this is probably the first or one of the first oncolytic virus therapy ever approved for any cancer. We are the group now for malignant glioblastoma. This is really an innovative therapeutic regimen that we implemented moving forward. It's very nice and very proud of this technology advance. We're doing this really to address our innovative ways to address unmet medical needs and taking advantage of our unique strength in modalities that we'll be hearing about. Next slide is a little bit more on one of these next pillars, the DS-3201. It's called valemetostat.
This is a dual EZH 1 and 2 inhibitor. It overcomes the weakness of the EZH 1 only inhibitor because there's a potential that the EZH 1 expression could overcome the suppression of EZH 2. By inhibiting both, we may be able to get a better efficacy. So far what is really very interesting is that we are seeing activity in both T- and B-cell lymphomas, which makes this agent quite unique in the world of lymphoma, where vast majority of agents are active in only one or the other, but not both in MT. Right now, here's where we stand with this program. We have completed a registration study in adult T-cell leukemia/lymphoma, and we are about to file an NDA in Japan for this disease in December 2021.
We also have an ongoing registration phase II trial in peripheral T-cell lymphoma, a very bad disease with very bad prognosis. We have an accelerated designation based on some early data in PTCL. From a patient number standpoint, very important to mention that we have ongoing right now a B-cell lymphoma program in collaboration with the French cooperative group, LYSA, in which we are studying many different types of B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma. We are again seeing some very promising early signals in B-cell lymphoma. This is good. Next slide. A couple additional new programs other than cancer right now. This one is for systemic lupus erythematosus and vasculitis.
This is an anti-TLR7 antibody targeting, we think, is a very important target, and that by inhibition of the TLR7, we hope to be able to reduce the activity of this cytokine and hope to benefit these patients. Next slide is a study that we just very recently completed and obtained results with, quizartinib. This is a targeted agent against a FLT3 target. We recently reported that in this clinical trial called QuANTUM-First, we met the primary endpoint of overall survival. The results will be presented in a conference next year, but we are actively planning a global submission and launch plans are underway.
Yeah.
Okay. Next. Slide 58 and 59. We want to go through with you in the next few slides what we are doing in our research program. We're going into the preclinical research program. The next slide is slide number 59. Here is. I think you saw this slide earlier in the presentation. I think it's very important to recognize that these three components, human resources, corporate culture, and core technologies, form the basis for our strength in science and technology. You have already seen one product of this research program, the DXd ADC technology, which we think is one of the best, if not the best ADC technology in pharmaceutical industry today. Why were we able to to grow such great technology internally?
It's because we have these three combination that I think really are essential to promoting innovation in research. Next slide is a summary of our research program. We want to bring our innovations to meet unmet medical needs. We're going to have a research focus to maintain competitiveness in the global pharma arena. We have a comprehensive and continuous review in both oncology specialty medicine and specialty medicine research programs, including a lot of external input from academic investigators. We want to emphasize here that we are not doing. We don't want to be doing everything. We are really focusing on what we think are our own scientific areas of strength, and they're listed here. One is our ADC technology. You also will be seeing a little later our wide range of modalities and technologies at the moment.
I also want to mention to you that we provide our researchers with quite a bit of scientific freedom at the discovery stage with a close access of these researchers to product expertise to understand unmet medical needs. Slide number 61 is just one example of how we are utilizing our scientific strengths in ADCs. You are familiar now with our DXd ADC technology that has given rise to, so far, seven ADC programs. We are also actively working on what we consider to be next generation ADC, including one that is already named here, the DS-9606 program. This is a next generation because the payload is a little bit different.
We have what we call new concept ADCs, in which the entire thinking about ADCs and linkers and payloads is really refocused and reformulated to address biological targets. You can see that there's a whole lot of evolution of our original ADC technology into next generation and new concepts. Okay. Now with next slide. Starting with the next slide, I'm going to turn over the presentation to Dr. Takahashi, who will go over with you our multi-modality strategy.
Thank you, Ken. I'm Takahashi, the General Manager of the Research Division. As Ken has just mentioned, following on from DXd ADC, I will introduce some of the modalities generated from our science technology, which is Daiichi Sankyo's strength, and the points we are focusing on today. For the past 10 years, in addition to small molecule drug discovery, we have also developed our own technology for drug discovery modality itself, such as antibody drugs and nucleic acid drugs. Currently, as shown here, we have various modalities such as antibodies, ADCs, next-generation medical chemistry of TPDs and peptides, nucleic acid drugs, and bispecific antibodies.
Until 10 years ago, there was a strong tendency to attack one target or one type of modality. Now we have adopted a multi-modality strategy that puts multiple modalities in the company into one target at once.
While small molecule drug discovery is the most excellent modality in terms of convenience, such as oral administration and COGS, it takes a certain time to separate it from any side effects. On the other hand, antibodies and ADCs can be expected to have high safety and high specificity. On the other hand, initial investments such as manufacturing equipment is required. Our mission is to deliver innovative medicines to patients faster. To save time, we prioritize the creation of candidates with multiple modalities in the early stages of research.
On the other hand, what I learned from DXd-ADC is that once it is made into a platform, knowledge of pharmacology, synthetic chemistry, or regulatory science can be shared with hardware aspects such as manufacturing equipment. We are looking at multiple ongoing themes within the company from a bird's eye view to identify the next growth driver following DXd-ADC.
I'd like to introduce the modality that can be a growth driver, though it is part of it. Please go to slide 63. The first is about the LNP messenger RNA vaccine. Regarding this technology, in fact, we have been paying attention to this even before the COVID-19 pandemic struck the world, and we have been advancing several themes. This is the reason why we were able to respond quickly this time. The competitiveness of our technology includes the cationic lipids that make up lipid nanoparticles selected from the viewpoint of safety and a drug efficacy that can even activate cellular immunity together with humoral immunity.
Also, regarding the DS-5670, the messenger RNA that is only for receptor binding domain instead of the entire spike protein is included this time. We are aiming for higher neutralizing antibody production by including only the domain involved in infection.
The point of this technology is that you can easily create a new vaccine simply by changing the sequence of the messenger RNA to be put inside. Therefore, as soon as the pathogen gene sequence of emerging infectious disease is identified, it is possible to make a mock-up by using the existing manufacturing equipment and quality control know-how as it is. In addition, since antigen proteins are expressed in the human body, they do not require large-scale manufacturing equipment, and the quality control and the biosafety level control are much easier than before. Currently, we are conducting research on multiple virus vaccines other than COVID-19. Regarding COVID-19, we are participating in the vaccine development support program supported by AMED. Please go to slide 64. Next, I'd like to introduce the siRNA platform.
siRNA is a method of suppressing the production of a pathogenic protein producing messenger RNA in the body by decomposing it. Attempts have been made to discover siRNA for a long time, but due to problems such as sustainability of drug efficacy and organ specificity, it has been difficult to produce a commercial product after patisiran sodium. In order to overcome this problem, we have combined our proprietary 2'-O-methyl RNA and DNA to prolong blood retention. Although I cannot discuss the details this time, by conjugating a specific ligand, we have a feeling of achieving various organ specificities.
This modality can also be mocked up, and multiple research themes are currently underway. Slide 65, please. Finally, regarding gene therapy, there is no doubt that gene therapy is a modality that can be expected to have epoch-making effects that cannot be achieved with conventional small molecule drugs and antibody drugs.
We want to improve our technical capabilities and increase the success rate of clinical trials by first entering the field of rare diseases that require high efficacy and launching products. Beyond the manufacturing capacity backed by our technological foundation, we want to expand to serious non-hereditary general diseases and provide a transformation of SLC. The disease areas include central nervous system and retinal diseases which have high unmet medical needs. For this reason, in addition to Ultragenyx this year, we have also partnered with ViGeneron, which has strength in ophthalmology as well as with LogicBio Therapeutics, which can possibly resolve the problem with gene therapy of reduced efficacy with growth. Please move to slide 66. On the other hand, I'd like to introduce the status of our alliance with Ultragenyx, which was signed in March 2020.
We, Daiichi Sankyo, unfortunately have been behind in the development of antibody drugs and decided to partner with Ultragenyx because we thought that it was essential to introduce excellent manufacturing technology from an early stage of gene therapy. Initially, we were planning a technical transfer on-site, but as you know, we could not go to the United States due to the situation of COVID-19. As a countermeasure, we tried online virtual transfer.
Fortunately, by last month we achieved the same level of vector production capacity as Ultragenyx for both the triple transfection method using HEK293 cells and HeLa cells stable expression strain, which is one of Ultragenyx competitiveness. We have achieved the goal of technology transfer. In the future, we will expand this technology to multiple in-house projects aiming to manufacture investigational drugs by the mid-2020s as targeted. Now I will hand it back to Ken.
Okay, thank you very much. I have 2 more slides then we'll finish up. We've been talking so far about mostly science and technology. In the next two slide, next slide is slide 68. I'm going to tell you about what we are doing internally to transform our R&D organization to something that is fitting of a global pharmaceutical company. We know already that our DXd-ADC technology is producing world-class drugs, and now we are creating an organization that can really, truly support the development of these world-class drugs. Previously, many of you might be aware that our development organization especially were divided into regional teams. One located in Tokyo and another one located in New Jersey in the States.
There were a lot of multiple layers of decision-making resulting in inefficiency and a lot of redundancy in resources and changes. We are creating now a unified global R&D organization with a highly simplified governance system and more empowerment of individual study teams and asset teams to make decisions. We want to make a streamlined, scalable, and sustainable program. Next slide. We especially want to enhance our capabilities. By capabilities, what I mean is capabilities to conduct global drug development. We see in research that our especially our oncology research platform is very solid. Our ADC technology is first class and will really continue to be very productive in the years to come.
You already heard today that we have many other unique scientific strength in both oncology and specialty medicine, including a lot of applications of therapeutic modalities far beyond traditional small molecules and antibody conjugates. We also have in place now what we call a precision medicine translational research and translational science programs that really get at to what is a drug doing in patients as opposed to cell line models and animal models. They really give us a lot of information about what is going on in patients. We are now creating new project teams, cross-functional teams that are going to be enabled and empowered to develop our drugs. We're really therefore enhancing our drug development capabilities.
Very important here to note that our vision here is to develop these capabilities regardless of the geographic location of the study teams and clinical teams are located. Whether it be Tokyo or U.S. or Europe, we are going to be creating global capabilities everywhere and anywhere in the world. Okay, so with this, I want to close the presentation portion of the meeting and go to the Q&A session.
Now we'd like to move on to a Q&A session. First, Mr. Yamaguchi from Citigroup Securities, please.
Hi. Good morning. Can you hear me? Okay, thank you. Quickly first on ENHERTU, several questions on ENHERTU first of all. Page 19, you show the highlight of a basic strategy of ENHERTU. You already cover almost all the HER2-positive breast cancer. As far as the HER2-low is concerned, of course, we are trying to get the DB-04 and DB-06, but there are the wide open space on the first line and also neoadjuvant. As a, of course, open and natural strategy, if DB-04, DB-06 works, it does make sense to go for all the first line and the neoadjuvant on HER2-low in the near future. Thank you. That's the first question.
I thought that was a comment rather than a question. I agree absolutely with your comment that if DESTINY-Breast04 and DESTINY-Breast06 give good data, then we are certainly going into early therapy in the HER2-low patient population. I am in complete agreement with you.
Thank you. The second quick question on the. You talk about the brain mets kind of subgroup study on DB three this time. But also you are saying that it is a stable brain mets rather than active brain mets. I understand it's more of a marketing side of our strategy, but your competitor is always trying to get share on the brain mets patients. So is this state DB three subgroup data good enough to battle this segment or you already have to show the active brain mets to compete directly on this front as far as evidence is concerned? Thank you.
Well, this is a very important question, and the patient population that we studied are basically patients who had what we call stable brain metastases, which are very different, like from active brain metastases.
Mm-hmm.
It really means that patients have had recent treatment, typically radiation therapy, and have stability of the brain metastases. At the same time, I do want to emphasize this observation that we observe complete remissions in the brain metastases.
Yes.
in many patients. That, I have to say, that's kind of a remarkable observation knowing that we're dealing with a very large molecule ADCs. Now I'm going to speculate really here because we don't have direct data, but I'm going to speculate that there is enough permeability in a broad brain area that allow these large molecule ADCs to get into the brain and eliminate the tumor cells.
Okay. Finally, it's not in your presentation, but it was the on the sub-analysis by Gustave Roussy from France, from Paris, which is called the DAISY trial. I don't want to detail, but there are some comments from the investment committee that DAISY trial, including HER2-low, the PFS is rather low compared to what you have been done in the past. Can you give me the quick comment on how you see DAISY studies given their low PFS? It sounds like patient condition might be a little bit different from your control study as well. If you make a comment, thank you very much for that.
I guess I can only say that at the moment that we will be looking at all the data in this patient population and really make data-driven decisions. You know, there's all kinds of data coming in in this patient population, so we're very anxiously awaiting collective data and collective wisdom on how to think about this. I don't know. Gilles, would you like to add any additional comments?
Thank you, Ken. The DAISY trial that you are mentioning, Yamaguchi-san, is a study that is run by Gustave Roussy and Unicancer trial France. It includes breast cancer patients that are very advanced and that have HER2-low and HER2-zero as well. HER2-zero as seen on IHC. What they reported at San Antonio is actually that the drug has activity not only in HER2-low, but in a good number of patients with HER2-zero as well. I think that's important information that is coming out from this study. In terms of PFS, these patients indeed are very advanced. More follow-up are needed to be able to actually evaluate this entire population. I think the study is ongoing, and we'll get more results in the future about this study.
Thank you. This concludes my question. Thank you very much.
Next is Mr. Wakao from JPMorgan Securities . Please go ahead.
This is Wakao from JP Morgan. Hello, everyone. Can you hear me? Okay. I'd like to ask you about the sub-analysis of ENHERTU. Regarding the result of the sub-analysis of ENHERTU, the data for patients who received more than second line appears to be better than the data for patients who received zero to one line. What are your thoughts on this? I'd like to know over two line appears better than data of a patient who received zero to one line. In general, I think that patients with fewer lines of therapy have higher efficacy, and we are seeing this trend with T-DM1.
I guess I would say that, well, I mean, agreement with your statement that and also really fascinating this observation that this drug really appears to be active in every line of treatment. It's really a remarkable development.
Okay, thank you. Next question about TROPION-Breast01 study. I'd like to know the background to the launch of TROPION-Breast01 study. Is it correct to understand that you are moving ahead with the development, HR-positive or HER2-negative rather than triple-negative breast cancer? Also, I think you have not announced the data on HR-positive and HER2-negative. Do you have data on this study in your company? If so, what kind of data you have, and do you plan to announce it? Also, what is the development plan for triple-negative breast cancer for the approval application? Is there any possibility of filing an application with the data of the TROPION-PanTumor01? This is the last question.
Okay. I think there's a lot of what I would call the data not yet published or made public here in this Dato-DXd program. Yes, I think we recognize that the triple-negative breast cancer data that was publicly presented at San Antonio looks quite good. We're not ignoring that. We're actively working on our triple-negative breast cancer strategy. It's just that we have not yet announced it. You correctly pointed out that the TROPION-Breast01 study is a hormone receptor positive patient population, but we have announced that even though we have not actually presented any data, and it's in part at least on some data that we have already heard.
Some early looks seen in other clinical trials that really led us to think that this Breast 01 study merits us conducting. It's a kind of a mix of public data and non-public data. It's a little bit difficult for you, but just to mention that, we're very interested in both types of studies with Dato- DXd. Gil, any additional comment on this?
No. Just to remind everybody that this particular drug, we're thinking it's possibly best in class. We're in a very competitive area with another drug already on the market. The data that you're mentioning has not been presented, but we can assure you it will be presented probably in 2022 at some point at one of the major medical meetings.
Okay. Thank you. Last question from me. About next generation ADC, can I assume DS-9606 enter phase III in next year? Also, could you tell us about the strategy for targeting antigens and their cancer types, indication for the next generation ADC? Will you be targeting antigens and cancer types that are different from the first generation ADCs, or will there be some overlaps?
Let's see. For the next generation ADCs, I don't think we have made any announcements, so I don't want to disclose too much except to say that these are very important scientifically validated targets as well as scientifically validated extremely interesting payloads.
Okay. Thank you. That's it from me.
Okay.
Next, Mr. Muraoka from Morgan Stanley Securities, please. Okay. Please allow me to speak in Japanese. I'd like to hear about your philosophy behind DESTINY-Breast04 study once again. I think this is a PFS study. If the results are good, you can file your submission just based on PFS data. Is my interpretation correct? Have you mostly reached agreement with FDA on that? Again, with regards to DESTINY-Breast04 study, I wonder which page it was. On page 19, I'd like to know the number of patients. Among the HER2-low patient population, how many patients in the first-line segment? How many patients in the second-line and the third-line settings? If you have information by region, like U.S., for example, that would be great. I'd like to know the number of patients in each segment.
Okay. Just to comment on the DESTINY-Breast04 studies. It is intended to be a registration study. It is for PFS as the primary endpoint. The study design has been discussed with various regulatory agencies, including the FDA. In terms of patient numbers, I have to say, I'm not the epidemiologist here or the commercial people. So I don't know the exact numbers. I can only say that it's a fairly large number of patients. I don't know. Gilles, do you have any numbers that you know?
Unfortunately, Ken, I don't have the numbers. As you mentioned, this is a fairly large patient population. Everybody understands, HER2-positive is about 20% of the entire breast cancer population. HER2-low would be probably around, I would estimate at 60%-65% potentially of the breast cancer population. A significant number.
As for DESTINY-Breast04 study, there is no need to wait for OS data in filing the submission. Is my understanding correct?
I think that's correct that the primary endpoint is the key endpoint. The other key secondary endpoints that are listed on the slide in that DESTINY-Breast04 study are key important secondary endpoints. The important one is the primary endpoint.
It is on slide number 27.
Understood. Thank you. I understand this is a little bit out of scope for this R&D Day meeting today, but I appreciate your comments on your litigation with Seagen. The schedule has been shifted to the January-March period according to Seagen. Are you fine with this sequence of events? I am curious, timing-wise, which do you think is going to be earlier, the timing of the results of arbitration with Seagen or the timing of DB-04 study results becoming available? Do you have any idea? Manabe-san, would you like to respond. Seagen has disclosed the timing of arbitration results. Our understanding is almost the same. We cannot say clearly here that it is really going to be the case. We cannot say here as of today which timing will be earlier. Understood. That's all from me. Thank you very much.
Next is Mr. Sakai from Credit Suisse. Please go ahead.
Yes, please go ahead.
Oh, good. Yeah. Two questions, please. Just coming back to DB-04 results. What do we really expect? What we should expect or what you're expecting in terms of the PFS? Because DB-03 data was really too good to be true, right? You set your bar already high. Even you say you're gonna meet with the endpoint, probably some of us facing that DB-04 data may not be good enough unless you meet with the DB-03 standard or even exceed all three data. That's excellent. You know, the data coming soon next year. We gotta be prepared for positive surprise and negative surprise. What would you say at this moment, what we should really expect?
You know, it's difficult to predict exactly what the data is going to look like. I have to say that the results of the DESTINY-Breast03 study surprised many of us at how positive that data was. Now, whether that magnitude of superiority in HER2-positive patients, how is that gonna translate into the HER2-low patient population? You know, I have to say that we all have our hopes and guesses, but ultimately we're not gonna know until we see the actual clinical trial data. I do believe, I think I did, as you suggested, that the results of the DESTINY-Breast03 data allows us to think that the likelihood of a positive study with DESTINY-Breast04 has increased quite a bit based on the 03 study.
Okay.
Exactly what you think it'll show, I think we'll have to wait and see.
Yes. That's what I expected. How do you plan to release the result for all four? It's just by official release or you say you're gonna just say top line result? Good or bad?
Yes. Typically, once we have some data, we will issue a press release saying that it's positive data with the details of the data to be presented at our scientific conference later in the year.
Right. Thank you. Just a last question. I'm getting quite impressed with your, let's say, capability of finding new targets. Now, this probably has something to do with your translational research. like this time you said you are very optimistic with the cadherin-6, for example. This may not be a question, but do we have an opportunity to see your basic translational research progress? How are you coming up with all these new targets? Because with ADCs, we could find the target. Could easily, well, I shouldn't say easily, but practically, make the technology available for new type of the basics, drugs, antibiotics. Am I understanding right?
Yes. I think you understand. Like, I think what you're suggesting is that this ADC technology can be applied to many, many diseases as long as we have the right targets. Yeah, I think that's a correct statement. I think I also agree with you that translational research could be a very important component of that target discovery and binder generation.
Oh, yeah. Yes. Okay. Yeah. I mean, then if you have opportunity to you know, present your translational research progress we'll be very much appreciative.
Of course.
That's my comment.
Okay. Perhaps we can do that in one of our next investor calls, and so we can see.
Thank you very much.
Next, Mr. Hashiguchi from Daiwa Securities, please. Hashiguchi speaking.
Thank you for your time. Today, you also talked about your strategy for sustainable growth beyond DXd-ADC. In order to further reinforce this strategy, what about the need to pay a large amount of money to a third party to acquire assets? I'd like to know the opinion of the research function on this point. With the three ADCs, there's a possibility that your operating cash flow will increase substantially more than before. Is it going to be fine to use the increase in operating cash flow mainly in areas other than the research functions, such as returns to shareholders? If the research function also requires huge investments, what kinds of assets are still missing at Daiichi Sankyo where you would need acquisitions in the future?
I think this can change a lot, particularly depending on how broadly and how deeply you're going to implement your multimodality strategy. I'd like to hear the opinions of the research function.
Well, maybe just if I could make a brief comment, and then I can turn it over to Takahashi. You know, I think that we can see that this ADC program at Daiichi Sankyo has been incredibly productive. Investments in that program has generated so much into our platform. But yes, there is, of course, an interesting need to be thinking in the future beyond ADC. That's where this modality strategy comes in. Takahashi.
Takahashi would like to respond. Acquiring pipelines or ventures are not within the scope of our responsibilities, so I cannot say anything in my capacity. Regarding the future potential of multimodalities, through our open innovation activities, we are also engaging in activities to apply our own modalities to seeds from academia. In that sense, I'd like to focus on activities to generate next pipelines by matching with seeds from academia in Japan and abroad. Did I answer your question? In other words, you think major acquisition will not be necessary in implementing your multimodality strategy, correct? Correct. That's our view as of now. Okay.
Understood. That's all from me. Thank you very much.
Thank you very much. We are running over, so we'd like to close Daiichi Sankyo's R&D Day meeting here. Thank you very much for joining today.