Thanks for joining us for the Oncology Strategic Update. We're looking forward to taking a deeper dive into our oncology pipeline. We have about a 40-minute presentation for you guys today, and the remainder of the time will be used for Q&A. We are hoping that the Q&A is very interactive, so if you have a question, please ask it through the Zoom platform by raising your hand with the raise hand function at the bottom of the screen. Today, joining us is Teresa Bitetti, President of Global Oncology Business Unit, and Chris Arendt, Head of Oncology Therapeutic Area. We also have Andy Plump, President of Research and Development, and some other members from the oncology team that will be joining for the Q&A session. Before we start, I'd like to remind everyone that we'll be discussing forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may vary materially from those disclosed today. The factors that could cause our actual results to differ materially are discussed in our most recent Form 20-F and in our SEC filing. Please also refer to the important information on page two of the presentation today. Now I'll hand it over to Teresa to get us started. Teresa. Great. Thank you, Elizabeth. Good morning, good afternoon, good evening. Thank you for joining us here. We are delighted to have this opportunity to share with you an update on Takeda Oncology. Now, our goal over the next 30 or 40 minutes is to give a little background on our mission, our focus, and our structure, discuss the strong growth in our current in-line portfolio, share excitement over our two near-term launches with mobocertinib and pevonedistat, and give you some flavor as to why these medicines are so exciting, and tee up the fantastic future we have with our unique and differentiated pipeline. Now, the next slide. We aspire to cure cancer. That is our mission. It is an audacious one, but one that we remain dedicated, passionate, and focused on. We have a strong foundation in heme malignancies, and we've demonstrated step changes in that field. And I've also entered the space of solid tumors. There is so much scientific innovation happening, and we're focusing our efforts on harnessing the power of the innate immune system in the battle with cancer. And we source our innovation both internally from our own labs as well as externally with a strong partnership model collaborating with both academia and biotech. Now, as we move to Slide 5, for those of you not familiar with our model, Takeda Oncology is a distinct and separate global business unit as opposed to the rest of Takeda, where all of the other therapeutic areas are organized regionally. Both of our commercial and oncology R&D operations are based in Cambridge, which, of course, is the epicenter of biotech, and indeed, we're housed in the same building. This allows for real-time interaction and collaboration. So why is that important? We need to move fast. We need to keep pace with the speed of science, with the rapid-fire changes that are happening in the treatment and competitive landscape, the high unmet needs, the regulatory pathways that are becoming more and more innovative. It's important that we remain agile. Our approach is working, as demonstrated by the growth of our in-line portfolio and the uniqueness of our robust pipeline. Moving to the next slide, here's a visual of the results from our approach. What you're looking at here is a mapping of our global oncology revenue. First takeaway here is that we have a broad global footprint. The second is that we have a strong portfolio of in-line medicines that are addressing high unmet need, as represented by the numbers and the patients that those numbers represent. Finally, these numbers are reflective of strong commercial execution. Now, if we go to the next slide, here you're looking at the entire global oncology portfolio. The stack bars on the left contain two medicines that are post-patent expiry. But I would draw your attention to the four medicines called out on the right, where we are actively promoting. Keep in mind that these have been approved and available for several years. To see this type of long-term performance by these four medicines is impressive. It speaks to strong commercial execution and, quite frankly, the unmet need that these medicines are addressing. So over the next two slides, I'd like to highlight two of these medicines. So on the next slide, to start with ALUNBRIG. So this is our medicine for patients with non-small cell lung cancer who are ALK+, which represents approximately 3% to 5% of the entire lung cancer population. Now, ALUNBRIG was approved for use in the second line, and in April of 2020, we received approval for a first-line indication. So this is very exciting for patients, particularly patients who have CNS metastases, where we have strong efficacy and tolerability. We launched this medicine, the first-line indication, last year in the early days of the pandemic. And despite that, we continue to grow, new patient share, and have achieved reimbursement in all of the major EU markets, as well as Japan. Now, if we look at ICLUSIG here on slide nine, it was a reminder Iclusig is a highly effective agent for chronic phase CML. Takeda promotes this drug in the U.S., and we have several partners promoting Iclusig outside the U.S. We released the final analysis of the OPTIC study this past weekend during an oral presentation at ASCO. It was this clinical study that formed the basis of our recent sNDA approval in December, which expanded the indication to include not only T315I patients, but move usage to after two lines of therapy. By way of background, the T315I mutation occurs in over a third of patients taking second-generation TKIs. Of course, that emergence increases with each line of therapy. This mutation renders those second-gen TKIs ineffective. Iclusig really brings important value. We have also refined the recommended dosing schedule to be a response-based dosing, which results in better patient management. This is the only drug with the validated efficacy that specifically targets the T315I mutation, but also offers significant efficacy for patients with or without that mutation. ICLUSIG is a very effective drug, and it is gratifying to see specifically the strong uptake that we have seen in new patients share month over month since our launch in December. But we're not stopping there. ICLUSIG is an effective agent as well in Philadelphia positive ALL, where the occurrence of the T315I mutation is even higher, so roughly 40%-70% of patients after first-line treatment. ICLUSIG is currently indicated for first-line relapsers. We are conducting a phase III registration trial for first-line use called the PhALLCON study, and we look forward to sharing that data when it reads out. So more to come on ICLUSIG. So now, if we shift gears from our in-line portfolio, I'd like to focus your attention on our pipeline and specifically the two new medicines that we hope to bring to patients shortly. So Slide 11 to set the stage here. Mobocertinib is for EGFR lung cancer patients that have a very specific Exon 20 insertion mutation. These patients represent approximately 1%-2% of the overall lung population. Now, if you are unlucky enough to be one of those patients, standard treatments are not very effective. Overall survival is less than a year, response rates less than 15%. So these patients have been waiting for new treatments. And mobocertinib is one of the soon-to-be-launched treatments that will be the first and only oral therapy specifically designed to target Exon 20. So not only does that mean the patients have the ability to take a medicine in the comfort of their own home, but I would draw your attention to the data on the right, which Dr. Ramalingam shared at ASCO. The left bar is the median duration of response of 17.5 months. Those patients are getting deep and durable responses. On the right, mobocertinib has demonstrated median overall survival of two years. This population, not to be too hyperbolic, is outstanding. We're preparing for launch. We're ensuring there is knowledge of testing. At launch, we will be ready immediately to share the strength of our efficacy data and ensure physicians are knowledgeable in managing what is a well-characterized safety profile for EGFR agents and one that they're generally comfortable managing. We remain excited. More to come as we anticipate approval in October of this year. Now turning our attention to our second near-term potential launch, pevonedistat. Here, we're talking about high-risk MDS, which is a very tough-to-treat disease where there have been no new or novel agents for over a decade. Current treatment options are limited. Principally, hypermethylating agents such as azacitidine and outcomes remain poor, with the average survival of less than 15 months, so life is not easy for these patients. Cytopenia or low blood counts are a hallmark of these patients. And consequently, they suffer significant fatigue, bruising, infections, with many requiring hospitalization and many dependent upon transfusions. With pevonedistat, we have the opportunity to transform survival outcomes, extending survival and delaying transformation to AML with a safety profile similar to azacitidine alone. In our phase II trial, which was presented at the most recent ASH meeting, we saw encouraging results with 20 months median event-free survival as well as almost 24 months median overall survival. We are awaiting top-line results of our phase III PANTHER study, and we look forward to confirming in the first half of this year more positive data and ultimately sharing that at an upcoming medical congress. So now, if we go to the next slide here, on Slide 13, if we look beyond the two near-term launches that are highlighted at the top of this slide, we have a strong lineup of therapeutic candidates, which reflects our focus on the innate immune system. So we've bucketed these compounds into two categories. We've got the cold to hot and redirected immunity. What is striking about our pipeline is that all of these compounds are unique and differentiated. There's no me toos here. Each represents exciting scientific advances. And we are excited that for two of our compounds in the cold- to- hot bucket, TAK-981 and TAK-573, we anticipate proof of concept inflection points in this fiscal year. So to further elucidate our pipeline and why we're so excited about it, I am going to turn it over to Chris Arendt, who is the head of our oncology development here at Takeda. So over to you, Chris. Thank you very much, Teresa. Greetings to all of you who are joining us for this event from all across the world. It's a great pleasure to be here today and to unveil our emerging pipeline in oncology, which let me just get my video started here, which I think looks nothing like the later-stage portfolio that Teresa just highlighted earlier. This is a pipeline that seeks to catapult Takeda into a bold future by taking full advantage of emerging science and world-class partnerships to advance platforms that are focused on novel mechanisms of action. At the heart of this strategy is our aspiration to offer patients differentiated and durable cancer therapies that can transform their lives. Today, I'll update you on where we are in the clinic with a number of programs that we believe have this potential. Let's get started on the next slide. By contextualizing our strategy with a graphic, it's a graphic that depicts what we call the cancer immunity cycle. This is a paradigm for explaining how immune potentiation can drive tumor eradication, which you can see depicted there on the lower left, that explosion. Now, most of the action you see in this representation is driven, in fact, by T cells. And this is the space where most of the field is focused today. The PD-1 checkpoint therapies and the CAR T-cell therapies operate mostly in the box that you see on the right side of this cycle. And they've both shown us what is possible in terms of the potential of cancer immunotherapies, as well as what is not possible via the current generation of T cell-based approaches. At Takeda, we're thinking outside the box. In fact, as we click through this animation, what you can see is that we've been focusing on what is depicted in the center here, which is a whole other dimensionality of the immune response called innate immunity. The violet-blue colored cells that you see in the central region, those cells are intended to represent natural killer cells, macrophages, dendritic cells, and gamma delta T cells. They can be thought of as generals in the immune army because they have the power to orchestrate responses in this tumor microenvironment. They have the power to shape the magnitude of these responses and the power to shape their durability. This is a space where we are intensely focused as we tap into emerging science and as we explore platforms with the potential to define the next wave of totally new immunotherapies. This next slide breaks down where we're specifically focused with our emerging pipeline. Let me give you the key takeaways. We have two major areas of focus with the pipeline. On the left, you can see our cold- to- hot portfolio at the top. On the left side, this is all about pushing that cancer immunity cycle that I just showed you forward by heating up the immune response to achieve tumor eradication. You can see that we've listed a number of our innate immune-focused programs on the top. TAK-981, I'll tell you a little bit more about, as well as TAK-676. Teresa mentioned TAK-573. We also have some innovative checkpoint molecules in that portfolio. Underneath, a very exciting partnership with Turnstone on an oncolytic virus with three payloads, three immunologically potentiating payloads that have this same potential to shift that hostile tumor microenvironment into one that's immune permissive. On the right, it's all about modalities that direct or redirect immune cells to tumors and initiate their killing of the cancer cells. So here, we spotlighted a number of novel innate immune cell therapy platforms on the top that are followed below by cell engager platforms. And these are focused on cutting-edge approaches to unlock the potential of these modalities to address solid tumors. Today, I'm going to take you through a double click on a number of these programs, starting with some examples from our cold- to- hot portfolio. But first, what exactly do we mean when we say cold to hot? On the next slide, we have an illustration to illuminate this. You can think of a cold tumor on that first click as a car engine that's stalled in the winter. It's a situation where the cancer is outsmarting the immune system and keeping immunity in a dormant state. It has the upper hand. So through our novel therapeutic approaches that are directed at immune cells, what you can see is that we're seeking to overcome this suppression and fire up this engine, which is represented by those immune cells, the yellow cells that are lighting up. They're being awoken. And the ultimate intention here, as we click one more time, is that the cancer is no longer able to persist in a stealth mode, okay? And the upper hand is provided to the immune system, which leads to effective responses against the tumor. So this brings me to our first program snapshot on the next slide. This is focused on TAK-981. This is our first-in-class inhibitor of SUMOylation, which is a post-translational process that's attracting increasing interest. TAK-981 is an incredible molecule. And in fact, it was developed in Takeda's chemistry labs. And through it, we're learning a lot. What we're learning is that SUMOylation may be a master repressor of immune cell activation in certain cancer settings and specifically a repressor of type I interferons. We have quite a rich and compelling preclinical package that lends support to a number of different mechanistic hypotheses that focus on TAK-981's capacity to warm up tumor responses. This includes experiments that reveal its potential to enhance the activity of therapeutic antibodies, which is depicted on that left graphic, as well as its potential to synergize with T cell checkpoint inhibitors, as shown on the right, as it sets off that entire cancer immunity cycle that ultimately potentiates also that T cell immunity piece, so I showed you a moment ago a cartoon depiction of a tumor transitioning from that stalled engine, a cold one to hot, but on the next slide, let me share with you some actual clinical data that I think is much more satisfying, at least for me, than looking at a cartoon depiction of our hypothesis, and in fact, really thrilled to be sharing with you some data from an ongoing phase 0 study. It's data that we've never before released. It's a study, in this case, that is evaluating a head and neck tumor that's been microdosed with TAK-981 prior to its resection, which is then followed by these imaging evaluations shown on this slide. What you can see in the first two images is evidence that TAK-981 was successfully microinjected into that central region. You You can see circles. That's where it's accumulated at the highest level. That's what the first image tells us. The second image tells us that, in fact, we are successfully inhibiting the pathway. We're doing that most strongly in the region where there's the most TAK-981. Now, the next two images, they're really interesting because they start to build a case, a body of evidence that shows us that we're leading to something very interesting immunologically in response to this. The third image shows evidence that we're potentiating a chemoattractant. And the fourth image, the final one, shows us that effector cells are becoming enriched, activated effector cells in the region where there's more TAK-981. And this is exactly what we'd hope to see if, in fact, there's a warming up of this tumor microenvironment. So it's a very illuminating phase 0 study. It's challenging to get this level of information out of an early clinical phase I study. We've had this information from, in fact, the same platform in mice. But this is really helping to bolster our mechanistic hypothesis. And so with that, let me update you as we advance to the next slide on some of our ongoing clinical studies with this very exciting molecule, TAK-981. In addition to our single-agent dose escalation study in a diversity of tumors that's indicated at the top, we're also evaluating TAK-981 in relapsed refractory settings in combination with a variety of therapeutic antibodies, as informed by our preclinical studies that I mentioned, that stand to benefit from innate cell activation and this cold- to- hot tumor microenvironment conversion. Specifically listed first, rituximab, second, daratumumab, and then third, pembrolizumab. Of these three studies, it's the rituximab combination study that's been opened the longest. And so I'm very pleased to be able to share with you that we're encouraged by these data. We've seen evidence of patient benefit. We've achieved complete responses. We've achieved durable responses. And we've seen so far what appears to be a very favorable therapeutic index. So quite encouraging. We're also sharing a significant update on our preclinical dossier in a publication that's forthcoming in Science Translational Medicine. And we look forward to updating you further on our clinical results with TAK-981 as the program matures and as we advance towards some very important data inflections this year and early proof of concept selection of our recommended phase two dose as well. So let's move on now to a quick spotlight on our STING agonist programs. These focus on, in fact, another highly interesting pathway with the potential to also engage type I interferons to transform a cold and immunosuppressive tumor, which you can see on the left, to one that is immune potentiated, which we hypothesize can be achieved by activating the STING pathway. So STING is so named because, in fact, it is a stimulator of interferon genes. It functions to alert innate immune cells to activate a broad and deep immune response, which is depicted on the right. We're pleased to be advancing two approaches on STING that make use of, in fact, the same STING agonist molecule, which was also developed in our amazing Takeda Chemistry Labs. Like TAK-981, it is not an easy molecule to develop. On the next slide, let me take you through, in fact, a summary of our ongoing clinical study. At the top, what you can see is the studies with our intravenously infused STING agonist. This is known as TAK-676. It's currently undergoing dose escalation with and without anti-PD-1. We're now in the process of adding radiotherapy to this equation. We've also embarked on a phase 0 study with Presage's microdosing platform. This is the same platform that I just showed you for TAK-981 to understand, in this case, what chemotherapeutic combinations could have the most potential in a head and neck tumor microenvironment, so as for TAK-981, we're entering a very data-rich period for this program. It's going to generate a critical package towards the end of this fiscal year to guide further decisions around some of our expansion studies. Now, we have a great deal of conviction in the underlying biology around the STING pathway and in the power of the type I interferon fulcrum in the tumor microenvironment, and this forms the basis for our approaching STING as a platform opportunity, and with this, we have a second approach that's not far behind TAK-676. It's known as TAK-500. It's a novel antibody-targeted STING agonist that we are readying to enter the clinic in this fiscal year and that we hypothesize will have a differentiated profile with regard to its ability to elicit a cold to hot tumor microenvironment conversion in specific settings, allowing for potent anti-tumor responses. With that, let's turn our attention now to this other high-priority area of focus for Takeda Oncology on the next slide, which is our redirected immunity portfolio represented on the right here. This includes assets that, again, seek to program immune cells to directly attack tumors using either infused engineered cells, as you see on the top, or infused cell engaging biologics, as you see at the bottom, as the therapeutic modality. As you'll see on the next slide, over the past years, we've assembled a world-class network. It's a network that includes access to three novel cell platforms that leverage innate-like immune biology, which we hypothesize will have advantages for safe and convenient off-the-shelf cell therapies that ultimately aim to address solid tumors. Shown on the left, it's represented our most advanced innate cell platform, which is a cord blood-derived, cytokine-armored, natural killer cell-based approach that we are advancing with MD Anderson. In the center, our partners, Gamma Delta Therapeutics, have been developing a novel gamma delta T cell platform that is now set to enter the clinic. In fact, their first IND just cleared, and which we see as having unique advantages over T cell platforms. And then last but not least, shown on the right, through our CiRA partnership in Japan, we're advancing novel cell therapy concepts based on clonal induced pluripotent stem cells that are amenable to serial engineering and gene editing and have the potential to be manufactured at scale with additional ease and sort of comparability. So I wanted to emphasize that we are in cell therapies with a longer time horizon perspective. And on the next slide, it's captured that we are heavily invested in the development and delivery of next-generation allogeneic cell therapies. With this, our focus is on optimizing off-the-shelf cell therapy approaches that can reach a broader population of patients, both locally, for example, in community centers, and globally, and that can be administered upon demand and irrespective of the status of a given patient's immune cells, since we're not requiring that the individual patients contribute their cells to a manufacturing process. And this obviously has some considerable advantages, both from the delivery perspective and from the patient experience. Of course, it's not just about coming up with a better cell-based therapeutic. It's obviously also incredibly important to be able to manufacture these complex medicines, to be able to deliver them at scale, to be able to do that with speed and with quality. And as captured on the next slide, we're very pleased to have established cutting-edge manufacturing capabilities in our Cambridge hub. These capabilities are co-localized with our oncology teams. They're capabilities that are allowing us to supply our clinical trials with GMP batches, as well as with the capability to support commercial supply. And in fact, we've just broken ground on a massive commercial manufacturing facility. In fact, it's almost 40,000 sq ft. It's located in our Lexington, Massachusetts campus. And it's poised to deliver cell therapies globally. So let's take a moment and double-click into our cord blood natural killer cell platform. Our partnership with MD Anderson is foundational in allowing us to generate important insights into the development of innate cell-based therapies. The team of Dr. Rezvani has provided encouraging initial proof of concept for CD19-targeted, IL-15 armored, cord blood-derived NK cells, natural killer cells. Over the past year, in fact, in the midst of the COVID pandemic, our Takeda team took these notoriously difficult-to-freeze and thaw natural killer cells from cord blood and developed a robust cryoformulation process that serves as the basis for TAK-007, an off-the-shelf next-generation natural killer cell therapy. We have completed all IND-enabling experiments and hope to embark on the first clinical evaluation of TAK-007 in the coming months under our own IND. Provided that those clinical data are supportive, we would plan to embark on a registration-enabling study in fiscal year 2022. As we continue to pursue differentiated cell therapy platforms, I want to emphasize on the next slide that we're also paying attention to innovation in the cell engager space. We're very pleased to have recently taken a decision to acquire Maverick Therapeutics, who, with the support of Takeda's funding over the past years, have developed a novel scaffold called COBRA. It's a scaffold that seeks to unlock solid tumors to the power of immune cell engagers, something that has not been robustly possible to this time. And in fact, COBRA molecules are a first-in-class design. The molecules are half-life extended, which is represented by that pink domain on the right. And they are inactive until they reach a protease-enriched tumor microenvironment, which then cleaves that linker in the middle that's in blue and licenses the molecules to serve as incredibly potent T cell engagers in that specific domain where we most desire to have that activity to be localized. So let me briefly update you on our clinical efforts here on the next slide with the COBRAs. TAK-186, it is an EGFR-targeting COBRA molecule. It's the first COBRA to enter the clinic for evaluation across a number of EGFR-enriched cancers. And it's currently advancing successfully in dose escalation. Not far behind, TAK-186 is TAK-280. This is a COBRA that's designed against another difficult solid tumor target. It's a target called B7-H3. And it's a program that we hope to have enter the clinic in the second half of this fiscal year. And it's one that will benefit tremendously from the initial learnings around TAK-186. Now, as we continue to learn about the COBRA platform, our incredible Maverick team are continuing to innovate with additional exciting programs ongoing in preclinical development. And we look forward to sharing more of that when we can. So with that, let me wrap up by thanking you for joining us as we had the chance today to pull back the curtain on what we think is one of the most interesting oncology pipelines in industry in terms of its focus on promising areas of emerging science, including innate immunity, on compelling mechanisms of action with platform potential, and all of this across a diversity of cutting-edge modalities. On the horizon for the remainder of this fiscal year are a number of important inflections for our portfolio, including, of course, the pivotal readout of our PANTHER study for pevonedistat and the decision on our U.S. NDA filing for mobocertinib. Before closing and handing back to Teresa, I'd like to acknowledge our team members and all of our colleagues and collaborators across the world who share our inspiration around the potential of this innovative oncology portfolio to make a difference for patients. So with that, Teresa, let me hand it back to you so that we can wrap up and kick off our question and answer session. Awesome. Thank you. Thank you, Chris. So I think it's abundantly clear that we have an innovative and promising pipeline, lots of potential, and with near-term launches. So a couple of this. With the strong growth of our inline portfolio, where we've showcased and demonstrated strong commercial capabilities and a very strong and unique pipeline, we look forward to an exciting future at Takeda Oncology. In our last slide, just to close, we will continue to drive and follow the science and advance Takeda Oncology's position as a leader in the discovery, the development, and the delivery of innovative medicines as we continue to drive towards our ultimate goal of curing cancer. Thank you for your attention. Now, I'd like to open the lines for Q&A. For this portion of the session, Chris and I will be joined by our colleagues. We have Andy Plump, who is the president of our R&D here. We've got Dion Warren, who is the head of our U.S. oncology business, and Erkut Bahceci, who is the VP of our clinical development program. With that, I'll turn it over to Elizabeth. Thank you, Teresa. All right. We'll now open it up for Q&A. As a reminder, to ask a question, you'll use the raise hand function that's at the bottom of your screen. We will call on you to ask a question, and then we will open up your line. At that time, you can unmute yourself. Please state your name and your company and ask your question. So let's go to our first question. Thank you, everybody, for joining the Q&A session. We will take our first question from Wakao-san. I will open your line, and please go ahead and unmute yourself. Thank you. Hi. This is Wakao-san. I'm J.P. Morgan. Can you hear me? Thank you. So thank you for the question. So first, I'd like to know about STING. I'm interested in STING, not agonist. So there are some drugs in developing stage products. So I'd like to know the drug advantages or differences compared to other STINGs. I understand that the structure of STING varies by race. For example, this drug overcomes this point? This is the first question. Great. Thank you. Thank you for the question. We are excited about our STING program. So I'm going to turn that over to Chris to address that question. Thanks. I might have missed just the. I lost just the end of the audio, but I think I got the question, which was around whether we have activity across all of the STING variants. And I can address that. And if I didn't catch, if I missed anything, just let me know. So it's my pleasure. We're making a significant effort, as you, I think, saw from my presentation, around type I interferon as a critical fulcrum that has this potential to reprogram in a very favorable way immunity and its response to cancers and in a way that's different from the T cell checkpoints. In fact, type I interferon has been developed itself as a therapeutic and has achieved responses across a variety of tumors, but is limited by its therapeutic index. And one of the reasons we're very excited about STING is because of the data we've achieved preclinically around showing its remarkable capacity to be able to take quite a minimalistic dosing schedule to be able to just turn the tide on a tumor in a single-agent manner. And we can characterize a lot of that immune biology. And in fact, we're tracking a lot of it in our clinical studies. We're developing, as I mentioned, two different approaches on STING. It's different from where the field initially embarked around intratumorally administered STING agonists. So TAK-676 is being administered intravenously. It does activate all of the STING variants, which I think was one of your questions. But by virtue of its intravenous administration, we have the capacity to evaluate its activity in principle across all different tumor subtypes. And we're also distributing it in a way that is allowing it to reach multiple metastatic sites all in the same dosing regimen versus being restricted to having to figure out how to do intratumoral, how to sort of manage an intratumoral dosing therapeutic, which is quite variable, in fact, across different patients who have different tumor conditions. This is one last piece to capture, which is that dosing a very high level or a high local level of a STING agonist inside a tumor may not be desirable from a number of perspectives, in fact, including the potential to actually have adverse events on specific desirable immune populations like T cells. So we're very interested to see what an IV STING can bring. And as I said, all of that data and knowledge is being channeled into our highly innovative antibody drug conjugate STING agonist program. And we're hopeful that we can be the first to the clinic with that innovative mechanism. Okay. Thank you, I understand. I'm also interested in TAK-500. I'd like to know the detail of these drugs. So what are the target antibody parts in this drug? About this drug. So I understand this drug is ADC. So antibody part will attack some cells. This drug attacks ADC or cancer cells or something. So I'd like to know the detail of this drug. Thanks. So as I mentioned, we're close to being able to embark on our IND submission for this program. And at that time, we'd be in a position to share that level of detail with you. What I can tell you is that our preclinical package around this is giving us a number of critical insights. First of all, that we think we're able to really optimize that efficacy to safety aspect around STING agonists and really have what we think is going to be an improved margin, number one. Number two, that we're able to address a breadth of tumors, not be restricted to too narrow of a space. And also that we believe that we will be able to take advantage of a mechanism in the immuno-oncology space that's been of great interest to the field but has not yet been fully realized by any other therapeutic. And so that's a little bit of a teaser. And we'll be looking forward to being able to share with you more, including the identity of that antibody target as we file that IND. Okay. Thank you. And the last question about TAK-280. So I'm interested in this target, B7-H3. So I want to know the potential B7-H3 as a cancer target. This is the last question. Thank you. Well, thanks. As mentioned, it is what we've been focused on with the Maverick partnership and the COBRA platform is the kinds of solid tumor targets that are not available to many of the conventional therapeutic approaches with antibodies because of the fact that they're what are called dirty targets. Now, it's true that B7-H3 is being explored by others. It is, however, found on non-tumor tissues, and the design of the COBRA platform is really intended to optimize that killing and that potent T cell response to a tumor microenvironment, so we believe that we have a highly differentiated approach on this target. It's a target that, as you know, it's a very exciting one because of the breadth of solid tumors that it covers. And it's also, for that reason, a wonderful opportunity to learn about the COBRA scaffold and its inducibility in these different tumor settings and to take those learnings back to further capitalize on as the platform evolves. Okay. Thank you. Thank you, San. Thank you. Thank you very much. Going forward, if you could ask all of your questions at once, that would be very much appreciated. And we'll go through them one by one. Next, we'd like to go to Yamaguchi-san. Yamaguchi-san, I will open your line. And please go ahead. Hello. Hi. Can you hear me? Hi. We can hear you. Thank you. So shall we start the question at once, right? Yes, please. Yeah. Okay. The first question is that the 981, which is interferon thing. The question is that you are chasing hematologic cancer and also solid cancer at the same time, which is really targeted as kind of a new approach. But at the same time, do you think for STING agonists, which space you think is more effective given the data you saw? Is this more hematological area or a solid area? That's the first question. The second question is a little bit overlap with Wakao-san's question about TAK-500 ADC. Given you're talking about bringing STING agonists into the cell is very important. That's what you say. So it might be the case in the future that the TAK-500, if it's given, if the case is you're going to switch to 500 rather than 676 because they have better distribution of the 676 into the cancer cells. That's the second question. The third question, you mentioned about some phase 0 microdosing research, which I'm not quite familiar with it, but it sounds like a very new way of speeding up R&D, especially talking about head and neck cancer space. Can you educate me? Is this a new way of using to speed up, or it's not really kind of standard research everybody's doing or not? Thank you. That's the third question. Great. Thank you for those questions. So, Chris, there were three categories. There was TAK-981 in terms of heme and solid, what we're seeing there, TAK-500, and also the phase 0 microdosing, if you can elaborate on that a little bit. So I'll turn it over to you to address that. Terrific. Thanks, Teresa. Thanks, Yamaguchi-san, for those questions, all really interesting ones. Let me start with 981 and the question around, is heme more interesting than solid or vice versa? So, in fact, one of the mechanisms we have revealed that is important to the activity of this molecule focuses on type I interferon. Type I interferon has been evaluated clinically as a therapeutic in both heme and solid tumors, and it's shown activity in both of those settings, but again, it's been limited by its therapeutic index. We think this can represent a totally new mechanism in the immuno-oncology space. When I showed you that cancer immunity cycle and pointed to that central space around innate immunity where we're focused in Takeda Oncology, the whole point of that focus is to be able to develop a class of immunotherapeutic that can rival a checkpoint therapy, for example. What we've seen is that we do have activity both in heme and solid tumor settings. We're seeing a very nice correlation between the types of preclinical responses, mechanisms, and readouts that we can now match up in the clinic. And indeed, without telling you more, going into a lot more detail, we have some confidence that there will be solid tumor activity in the clinic, but obviously, we're still very early in some of those studies. That said, we're moving very quickly and broadly in the clinic, and we are poised to invest very, very significantly in this program. TAK-500 and the question around bringing a STING agonist into an intracellular location where it can directly activate STING, it's a great point. As you're aware, there's some body of research that suggests that tumor cells try to evade immunity by not releasing this type of an agonist to the immune system, and what that suggests is if you can get that agonist into the right immune cells directly, it might be favorable. And so with that, again, as a teaser, we'll be able to tell you a lot more about our TAK-500 approach in a subsequent update. And then the last question about the phase 0, you're absolutely right that in the clinic, it's really a challenge to be able to have those readouts early in a program around glimpsing into what's happening in a tumor microenvironment. We do need to wait. Usually, when we design our studies, we're not doing biopsies generally until we have evidence of pharmacologic activity. That takes some time. So you could be months and months into a clinical development before you can even start to collect biopsies, let alone analyze them. We've been working with Presage, which is a partner who developed this special microinjection platform, lets you deposit simultaneously multiple different conditions, doses, combinations of a molecule of interest, and track it with a dye and then do the histology. What we've learned from the years that we've been working with this is that, again, the types of data we see in mice really are matching up in programs like 981 with the type of data we're starting to see in that head and neck study. So indeed, we're thinking of this actually as a very interesting translational platform that can be actually decision-enabling for our programs. And one of the platforms we may hope to apply it to next will be the COBRAs. So the COBRAs, as I said, get switched. The hypothesis is they're getting switched on in a tumor microenvironment. Wouldn't it be great to be able to take an early look at that across different tumor microenvironments directly through this kind of a phase 0 approach? So we're hoping to be able to advance those kinds of studies in the future. Thank you. Yamaguchi-san, thank you very much. Appreciate the great questions. Next, we'll go to Hashiguchi-san. Hashiguchi-san, I have opened your line. Please go ahead and unmute and ask your question. Thank you. Thank you for taking my question. I'm Kazuaki Hashiguchi from Daiwa. My question is about the pevonedistat. In the PANTHER study, did you achieve the primary endpoint or did you not? Are the results sufficiently satisfying the conditions required for filing? Have you gotten strong confidence on the approval based on the PANTHER results? Thank you. Great. Thank you. We're always delighted to get a question on pevonedistat because we're very excited about that molecule. Erkut, I'm going to turn that over to you to answer the question there around our PANTHER trial and what we'll be expecting a readout. Thank you, Chris. Thank you for the question. We are really excited about the pevonedistat, as Teresa and Chris mentioned. We currently do not have the results. We have accumulated all the events required for primary endpoint. Currently, we are in the process of filling up the data and analyzing the data. We expect the data towards the end of this year for the primary endpoint and the OS endpoints. This is Dion. If I may add to what Erkut mentioned, I think it is important to note that the robust phase two data gives us great confidence in terms of the complete remission, the overall response, the EFS, and the overall survival we saw from the only randomized phase II study. So we are very encouraged and enthusiastic for the PANTHER readout, as Erkut mentioned. Thank you very much. Thank you very much, Hashiguchi-san. Next, we'll go to Sakai-san. Please unmute and ask your question. Can you hear me? Yes, we can. Yes. Oh, hi. Hi. Thanks for taking the question. Two questions. The first one is broadly, I'm interested in your innate immunity approach. All of the latest compounds, interesting compounds, I should say, TAK-981, TAK-500, and TAK-676 come from this approach. So can you elaborate a bit more about your future strategy to leverage or enhance this modality going forward? That's my first question. And the second question is coming back to, well, if I may ask about the marketing side. ALUNBRIG, it's always sticking in my mind that after you've given the first line indication, what things have changed or things have not changed? I would appreciate if you could update on this front. Thank you. Great. Thank you for the question. Why don't I address the ALUNBRIG, and then I'll ask Chris to pick up on our approach in innate immunity. So we've been very pleased with the performance that we've seen since we launched ALUNBRIG in first line. As I mentioned, that first line indication, shortly after the globe really went into pandemic mode, was when we launched. And so the teams pivoted very quickly to move to a virtual approach to continue to sort of drive and making sure that we got the reimbursement across the globe in the key markets that we needed. And so we continue to see new patient share moving up and up. I will tell you that one of the things, as I mentioned on the COVID, we did see an impact. And I think that this was true probably across the board in other therapeutic areas as well, but particularly in oncology. We saw that there was a decline in new patient diagnosis as a result of COVID, patients being more hesitant to go into the system. But I am pleased to say that our teams have made sure that we continue to inform physicians and that we continue to make sure that the patients are getting the data that they need so that they're being started on Alunbrig. So that's the news there, and we continue to watch and drive against that product. So with that, Chris, maybe you can address the first part of the question, which was around our approach in innate immunity. Terrific. Well, thanks for the question. And as we tried to walk you through it today, our innate immunity focus runs across a whole breadth of modalities, including the cell space. But what you highlighted were a number of our very interesting cold-to-hot programs, all programs that seek to take interferon biology as one of the pieces to the next level, right? And why is it interesting to us? Because, again, this is one of the very few molecules or mechanisms that has shown responses in a single-agent treatment setting that hasn't been optimized yet for a therapeutic. So we believe, again, that there's broad potential to these programs like 981, 500, 676, and 573. 573 is another program that involves attenuated interferon, and it's being delivered on a CD38 antibody. We'll look forward to sharing more on that with you in the future. So the breadth of the potential is something that we're certainly betting on. You'll notice that we're taking several different bets because, in fact, we think each of these assets is going to be different. We're going to learn a lot from them. They're going to cross-inform, and certainly, we're going to take decisions, go/no-go decisions. I think to address how will we win or kind of what is the strategy, it would be remiss of me not to focus on or to highlight that getting through those early clinical studies in an agile manner and making the best possible decisions requires a number of things. It requires innovative clinical trial designs, and that's what Erkut and his team are bringing. But it also requires a rich translational toolbox. Today, I had the chance to highlight some examples of how we're reading out the activity of TAK-981. We're not just looking at something like receptor occupancy and then waiting to see a tumor response. We're monitoring pathway inhibition. We're monitoring interferon signatures. We're monitoring chemoattractants and cell responses in the innate and adaptive compartments. And we're putting all those pieces together, doing sophisticated modeling around that, connecting it to tumor subtypes and biology to try to really allow us to make the very best enrichment decisions in clinical development. And we are also willing to invest in those studies. And we've had significant investments at the level of our R&D to be able to broaden out those studies. So I hope that helps to capture sort of the different dimensions of why we're excited about innate immunity, where we're focused, and how we want to win in our clinical strategy. Sakai-san, this is Andy. I'd just like to add on to Chris's comments and just go through the history a bit with you of Takeda Oncology. When I joined the company in 2015, our focus was predominantly in protein homeostasis, taking off from the work that had been done in the Legacy Millennium Research Organization. Chris, who's quite modest, joined shortly after I did in late 2015 as our immunology head. Chris is a world-class immunologist. Shortly thereafter, Chris also assumed responsibilities for research in oncology. In 2016, 2017, really started to redirect our focus. That was when we signed our partnerships with companies like Maverick, for example, that we just acquired. That's when we started to build our cell therapy activities. That's really when we started to really sharpen our focus. I mean, there's so many different directions you can take in oncology. It's very easy to get defocused and distracted, and we didn't. Chris, a year and a half ago, was promoted to run all of R&D within oncology to take this really exciting portfolio of innate immune mechanisms forward. So you see advanced programs like pevonedistat and mobocertinib that we'll be bringing forward in the next year or two. Then after that, you're really going to see some exciting data that's going to come out. We've already, as Chris alluded to, seen some really exciting results with TAK-981, but it's not going to end there. The theme, the innate immune biology theme, really allows us to create core capabilities like in translational sciences that cut across many of these programs, but for which there are synergies across those programs. It's a really exciting space. Thank you very much for the update. I'm looking forward to it. Thank you. Thank you very much, Sakai-san. Okay. Next, we'll go to Stacy Ku. I have opened your line. Please go ahead and unmute and ask your question. Hi. Stacy Ku, Cowen. Thanks for taking my questions. I have a few. So starting from the most latest TAK-981, Chris, you mentioned this, but wondering if you go a little bit deeper in terms of where your team is focused in terms of safety from inhibiting SUMOylation systemically, what could be the potential consequences? And then for the phase 1 CD19 targeting CAR-T program, so TAK-940, could you provide a little bit more background in terms of the collaboration with Sloan Kettering and how it might be differentiated? And then my third question is on mobocertinib. For the additional phase II study in second line, could you discuss potential exclusion criteria? More specifically, would you enroll any patients that might previously be on RYBREVANT or J&J's amivantamab? Thanks. Great. Okay. Thank you for that. Actually, Chris, I'll have you address the TAK-981 about our safety focus given the systemic SUMOylation inhibition, the TAK-940, which is on our Memorial Sloan molecule. And then Erkut, I'll ask you to address the question around mobocertinib and some of the exclusion criteria and the use of amivantamab in that trial. So, Chris, we'll start with you. Great. Hi, Stacy. Thanks for those questions. So indeed, let me start with TAK-981. And obviously, I just shared with you that a lot of our preclinical findings really jived extremely well when we moved to the clinic, and that spoke to some of the mechanistic models, a lot of the pathway readouts, and so on. There was one piece that, in fact, didn't translate perfectly well, and that was some of the heme tox we were seeing in the therapeutic index window around some of the hematological AEs in our preclinical dossier. We're not yet prepared to release all the significant data simply because we're wrapping up the first parts of these studies. But what I can share with you is that the therapeutic index looks so far to be very favorable for this molecule. We're just at the point of selecting a recommended phase two dose, and we've been able to dose escalate in a way that's been pretty worked out. It's been pretty seamless and encouraging. So we'll look forward to sharing more with you. But indeed, considering that this biology has quite a lot of breadth, and we point to some of the mechanisms that we know about, but certainly, there's likely others, we're very encouraged to see the safety profile that we've seen so far. And again, it's in a variety of patients who are, frankly, often quite sick. So seeing that therapeutic index, seeing the durability that we're seeing in the rituximab combo study that's run for some time now, also highly encouraging. And with regard to TAK-940 and the partnership with Memorial Sloan Kettering, the hypothesis being tested is that some attenuation of the signal transduction of a CAR could be advantageous. So this is evaluating what's called a 1XX. It's a signaling attenuated CD19 CAR in the clinic. It's by the team who has a tremendous amount of experience, obviously, the team of Michel Sadelain and Isabelle Rivière. Jae Park is a clinician in this space, and what this initially is evaluating is a hypothesis that we could, with a lower number of T cells, achieve responses that are even better, potentially more favorable from a safety perspective, certainly with the efficacy and durability that would be best in class. The study started with a very low dose of cells, 25 million, and it's stepping up from there. We'll really look forward to sharing with you data as we can, but what I will say is initially, it's looking encouraging in this study, and I'll be very pleased to update you when we can further in the future. I guess there was one more question around the inclusion criteria. Maybe Erkut, you'd like to take that one on the inclusion criteria for the second-line mobocertinib study. Yes. Thank you, Chris. As we have mentioned, we are now running a randomized phase three trial for mobocertinib as a confirmatory trial, and we are really excited about being able to provide this drug to patients in this trial and also definitely to prove the efficacy of the compound. Our exclusion criteria does not actually have any specific exclusion for any EGFR inhibitors. The only exclusion, if they had any exposure to TAK-788 itself, those are excluded, but we are not excluding anything else, including amivantamab. As you know, the mechanism of action for amivantamab and TAK-788 are different. That's an antibody looking from outside, and ours is an inhibitor of the molecule itself. So we do not have any reason to exclude those patients. So it is a highly inclusive clinical trial, and we are really excited to be able to start the trial real soon. Thank you, Erkut. This is Dion again. And maybe I know it's a little bit broader than the question, but as we're preparing for launch in the U.S. and hopefully globally as well, we're getting feedback from physicians across the globe and in the U.S. And clearly, we're getting feedback around the efficacy profile and the 17.5-month duration of response and the 24-month overall survival for this original pivotal data set that we're looking to register now with the FDA. So we are getting pretty remarkable feedback on that in a positive way. So we're excited about this one too for the launch coming up. Thank you very much. Thank you, Stacy. Next, we'll go to Stephen Barker. I have opened up your line. Please unmute and ask your question. Thank you. Stephen, can you hear us? Oh, yeah. Sorry about that. Yes. Yes. So Steve Barker from Jefferies. Thanks very much for taking my questions. Firstly, on pevonedistat, you have guided for approval in fiscal 2022 ending March 2023. Are you confident that you will be able to apply for approval this year on the back of the PANTHER trial, or is there a risk that if the data does not read out in time, that approval in fiscal 2022 might be difficult? And a related question, is it also possible that further trials might be required? The second question relates to TAK-007, reprogrammed NK cells are becoming a very hot area. Fate Therapeutics, for example, has a number of programs in clinical development. Could you please help us put your research in context? Is there something that distinguishes Takeda's approach? And then a related question with specific reference to page 28. Could you share any details of the work that you've done to improve the cryoformulation of 007 and the process refinement? And for example, what sort of yields are you achieving? Any of those details would be helpful. Thank you. Great. Thank you. Thank you for those questions. I think I shall ask Erkut to address the question around pevonedistat and our studies there. And then, Chris, I'm delighted we did get a question here on cell therapy because I will tell you that that is an area that we are very excited about, and we've obviously invested a fair bit to make sure that we are ready commercially, that we've got the manufacturing facilities ready to go. And so I'll turn the TAK-007 question over to Chris. So why don't we start with you, Erkut, on PEVO? Yeah. Thank you, Teresa. And thank you for the question. As I have mentioned in my prior answer, we actually did achieve the number of events required for the primary endpoint and also for the final analysis. So we do not have any concern about requiring to have a further analysis because this is going to be a primary analysis and the final analysis done all in the second half of this year. So from that perspective, there is no question. And you did mention about the need to do another trial, but I just would like to remind you that this was a randomized trial against a standard of care. So if, as we hope we will, to show that we are better than the standard of care, we don't think there will be a requirement for any further studies in this particular indication. As Dion nicely pointed out before, we do have a phase II trial, that randomized phase II trial that did show us that we were better than the standard of care. That is also the part of the phase III trial. So we are really optimistic and filing on time and getting the approval on time, of course, as long as the data is supportive, as we hope. Thank you, Teresa. Great. Thanks, Erkut. Over to you, Chris, for the TAK-007. My pleasure. Hi, Steven. So I'd maybe begin by stating that TAK-007 is really just the tip of the iceberg when it comes to our cell therapy ambition. I mean, as mentioned, we're in this for the long haul, and we are therefore making a number of different investments with top teams who have top capabilities, top platforms. The cord blood NK cryo development is, for us, a foundational opportunity for us to work with our new capabilities, our manufacturing capabilities. What we achieved is to be able to have a robust process that we are very pleased with when it comes to the yield, very pleased that we're getting robust in vitro and in vivo data from these cells post-thaw. We've worked through all the analytics and associated parts of the package, and that was work that was done over the past year. These are extremely challenging cells to work with at that level. And so we're interested to see what this will look like in the clinic and how a little bit more diverse of a cell population than a clonal cell population will behave now that we're having learnings from some of the other competitors. But as I also showed you, we're deeply invested in the iPS space. And And so we are very enthused also around the potential of the gamma delta T cells, which also, because they don't have a conventional alpha beta TCR, are amenable to being even without gene editing and off-the-shelf frozen vial product potentially. And so we are extremely interested in some of the unique biology around these cells and some of that's been characterized by the founding scientific team of Dr. Adrian Hayday. We entered that partnership around the same time that we entered the Maverick partnership, and it was also with the hypothesis that these cells have unique advantages over T cells, including when it comes to tackling the solid tumor challenges. And so with that, think of these as puzzle pieces that are bringing some important learnings. As we're taking the learnings from these puzzle pieces and interpolating them, what we want to do is be able to develop the safest cells that are available globally, ones that can overcome some of the solid tumor barriers. And we think by focusing where we are, we're going to have that potential in the coming years. But 007, it's the tip of the iceberg, and it's an opportunity to be in the clinic now with outstanding partners and to start to integrate some of these critical learnings. Okay. Thank you very much. We'll now take our last question. Yamaguchi-san, please go ahead and unmute and ask your question. Thank you. Thank you again. Just one general question. You talk about some CAR NK space. One general question for me, there is another approach you touched upon a little bit on the universal donor cell-based NK cells or gene editing-based NK cell rather than CAR NK. So there are some approaches coming through, even though they are not in the clinical trial as far as I know. So can you scientifically comment on those approaches, which may be a little bit different from you on the universal donor cell approach or gene editing approach on a CAR, sorry, NK, a natural killer cell? Thank you. Great. Thanks. This fits. Fill your wheelhouse, Chris. Sure. Jumping in already. Thanks for the question. This one sits in that third pillar that I spoke to, the partnership with CiRA, which is allowing us to extend our capabilities in working with clonal cell populations that have the ability to be really tailored. Think about this as programmable. We think of this as programmable biology, right, that we have the capacity to develop over the coming years. And we're not doing that in isolation, kind of following some people's publications. We're doing it, first of all, with the world experts, with Shinya Yamanaka's team, experts in this space. But we're also doing it while we're developing innate cell therapies, innate cell therapies that are going to teach us important things around some of the engineering approaches that can bring the most value in a clonal setting. And so that's why we're excited about the clonal space. We're not ignoring it. You're right. As there are many different immune subtypes that are potentially interesting ones, I think we have the capabilities to follow that science and move with agility to develop different kinds of platforms. But certainly today, a lot of interest on our side around those innate cell subtypes that I've shared with you in some detail today. Okay. Thank you. Great. And this will bring the event to a close. Thank you so much for joining us. On On the last slide, we do have a summary of some of our upcoming events. One thing I'd like to highlight is we have a Finance Strategy Day coming up. So please look out for an invitation for that coming your way. And that is all for today's event. Have a nice evening or day. Bye now.