Gilead Sciences, Inc. (GILD) Earnings Call Transcript & Summary

Good morning or good afternoon to you all, and thank you for joining us for our Gilead Oncology Deep Dive. We're looking forward to spending some time with you today discussing our oncology portfolio, focusing on our pipeline, which is addressing a broad range of solid tumors and heme malignant disease. Our presenters today are Daniel O'Day, Gilead's Chairman and Chief Executive Officer; Bill Grossman, our SVP and Head of our Oncology Therapeutic Area, Janet Dorling, our SVP of Global Commercial Product Strategy; See Phan, VP and Head of our Oncology Franchise for Breast; Bilal Piperdi, our VP of Oncology Clinical Development; Giri Ramsingh, Executive Director and Group Development Leader for Heme; Frank Neumann, our SVP and Global Head of Clinical Development for Kite; Bernard Fine, VP and Head of our Oncology Franchise, Early Development; and Jackson Egen, our VP of Research. We have roughly 2 hours of prepared materials, after which we'll host an open Q&A session where you'll be able to ask a question live or submit a question through the Q&A function. Please do save those questions for the Q&A. At that time, in addition to our speakers, we'll be joined by Andy Dickinson, our Chief Financial Officer; Merdad Parsey, our Chief Medical Officer; and a number of other colleagues from across our oncology organization. Before we get started, let me remind you that we will be making forward-looking statements, including those that may relate to plans and expectations with respect to products, product candidates, including related clinical trials and regulatory approvals, corporate strategy, including research and development strategy, business and operations and financial projections, all of which involve certain assumptions, risks and uncertainties that are beyond our control and could cause actual results to differ materially from these statements. A more detailed description of these and other risks can be found in the presentation materials as well as our latest SEC disclosure documents. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements. Additionally, please note that this call is being recorded. With that, I'll hand over to Dan to get us started.

Thanks, Jackie, and thanks to all of you. I really appreciate your time joining us here today. I'm particularly delighted to have a chance for you to get to meet some of the -- many of the colleagues behind this work here today. I think that's critically important. This is something new for Gilead. We haven't really done a deep dive into our portfolio like this. It's something that we very much wanted to do with all of you and particularly in light of how the portfolio has progressed over the past few years. We just don't get the time on our quarterly calls to really dive into the portfolio like we want to with you. And this follows also our virology deep dive that we did in February that really established the depth and breadth of our portfolio and virology, our leadership in HIV and other viruses. And why we think that base business is so durable and strong for the next decade and beyond. And then on top of that, we have this robust oncology portfolio that we're looking forward to speaking with you today about. I mean this commitment to oncology is on a different scale than anything Gilead has done in the past. And I say that from the perspective as many of the presenters here today will from decades of experience in working in oncology and building oncology portfolios. And I would say that the portfolio that we have here, Gilead, in my mind, has some of the greatest patient benefits and values that I've seen in the industry. We look forward to really articulating that with you and giving you the data and the evidence behind that over the course of the next couple of hours here today. There will also be new information today for all of you that as you can imagine, with all the opportunities we have in this portfolio, we're constantly working up and starting new trials. And so we'll be discussing a lot of new disclosures with you today around new trials that are either intended to be started or have been started to give you an idea for the breadth of the portfolio. In this introduction session, I'm really pleased to be joined by Bill Grossman and Janet Dorling, who will introduce themselves in a minute. And then as I said, a lot of other great colleagues from Gilead, all of whom will express to you why they've joined Gilead and what their enthusiasm is around this portfolio having had a lot of experience at other companies in oncology. So if I could have the next slide, please. This is important to note that we already have a very strong oncology business out there today, more than $1 billion last year. Yescarta, Tecartus from Kite and TRODELVY are really just in the beginning, I think, of their ability to have impacts on patients. Terrific news on the approval for Yescarta in second line, and Frank will talk more about that later today. But we're really at the beginning of decades of innovation in oncology. And you can see our conviction and our confidence around our 2030 milestones for oncology there on the right-hand side of the slide. On the next slide, it really gives you the framework for how we think about oncology [indiscernible] and how we're going to approach today's discussions as well, which is really around articulating this pipeline of transformative science. And the key strengths that Bill is about to get into in a few minutes. But equally and in parallel, of course, is the buildup that we've done over the past several years and will continue to do on the capabilities to deliver that. Now I'll come back to that a little bit later in this setup presentation. But both are important, and both have made significant progress over the past few years. And we've created a pipeline, we believe, with exceptional quality, both on the individual asset level and in terms of combinations. So we're going to be spending most of our time today on the first of these topics in the pipeline in a transformative science to really dive into that with you. I just want to set up on the next slide where we are in the journey, right? So this has been very purposeful since I've joined the organization and others have joined the organization around the strategic and thoughtful build of medicines within our portfolio. And I'll just point out that now it's been 5 years since the Kite acquisition. And we're beginning to really see, I think, the future and potential of cell therapy, particularly the promise of curing more patients as we move up in lines of therapy. And I would just point out that acquisitions like Immunomedics are only about 18 months old. And we are systematically expanding on what a small company can do with the breadth and scale and expertise of Gilead. We've done more than 30 strategic transactions across clinical and preclinical assets that give us the confidence on the short, medium and long-term growth. So this has all been purposeful. And as you'll see from Bill's presentation, how it links together from a scientific perspective. It is very important in terms of how we believe we can be unique in bringing individual assets and combinations to patients. On the next slide, I just further articulate that point of what it takes, I think, particularly all of these examples on this slide are medicines that are -- what we would term as pipeline in a product. They have the potential to go across multiple indications, usually starting in later-line therapies, not always in moving up in therapies. And we're at the beginning of the journey, as I said, Kite has the longest runway. And in terms of developing that Forty Seven and Immunomedics are obviously more recent in our portfolio. But you can see in addition to shoring up what each of those companies did individually, the progress sets to close at the lower part of this slide as well. And still, as we'll explain to you today, just beginning to kind of scratch the potential of each of these molecules. And we highlight Arcus because it's a collaboration that we believe is very important to us and has many individual assets that can be also combined with other assets within our Gilead portfolio and beyond. So with that now, I want -- I'm delighted to hand it over to Bill to walk you through how we're approaching the development of this robust portfolio. So over to you, Bill, please.

Great. Thanks, Dan. I'm Bill Grossman, and I'm the oncology TA head here at Gilead. And for some quick background on me. I'm a hem/onc, transplant physician scientist. And I've spent most of my academic years performing bone marrow transplantation for oncology patients. I also ran independent basic research and diagnostic labs, focusing on investigating pathways of immune regulation across many different disease areas, including oncology. I then transitioned to industry about 15 years ago now, where I spent my entire time developing oncology drugs in cancer immunotherapies in larger pharmaceutical companies, but as well as biotech. And my last position was CMO at Arcus Biosciences. So I've been here at Gilead now for approximately a year, and I'm very excited to be here and help build out what I truly believe and is already in a world-class oncology pipeline. And I hope by the end of today's presentation, you'll feel the same. So first, I'd like to walk you through our scientific framework shown on this slide, which is helping to guide our pipeline growth. As Dan mentioned, our targeted acquisitions and partnerships over the past several years have really dramatically expanded the scope of our oncology pipeline in scientific areas of focus. First, if you look at the bottom schematic on the left-hand side, you'll see a basic tumor microenvironment picture. With proliferating tumor cells shown in red, immune cells such as T cells and NK cells shown in blue, which are normally involved in recognizing and killing cancer cells. And finally, the tumor microenvironment itself in green, which is a collection of cells and factors that help tumor cells grow and avoid being attacked by our immune system. The ideal goal in developing effective oncology therapies is obviously to selectively kill cancer cells while sparing other noncancerous cells in our body. Hence, our scientific framework is focused on 3 core areas noted on the right-hand side of the slide and which really highlight the key biological pathways we are targeting. These core areas have helped guide our portfolio build-out, as Dan mentioned, with assets that have complementary mechanisms of action, which have strong scientific rationale for combinations as you'll hear more later today. First, we are targeting therapies that trigger tumor-intrinsic cell death, resulting in potentiation of immunogenic responses by releasing and presenting tumor antigens to the immune system. Second, we are targeting cancer therapies that promote immune-mediated cell killing, which further drives immune cell expansion, differentiation and activation of effector T cells, NK cells and macrophages to help result in robust tumor cell killing. And lastly, we are targeting therapies that remodel the tumor microenvironment itself, making it more -- promoting more immune responses against cancer cells and actually inhibits their growth, both indirectly and directly through changing the tumor-permissive microenvironment. Pictured here against these 3 scientific pillars is our current broad clinical pipeline of 20 internal and external assets, which have been rapidly and purposely brought together over the past few years, as Dan mentioned, and gives us multiple shots on goal against some of the most promising pathways being targeted in cancer biology today. This diverse pipeline is also built around the potential for orthogonal combinations that's [indiscernible] or even more core mechanistic cancer pathways, which have the potential to deliver additive or even synergistic clinical efficacy. As we walk through each of the disease area section today, we will highlight these multipronged attack modes on cancer cells that we're pursuing, which we believe, again, will give us a differentiating position against some of the biggest players in oncology. I would like to next walk through some key features of our pipeline assets and their potential opportunity to unlock significant value across our multiple tumor types as well as lines of therapy within our pipeline. First, many of our assets outlined here in yellow, have first-in-class or best-in-class opportunities. Examples of these assets that will be covered in more detail later on, include our first-in-class Trop-2 ADC, TRODELVY, our first-in-class, best-in-class assets like the adenosine assets, which we recently opted in from Arcus at the end of 2021. Our first-in-class anti-CD47 antibody magrolimab, our CAR-T therapies as well as some select first-in-class and best-in-class early development assets like MCL1, CCR8 and [indiscernible] TREM2 and HLA-G antibodies. Next, we have also acquired several assets that we believe will become future backbones across multiple tumor types and indications. Examples of these backbone products are shown below and include combinations with our TIGIT antibodies with checkpoint inhibitors such as Zimberelimab or zim, combinations of TRODELVY with checkpoint inhibitors, which we believe is just the tip of the iceberg for TRODELVY combinations, and we're just getting many of those started now in combinations with magrolimab with chemo or tumor-directed antibodies. And of course, our cell therapies that have already -- are already establishing themselves as a new standard of care in several CD19-expressing heme malignancies. As I mentioned earlier, with our already differentiated portfolio, we have the potential for novel combinations across our assets that target orthogonal biological pathways that are likely to help deliver even deeper and more durable antitumor responses when put together. Some of the examples, as shown on the bottom of the slide show potentials such as combining TRODELVY that directly kills tumor cells, along with immune potentiating agents like our PD-1 antibody zim and one of our many [ TME ] modulating assets like the adenosine pathway targeting assets [ etrumadenant and quemliclustat ]. In fact, when you look at our significant progress in evaluating these novel combinations, over the last just couple of years alone, we currently have over 25 unique pipeline combinations being evaluated in the clinic today, including 7 combinations already in Phase III. We strongly believe that many of these novel combinations will really ultimately unlock significant value across our pipeline. Finally, many of our assets have a high probability of what we -- what we call a pipeline-in-a-product where they have potential to be used across a variety of solid and heme malignancies. Examples of these products, again, include TRODELVY, where Trop-2 tumor expression is highly expressed across a number of solid tumors, which we'll get into; magrolimab, which has the potential to be used not only across the majority of heme malignancies, but also the potential to be used in solid tumors; and the PD-1-TIGIT combinations, which had the potential to be used across most solid tumors for checkpoint monotherapy or in combination with chemo, are already currently the standard of care. Our development approach across these potential pipeline and product assets leverages broad application across many tumor types, but often differ on their initial approach to pivotal trials based on their level of single-agent activity. For instance, some assets that have significant monotherapy activities such as TRODELVY and our cell therapies, we initially established a registrational foothold in later lines of therapy like we've already done and then move quickly into lines -- early lines of therapy versus other assets such as our anti-TIGIT and anti-CD47 antibodies, they're known to have optimal clinical activity when really combined with other assets like checkpoint inhibitors or chemotherapy, respectively. These assets often begin registrational trials in combination in earlier lines once we've established proof of concept and then build in parallel for their novel and differentiating combinations. As mentioned, TRODELVY is one of our pipeline-in-a-product assets that has significant single-agent activity, leading to our broad development program, as we've shown here, and then we'll get into more later on. We've already established our market foothold initially in high unmet need, late-line indications, such as our current approvals in second-line TNBC and second-line bladder cancer. We are now quickly moving into earlier lines of therapy in these indications. In parallel, we are also establishing proof of concept across many other solid tumors in later lines of therapy where Trop-2 expression is also very high. We have a very similar approach to our CD19 CAR-T programs, where there's clear and overwhelming clinical efficacy in late-line heme indications and where we have already had approvals in large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma and adult ALL. And as noted by our recent second-line approval in large B-cell lymphoma, we continue to move these highly active cell therapies up into early lines of therapy [ with plans ] to continue to go even further into frontline as you'll soon hear from Frank. In contrast, we know that, again, some optimal activity of certain agents like magrolimab in heme malignancies is best when combined with other assets that enhance the eat me signals such as chemotherapy or tumor targeting antibodies. As such, once the initial proof of concept is established in combinations, our registrational strategy is a little bit different in which we go into first targeting earlier lines of therapy, such as our frontline indications where we've already begun pivotal trials for MDS and AML and where we can quickly add on to existing standard of care assets, along with parallel development of novel combinations. This is also a very similar approach to what we are using with our TIGIT and checkpoint combinations as you'll see later on in our discussions. So then this leads me to my last slide, which gives you a high-level overview of our significant and quickly advancing pipeline of assets with currently 20 assets being evaluated over 40 active and planned clinical programs covering 18 indications. I fully expect to see continued growth and advancement of this pipeline, and I hope you'll appreciate at the end of today's presentations. The balance of studies across the different phases of development and the significant advancement we've already made to date across all of our clinical programs. Finally, as you'll see here, and as Dan mentioned in this slide [indiscernible] throughout the presentations today, we have a number of new disclosures as they are highlighted by the stars in each of the slides and sections. And with that, I'd like to now hand it over to Jan Dorling to give a high-level view of opportunities across the different disease areas.

Thank you, Bill, and hello, everyone. I'm Janet Dorling, and I lead up our Global Commercial Product Strategy Group. A little background. I have over 20 years of experience in biopharma and commercial [ roles ], working across multiple therapeutic areas, including a strong focus in oncology. And I joined Gilead 2 years ago to help build our global commercial capabilities in support of the company's evolving and expanding portfolio with oncology being a critical component of that. And I'm excited to be here today with the team to speak with you more about our emerging portfolio. So Bill has just walked you through how we think about the potential of the pipeline and some specific examples. And I want to reiterate, as you look at this slide, it is just tremendous, the progress we've made over the last few years at Gilead as we've built out oncology. With our current pipeline beyond a nice distribution across phases, you can also see by the color coding here that we have the potential to address many different disease areas as well. So the groupings of lung, breast, GI/GU, hematology and other solid tumors depict how we categorize our programs. And this will also be how we organize the presentation sections today. Beyond the breadth and depth, the pipeline also represents a significant opportunity from a patient impact and commercial value perspective. Our current portfolio covers the opportunity to impact up to 1.5 million patients. And just to quickly orient you to this slide, the colors correlate to the groupings we just saw in the previous slide, checkmarks are marketed programs, and the circles represent ongoing clinical studies. So we've targeted disease areas and patient segments where we think we can really make a difference. We have areas like second-line metastatic triple-negative breast cancer, which Bill just mentioned, where we've brought TRODELVY to a patient population with really high unmet need and very limited options for treatment. We've also focused on first-line, non-small cell lung cancer, where there is a very large opportunity across multiple patient segments. And thus, we have multiple therapeutic approaches and shots on goal, as you can see on the slide. So given the portfolio and opportunity ahead of us, it's also very important to look at the totality of what's ahead for Gilead and Kite in oncology from a data perspective. And what's exciting and important to note is that we have data reading out across multiple programs in the near to midterm. So we break this slide up into 2022, '23 and '24 and 2025 plus. And for '23 and '24, I should note that we'll be providing more detail on timing as we get closer. But the data readouts highlight several different important parts of our strategy across the portfolio. As Bill just mentioned, we have data driving submissions and new assets and tumor types such as TRODELVY expanding into non-small cell lung cancer and magrolimab with its first indication in high-risk MDS. We also have readouts for expansions into earlier lines. And this includes first-line metastatic triple-negative breast cancer in both PD-L1 negative and positive patient segments. And finally, what's very important to us, as we look ahead, is clinical data that really informs how we'll differentiate and start our next wave of differentiated Phase III clinical studies. And things like ARC-10, which looks at a chemo-free regimen in PD-L1 positive frontline non-small cell lung cancer or our lung platform study that's exploring those novel combinations so that we can set our clinical strategy are really critical data readouts for us as well. So you'll be hearing a lot more about the specifics of these studies further on in the presentation. But to wrap up this slide, I'd just like to reiterate our excitement for the many readouts to come as our oncology portfolio matures. And with that, I'll pass it back over to Dan.

Thanks a lot, Janet. Thanks, Bill. So I just wanted to also then emphasize based upon what Jan and Bill just covered about the pipeline emphasize the work we've been doing around building any capabilities. It's really all about the people at the end of the day that you have in place with the right experience set, with the right capabilities to help us make decisions and choices in the portfolio. I can tell you in witnessing and I'm an observer on our portfolio committee, it's pretty extraordinary to see both the level of discussions that are occurring there now, but also the competition for resources and assets within Gilead. It makes sure that the bar stays high in terms of what we're going to invest in to make a difference for patients. And I think that's really about people and choices that we make. And some of the examples you see here we've had more than 2,000 oncology-focused folks joined our organization over the past couple of years. And you can see that's been in all areas, from research and development to manufacturing. And certainly, we've continued to invest in our manufacturing capabilities around biologics, ADCs and cell therapies. And just to give a little bit more color to that, we've tripled our oncology field force over the past couple of years. Our [indiscernible] organization has more than 150 new members. We've had a real focus on expanding our real-world evidence and AI effort, something that I have a lot of passed around from also my previous roles in the industry. And we've created a biologic center of excellence now down in Oceanside, California and just recently actually we'll be opening a new plant for Kite in Maryland. So these types of investments to make sure that the entire value chain has the expertise and the resources need to be successful, we have done and we will continue to do. I just want to take this opportunity to thank the teams that you're not going to see today as well as those you will see today, that have been working incredibly hard to build out this oncology presence. And then on the next slide, we don't intend to do it all ourselves. I mean we have very much of a science occurs all around us and partnerships help us leverage our bandwidth for our own internal medicines. And you can see a variety of those types of collaborations here, everything from our collaboration, for instance, with Merck, in working on operationalizing the TRODELVY study in first-line cancer with -- along with KEYTRUDA, where that is the standard of care to collaborations with companies like Arcus, who have a depth and breadth of experience in operationalizing both research and development programs in cancer that we value greatly and many others. So you can see here that we have a tremendous ability to leverage the ecosystem and the network around us. I also believe there are some real fundamental capabilities for Gilead that we can use to continue to differentiate how Gilead approaches customers and patient groups and community organizations out there. And so from our long heritage and pedigree in HIV in the astonishing and very innovative work we've done with communities to make sure that we're addressing health equity and health inequities around the world, we can leverage that as we go into oncology in a way that I think will be unique compared to other companies. On the next slide, this is what we really want you to take away from today. There's going to be a lot of detail, but just to pull it back up, I think -- here are the 3 key messages. Number one, we've carefully assembled and strategically and purposely and thoughtfully assembled portfolio with significant breadth and opportunity and differentiation, both at the individual medicine level and also in combinations. Secondly, we're expanding the clinical trials to optimize that potential from 12 trials in early 2019 to -- we'll have more than 50 active trials planned for the -- between now and the end of 2023. Just gives you an emphasis. Again, all of those being thoughtful and competitive within a robust portfolio and our portfolio committee. And then finally, we're already a significant player in oncology, and we are just at the beginning. We're growing and we have a lot of potential to untap as we look at the months and years ahead. So with that, I would take you to the next slide in terms of how we're going to approach the entirety of this portfolio. You'll see we're going to break it down to different disease states now. But within each disease state, you'll see we'll have an introduction, a strategy component around the opportunity, a development plan summary, study data and details as appropriate for that section and then a summary accordingly. And we really look forward to your questions at the end of this presentation and interacting with you to see what's on your mind as well. So with that, I'm delighted to turn it over to get us started in Breast with See Phan who heads our breast cancer franchise. So over to you, See.

Thanks, Dan. So I'm See Phan. I oversee clinical development for our breast cancer franchise. I've been at Gilead for about 1.5 years after spending 10 years -- over 10 years at Genentech working on a variety of late-stage assets. As a medical oncologist, my primary focus has been seeing breast cancer patients in the clinic, and I maintained a breast cancer clinic even after I joined Genentech. And what attracted me to joining Gilead was the opportunity to work on TRODELVY, having seen the really significant benefit that it was providing to triple-negative breast cancer patients, and I wanted the opportunity to come over and really expand the number of breast cancer patients who could then benefit from TRODELVY. So why TRODELVY and what's unique about it? So TRODELVY as an ADC shares the common antibody and payload that all ADCs have. But there are several differentiating factors that make TRODELVY unique. One is the target Trop-2. TRODELVY is the first ADC in the clinic to target Trop-2 and the first to be approved with an indication. Now with the significant activity we've seen in early trials and now 2 positive Phase IIIs as well as approvals in 2 different tumor types, Trop-2 is real clearly a validated target for cancer. In addition, the cytotoxic payload for TRODELVY is different. Most ADCs incorporate a very toxic payload which then gives the risk of having off-target toxicities. TRODELVY incorporates SN-38, which is the active metabolite of a commonly used chemotherapy Irinotecan. And as such, the safety profile for TRODELVY is predictable and familiar to most oncologists. To maintain the potency of the overall ADC, we then have a high drug-to-antibody ratio on TRODELVY. And finally, the last unique characteristic is around the hydrolysable linker. Similar to other ADCs, TRODELVY is internalized once attaches to a target on the tumor cell and the payload is released internally and effects cell kill. But by also using a hydrolysable linker, we can release the payload, SN-38, in the tumor microenvironment in a pH-sensitive manner. And given the moderate toxicity of SN-38, we don't have the off-target toxicity. So Trop-2, the target for TRODELVY is highly expressed on multiple cell tumors. We already have positive trials where we based it on the high expression in breast cancer, not just triple-negative breast cancer, but also the other subgroups, including hormone receptor positive. We know Trop-2 is highly expressed in non-small cell lung cancer, colorectal cancer and the other solid tumors you see here on the slide. The other key aspect of Trop-2 over expression is the pattern in which it's overexpressed. So you can see in triple-negative breast cancer that nearly 90% of the tumors will express moderate-to-strong staining and showing that the majority of triple-negative breast cancers will overexpress Trop-2. But when we've interrogated the ASCENT data, we see that there's activity for TRODELVY compared to control, even down to weak expression. The implications of all of this is that we do not need a companion diagnostic. There does not need to be patient selection for TRODELVY to be effective. And we believe this is true in the other solid tumors with Trop-2 is overexpressed. So we have an expansive clinical development program for TRODELVY, spanning from Phase I through Phase III, and it meets 4 key strategic objectives. We plan to expand the global approvals in our primary indications. We've completed the ASCENT trial under 38 approvals globally. We do need to support that with some additional clinical data in certain countries that's the ASCENT-J02 trial, which is developing data -- clinical data in Japanese patients to facilitate registration in Japan. We have the accelerated approval based on the TROPHY Cohort 1 trial in the U.S. Confirmation for that approval will come from the TROPiCS-04, which will then ultimately enable global registration in the bladder space. We plan to advance TRODELVY into earlier lines of therapy where we've seen significant activity. And as necessary, depending upon what the standard of care looks like in earlier lines of therapy, we will establish novel combinations. And you can see that reflected in multiple Phase III registration trials listed there. In addition, with all the solid tumors you saw in the previous slide, which overexpressed Trop-2, we plan to expand TRODELVY's reaching to those solid tumors. We've already reported in early March that we hit the primary endpoint for our Phase III trial in hormone receptor-positive breast cancer. We have a registration trial in non-small cell lung cancer following platinum and immunotherapy treatment. And in addition, we have a wide variety of Phase I and II programs evaluating multiple other tumor types as well as novel combinations. So more detail on our breast program. This is the slide that Bill showed earlier with our entire clinical development program now highlighting those focused on breast cancer, with breast cancer for TRODELVY further along with the registration in triple negative. We have more Phase IIIs here where we're planning to expand the label. In addition, we have Phase I and II trials where we're looking at novel combinations with TRODELVY as well as novel pipeline products, which may eventually become combinations with TRODELVY. Our strategy for TRODELVY in breast cancer is to build on the early data we've seen in later-line disease. We think with the tremendous benefit that you've seen for our TRODELVY and triple-negative breast cancer patients, that all triple-negative breast cancer patients should be treated with TRODELVY at some point during their natural history. And to effect that, our goal is to move TRODELVY into earlier lines of treatment and ultimately even into the curative setting for triple-negative breast cancer. Building on that, once TRODELVY is the backbone for all triple-negative breast cancer treatment, we feel that we can expand upon its efficacy by adding novel combinations. Now with the registration data that we have for our TROPiCS-02 will employ a similar strategy where we're looking to move it into earlier lines and ultimately include novel combinations. So our current clinical development program for breast cancer is listed here, consists of the 2 completed Phase III registration trials. We have upcoming Phase III registration trials with the intent of expanding the label. And we have exploratory trials, over 5 that are looking at novel combinations once we establish TRODELVY as a backbone in breast cancer. If you look at how we arrayed this clinical development program over the landscape for the 2 major types where TRODELVY as activity in triple negative and hormone receptor -positive, HER2-negative breast cancer, you can see that on the right is where we have our registration data in later-line disease. But ultimately, we want to move TRODELVY towards the left, into earlier lines and into the curative setting. So a little more detail on what our clinical development programs look like in these settings. Number one, we're building off of the data that we've seen from ASCENT. ASCENT showed tremendous efficacy in both PFS and OS with hazard ratios of 0.43 and 0.51, a tripling of PFS and a doubling of overall survival. It's not often that you see cancer drugs have hazard ratios in this range. The other remarkable thing about TRODELVY in the clinic is that we've seen really consistent results in the early trials as well as in the Phase III trials and how TRODELVY performs. And when we've done subset analyses and drill down into the ASCENT data, we still see the same consistency. And importantly, in one key subgroup from the ASCENT trial in earlier line disease, the second-line subgroup, we saw efficacy in overall survival as well as PFS that was very similar to the overall population. And of note, these second-line patients, these earlier line patients who are the most refractory patients because they get on the trial, they must have had early relapses from their earlier treatment. Seeing that similar efficacy in these earlier lines gives us confidence that we can move TRODELVY into the earlier line setting as well as in their curative setting. And so our plans for first-line metastatic triple negative consists of 2 trials, ASCENT-03 and ASCENT-04. We have these 2 sister trials, and we intend to open them at the same site so that all first-line metastatic triple-negative breast cancer patients will have these options. The reason for the 2 trials is that the current first-line metastatic triple-negative breast cancer space is dictated by the recent approval of immunotherapies for these patients. And so pembrolizumab is approved for first-line patients whose tumors overexpress PD-L1. In both cases, for a PD-L1 negative and the PD-L1 positive patients, chemotherapy still forms the backbone for their primary treatment. So our aim with these trials is to have TRODELVY replace the chemotherapy for superior efficacy. And we'll combine with pembrolizumab for the PD-L1 positive patients and give TRODELVY alone for the PD-L1 negative. In addition, we note that recently, pembrolizumab was approved for the neoadjuvant and adjuvant space. So some patients who are entering the first-line space may have previously had pembrolizumab in the treatment course. And so these trials have been designed so that physicians can opt to either retreat with PD-L1, if they're PD-L1 positive or not give pembrolizumab if they've already received it. So TRODELVY will cover all of the patients available in the first-line space. Moving into the curative setting. Here's where we think TRODELVY would really have a significant impact for patients by improving the cure rate for patients who are receiving a curative treatment. And we've identified 2 unmet needs where TRODELVY could have a potential benefit. We know that pembrolizumab recently got approval as a neoadjuvant and adjuvant treatment for early-stage triple-negative breast cancer. The benefits seen with adding pembrolizumab to neoadjuvant treatment was primarily in the increase in the number of patients who got pathologic CRs. And if you look at the Kaplan-Meier curve, those patients who got pathologic CRs had significantly better outcomes compared to those who didn't, right? But the addition of pembrolizumab still really only gives less than 2/3 of the patients of pathologic CR. So there's over 1/3 of patients who don't achieve pathologic CR, and we feel that, that's a space where the addition of TRODELVY could potentially increase that rate and improve outcomes for patients. The other space we've identified is those patients who don't achieve pathologic CR, and you can see on the Kaplan-Meier that these patients have significantly worse outcomes. Those patients who don't achieve a pathologic CR are patients who have received platinums, taxanes and anthracyclines, similar pretreatment to those patients who were enrolled on ASCENT and feel that introducing TRODELVY into that space could really significantly improve outcomes for these patients. So we have 2 trials looking at this area. The ongoing Neostar trial is a Phase II evaluating different cohorts using TRODELVY as the basis for neoadjuvant treatment. TRODELVY is given alone or in combination with KEYTRUDA. And of note, this also includes a hormone receptor positive cohort. Based on the results from that trial, we'll be able to develop a registration plan for TRODELVY as a potential neoadjuvant treatment. For the high-risk patients who don't achieve pathologic CR, we have a Phase III in development. We are in advanced discussions with the Alliance Cooperative Group on the trial design. We aim to meet with regulators to get feedback on the registration possibilities, and this trial is targeted to open in the first half of 2023. Moving from triple-negative breast cancer to hormone receptor positive. While triple-negative breast cancer is the most aggressive subtype, hormone receptor positive, HER2-negative breast cancer is the most common. And while it's not as aggressive as triple-negative breast cancer, 1 in 3 cases of early-stage hormone receptor positive breast cancer still relapse and once metastatic, their disease is incurable. We've already announced at the beginning of March that we've hit the primary endpoint in our trial addressing these patients, TROPiCS-02, reminding people of what that trial -- that schema looked like. The trial design is very similar to ASCENT when you look at the schema with TRODELVY compared to control options of different single-agent chemotherapies. However, the patients going into this trial are very different. Besides being hormone receptor positive, there was a requirement for exhausting all the typical standard of care treatments for these patients, including endocrine therapy, targeted CDK4/6 inhibitor and then 2 lines of chemotherapy, including taxane, but no more than 4 lines. As a result, the patients who were enrolling in this trial, were much later in their natural history compared to patients who potentially are going to other trials. We announced that we met the primary endpoint of PFS in this trial earlier in March. We also noted that we have a favorable trend in overall survival at our first interim analysis and survival follow-up continues. These data have been accepted for presentation at ASCO, but we look forward to sharing it. We're having ongoing discussions with health authorities about the submission of this for registration, and we're continuing to follow OS with data expected in 2024. With our presentation at ASCO, we know that there's likely going to be comparisons to another ADC in the breast cancer space, so we wanted to highlight the differences between the TROPiCS-02 and the DESTINY BREAST 04 trial for [indiscernible]. We note that for TROPiCS-02, it's a pure hormone receptor positive trial. And as such, all patients must have exhausted their standard of care treatments before going on TROPiCS-02 and TRODELVY. And so all patients required to have endocrine, CDK4 and at least [ 2 ] lines and up to 4 lines of chemotherapy. The difference between that and DESTINY 04, is DESTINY 04 was looking at a selected population of HER2-low patients. They did have to require endocrine, but CDK4/6s were optional and only one line of chemotherapy. As such, we think that the patients on these 2 trials are not necessarily comparable. So building off our TROPiCS-02 results, we do plan to employ a similar strategy to what we're doing in triple negative. We are in the midst of looking at developing a first and second-line trial addressing the first-line space for these patients. And ultimately, we will look at the curative setting. Beyond these registration trials that we're looking at for TRODELVY in the triple negative and hormone receptor space, we're also looking at novel combinations and utilizing a combination of either our own pipeline products like the MCL1 inhibitor and magrolimab for CD47. But also in collaboration with other sponsors looking at other agents such as pembrolizumab and [indiscernible]. So in summary, for breast cancer, we aim to bring TRODELVY to the majority of breast cancer. We need to address 2 key subgroups, triple-negative breast cancer and hormone receptor positive disease. We feel that the results we've seen in ASCENT will establish TRODELVY as a foundational treatment in triple-negative breast cancer, a treatment that we want to bring to all patients who have triple-negative breast cancer. Once established as a foundation, we intend to expand that with novel combinations using TRODELVY as a backbone. And ultimately, our plans in hormone receptor positive breast cancer will mirror what we're doing in triple-negative breast cancer. Moving on to bladder cancer. Again, looking at the clinical development program for bladder cancer, we're highlighting those specifically targeted to bladder cancer. In Phase III, we have the confirmatory trial in addition in Phase II, we have multiple trials looking at novel combinations. The strategy in bladder cancer is to build off of our initial accelerated approval that we have in the U.S. for second-line bladder cancer post-platinum, post-immunotherapy. And so the key would be to execute on the TROPiCS-04 Phase III trial, which is the confirmatory trial for that indication. Building off of that, we'll use the same strategy to move TRODELVY into earlier lines. And given the current landscape in bladder, where multiple immunotherapies in addition, another ADC in the space, we'll be looking at various novel combinations to advance TRODELVY. The clinical development program in bladder cancer consists of the ongoing confirmatory Phase III trial. We are planning 2 new Phase III trials -- registration trials for cis-eligible and cis-ineligible patients, and we have multiple trials in Phase II looking at novel combinations. So going over to the bladder cancer, [ CDP ] in detail. This is where we currently are in a second- and third-line post-platinum, post-immunotherapy space. We have the accelerated approval based on the TROPHY data and the confirmatory study, TROPiCS-04. That accelerated approval was built on the data you see here with 76% of patients seeing a tumor reduction with treatment with TRODELVY, a confirmed response rate of nearly 30% and 5% complete responses. Given that the expected response rate in this setting from chemotherapy is usually around 10%, we're confident that we'll be able to confirm these results in the TROPiCS-04 randomized trial. This trial is designed to put TRODELVY head-to-head against the choice of chemotherapy, docetaxel, paclitaxel and vinflunine, again, enrolling the same patients that were enrolled in the TROPHY Cohort 1. This trial is open and enrolling right now, and we expect the last patient in the second half of 2022. So moving to future plans for TRODELVY in bladder cancer. Our goal is to move it into earlier lines. And we do see that in first-line metastatic bladder cancer that cisplatin is likely to play a continued important role there as the landscape evolves in muscle invasive breast cancer. With that in mind, we have 2 cohorts in TROPHY where we are looking at the efficacy and safety and tolerability of combining TRODELVY with cisplatin. And based on those results, we'll design a registration Phase III for cis-eligible patients. We know that a significant portion of bladder cancer patients remains cis-ineligible with the plethora of immunotherapies now in bladder cancer, we feel that this gives us opportunity to combine TRODELVY with immunotherapies, including expanding that with other pipeline products that Bill showed earlier. Our belief in this strategy is built on data that was recently presented at ASCO GU in a population of patients, which were refractory to platinum for having recently progressed, the combination of TRODELVY and pembrolizumab was able to achieve a 38% response rate and 63% of patients had tumor shrinkage. And this informs our plans to combine TRODELVY for IO-based therapy in the first-line setting for cis-ineligible patients. In addition, we're looking at the possibilities for putting TRODELVY into the muscle and invasive bladder space. 3 Phase II trials are shown here, 1 with TRODELVY alone as neoadjuvant treatment, SURE-02 looks perioperative, TRODELVY in combination with pembrolizumab and the RAD-SG trial is looking at bladder conservation combining TRODELVY with radiation. In addition, we're looking at -- actively looking at novel combinations. As expected, we're looking at combinations of immunotherapies, while I highlight that we're also combining with the other ADC in the bladder space, PADCEV and so having a dual ADC regimen. Moving on to prostate cancer. Prostate cancer, which overexpress Trop-2 presents a potential significant unmet need that we could tap into TRODELVY's potential here. We see opportunities to combine TRODELVY with multiple agents from our pipeline. In prostate cancer, it's very similar to hormone receptor positive breast cancer and that once patients have exhausted their androgen-based treatment, they run out of options and a significant unmet need exists for these patients. Utilizing the compounds within our pipeline, we see multiple combinations where TRODELVY could benefit these patients. We can combine TRODELVY of the current androgen-based treatments as well as various immunotherapies we have in our pipeline. In addition, I want to highlight that we are also looking at immunotherapy combinations without TRODELVY in this space. In summary, for GU, we're building on the accelerated approval that we have from TROPHY Cohort 1 with a confirmatory study, which we believe will lead to a global registration of TRODELVY for bladder cancer. Establishing TRODELVY in this space, we'll look at novel combinations of TRODELVY with either established chemotherapies or immunotherapies to expand into the earlier line space. And we're looking opportunistically at other indications like prostate cancer. So with that, I'll pass it on to my colleague for Lung, GI, Bilal Piperdi.

Thanks, See. Hi, everyone. My name is Bilal Piperdi. I'm a thoracic oncologist by training. And like See, until recently, I've been seeing patients -- lung cancer patients in the clinic. I've been with Gilead for about a year, and I've been in the industry for about -- close to about 10 years. Prior to Gilead, I was at Merck in the clinical development team. I was a product development lead for non-small cell lung cancer for KEYTRUDA and other assets at Merck. It's very exciting time here to be here at Gilead. I think we have a very robust portfolio of drugs. And very importantly, we are a very committed group of leaders who are very committed to oncology and delivering a transformative therapy to patients with highest unmet medical need. What I'm going to do over the next few minutes is just to walk you through our portfolio in lung and GI tumors. As you saw from those presentations, oncology portfolio and Gilead is expanding via organic growth, acquisitions and partnerships. And I think our opportunities in lung cancer look very promising. Our clinical development program in non-small lung cancer is broad and deep, with multiple assets in various phases of development, as you see on this slide here. I'll work through our strategy in non-small cell lung cancer and provide you with more details on some of the studies that we are planning to launch later this year. Despite recent advances with targeted therapies, immunotherapy, the overall prognosis of non-small cell lung cancer patients remain poor with very low 5-year survival rate. There's a huge unmet medical need for safe and transformative therapy across all segments of non-small cell lung cancer. We have a very ambitious goal here at Gilead to be a key player in non-small cell lung cancer space and our strategy will be agile and evolve as the program expands. Our current strategy is to establish TRODELVY as a foundational therapy in patients who have been exposed to IO and chemo. We also have multiple shots on goal to replace current standard of care in the first-line non-small cell lung cancer setting, which I'll walk you through a little later on. Very importantly, with some of the very important data readout from the Phase II studies will be moving very quickly into an earlier line of treatment, including an adjuvant and neoadjuvant setting. Gilead is in a unique position with the novel ADC, TIGIT and adenosine axis inhibitors to develop differentiated and novel combinations in lung cancer. Our initial trials will lay foundational treatment to build future novel transformative combination with both internal and external assets. As you see on the slide here, we currently have 3 ongoing Phase III registration studies and 4 ongoing Phase II registration study with near-term readouts. In addition, we are planning for 2 other Phase III registration study in first-line non-small cell lung cancer, which I'll talk a little later on. With multiple assets in the hand, we have a very near-term potential for some registration studies in lung cancer. As you see on the slide here, we have 3 assets in the registrational program: TRODELVY, our first-in class Trop-2 ADC; Zimberelimab, our monoclonal antibody against PD-1 and Domvanalimab, our Fc silent TIGIT antibody that we opt in from Arcus. In addition, we have first-in-class and best-in-class adenosine inhibitors in a Phase II program, which will further help us out for the novel combinations in the future. Non-small cell lung cancer market is large, competitive and segmented by the disease state and line of therapy. Each segment represents a unique opportunity to improve outcome for patients over current standard of care. In the second line plus setting, majority of the patients in non-small cell lung cancer progress after initial IO and chemotherapy. But the current standard of care in this setting, unfortunately, still remain docetaxel plus or minus ramucirumab. And there's a huge unmet medical need for safe and effective therapy in this group of patients. As you move into a first-line non-small cell lung cancer, the treatment is somewhat segmented by the PD-L1 expression levels. In high PD-L1 expression group, IO monotherapy was most commonly used and TIGIT pathway is seen as a highly promising based on the Phase II data from the [indiscernible] data. For majority of the patients that are PD-L1 low or negative, the current standard of [indiscernible] therapy is IO plus chemotherapy. TIGIT plus standard of care PD-L1 plus chemotherapy is being pursued in all-comer trial. We talk to a lot of treating physicians, there's a strong desire to replace chemotherapy in this setting and ADC like TRODELVY can play an important role in replacing the chemotherapy as the data emerges. As we move into an earlier line of treatment in stage III disease, the current standard of care is Imfinzi after chemo radiation and some of the novel IO including TIGIT and anti-CD73 are expected to move into that space. Based on recent approvals and readout, anti-PD-1 and PD-L1 therapies are moving into an earlier line of treatment in adjuvant and neoadjuvant therapies. We are very well positioned to be a key player in all these segments of non-small cell lung cancer with a novel ADC, TIGIT and adenosine axis inhibitors being evaluated across all PD-L1 subgroups. Our current clinical development plan. Further, all these segments of non-small cell lung cancer with near-term readout from Phase II studies like ARC-7 and EVOKE-02 that will inform us a broader strategy for transformational combination in the future. Based on some of the readouts from Phase II study, we also plan to double up very quick and rational combinations into earlier line of treatment, including in the adjuvant and neoadjuvant setting. I'll -- over the next few minutes, I'll discuss in detail pivotal registration study EVOKE-01 as well as provide you with some of the study design details on EVOKE-02 and a new disclosure Phase III study, STAR-121, a little later on. As I mentioned earlier, there's a huge unmet medical need in patients who have been treated with IO and chemotherapy. The current standard of care is either docetaxel plus or minus ramucirumab with a medium survival only for about 9 to 11 months. Many physicians view ADC as the most promising near-term agent in this setting, particularly due to non T cell mechanism of action and positive early data. It's a fairly large patient population with close to about 60,000 patients a year only in U.S. Top 2 ADCs like TRODELVY are seen as the most promising agent in this setting. Some of the early data from the -- with the TRODELVY for a new 132-01 study fairly show that TRODELVY has a single-agent activity in very heavily pretreated patients with non-small cell lung cancer. This data has been presented and published a while ago. In the intent to treat population, TRODELVY has an objective response rate of 17% with about 1/3 of the patient having some form of clinical benefit. And if you look at a waterfall plot, majority of the patients have some shrinkage in the tumor size. Very importantly, in a subgroup of patients with prior exposure to IO, the median overall survival in this group went about 14.61. And very importantly, safety data with TRODELVY in lung cancer is consistent with our established safety profile from bladder and triple-negative last breast cancer. With confidence in TRODELVY as well as looking at the totality of the data from Trop-2 ADCs, we initiated pivotal registration Phase III study in EVOKE-01. This study will enroll patients with metastatic non-small cell lung cancer who have previously received IO and platinum chemotherapy with radiological progression. We are also allowing patients with the actionable mutation if they have at least received 1 prior TKI and also meet the criteria for prior IO and chemo exposure. The study will randomize 540 subjects in 1:1 ratio to TRODELVY versus docetaxel with the primary endpoint of overall survival and a key secondary endpoint of other efficacy measures as well as safety and patient reported outcomes. The study is fully powered for a meaningful OS benefit. As I mentioned earlier, we're also including patients with actionable mutations. So there's a larger set of patients that's going to be enrolled in the study. Moving into a first-line non-small cell lung cancer, we have multiple shots on goal to evaluate transformative combination that could replace current IO and standard of care therapy. Just to draw to your attention that prior to IO, the standard of care chemotherapy in the setting has a response rate of around 20% with a progression-fee survival of around 4 to 5 months. Many physicians expressed a strong desire to replace platinum-doublet chemotherapy with more effective and safer therapy like ADCs. I'll be discussing a little bit more details regarding our Phase II EVOKE-02 trial. EVOKE-02 is a Phase II study to look at the TRODELVY and KEYTRUDA combinations in first-line non-small cell lung cancer in patients without actionable mutation. The study has 4 different cohorts. Cohort A and B will enroll patients and treat them with TRODELVY plus KEYTRUDA, and Cohort C and D will treat the patient with TRODELVY and KEYTRUDA with 4 cycles of carboplatin. There's going to be a short safety run-in prior to Cohort C and D to make sure that we do not have any unexpected overlapping toxicity from the drugs. Cohort A will enroll patients that are high PD-L1 expression and cohort B will enroll patients who are PD-L1 low or no expression. Primary objective of this trial is the objective response rate with key secondary safety endpoints. This trial will be initiating in the first half of this year. There's a very strong rationale to look at TRODELVY in combination with IO. TRODELVY causes immunogenic cell death, and many physicians believe that TRODELVY activity is expected to be much better in chemo-naive patients in the first-line setting. We really think EVOKE-02 could unlock multiple potential combination for TRODELVY in first-line non-small cell lung cancer as well as other solid tumors. As I've discussed previously, we are expecting TRODELVY plus KEYTRUDA to be additive and potentially synergistic in the first-line non-small cell lung cancer. As you saw from See, we have a very good safety data from the 2 drugs in bladder cancer in a fairly good large number of patients. Very importantly, based on the data from Cohort B, there's a potential that TRODELVY could completely replace a platinum doublet in PD-L1 low and negative segment. On the flip side, if we can safely combine TRODELVY with platinum and IO that could open up multiple opportunities, not only in lung cancer, but many other solid tumors because IO plus platinum doublet is the current standard of care in many diseases in the first-line setting. In parallel with the EVOKE-02, we are actively working with our partner, Merck, for a Phase III registration study of TRODELVY plus KEYTRUDA in PD-L1-positive non-small cell lung cancer. The details of the study will be shared with you in the future. The study is expected to start later this year. As you all know, end of last year, we opted in TIGIT and adenosine axis inhibitors from Arcus Biosciences. These Arcus opt-in assets provides us with a robust portfolio of novel IO agents that are going be backbone for non-small cell lung cancer program. Together with that opt-in, we have 2 ongoing registration studies ARC-10 and PACIFIC-8 as outlined here as well as the Phase II ARC-7 study with the near-term readout and very importantly, in ARC-7, we'll, for the first time, see the triplet combination of anti-TIGIT, anti-PD-1 and adenosine inhibition. As I mentioned a little earlier, first-line non-small cell lung cancer patients are segmented by PD-L1 expression. In PD-L1 high expresses, TIGIT has been explored in combination with anti-PD-1 therapy without chemotherapy. Very similar to what we have seen with anti-PD-1 agents, combining TIGIT with PD-1 and chemotherapy could potentially expand the benefit of TIGIT to other patient segments, including PD-L1 negative and low expresses. With full confidence in the TIGIT molecule as well as the overall TIGIT pathway, later this year, we'll be initiating a Phase III study of Zim and Dom in combination with chemotherapy in first-line non-small cell lung cancer. STAR-121 as we recently named is our Phase III registration study in first-line non-small cell lung cancer. This is regardless of histology and patients with all PD-L1 expression is going to be enrolled. We planned to enroll roughly about 720 subjects in 4:4:1 randomization into one of these 3 cohorts. Cohort A is our experimental arm where patients would be treated with Zimberelimab, Domvanalimab in combination with platinum doublet. Cohort B is the control arm, and just a standard of care chemotherapy of pembrolizumab plus platinum doublet. And we had a small cohort of cohort C of Zimberelimab with platinum doublet to satisfy the regulatory need for contribution of component. Patients will be stratified based on histology, PD-L1 status and region of enrollment. We really hope that this study will establish Zim and Dom as effective and accessible IO backbone to enable novel combination with other TIGIT portfolio assets in the future. It's really an exciting time to be here at Gilead. With a scientific framework that Bill outlined with all the assets in our hand, we are in a very unique position to develop very novel combinations that's going to deliver transformative therapy for lung cancer patients. What you see on the chart here on the right, our current ongoing combinations in the Phase I and Phase II. And what we see on the left, other potential novel combination that we can achieve based on a scientific framework. I also want to mention that later this year, we'll be initiating a lung platform study, which will give us a unique opportunity to evaluate these multiple combinations in a very efficient way. In conclusion, we are in a very unique position with all these assets in our hand to expand opportunities for patients with non-small cell lung cancer. We have a huge potential to build off of this space's current standard of care with drugs in our pipeline. Very importantly, I think the future of lung cancer patients is really bright, and we might -- we'll be able to deliver a very differentiated transformative combination to address unmet medical need for this disease. I'd like to move on and walk you through a GI and other cancers within the next few slides. Very similar to what you have seen in breast and lung cancer, our opportunities in lung -- our opportunities in GI cancers with our expanding portfolio is quite promising. We have multiple Phase II that's going to be reading out. That's going to inform our plans for Phase III registration study in very hard-to-treat GI malignancies. Our strategy here in GI cancer is to leverage TIGIT and adenosine axis inhibitors to unlock potential IO combination in hard-to-treat GI malignancies. We also have several ongoing Phase II studies with our own internal assets, including TRODELVY and magrolimab that will inform as future novel combinations that we can make a difference in this disease. Over the next few minutes, I'm going to walk you through several disease areas, including pancreatic cancer, microsatellite stable colorectal cancer and upper GI malignancies and walk you through several Phase II studies with the near-term readout that could lead up to our Phase III registration trials. With the Arcus opt-in with our [indiscernible] from Arcus, we have been developing our anti-CD73 molecule, quemliclustat in patients with pancreatic cancer. If some of you may have seen this data previously, the combination of queml, Zimberelimab and gemcitabine and Abraxane produces a very impressive responses as a first-line therapy in patients with advanced pancreatic cancer. This is a disease area with a very high unmet medical need and very little advances have been made over the last 10, 15 years. The impressive thing about this waterfall part on your right, it's not only increased responses, responses are very deep and very durable, which you don't typically see with a chemotherapy alone. This study, ARC-8 has completed accrual in the randomized Phase II portion with the near-term data readout that will help us to inform the future design for the Phase III study for this disease with very high unmet medical need. Switching gears and getting into a colorectal cancer, we have several opportunities that are being evaluated in the Phase II setting. Despite initial response to chemotherapy, metastatic stable colorectal cancer is another area where not a lot of major progress have been made over the last several years. These tumors are considered relatively cold and not responsive to traditional immunotherapy. CD47 is very highly expressed in colorectal cancer. And based on some preclinical models, there's a good synergy with CD47 in irinotecan and magrolimab is being evaluated in combination with bevacizumab and FOLFIRI in the second-line setting in the Phase II study. Very similar to pancreatic cancer, our colleagues from Arcus have ARC-9 trial where the tumor is being looked at in combination with Zimberelimab and bevacizumab and FOLFOX chemotherapy in second and third-line setting. The data readout from some of these studies will inform us regarding a future plan for registration study in this disease. Moving into other GI cancers. These include esophageal, gastric and GE junction adenocarcinomas. Although there have been recent advances with IO in combination with chemotherapy in this setting, the overall prognosis of these patients remain quite poor, and there's still significant unmet medical need to improve the outcome in these patients. Very similar to what we saw in lung cancer, we really believe that addition of TIGIT to PD-1 plus chemotherapy could play a significant role in this disease. In the Phase I trial, the Arcus has conducted with Zim and Dom, this impressive response in a patient with metastatic esophageal cancer who have been previously treated with chemotherapy and pembrolizumab. The pictorial that you see on the right is a sagittal cut of CAT scan. What you see the arrows are covering is very large metastasis in the liver from esophageal adenocarcinoma. After 6 cycles of treatment with Zim and Dom, there is a significant shrinkage of the tumor. This patient has been under disease control and continuing in treatment for over 2 years. In collaboration with our colleagues from Arcus, we'll be initiating a Phase II study of Zimberelimab and Domvanalimab combinations in upper GI adenocarcinoma later this year. The ARC-21 study will evaluate Domvanalimab and Zimberelimab either alone in the second-line setting or in combination with chemotherapy for FOLFOX in the first-line setting with the primary objective response rate. We'll leverage the data from this study to fairly quickly move into a Phase III registration study in this disease. So in summary, with current Phase II studies, we have a really good potential to unlock novel IO and chemotherapy combination in GI and other solid tumors. There's even a larger potential for future combinations, including TRODELVY and other Gilead assets. We are quite hopeful that these novel combinations will improve outcome in GI tumors that are marginally responsive to immunotherapy. Our near-term Phase II readout will unlock potential Phase III registration studies so that we can definitely impact the life of these patients. Exploring the TIGIT and adenosine access inhibitors with IO and other assets from our pipeline, including TRODELVY, we hope that we could provide a meaningful improvement to the life of these patients. With this, I'm going to pass over to Giri, who's going to go over Hem program.

Thank you, Bilal, and thank you, everyone, for your time today. I'm Giri Ramsingh, I'm the Global Development Leader for Hematology. I've been at Gilead for a little over 1.5 years. I'm a medical oncologist, physician-scientist researching and treating patients with cancer for the last 15 years with a focus on hematological cancers. I came to Gilead from Genentech, really feeling excited about the science and promise of magrolimab and to work on the next potential breakthrough in hematology and to be really part of this growing oncology team that you saw today at Gilead. Since the Gilead Kite hematology pipeline, it includes cell therapy, biologics and small molecule inhibitors. It's a broad pipeline across several indications, including 5 Phase III studies. I will focus on magrolimab's hematology indications and my colleague, Frank, will focus on cell therapies and beyond. Magrolimab is a first-in-class macrophage checkpoint inhibitor targeting CD47, it's binding to CD47 and cancer cell activates macrophages to phagocytose the cancer cells. The key to magrolimab's efficacy is combining it with the right combination partner to amplify the pro-phagocytic signals. A wide range of combination partners have been shown to activate these signals from preclinical models and across various tumor types. This includes monoclonal antibodies, immune checkpoint inhibitors, chemotherapy and hypomethylating agents, the strongest proof of concept for synergy has been demonstrated in hematological cancers with hypomythelating agents and monoclonal antibodies and our clinical development plan reflects this to the most advanced development plan in these indications. A quick update on the partial clinical hold for the magrolimab studies. The FDA has lifted the partial clinical hold for studies of magrolimab in combination with azacitidine in AML and MDS. These are our lead indications and the top priority. Enrollment has resumed in all pivotal studies in these indications. The response to partial clinical hold from FDA for lymphoma and myeloma, which is handled by a different division that's currently ongoing. DLBCL study was fully enrolled at the time of the partial clinical hold and multiple myeloma was just getting started, and hence, there has been no major impact to the program. Solid tumor studies were not impacted by the partial clinical hold. As discussed earlier in the presentation, magrolimab is being studied in several solid tumor indications. To answer key scientific questions on synergistic combinations and to generate proof of concept, including our portfolio combinations such as with Trodelvy. In hematology, we have a lofty vision for magrolimab. We have a broad and advanced development plan informed by a strong proof of concept in areas of high unmet medical need with near-term approval opportunities in acute myeloid leukemia and myelodysplastic syndrome. In addition to addressing these unmet needs, our strategy is really to establish magrolimab combinations as backbone for future therapy. We are the clear leaders in the CD47 space in hematology. We are well ahead of our competitors by several years and we are the only ones with ongoing pivotal studies in the U.S. and globally. We hope to address the needs of several thousand patients with hematological malignancies. Our near-term opportunities in frontline acute myeloid leukemia and myelodysplastic syndrome where there is strong proof of concept, but we have multiple other life cycle opportunities in broader hematological malignancies with the promise to move these to frontline in [ those ] medication. In this presentation, I'll be primarily focusing on the 3 pivotal studies in indications of first-line high-risk myelodysplastic syndrome, first-line TP53 mutated acute myeloid leukemia and first-line unfit acute myeloid leukemia. Now I'm going to discuss our lead indication, which is the high-risk myelodysplastic syndrome. These patients have a huge unmet medical need. It has been a challenging area for drug development with no new major class of drugs for nearly 15 years. The current treatment option is characterized by low response rates, which are not durable, transplantation, which is only curative option is applicable to a limited few because these patients are typically elderly with many co-morbidities. Hence there's a great need for developing treatments that are efficacious and safer for these patients. And magrolimab will be the first-in-class with no in-class competition in Phase III studies in the U.S. out of class competitors are expected with venetoclax and sabatolimab but magrolimab is the potential to be the best-in-disease with expected favorable benefit-risk profile compared to other novel combinations in this indication. Magrolimab has demonstrated a strong proof of concept in our early phase studies. This data was presented last at ASH2020. In combination with the azacitidine, the CR rates are almost doubled that up historical controls with azacitidine alone as we see on the right side. The blast clearance of the bone marrow is depicted in the waterfall plot. This data helped us secure Breakthrough Therapy designation, PRIME designation and PIM designation updated data with the larger sample size and longer follow ups will be presented at ASCO this year. With the strong proof of concept, we have initiated enhanced placebo-controlled Phase III study in this patient population. And this would be comparing magrolimab azacitidine to placebo azacitidine. This study has a dual primary end point with complete remission rate and overall survival. And the enrollment has been completed for this year end point, and this was not impacted by the partial clinical hold. The data readout is expected in the first half of 2023. This would be the first-in-class therapy successful and it has the potential to be the best-in-disease with a favorable benefit-risk profile compared to other novel combinations. Our second indication is frontline TP53 mutated AML patients. These patients have a uniform really dismal prognosis with all existing standard of care, and this includes intensive chemotherapy and nonintensive treatments with a median overall survival of just 5 to 7 months. The long-term survivals are extremely rare. And for me, personally, it has been one of the most heartbreaking things to experience treating these patients in the clinic with really no meaningful benefit with any of the treatment options that these patients have currently. P53 mutation, as we all know, it's one of the most challenging mutations in oncology to target. Venetoclax, which is the most recent and significant advancement in treatment in the AML in the last several decades does not appear to benefit this patient population. These patients are older compared to other AML subtypes and mostly are ineligible for transplant which is potentially curable. Hence again, there is a huge need for treatment that is safe and efficacious in this patient population, and we hope that magrolimab will be able to accomplish. Magrolimab's data from early phase studies have been quite encouraging in this hard-to-treat patient population. Shown here again is the data from ASH 2020. The initial median overall survival of 12.9 months in this patient is favorable compared to historical data with azacitidine alone. Azacitidine in combination with venetoclax or even intensive chemotherapy but the median overall survival is just 5 to 7 months, no matter what the current standard of treatment that's given to these patients. The blast clearance in bone marrow is depicted on the right side in the waterfall plot, where you see P53 in red and the wild type in blue. You see similar blast clearance in both wild type and p53 mutated. As mentioned earlier, though venetoclax offers responses, they are not durable, and there has been no meaningful impact on survival of this patient population. Updated data with more patients and longer follow-up will be presented at ASCO this year. With the strong proof of concept and high clinical confidence, we have initiated a randomized Phase III study ENHANCE 2. It's a bold study comparing magrolimab azacitidine to venetoclax azacitidine and intensive chemotherapy. The primary endpoint is overall survival. The patient population includes both fit and unfit for intensive chemotherapy. This study has a high strategic value for us. Venetoclax, as I mentioned, is the most recent improvement in standard of care in acute myeloid leukemia. This study offers the opportunity to go head-to-head against venetoclax and potentially establishing magrolimab as a backbone for future AML treatment. We can clearly see how the treatment for AML is evolving now with many nonintensive approaches using triplets or maybe even quadruplet in future just like in multiple myeloma. I remember as a medical student seeing multiple myeloma patients being treated with intensive chemotherapy in frontline. It's hard to imagine that now and AML is taking a similar journey. And magrolimab is part of the pioneering effort in trying to replace intensive chemotherapy to non-intensive treatment approaches, which is clearly the way the field is moving in future. So as I mentioned, there's a strong desire to replace intensive chemotherapy, which is quite toxic. These patients stay in the hospital for over a month and nearly 10% of them die from complications and the study could be the first step in replacing intensive chemotherapy. Our third pivotal study is in frontline, unfit AML patients. Patients who are ineligible for intensive chemotherapy have a significant unmet medical need. Despite recent advances with venetoclax, the CR rate is less than 40%, median overall survival is less than 15 months, which is clearly suboptimal. Non-intensive treatments are largely considered incurable without a bone marrow transplantation. And again, these patients don't tolerate bone morrow transplantation because of their age and comorbidities. And there is a huge need for treatment that is efficacious and tolerable. we have an ongoing investigator-initiated study at MD Anderson with the triplet combination of magrolimab, venetoclax and azacitidine in this indication. And this data was presented at ASH 2021. The study here showed a very impressive CR rate of 64%, which is a significant improvement over the recent standard of care with venetoclax, which is 37%. P53 mutated unwild type showed similar responses. The responses were deep, as shown by the minimal residual disease data here. The tolerability appears comparable to venetoclax azacitidine alone. And with the data like this, we expect to see a survival benefit. This study is currently actively enrolling at MD Anderson and was not subject to the partial clinical hold. With this data, we have initiated ENHANCE-3 Phase III studies. Our strategy here is not to replace the existing standard of care like with ENHANCE-2 but to build on it, magrolimab, the first CD47 molecule is the first drug to go into the Phase III study globally in this patient population. The study compares the triplet magrolimab, venetoclax, azacitidine to the doublet venetoclax azacitidine with the dual primary endpoint of CR and overall survival. Our first opportunity to file would be based on a CR endpoint and the data readout is expected in the second half of 2020. We've known immune system to play a major role in these diseases for decades. And in fact, bone marrow transplantation is the type of immunotherapy that has been used to treat hematological cancers for several decades, including AML and MDS. But surprisingly and disappointingly conventional T-cell immune checkpoint inhibitors have not shown a benefit in these diseases, but showed a benefit in some tumors where transplant did not work. It did not make sense then, but we are just beginning to make sense as to how the immune system works. The magrolimab is expected to be the first major class of immunotherapy drug to show a benefit in these diseases, and I'm really excited about that possibility on really getting magrolimab to patients very quickly. And finally, in addition to the pivotal studies we discussed in AML and MDS, magrolimab is being broadly studied across various indications in hematology in early phase study, including several novel combinations and we hope to bring these to late phase studies in future. With that, I'd like to hand over to Frank to go over cell therapy and beyond. Thank you.

Thank you very much, Giri. Hi, everyone. My name is Frank Neumann. I'm the Global Head of Clinical Development at Kite. I'm a hematologist oncologist by training, and I joined Gilead Kite about 15 months ago. Prior to that, I worked at Takeda and bluebird in cell therapy and prior to that MD Anderson in Germany in academia. Today, I'm honestly as excited, inspired and proud to be part of the Gilead Kite family than I was on the first day 15 months ago. I think Kite is and remains a leader in cell therapy and we differentiate ourselves from the competition by focusing solely on cell therapy on a global scale. And Kite has had a huge impact on patients' lives in the past. And we plan and we will continue to do so. And I'm glad that you allow me to lead you through a few slides that will tell you more about how we're going to do this. Now, in a nutshell, Kite's singular focus is cell therapy to treat and potentially cure cancer. The strategy, therefore, is advancing from establishing cell therapy as a viable approach in oncology to actually delivering revolutionary therapies to more patients. And top line growth drivers here include Yescarta second-line large B-cell lymphoma. We just got approved almost 14 days ago. Class share expansion, geographic expansion, including the Daiichi Sankyo and Fosun Kite partnerships in Asia. And of course, I lead you through our approach is to advance a multi-modality next-generation pipeline driven by best-in-class research capabilities. Now let me show you first maybe 2 examples of how Gilead and Kite has really had a huge impact on patients' lives, has delivered hope to patients. And this is data that we presented last year at ASH where Yescarta demonstrated impressive and durable survival benefits 5 years post-treatment in third-line plus relapsed/refractory large B-cell lymphoma. 43% of the patients were alive at 5 years. And most interestingly, striking to me, honestly, is that 92% of these patients were alive at 5 years, and they did not need any additional cancer therapy after the onetime infusion of Yescarta, which I think is quite impressive. The second example where we take -- we took the challenge is in second-line relapsed/refractory large B-cell lymphoma. As you know, probably better than I, the outcomes remain poor. And despite transplant being the historic standard of care, it has significant challenge and reflected in our most recent approval and the fact that we are now in the NCCN guidelines, we think we will become the new standard of care, and we have written a little bit of history for these patients. Now this is driven by this data, which we think is really shifting the paradigm. That was the first and largest Phase III in that patient population was the only primary analysis with the longest follow-up, met our primary endpoint, and we had clinically meaningful improvement with a median EFS 4x longer, 2.5x more, 2 years EFS 33% higher ORR, and we doubled the CR rate in this patient population with a safety profile consistent with prior studies. Now based on that, our ambition is really to reach more patients, 25,000 and plus at 2025. And we are on track with that. We have today treat a little bit over 6,800 patients. So we think we are well equipped, and we will make it in 2025 to reach even more patients with our therapies, in particular, Yescarta and Tecartus. Now how are we planning to do this? Well, number one, we're going to defend and stay the undisputed leader in cell therapy. We are advancing a multimodality next-generation pipeline. And I'm going to talk about it a little bit in more detail. We are working on manufacturing improvements and innovations and also we are advancing the science through best-in-class research. Now in detail, that is our pipeline. And as I alluded to, we are planning to treat 25,000 patients by '25, basically through life cycle management of Yescarta, a frontline Phase III in high-risk patients with large B-cell lymphoma, advancing the third line indication for follicular lymphoma into second line characterize the profile of Yescarta in the outpatient setting. And last but definitely not least, rare B-cell malignancies, we're going to explore Tecartus' efficacy. Now while we are probably almost likely the ones to chase or be it in displacing current CD19 therapies, we are doing this effort on our own. So we'll talk about KITE-363, which is already in Phase I. We are also exploring next-generation CD19-targeted CAR-Ts with dual targeting CAR-Ts and novel targets and all of this we are doing with different cell therapy modalities, autologous and allogeneic and different approaches to improve the speed of manufacturing. Also, we are building together with Gilead, a leading AML franchise. KITE-222, which we'll talk about, is already in Phase I, and we are exploring other targets in cell therapy modalities to address this huge unmet need for patients. And at the same time, we are expanding the promise of cell therapy here into solid tumors, KITE-509, a GPC3 targeting asset to treat and help patients with hepatocellular carcinoma and with activities ongoing in multiple myeloma and T-cell lymphoma. Now why are we so excited about going into the frontline setting with Yescarta is really driven by the data we have seen in ZUMA-12 where we have treated a very tricky to treat patient population frontline with high-risk large B-cell lymphoma. What we saw, we think unprecedented was an 89% ORR rate, high rates of rapid and durable responses with 78% complete responses with only few percent of these patients remained in response. And that really prompted us to move forward and have discussions with the agency about Phase III in this difficult-to-treat patient population, front-line, high-risk that is about to start in the second half of this year. Then very, very important for the patients and us is to further characterize the outpatient profile of Yescarta. There's an increasing demand from patients to be treated in outpatient setting. And currently, Yescarta is the only CAR-T cell therapy with label information that allows the use of prophylactic corticosteroids. And together with the new safety management guidelines that we have tested in Cohort 4 and Cohort 6 of [ similar one ] based also on the feedback of our investigators, this is the opportunity to characterize the outpatient profile and help even more patients with large B-cell lymphoma. As I alluded to, this Phase III trial where we expect the FPI to be in the second half of '22. There's a great opportunity to go into earlier lines with Yescarta in follicular lymphoma, where we are approved in third line plus. And this is really a great opportunity, as I said, to go into second line. The next trial about Tecartus life cycle management is great and exciting for me because based on the feedback from the field, based on the feedback from our investigators and patients, we are exploring the effects of Tecartus in 4 underserved and unmet needs, Richter's transformation, Waldenström and Burkitt's lymphoma and finally, hairy cell leukemia, and this trial is expected to launch in 2023. Now if we go away from the life cycle management, a bit into the early development, I alluded to already that we are launching to become an AML franchise. And the first trial that is already in the clinic Phase I dose escalation is KITE-222 targeting CLL1, which is a unique target because it's almost ubiquitously expressed on AML blast and not so much to almost 0 on normal bone marrow cells, making it the perfect target for CAR-T. And I'm more than excited in the future to update you about the results. Again, Phase I is ongoing and we will see if this is a potential to bridge to transplant or maybe even a stand-alone therapy on its own. Now talking about replacing current CD9 approaches cannibalizing Yescarta and Tecartus, we had started in the clinic KITE-363, which is a bicistronic CD19, CD20 dual-targeting CAR-T, which is really addressing the unmet need of patients who relapse and lose their expression of CD19. And this construct really has still a high anti lymphoma potential as the CD19 arm is based on Yescarta that is already very, very doing well in the clinic for patients. Now this is our move into solid tumors, expanding the hope of cell therapy, where we have KITE-509 that is a GPC3 targeting CAR-T. And as you know, most patients with liver cancer have elevated serum TGF beta. And this really correlates with poor disease outcome. And what we haven't disclosed here is the walking of the TGF-beta signal, which we think will be a key differentiator of this GPC3 targeting asset in the near future. Now with all these autologous approaches, we clearly believe that allogeneic approaches will play a significant role for patients in particular because this will address 1 question, availability -- fast availability of sales. And we have placed our bets on healthy donor CAR-T cells, iPSC-derived CAR NKs and healthy donor car iNKTs. And together with our collaborators, Appia, Shoreline and Sangamo, this is our approach to come up with an off-the-shelf solution to increase the safety, lower the cost of goods, increase patient access and convenience and also these approaches coming from healthy donors might mitigate poor cell fitness for certain diseases. I'm not going to go into too much detail of this slide. This is just to show you that with these 3 approaches, we will be providing an off-the-shelf option. We are looking into opportunities to address the risk of graft and host disease and also the allogeneic CAR NKs offer us the advantage to lower toxicity of the approaches that we are currently using. Now to address the availability of cells and generate a situation where patients might have to wait for definitely fewer times than currently, we are advancing rapid and enhanced manufacturing innovations. While we are still having an industry-leading standard of about 17 days of manufacturing and sterility testing by focusing more on juvenile, T cells, less differentiated T cells, we think that we'll have the potential to improve the product potency. We might be able to lower dosages. Definitely, we are working on reduced turnaround time, reduction in costs. And also, we are aiming for a more robust manufacturing with lower cost of goods. And with these approaches, we are very confident that we'll be able to reduce the time of manufacturing significantly and potentially address the long wait time for patients for their cells. Now looking at the research priorities. These are the 3 pillars that our research group and obviously, the rest of us, this is the future, are very, very excited about. One is optimizing cell enhancements. So we're working on optimizing the CAR architecture, but at the same time, [indiscernible] and his group are working on intrinsic, epigenetic reprogramming approaches and also extrinsic cytokine combinations to modulate the tumor microenvironment to enhance persistence and fitness of the cells in [indiscernible]. Now the second pillar for us extremely important is our translational research. As I alluded to with 6,800 patients and more being treated, we have the largest and growing proprietary data lake in cell therapy. And we are in the process of asking and answering very important questions in cell therapy with this data, who is susceptible for toxicity, what might predict efficacy and others. Now last but not least, and that's the third pillar, which really, really excites me, and I want to leave that as my last slide is what we do expanding beyond traditional CAR-T cell therapy in CAR-T cell manufacturing. On the one hand, we are working diligently on nonviral delivery for ex-vivo CAR-T generation thereby avoiding the known disadvantage. There's a lot of advantages but also the known disadvantages for viral delivery for ex-vivo CAR-Ts. But what I think is really most exciting is our approach is to generate CAR-T cells in vivo following our strategic investment with the ORNA company to use mRNA and certain transport mechanisms to T cells to generate the CAR-T cells in vivo. So avoiding to having to [ raise ] the patient having the way for the success of whether these cells can be delivered to the patient. We are extremely successful, a 97% success rate industry-leading, but this would really be something we'd be very excited about in vivo CAR-T generation. Now in summary, I hope I conveyed the message that Kite within Gilead is changing the way cancer is treated. We are the undisputed leader in cell therapy, and I hope I could convince you that this is a good strategy to remain the undisputed leaders. We're advancing multi-modality next-generation pipeline. We're working on rapid manufacturing and innovation, and we are advancing the science through best-in-class research. And with this, I'd like to hand it over to Jackson and Bernard, and thank you very much for your attention.

Great. Thanks, Frank. So I'm Bernard Fine. I lead the early Clinical Development Oncology Group at Gilead. I joined Gilead about a year ago to take on this role after over 15 years in early clinical development oncology at Genentech. And I was really excited to come to Gilead and join this growing oncology group, really to help build and grow the overall program, especially early development. And so I really appreciate the opportunity that Jackson and I have to tell you a little bit about early oncology at Gilead. So I think one of the key points I'd like to make is that really -- the key to success in early oncology, early clinical oncology is having a broadly diversified portfolio. And as this slide illustrates, we're already there in that sense. We have molecules spanning the breadth of different mechanisms of action, spanning the breadth of our oncology scientific framework. You see that the various molecules listed on the right. I'll spend a little bit of time highlighting just a few of these to give you a sense of the type of programs we have and then the scientific rigor with which we're selecting and advancing programs. Before doing that, I think just one other thing to emphasize is how we've gotten to where we are in early clinical development. And that is through both internal programs, internally developed programs and through collaborations. And as this slide illustrates, right now, we have roughly an equal balance of programs that we are executing ourselves, so the one shown on the left and those that are being executed by our partners, the ones shown on the right. And this is, I think, going to continue to be a theme that we will continue, for sure, as you'll hear from Jackson developing internal programs and that may become actually an increasing part of the balance. But we'll also continue to work with external partners. And through both internal and external work, we anticipate that we'll be filing INDs for our 2 to 3 new programs in the coming year and probably a pace similar to that in the years to follow. So in the next few minutes, just to give you a sense of the programs, I wanted to talk a little bit about four examples of the programs we have in early clinical development. The first one to start with is GS-9716, an MCL1 inhibitor. The MCL1 is an anti-apoptotic molecule that's thought to be important in cells resisting apoptosis across a variety of different tumor types, both hematologic and solid tumor. GS-9716 is a potent, selective, orally bioavailable molecule that we think because of its superior potency in PK relative to competitors, has the potential to be a first-in-class molecule in solid tumors and best-in-class in heme malignancies. It has picomolar binding affinity to human MCL1. And based on preclinical data is broadly combinable with chemotherapy, targeted agents and IO agents as shown on the lower right, this is just a couple of examples from mouse tumor models of breast cancer, showing both single-agent activity of this molecule and very interesting activity in combination with Trodelvy in triple-negative breast cancer model. And these data were just presented at AACR, just a couple of -- just earlier this week. This program is currently in a Phase I study in solid tumors, and this Phase I study includes testing combinations, including with Trodelvy. And we're also now moving forward with a Phase I study in heme malignancies that we hope to get started fairly soon. Moving on to the next example, GS-1811. This is an antibody targeting CCR8 that we acquired from Jounce and that we are executing. CCR8 is highly expressed on regulatory T cells in solid tumors, but not on the majority of circulating regulatory T cells. This antibody is designed to deplete tumor-infiltrating T regs and thereby remove that -- the immunosuppressive effect of these regulatory T cells and restore T effector cell function in solid tumors. And particularly interesting in combination with PD-L1 checkpoint -- PD-1/PD-L1 checkpoint inhibitors. An example, preclinically, shown on the right side of this slide shows the combination activity of an anti-CCR8 monoclonal antibody with anti-PD-1 and showing the interesting combination activity. So this study -- this molecule is currently in an ongoing Phase I clinical trial that initiated early -- middle of last year. And this trial does include the combination with the PD-1 antibody. As this moves forward, we think that this molecule really has the potential to be first-in-class with activity in a broad range of tumors and the potential for a combination with a broad range of therapies both established therapies and the range of different molecules you've heard about in our pipeline. So these are 2 examples of molecules that we are executing. And then 2 examples of molecules that our partners are conducting Phase I trials on. The first is Pionyr's PY314. This is a monoclonal antibody targeting TREM2. TREM2 is expressed on immunosuppressive tumor-associated macrophages or TAMs and the idea of this antibody is to bind to TREM2 and deplete the immunosuppressive tumor-associated macrophages, thereby relieving the immunosuppressive effect and resulting in improved cancer immunotherapy, particularly interesting in combination with anti-PD-1 antibodies, but also with a broad range of other molecules. Example of preclinical activity supporting this hypothesis is shown on the lower right. These are data presented at AACR last year showing a combination activity of a mouse version of PY314 and anti-PD-1, showing very nice combination activity. So this molecule has already completed dose escalation, both as a monotherapy and in combination with a PD-1 antibody and is now enrolling in expansion cohorts, both in monotherapy and PD-1 antibody combinations in defined tumor types. And then finally, the last example to share with you is Arcus' AB521, HIF2 alpha inhibitor. So HIF2 alpha is important in VHL driven cancers such as clear cell renal cell carcinoma and potentially also in other hypoxia associated cancers. The molecule that Arcus has developed has particularly favorable molecular characteristics as shown on the right side of this slide. These are data presented just about a month ago at ESMO TAT, showing really nice properties of binding to HIF2 alpha and inhibiting the downstream effects of HIF-2 alpha. As many of you may know, Merck has a HIF-2 alpha molecule that really has shown clinical proof of concept in clear cell renal cell carcinoma and other VHL-associated cancers. So what we think this molecule really has the opportunity to differentiate from competitors, both by its favorable molecular characteristics and also through its -- our ability to combine it with other pipeline molecules including, for example, the adenosine axis molecules we opted in from Arcus. This molecule started in a Phase I healthy volunteer study late last year and is now moving rapidly through that trial. So we're looking forward to seeing that continue to advance. So hopefully, that gives you a sense of the early clinical development portfolio. And now I'd like to hand it over to Jackson to tell you a little bit about research oncology.

Great. Thank you, Bernard. And it's a pleasure to be speaking with you today. So my name is Jackson Egen. I lead the oncology research group here at Gilead. I joined Gilead about 10 months ago, having previously worked in oncology, immunology and immuno-oncology research groups at Amgen and Genentech before that. So similar to many of my colleagues, what drew me to Gilead was, first and foremost, the exciting therapeutic portfolio that you've heard about today with tremendous opportunity to help patients -- with tremendous opportunity to help cancer patients as well as actually give us some new biological insight into this disease. And I think the second draw was really, of course, the opportunity to jump in and contribute to the growth of this portfolio by expanding our efforts in oncology research. And that's exactly what I'd like to talk to you about today by shifting the focus towards our preclinical oncology portfolio. So within Research & Oncology, we are working to build a strong oncology therapeutic development engine that capitalizes on Gilead's existing strengths and while continuing to expand our internal capabilities. And so this includes developing transformative best-in-class small molecule therapies by leveraging our world-class medicinal chemistry group, extending our protein engineering capabilities to enable a competitive large molecule portfolio -- and finally, exploiting the tremendous synergy we have within Gilead research across our 3 therapeutic areas, namely virology, inflammation and oncology. I think a good example of this synergy is the HIV/HBV cure efforts being pursued in virology. So here are the same approaches that our virology group is taking to drive immune-mediated killing of every last virus infected cell in the body is very similar to and sometimes identical to the approaches we are taking in oncology to promote immune-mediated killing of every last cancer cell in the body. And I think some of our synergies can be found in our research efforts and inflammation as well as fibrosis. So our long-term success in oncology will be enabled by a broad preclinical research pipeline that allows us to [ advance ] new therapies to patients that complement our existing clinical stage portfolio. And so within the scientific framework that you've heard about today, I tried to highlight several of the key research areas we are pursuing. So first, we're working to expand our portfolio of therapies, capable of directly triggering tumor cell intrinsic death. This includes targeting, high-value prevalent oncogenic drivers by pursuing synthetic lethality targets as well as investing in efforts to understand the basic mechanisms of resistance to Gilead as well as standard of care therapies with, of course, the idea of developing agents to then treat these risks in patient populations. In addition, we are continuing to invest heavily in immuno-oncology, promoting immune-mediated tumor cell killing by developing new therapies, targeting T cells and NK cells as well as tumor-intrinsic mechanisms of immune evasion. And finally, continuing to -- our work to remodel the tumor permissive microenvironment, we continue to focus on regulatory T cell and macrophage biology as well as targeting immunosuppressive tumor and stromal populations. So as you can see on the right-hand side of this table, we have multiple preclinical programs covering each of these focus areas coming from both our internal efforts as well as our external research collaborations. And as Bernard mentioned, these programs are expected to give rise to multiple INDs in the coming years and beyond. And so to give you a flavor of the types of programs we are bringing forward, I wanted to highlight one of the INDs that we're expecting in the second half of this year. And that's the GS-9911 program. So GS-9911 is a novel inhibitor of DGK alpha or a Diacylglycerol Kinase alpha, with first-in-class potential. So we're not aware of any other DGK alpha inhibitor in the clinic or in advanced preclinical development. And so how does this inhibitor work? So diacylglycerol or DAG is a key second messenger signal downstream of T cell receptor signaling and critical for T cell activation. As shown on the bottom right, DGK alpha converts diacylglycerol to phosphatidic acid, thus limiting the amount of DAG present in the cell and functioning as a key negative regulator of T cell receptor signaling. So inhibition of DGK alpha by GS-9911, thereby potentially T cell activation and drives enhanced T-cell mediated tumor killing. And that's exactly what we've seen preclinically. And so to dive a bit deeper into this preclinical data, First, you can see that GS-991 actually functions through a novel mechanism of action, degrading DGK alpha in both human T cells and in vitro cultures as shown on the left, but also in the blood of nonhuman primates that were treated with this compound and you see the degradation over time. This degradation of DKG alpha is associated with a concomitant increase in T-cell activation as measured by enhanced cytokine production shown in the middle panel. And finally, this enhanced T-cell activation translates to increased control of tumor cell growth in mouse models, both as a monotherapy as well as in combination with PD-1 blockade. And so we're very excited by this program and its differentiated mechanism of action, and feel it has broad combination potential with many of the agents in our pipeline that you've heard about today. And so with that, I think today, Bernard and I have tried to provide you an overview of our broad and diverse early clinical development and research portfolio that we feel lays a very strong foundation for long-term success in oncology. This is a portfolio that spans the breadth of our scientific framework, is composed of both internal and external programs and importantly, has first-in-class and best-in-class potential. In addition, our robust and growing preclinical pipeline will enable continued expansion of our early clinical portfolio over the coming years. We'll continue to expand our internal capabilities, and as Bernard mentioned, leverage multiple exciting external research collaborations in order to advance multiple new therapies into patients over the coming year and beyond. And with that, I thank you, and I'll hand it back to Dan.

Thanks a lot, Jack, and thanks, everybody, for walking through that. Well, every time I see that, I get blown away about the potential for patients. And I just want to thank the team here, the team that's going to join us through Q&A. I mean, I guess it's important to note that to get this quality of talent and experience in the organization, it takes a very promising portfolio and a portfolio that's playing out already today. I saw the difference dramatically in the past 3 years outside of Kite, where we already had a world-leading position. With these 30 transactions just see the level of talent that has come here, purposely come here, because they see the impact they can make on patients in their career. So I just want to point that out and thank everybody as well. This won't be the last time. I said in the beginning, this is the first time for Gilead that we dug deep into the portfolio. But rest assured, as you can imagine, with such a breadth and depth of portfolio, it's going to evolve and we commit to you to keep you informed over time. I just want to end with this slide that I started with. We hope that you got a very clear understanding of the broad sense of the portfolio, many new disclosures here on trials. We've been busy and we haven't had a chance to update you. And we are doing that now, and there's a lot of progress now with the scale we have in the organization in terms of what we can do. But we firmly believe we have the right portfolio of partnerships and people to make it all possible. With that, I want to get right into Q&A. I'll ask Jacquie to help kick us off here. and we look forward to your questions. And I would ask the rest of the team in addition to the presenters, as you can see, we have some other members of our team joining here today that are all available for Q&A. So with that, Jacquie, over to you.

As Dan said, we'd now like to invite your questions. [Operator Instructions] So while we let people raise their hands for the audio questions, I have a couple that come in on the Q&A. The first one, can you comment on your confidence in A2a and the triplet combination with TIGIT given the ability to differentiate from others and your confidence that this will be clinically meaningfully better than just a doublet in lung cancer? Do you plan to move A2a to Phase III like STAR-121? what is clinically meaningful in your opinion?

Thanks very much. Bilal, we'll go right to you on that one, please.

Thanks, Dan. Thanks, Jacquie. Thanks for the question. It's, I think we're very excited about our ability to combine the triplet. And we really look forward to triplet data from ARC-7 to guide us with a future clinical development plan in lung cancer. We'll announce this as appropriate date as we start to get more data. I mean a triplet to be meaningful in lung cancer, definitely have to show better efficacy than what we expect from the doublets to move forward. And as you all know, there's also very intriguing data coming out of course with the adenosine pathways. But I think overall, and on this path, we need to be a little more validated in the treatment of lung cancer. And I think we are very well positioned to look at all these various combinations. As I mentioned in my presentation, we're also planning to launch a platform study that will address some of these novel combinations across different segments that will be coming up a little later. So they will probably give us more confidence and information to make a rational decision for clinical trial designs in the future.

Great. I think we'll stay with TIGIT for a second. I was hoping to get thoughts on the Skyscraper 2 results. And if you could talk about the tumor type, patient PD-1 expression characteristics relative to the CITYSCAPE study, and what that could imply for dom development?

Bilal, it's you again.

Thanks, Jacquie. So I'd just remind everyone about what CITYSCAPE and Skyscraper is a little bit and then maybe give a couple of my thoughts on it. As you all know, CITYSCAPE is a Phase II study in metastatic advanced non-small cell lung cancer in high PD-L1 express cells, where Roche has look at [indiscernible] in that setting, and show us a very impressive result from this. The Skyscraper 2, the one that you are mentioning to is an extensive stage small cell lung cancer, which is a completely different disease. And as we all know, small cell lung cancers are not as immunoresponsive as non-small cell lung cancer. Very importantly, getting into Skyscraper 2, there's very little clinical or any data to support. So if you talk to a lot of physicians, they are quite skeptical about activity of TIGIT in small cell because this has not really been very steady. So I really don't think the results of Skyscraper 2 have any impact on confidence in TIGIT pathway as a potential therapy and treatment of non-small cell lung cancer. I mean we are very confident of domvanalimab. I think it's also differentiating. I mean it's Fc-silent monoclonal antibody. We'll have to wait and see how this is going to play out as the data matures. But clearly, that's clear about is, I mean, from the tolerability profile with the Fc-silence you get less infusion reactions, which could be a very big deal and when you're trying to combine with chemotherapy and other agents. So we really look forward to you. I mean I think there are a lot of data that's going to be reading out in TIGIT, and I think we have full confidence in our program for TIGIT in lung cancer.

Let's go to a live question from Brian Abrahams at RBC. Can we have Brian? All right. We'll come back to Brian once we figure out how we can hear him. Go ahead.

Sorry about that. First of all, thanks so much for the really comprehensive overview. Super helpful. A couple of questions on magrolimab. What gave you in the FDA comfort that the AEs that led to the partial clinical hold read [indiscernible] unrelated to drug or manageable? And how do you ensure physicians and patients will have the same comfort. Can you talk a little bit more about the interim analysis of the Phase III MDS ENHANCE study, the bar there and how confident you are in the study's potential to hit that at the interim? And then lastly, what's -- what more is left to be done to remove the partial clinical hold in the other indications, DLBCL and myeloma. Is it just a matter of logistics since there are different parts of the agency or are there other considerations for those indications?

Thanks very much, Brian. All really good questions to dig into. I think I'm going to turn it over to Giri and Bill, if you want to add or Merdad, but let's start with Giri.

Thank you for that question. And first of all, I'd like to say that the partial clinical hold was placed after the FDA reviewed a subset of the data, really a small subset of the data. And since then, we have done a comprehensive analysis of the safety data internally. And the comprehensive safety data from the ENHANCE Phase III study, which is the largest and most mature Phase III study was analyzed by the independent data monitoring committee twice in the last few months. And in addition to that, the FDA has reviewed a comprehensive safety data from our key studies, including the ENHANCE Phase III study and that includes the [ underlying ] safety data. With all of that, the FDA very quickly released a partial clinical hold, and that shows the confidence in the safety that we have and we don't anticipate any major safety with magrolimab going forward. And with regards to the other indications, and our top priority was AML and MDS, and that's why we had to work quickly to get the partial clinical hold lifted. The effort is ongoing for the lymphoma and the myeloma program, and this is being handled by a different division in FDA and hence, there has been a decoupling of the whole lift with these indications, those efforts are ongoing, and we hope to get the lift -- the hold lifted quickly as well. And as you all know, the partial clinical hold did not impact the solid tumor studies and those studies continue to enroll during this time frame.

Thanks, Brian. Did we get all your questions? Sorry, go ahead, Giri, you had 1 more.

Interim analysis. The plan for the interim analysis holds. So the enrollment for the interim analysis was completed prior to the partial clinical hold was placed. And hence, that has not been impacted, and our confidence is still high with a positive readout for the interim analysis. I wanted to reiterate that the diffuse large B-cell lymphoma is completely controlled before the partial clinical hold was placed and the multiple myeloma was just getting started. So the impact on our program has been quite minimal with the partial clinical hold. And as you've seen, the lift was lifted, I mean the hold was lifted quite fast, even for our pivotal study. So I would say the impact has been on minimal for us.

Thanks, Giri. Appreciate that.

Let's go to Matthew Harrison of Morgan Stanley, please.

Great. Appreciate it. Thanks for the information. I was wondering if you could just comment on Trodelvy in HR positive. You're obviously starting this Phase III study in earlier lines. Can you talk about why you have confidence in bringing that into an earlier line setting and how much impact the TROPiCS-02 data had on deciding to do that?

Thanks a lot, Matthew. I don't know, Merdad, if you want to start and maybe Bill wants to comment as well or if you just want to handle it.

Maybe I'll start and if Bill or See have anything to add, please. As you guys can tell, the smart folks are the people who spoke today, so they're trying to keep me quiet all day. So Matthew, as I think we discussed before, the TROPiCS-02 data, we've been planning on going into earlier lines for a while, and that work has been ongoing. And certainly, with the outcome of TROPiCS-02, that certainly did not dissuade us in any way for about continuing that path. As See outlined, we have a number of efforts that are going to be ongoing in earlier lines of both TNBC and HR-positive and that work is going to continue to proceed based on everything we've learned so far on the activity of the drug.

Thanks. See, Bill, go ahead.

The totality of the data that you've seen today continues to give us really high levels of confidence in Trodelvy to keep on bringing it into earlier lines of therapy with the positive endpoint readout for TROPiCS-02 along with our approvals in TNBC and bladder cancer. And then you saw many other data sets today in other tumor types that continues to add on to our confidence that we can bring that level of efficacy forward to other patients and see if you want to add anything else here.

Our next question will be from Tyler Van Buren at Cowen.

Hey, guys, thanks very much for the presentations. A lot to digest. I wanted to ask about the STAR-121 study as well as TROPiCS-02. So regarding the Phase III STAR-121 study, exploring zim, dom, and the platinum doublets [indiscernible] Q4. Is this a committed trial? Have you seen a recent interim look for ARC-7 that gives you additional confidence to start this study? Or is this still based on the data you saw in the fall prior to the opt-in. And is the study start potentially contingent on the upcoming Roche Phase III data and/or positive ARC-7 data later in the year. And then on TROPiCS-02, you noted that patients -- you made the case that patients were much more heavily pretreated than the DESTINY-Breast04 patients. So in retrospect, why didn't you or couldn't you enroll less pretreated patients than TROPiCS-02. And at ASCO, could you do a subgroup analysis showing data for more or less pretreated patients?

Thank you, Tyler. Really great question. So Bilal, do you want to handle STAR-121 Tyler's question and then see if you would pick up on the TROPiCS-02 patient population.

Yes. Just to answer your question correctly, we currently -- we have full confidence in the TIGIT program, and we're not creating anything to get this getting started. So I think that will be a short answer to it. And we're still looking for more mature data from ARC-7 for us to evaluate.

Yes. With respect to the TROPiCS-02 questions. TROPiCS-02 was designed by Immunomedics prior to the acquisition. And the design was based on the earlier data that they saw in the 01 trial. And so a lot of the design was meant to replicate what we saw in 01. And so -- that design involved in the current standard of care for these patients. We had patients who had endocrine therapy and also CDK4/6. And it replicates what patients would be getting now in the current landscape. As far as addressing the question, can we look at earlier lines? The eligibility criteria did require 2 prior treatments. And so there's a limited amount that we can do with looking at earlier lines. There are other ways we could probably address that question.

Great. And I think, Tyler had a question around expectations for any subset analysis in the future, See.

Yes. As I said, I think there's just a limited number of patients because of the eligibility criteria. The criteria were stricter for TROPiCS-02. And so we don't have the same flexibility that we had with ASCENT.

Great. Thank you, See. Tyler, hopefully that handle both of your questions.

Thank you. I will take one from the Q&A. Chad, can you share any color on future development and expected data readout of KITE-222 in AML?

Great. Frank, right over to you.

Thank you very much for that question. This is a truly exciting program. And like with all Phase Is, I would say once the first patient treated despite the fact that the Phase I, obviously, is designed to assess some toxicity, people will ask, where is it working? What is the efficacy. And we just started mid last year, we don't have problems to enroll. It's too early to say something regarding efficacy and/or toxicity. What I will say, though, is that we expect data readout to your question from the Phase Ia primarily in the second half of next year. And what I will say is that the field is very, very excited about this target because again, it's always extremely difficult to find something that is not only attacking the blast, which is the key enemy in an AML, but also trying to avoid to suppress the entire normal hematopoiesis, which comes with a lot of toxicity, obviously, for these. -- almost always heavily impaired patients from a hematopoietic perspective. So CLL1 is a great candidate. Where this is going is really depending on what we see in the Phase I. One could imagine that this CAR-T construct is leading to be a bridge to transplant. One could also imagine, depending on what the efficacy looks like, that is a stand-alone treatment. As I alluded to, we are not resting to find novel targets, novel mechanisms to improve this construct. That is our first in the clinic and also novel avenues and other cell therapy modalities to conquer the huge unmet need in AML.

Thank you. I think we'll stick with Kite. Could you provide any color on the strength of the CAR T cell therapy business portfolio in terms of profitability and COGS?

Yes, terrific. So we've got Thad here who's the finance head from Kite. So Thad, I think if you can start with the color, Andy, if you want to add anything, but Thad go ahead.

Thanks for the question. With our leading position in cell therapy with Yescarta and Tecartus, we have really strong momentum, and we're growing over 40% annually this past year. And we expect that to continue with our second-line DLBCL approval. At the same time, we've been expanding our capacity and reducing our manufacturing cost per patient. So we have a great deal of confidence in our ability to deliver both growth and profitability in the near term and longer term. So Andy?

I would just -- I think that's great that I would just add that the business is doing really well. And we've made a tremendous progress over the last couple of years. We're really pleased with both where we are today and where we see the business going over the coming years, and it's all consistent with the opportunity that we envision for patients and for our shareholders when we did the deal 5 years ago. So I think we're largely on track and the business is really shaping up nicely. So thank you. Thanks for the question.

Building on that, the anticipated approval of our Maryland facility, which includes state-of-the-art automation of the cell therapy process will further enhance reliability, robustness and reduce cost of goods by requiring fewer operators per unit operations. So we're excited about deploying that technology in that facility and across the network over time.

Thanks, Jack. Thanks for the -- there on the Maryland facility. I appreciate that.

Great. We'll go next to Robyn at Truist for a live question, please.

I guess 2 quick ones. On -- there's a lot of focus on off-the-shelf cell therapy. I was just wanting to see maybe an agreement with Shoreline, where you see that fitting in to your -- as you said, you're the dominant cell therapy platform. Like at what point do you think that those programs become derisking of it and where do you see them fitting in as far as the -- or the community versus academic? And then big picture, I mean, you've really outlined a really aggressive, I think, plan for entering like the space and very competitive different disease areas. How do you see yourself fitting in? Are you going to be more segmented versus big pharma? Or how do you see yourself really grabbing like a good stronghold within like long ladder ? I mean these are tough areas where there's very competitive combination strategies already ongoing.

Thanks, Robyn. So on the first question, I think it's great to talk a little bit more about off-the-shelf. We have a number of colleagues from Kite here. And also maybe folks, you can also talk a little bit about what we're doing to reduce manufacturing time as a balance to off-the-shelf a bit. And then on the second one, I'd love to hear Bill and Merdad's comments on the broader oncology portfolio. So why don't we start? Frank, do you want to kick us off and call up on some of your colleagues on the off-the-shelf Shoreline?

Yes, absolutely. Thanks for the question. So Shoreline, Appia, Sangamo, I mean we remain absolutely interested in next generation of cell therapy medicines, but quite honestly, we believe it will take some time before allogeneic will be emerging beyond autologous therapy. And autologous therapy, as I alluded to, will move in the earlier lines of therapy, and it will be more difficult for allo to compete in the short to midterm. At the same time, we think it's -- we're very well positioned with what we're doing not to compete just in auto but in allo as well. And I think key here is that what is the problem we're trying to address. The problem we're trying to address is definitely the availability of cells, the off-the-shelf situation for patients that can't wait for a therapy for a couple of days or longer. And with this, I really also would like to turn it over to Jack because, as I alluded to in my presentation, not only we are looking into the allogeneic off-the-shelves opportunities but also we are trying to improve the manufacturing time, speed up the autologous approaches that we have. Because we do think that not so much in the near future but more so in the long term, these 2 will have both a role in patient care. But Jack, let me turn it over to you to talk a little bit about the activities we have on streamlining and speeding up the manufacturing.

I would love to, Frank, and also building on what you mentioned earlier about Appia and Shoreline our process and analytical development and clinical manufacturing capabilities are being highly leveraged to help advance both the Appia and Shoreline portfolios with the internal capabilities here at Kite and improvement with autologous cell therapies. That's been an important part of our partnership with those 2 companies. Regarding autologous manufacturing, we have currently an industry-leading 17-day turnaround time from apheresis to product release. We're exploring different process science technology, process sciences and process technologies to further shorten that time and analytical development technologies because of that 17 days, only a portion of that is manufacturing, about half. And the other half is analytical testing. So we have activities going on in both of those spaces, doing different process changes, different technical changes to shorten the process from manufacturing from maybe 8 days down to 3 to 2 to 1 day. So we'll just see how that evolves over time. It's going to require some dialogue and some conversation with the health authorities as we do something that's never been done before as we continue to do work with our research and PD teams to collect the data to justify it and support the changes we'd like to make. So we're very excited and optimistic and we have a fabulous partnership with both the EMA and the FDA, and the future is exciting. We're looking forward to the next several quarters.

Thank you so much, Frank and Jack. Just with the opportunity of Robyn's second question, I thought we might start with kind of an R&D angle and how we intend to differentiate and approach the market. And then I also think it might be helpful to hear from Janet and Warner on how we intend the customer-facing portion of our business to be able to compete and differentiate. But should we start on the R&D with perhaps Merdad, Bill or Flavius or Jackson commenting, who wants to start? Maybe Merdad, do you want to start? Or do you want to build a start?

Maybe I'll take -- I'll do a brief and then I'll hand it off to Bill. Maybe the main comment I want to make is we didn't undertake this, I think, lightly. And I mean that a couple of years ago, when we made the decision to go into oncology, it wasn't -- we didn't sort of say, let's see how it goes. We wanted to be really committed to being competitive in oncology. And hopefully, you're seeing that play out both in terms of the portfolio that we've accumulated. And equally, you've heard from people today that you probably haven't heard from before, but we've been able to bring people to Gilead from around the industry with decades of experience. And that's been a very deliberate effort on our part because we know this is going to be hard. I don't think we have any illusions that even when you're Roche versus Merck, it's hard, right? So we're -- it's difficult for everyone in oncology. And so for us, it's, I think, on the R&D side, in particular, but -- and in my shop in the medical affairs side, it's really about talent. It's around bringing the people with the experience who are going to be able to come in and bring that. And we've -- I think we've been very successful both on the portfolio side and on the people side. The last thing I'll say is we've also tried to be somewhat focused in our portfolio. We're not taking a broad shock on approach. The portfolio is very deliberate in the staging, if you will, from Phase III to the early stage so that we have the ability to establish ourselves in the marketplace while some of the earlier bets start to declare themselves. And I think that allows the Med Affairs teams and the commercial teams to continue to grow and get established. So it's been very deliberate on our part and really a very focused effort to make sure that we are able to win. Bill, maybe I'll hand it off to you and then Janet.

You covered the 3 buckets I was going to cover as well is really the pipeline, I think you hopefully you saw, Robyn, it's a great question, that we have a really differentiated pipeline, I think even compared to some of the big oncology players here where some of the combinations that we're looking at are just not feasible. And hence, we are also reaching out to some of those larger pharma companies around continuing to expound on our development opportunities. And then the people -- so many people you don't see today, not just the set of experts today on video, but a lot of people have been driven to come here by the pipeline, as you heard earlier, by many folks, including myself. And then we're also trying to look at a balanced approach on how we can basically do more with less, too. So we're purposefully reaching out to and developing a lot of different partnerships, as you've seen with both biotech as well as big pharma companies to continue to really expound on our development opportunities across our pipeline. And I'd say lastly, I don't think it were done with our pipeline. I think we continue to really look for those combination potentials that will -- as Jackson outlined in his research talk. Thanks for the question.

Yes, thanks. And thanks so much, before we go to the customer-facing, maybe any comments, Flavius, from you?

Thanks, Dan. I appreciate the chance to help people really, R&D, it's great to see this interest. I just want to kind of give an even more high-level answer to that question. And it's what really humbled me when I joined Gilead a year ago is this company has, in their DNA, 2 things that I've never seen at this level. One is speed. Remember, we, Gilead developed antivirals in record times, and that's what they won against bigger, more resourced players. And two, a very, very robust and thoughtful corporate development strategy, which again played out in the virology space. And I -- part of the research group, again, I'm humbled by finding those in Gilead's DNA, and I think we'll take full advantage of it as we move into oncology. Thanks, Dan.

Thank you very much. So we pivot to the customer-facing side, Janet. Do you want to start, then Warner? I mean 2 different stages of progress there but...

Yes. I have to say I just echo so much what others have already said on the call. I mean our ability to commercialize effectively really starts with having remarkable, high-impact products that are doing things that are incredible for patients. And so Bill and the team are just, every day, making them more excited about the future of our commercial organization. I'd also say it helps attract the right talent, as others have said, when you look at our portfolio today, we just did a build in the U.S. field organization. You can just see that we are able to bring in really great, experienced people. And I would say we need to be humble and we need to be hungry, and we're out there really willing to build those right relationships. But we're making the right investments and building the capabilities for some of the presentation that you made, Dan, that make me very confident either as Gilead or called during collaboration with Kite and working with Warner's team that we can really show up and make a difference with our customers. So Warner, I don't -- pass it over to you if you have a few things to add.

Yes. Thanks, Janet. And hello, everyone. I think on the Kite side, we're competing in this space in a multiple different ways. First, we already touched on the industry-leading and world-class data that we have. In particular, our customers are very attracted to and find very, very important the long-term data and the overall survival data that Frank touched on earlier, which is having a huge impact in the marketplace in addition to obviously the second-line indication that's coming now. In addition, you combine that with not only the data but our ability to actually to deliver cells consistently, as Jack touched on, 97% of the time, and do it in record time is actually another competitive advantage for us. The other way that we are competing, though, is by expanding globally beyond the U.S. and our European markets. We're starting to expand through our partnerships into Japan, into China, and we're also looking to expand into smaller markets into Asia and South America as well. And finally, I think, Janet, you touched on this. We say this at Kite all the time, cell therapy is a team sport. And I think what our customers have consistently said to us over the past few years is our ability to work together as a team to deliver these products consistently to patients. So the customer-facing group, our field teams, our Kite Connect support systems that really help differentiate Kite as a company that our customers want to deal with. So a combination of things I think we're working on. But to your point, we have to continue to evolve these and continue to be humble as we continue to make these things better over time.

Thank you. Thanks, Robyn, for asking that question that allowed us to get some perspectives from a variety of the colleagues here. And Jacquie, over to you then.

Thank you. Yes. We still have plenty of questions, but I know we've been going for a while now. So we'll try to wrap this up within the next 10 minutes. We will go to Umer at ISI for the next live question, please.

Can you hear me? Sorry.

Yes, yes, Umer.

So my question really is for future Phase III trials of TRODELVY, and I'm talking other indications beyond breast, so for example, lung and urothelial carcinoma, OS is being used as a primary end point and not PFS. Just curious what your thought process is there. And also, as I look at the EVOKE-01 trial, which is in lung setting of TRODELVY versus docetaxel, the comps on docetaxel relative to how TRODELVY tracked in your Phase I trial, it looks like that's a higher-risk trial. Would you characterize it as such or not? And then finally, just may I also ask, there's an Asian study of TRODELVY coming up in HR-positive breast. Is there anything from TROPiCS-02 that would suggest we could get surprised to the upside in that Asian trial?

Thanks a lot, Umer. Why don't we go to rapid order, I mean, Bill, do you want to answer the general OS/PFS question? And then we'll go to Bilal for EVOKE-01 and See for the Asian HR-positive study.

Yes, sure. Thanks for the question, Umer, and I'll quickly hand it over to See and Bilal. The end points are obviously always discussed with health authorities and based upon what is the expectation of delivering clinical efficacy beyond those current standard of care. So a lot of that also depends on which lines of therapy we initially go into for those pivotal trials. As I discussed before, the later lines, usually PFS, is a standard-of-care gold standard. And when we move into earlier lines, then of course, you're looking more for overall survival benefit. So that's kind of a high-level overview, but I'll hand it over to maybe See first to talk about the ex U.S. studies and HR-positive.

Sure. I think you're referring to the Everest-run trial for HR-positive patients. So that trial is designed as a bridge from the TROPiCS-02 for the Chinese population. And you noted that there's a difference in the eligibility between that trial and TROPiCS-02, and that's a result of access to the CDK4/6. The CDK4/6s are clearly the standard of care now, getting all the data that we have. They're in all the global guidelines. They're not globally available. And certainly in China, the access was a problem. So they've designed it without that requirement. I would note that this trial, we expect, will replicate a lot of the results we see in TROPiCS-02. Everest has already run a trial in triple negative that replicated the results that we saw in this sense, so we're confident that we'll see similar results with the HR-positive trial.

Bilal, on EVOKE-01.

Sure. Thanks for that question. You see in the both side of post-chemo setting, the standard of care is docetaxel, which I think is still pretty little in that setting for you to have a meaningful clinical improvement. You actually need to have a overall survival improvement. I think a marginal improvement in PFS in this setting is really not going to be transformative. So I think that's why EVOKE-01 is designed as a OS trial in that setting and appropriately to look at it. And based on all the data we have seen, we are very confident. I think docetaxel was a pretty low bar to beat in this setting, so we are very confident about the success of this trial.

Thank you.

Great. I'm going to pull 2 magro questions from the Q&A. For magro, can you comment on your confidence in using CR as a primary end point for approval in the Phase III ENHANCE III trial of the magrotriplet with Dan and ASA in unfit AML. And the second question is, any -- is there any particular steps that you need to do to mitigate future risk of clinical hold on magro development and MDS?

So Giri, right over to you then.

Thank you for that question. I can address the CR end point for the ENHANCE Phase III study, I can answer that in 2 points -- in 2 parts. First, the probability of technical success with the CR, but we've seen the CR data from MD Anderson's triplet data, a CR of 64% compared to the standard of care benefit. It's in a combination of 37%. So just from the technical perspective, we are highly confident about the probability of reaching the CR end point. The second aspect is with regards to the potential for approval based on CR. We've had conversations with the FDA on the end points and the potential for approval based on CR, and we are confident that we'll be able to get an approval based on the CR end point. With regards to the second question, as I alluded to before, we have done a comprehensive analysis of the safety data internally, independently through the BMC and recently FDA reviewed the data. And our program is continuing with no safety signals identified in our program. And then we feel very confident about our safety data, safety in magrolimab, and we don't anticipate any future risk for magrolimab and MDS or another indications.

Thank you. I'm going to sneak in 2 more. The first one is on the Q&A, is when can we see Phase I data for the CCR8 program? What are the key tumor types and combos for that program?

Great. I think that's Bernard.

Sure. Yes, thanks very much for the question. So maybe to start with, I think the key combination for the CCR8 is really with PD-1 antibody, PD-L1 antibodies, and that we already have that in the study, investigating that. In terms of tumor types, I think really the potential is very broad. We would expect this molecule to work in clinical settings in tumor types where PD-1 or other immunotherapies are active. And then I think potentially to go beyond that to the indications where PD-1 antibodies may have not shown activity if the presence of Tregs is one of the reasons for lack of activity. So we think the possibilities are very broad. And the possibilities for combinations with multiple other molecules, including those in our pipeline, is very broad. In terms of when we can share data, I think I can just say we have a lot of enthusiasm from investigators. The study is enrolling well. But I think it's a little too early to say when we're going to be ready to share data from that study. I guess maybe I would just answer more generally that from an early clinical development perspective, we're certainly very interested in sharing data when it's ready at scientific conferences. And as an example, to make a plug for a different molecule, our FLT3 agonist 3583 has shown clinical data and has the data to be shown at ASCO. So when we have data to share, we're certainly excited to do so.

Thank you, Bernard. I think our last question for today will be a live question from Mohit at Wells Fargo, please.

Can you hear me now?

Yes, I can hear you.

Perfect. And maybe a question on EVOKE-02 trial. And given that you mentioned that they raise a strong desire to remove platinum doublet from the chemo checkpoint combination, do you think the bar is superiority here? Or do you think you can -- I mean it could be replaced even with the non-inferiority with some safety benefits? That's the first question. And second part is how important is the safety in this combination given that your competitor is also trying a similar trial and they have some more ILDs versus TRODELVY? So how do you think about safety playing into this combination eventually in the marketplace?

Thanks so much. Over to you, Bilal.

Thanks, Mohit. These are excellent questions, and I'll try to address that. Obviously, as I alluded to in a pre-IO era, the overall response rate from platinum doublet and PFS are pretty low. So we're really expecting that moving TRODELVY into an earlier line of treatment, particularly in T1-naive patients will have a significant response. It's a little too early to speculate on what type of subsequent registration study is going to look like, but we really want to see the data from EVOKE-02 trying to help us make a decision about how aggressive we want to go versus what type of chemo that we want to replace, and it will go to really give us the flexibility to generate that data across these cohorts. Your question on safety is very, very important. TRODELVY is approved. It's on the market. I think the profile is pretty well defined. A lot of physicians are very familiar with managing some of the side effects like neutropenia and diarrhea [ hallucination and bruising ] in the past. I think when it comes down to, we still have yet to see the data with other drugs in combination with IO. I mean pneumonitis, as you alluded to, is clearly a risk. And we are very confident in that combination. I think you have seen the data from bladder cancer, it's about 40, 50 patients have been treated with KEYTRUDA and TRODELVY. And the expected safety profile is really consistent with what you expect from TRODELVY or pembro alone. So I think from that aspect, we have a really great advantage, and we feel pretty confident. And I think that's why we've been in discussion with Merck to move our registration fairly quickly in that. Thanks for the question.

That is all we have time for. Dan, anything you want to share before we wrap it up today?

I just want to say thank you to all of you for joining here today, for your interest in Gilead. I hope you got a sense for the real commitment we have in oncology, the progress we've made so far, the progress we're going to continue to make, thank my colleagues here. But far beyond those colleagues that are just here, I want to thank them. And please give special thanks to IR for pulling this off and herding the cows to get us to this stage. But please continue to give Jacquie and the colleagues at IR here or Gilead your feedback on how we can continue to meet your needs in terms of information as well. So with that, Jacquie, just a huge thanks.

Yes. Thank you to everyone for attending today. And of course, if you have additional questions or questions we weren't able to get to in the meeting, feel free to reach out to myself for the others on the IR team. Have a great day. Thank you so much.