Okay, Jacquie, you can go ahead. Meeting has started.
Thank you, Saeed. 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 malignancies. 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 two 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, Jacquie, 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 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.
This follows also our virology deep dive that we did in February that really established, you know, the depth and breadth of our portfolio in 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. 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. 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.
I would say that the portfolio that we have here at Gilead, in my mind, has some of the greatest patient benefits and values that I've seen in the industry. We look forward to, you know, 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. 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. 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. If I could have the next slide, please. This is important to note that, you know, 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. You know, we're really at the beginning of decades of innovation in oncology. You can see our conviction and our confidence around our 2030 milestones for oncology there on the right-hand side of this slide. On the next slide, it really gives you the framework for how we think about oncology within Gilead and how we're gonna approach today's discussions as well, which is really around articulating this pipeline of transformative science and the key strengths that Bill's about to get into in a few minutes. 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.
I'll come back to that, a little bit later in this setup presentation. Both are important and both have made significant progress over the past few years. We've created a pipeline, we believe, with exceptional quality, both on the individual asset level and in terms of combinations. We're gonna be spending most of our time today on the first of these topics, the pipeline of transformative science, to really dive into that with you. I just want to set up on the next slide, you know why, you know where we are in the journey, right? This has been very purposeful, since I've joined the organization and others have joined the organization around this strategic and thoughtful build of medicines within our portfolio.
I'll just point out that now it's been five 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. I would just point out that, you know, acquisitions like Immunomedics are only about 18 months old. You know, 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 pre-clinical assets that give us the confidence on the short, medium and long-term growth. This has all been purposeful.
As you'll see from Bill's presentation, how it links together from a scientific perspective 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. 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.
You can see, in addition to shoring up what each of those companies did individually, the progress since the close at the lower part of this slide as well. Still, as we'll explain to you today, just beginning to kind of scratch the potential of each of these molecules. 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. With that, now I want to. I'm delighted to hand it over to Bill to walk you through how we're approaching the development of this robust portfolio. Over to you, Bill, please.
Great. Thanks, Dan. I'm Bill Grossman, and I'm the oncology TA head here at Gilead. For some quick background on me, I'm a heme/onc transplant physician scientist, and I've spent most of my academic years performing bone marrow transplantations for oncology patients. I also ran independent basic research in 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 and cancer immunotherapies in larger pharmaceutical companies, as well as biotechs. My last position was as CMO at Arcus Biosciences. I've been here at Gilead now for approximately a year, and I'm very excited to be here and to help build out what I truly believe is already a world-class oncology pipeline.
I hope by the end of today's presentations, you'll feel the same. 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 and 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. 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 non-cancerous cells in our body. Hence, our scientific framework is focused on three core areas noted on the right-hand side of this slide, which really highlight the key biological pathways we are targeting. These core areas help guide our portfolio build out, as Dan mentioned, with assets that have complementary mechanisms of action and which have strong scientific rationale for combinations, as you'll hear more of 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 in result in robust tumor cell killing. Lastly, we are targeting therapies that remodel the tumor microenvironment itself, making it more promote a 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 three 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 span two, three, 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 sections today, we will highlight these multi-pronged, attack modes on cancer cells that we are 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 MCL-1, CCR8, and our partner-in TREM2 and HLA-G antibodies. Next, we've 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 pembrolizumab 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 are already establishing themselves as new standard of cares 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 this 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 of etruma and quemli. In fact, when you look at our significant progress in evaluating these novel combinations over the last just couple years alone, we currently have over 25 unique pipeline combinations being evaluated in the clinic today, including seven 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 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 potential to be used not only across the majority of heme malignancies, but also the potential to be used in solid tumors. The PD-1 TIGIT combinations, which have the potential to be used across most solid tumors or checkpoint monotherapy, or in combination with chemo, are already currently the standard of care.
Our development approach across these potential pipeline and the product assets leverage 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 activity, such as Trodelvy and our cell therapies, we initially establish 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 that are 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 further novel differentiated combinations.
As mentioned, Trodelvy is one of our pipeline in our product assets that has significant single agent activity leading to our broad development program as we shown here and 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 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 have approvals in large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and adult ALL.
As noted by our recent second-line approval in large B-cell lymphoma, we continue to move these highly active cell therapies early up into earlier 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 suboptimal 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, you know, 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 began 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 were using with our TIGIT and checkpoint combinations, as you'll see later on in our discussions. 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 I mentioned in this slide, there's and spread throughout the presentations today, we have a number of new disclosures as they're highlighted by the stars in each of the slides and sections. With that, I'd like to now hand it over to Janet 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 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. I joined Gilead two 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. I'm excited to be here today with the team to speak with you more about our emerging portfolio. Bill has just walked you through how we think about the potential of the pipeline and some specific examples. 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, you know, 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. 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 on the previous slide. Check marks are marketed programs, and the circles represent ongoing clinical studies.
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 this slide. 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. What's exciting and important to note is that we have data reading out across multiple programs in the near to midterm.
We break this slide up into 2022, 2023 and 2024, and 2025 +. For 2023 and 2024, I should note that we'll be providing more detail in time as we get closer. 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 in 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. 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.
Things like ARC-10, which looks at the 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. You'll be hearing a lot more about the specifics of these studies further on in the presentation. To wrap up this slide, I'd just like to reiterate our excitement for the many readouts to come as our oncology portfolio matures. With that, I'll pass it back over to Dan.
Thanks a lot, Janet. Thanks, Bill. I just wanted to also then emphasize, based upon what Janet and Bill just covered about the pipeline, emphasize the work we've been doing around building the capabilities. You know, it's really all about the people at the end of the day that you have in place with the right experience, with the right capabilities to help us make decisions and choices on 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.
I think that's really about people and choices that we make. Some of the examples you see here, we've had, you know, more than 2,000 oncology-focused folks join our organization over the past couple of years. You can see, you know, that's been in all areas from research and development to manufacturing. Certainly, you know, we've continued to invest in our manufacturing capabilities around biologics, ADCs, and cell therapies. Just to give a little bit more color to that, we've tripled our oncology field force over the past couple of years. Our ClinOps organization has more than 150 new members. We've had a real focus on expanding our real-world evidence and AI efforts, something that I have a lot of passion around from also my previous roles in the industry.
We've, you know, created a biologic center of excellence now down in Oceanside, California. Just recently, actually, we'll be opening a new plant for Kite in Maryland. These types of investments to make sure that the entire value chain has the expertise and the resources needed to be successful, we have done, and we will continue to do. I just wanna take this opportunity to just thank the teams you're not gonna see today, as well as those you will see today, that have been working incredibly hard to build out this oncology presence. Then on the next slide, you know, we don't intend to do it all ourselves. I mean, we have very much of a, you know, science occurs all around us, and partnerships help us leverage our bandwidth for our own internal medicines.
You can see a variety of those types of collaborations here. Everything from our collaboration, for instance, with Merck in working on operationalizing a Trodelvy study in first line cancer along with Keytruda, where that is the standard of care, to you know, collaborations with companies like Arcus, you know, who have a depth and breadth of experience in operationalizing both research and development programs in cancer that we value greatly and many others. 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.
From our long heritage and pedigree in HIV and 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 gonna be a lot of detail, but just to pull it back up, I think here are the three key messages. Number one, you know, we've carefully assembled and strategically and purposely and thoughtfully assembled a 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 at the plan 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 in our portfolio committee. Finally, you know, we're already a significant player in oncology, and we're 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. 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 gonna break it down to different disease states now, but within each disease states, 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. 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. With that, I'm delighted to turn it over to get us started in breast to See Phan, who heads our breast cancer franchise. Over to you, See.
Thanks, Dan. I'm See Phan. I oversee clinical development for our breast cancer franchise. I've been at Gilead for about a year and a half after spending over 10 years at Genentech, working on a variety of late-stage assets. As a medical oncologist, my primary focus had been seeing breast cancer patients in the clinic, and I maintained a breast cancer clinic even after I joined Genentech. 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. I wanted the opportunity to come over and really expand the number of breast cancer patients who could then benefit from Trodelvy. Why Trodelvy and what's unique about it?
Trodelvy as an ADC shares, you know, 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 was 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 two positive phase IIIs as well as approvals in two different tumor types, Trop-2 is really 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. 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. Finally, the last unique characteristic is around the hydrolyzable linker. Similar to other ADCs, Trodelvy is internalized once attaches to a target on the tumor cell, and the payload is released internally and affects cell kill. By also using a hydrolyzable linker, we can release the payload, SN-38, in the tumor microenvironment in a pH-sensitive manner. Given the moderate toxicity of SN-38, we don't have the off-target toxicity. Trop-2, the target for Trodelvy, is highly expressed on multiple solid 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 overexpression is the pattern in which it's overexpressed. You can see in triple-negative breast cancer that nearly 90% of the tumors will express moderate to strong staining, showing that the majority of triple-negative breast cancers will overexpress Trop-2. 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 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 where Trop-2 is overexpressed.
We have an expansive clinical development program for Trodelvy, spanning from phase I through phase III, and it meets four key strategic objectives. We plan to expand the global approvals in our primary indications. We've completed the ASCENT trial, and there are 38 approvals globally. We do need to support that with some additional clinical data in certain countries, and 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 one 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 have seen significant activity.
As necessary, depending upon what the standard of care looks like in the earlier lines of therapy, we will establish novel combinations. You can see that reflected in multiple phase III registration trials listed there. In addition, with all the solid tumors you saw on a previous slide which overexpress Trop-2, we plan to expand Trodelvy's reach into 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. In addition, we have a wide variety of phase I and II programs evaluating multiple other tumor types as well as novel combinations. For 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 Trodelvy in triple-negative breast cancer patients, that all triple-negative breast cancer patients should be treated with Trodelvy at some point during their natural history.
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 treatments, 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, we'll employ a similar strategy where we're looking to move it into earlier lines and ultimately include novel combinations. Our current clinical development program for breast cancer is listed here, consists of the two completed phase III registration trials. We have upcoming phase III registration trials with the intent of expanding the label. We have exploratory trials, over five, that are looking at novel combinations once we establish Trodelvy as a backbone in breast cancer.
If you look at how we array this clinical development program over the landscape for the two major types of where Trodelvy has 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. Ultimately, we want to move Trodelvy towards the left into earlier lines and into the curative setting. 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. You know, ASCENT showed tremendous efficacy in both PFS and OS with hazard ratios 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 in how Trodelvy performs. When we've done subset analyses and drill down into the ASCENT data, we still see the same consistency. 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.
Of note, these second-line patients, these earlier line patients, were the most refractory patients because to 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 the curative setting. Our plans for first line metastatic triple-negative consists of two trials, ASCENT -03 and ASCENT-04 . We have these two sister trials, and we intend to open them at the same site so that all breast first line metastatic triple-negative breast cancer patients will have these options. The reason for the two trials is that the current first line metastatic triple-negative breast cancer space is dictated by the recent approval of immunotherapies for these patients. Pembrolizumab is approved for first line patients whose tumors overexpress PD-L1.
In both cases, for PD-L1 negative and PD-L1 positive patients, chemotherapy still forms the backbone for their primary treatment. Our aim with these trials is to have Trodelvy replace the chemotherapies with superior efficacy and we'll combine with pembrolizumab for the PD-L1 positive patients and then give Trodelvy alone for the PD-L1 negative. In addition, we note that recently pembrolizumab was approved for the neoadjuvant and adjuvant space. Some patients who are entering the first line space may have previously had pembrolizumab in their treatment course. These trials have been designed so that physicians can opt to either retreat with pembrolizumab if they're PD-L1 positive, or not give pembrolizumab if they've already received it. Trodelvy will cover all of the patients available in the first line space. Moving into the curative setting.
Now, here's where we think Trodelvy could really have a significant impact for patients by improving the cure rate, for patients who are receiving a curative treatment. We've identified two 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 benefit seen with adding pembrolizumab to neoadjuvant treatment was primarily in the increase in the number of patients who got pathologic CRs. 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. The addition of pembrolizumab still really only gives less than 2/3 of the patients a pathologic CR.
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. 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 receive platinums, taxanes and anthracyclines, similar pretreatment to those patients who are enrolled on ASCENT and feel that introducing Trodelvy into that space could really significantly improve outcomes for these patients. We have two 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.
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 a 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. Okay, 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. While it's not as aggressive as triple-negative breast cancer, one in three cases of early stage hormone receptor positive breast cancer still relapse.
Once metastatic, their disease is incurable. We've already announced the beginning of March that we've hit the primary endpoint in our trial addressing these patients, TROPiCS-02. Reminding people what that trial schema looked like. The trial design was 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 of the typical standard of care treatments for these patients, including endocrine therapy, a targeted CDK4/6 inhibitor, and then two lines of chemotherapy, including a taxane, but no more than four lines. As a result, the patients who are enrolling in this trial were much later in their natural history compared to patients who potentially were 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, where we look forward to sharing it. We're having ongoing discussions with health authorities about the submission for 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 gonna be comparisons to another ADC in the breast cancer space, so we wanted to highlight the differences between the TROPiCS-02 trial and the DESTINY-Breast04 trial for Enhertu. We note that for TROPiCS-02, it's a pure hormone receptor positive trial. As such, all patients must have exhausted their standard of care treatments before going on the TROPiCS-02 and Trodelvy.
All patients required to have endocrine, CDK4/6, and at least two lines and up to four lines of chemotherapy. The difference between that and DESTINY-Breast04 is DESTINY-Breast04 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, correct. As such, we think that the patients on these two trials are not necessarily comparable. 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. Ultimately, we will look at the curative setting.
Beyond these registration trials that we're looking at for Trodelvy in a triple negative and hormone receptor space, we're also looking at novel combinations, utilizing a combination of either our own pipeline products like the MCL-1 inhibitor and CD47, magrolimab for CD47, but also in collaboration with other sponsors looking at their agents, such as pembrolizumab and Piqray. In summary, for breast cancer, we aim to bring Trodelvy to the majority of breast cancer. We need to address two 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 wanna 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. 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. 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. Given the current landscape in bladder, where multiple immunotherapies, in addition, another ADC is 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 two 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. Going over the bladder cancer CDP in detail, this is where we currently are in the second and third line post-platinum, post-immunotherapy space. We have the accelerated approval based on the TROPHY data and a 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 chemotherapies docetaxel, paclitaxel, and vinflunine. Again, enrolling the same patients that were enrolled in the TROPHY cohort one. This trial is open and enrolling right now, and we expect the last patient in in the second half of 2022. 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 bladder cancer. With that in mind, we have two cohorts in TROPHY where we are looking at the efficacy and safety and tolerability of combining Trodelvy with cisplatin. 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 remain cis-ineligible. With the plethora of immunotherapies now in bladder cancer, we feel that this gives us the 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 platinums who haven't recently progressed, the combination of Trodelvy and pembrolizumab was able to achieve a 38% response rate and 63% of patients had tumor shrinkage. This informs our plans to combine Trodelvy with 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-invasive bladder space. Three phase II trials are shown here, one with Trodelvy alone as neoadjuvant treatment. SURE-02 looks at perioperative Trodelvy in combination with pembrolizumab, and the RAD-SG trial is looking at bladder conservation, combining Trodelvy with radiation. We're 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 overexpresses 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, in that once patients have exhausted their androgen-based treatments, 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 could combine Trodelvy with the current androgen-based treatments, as well as various immunotherapies we have in our pipeline.
In addition, I wanna 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 one with a confirmatory study which we believe will lead to 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. We're looking opportunistically at other indications like prostate cancer. 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 industry for about close to 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 next few minutes is just to walk you through our portfolio in lung and GI tumors. As you saw from Bill's presentation, our oncology portfolio in 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 cell lung cancer is broad and deep, with multiple assets in various phases of development, as you see on this slide here. I'll walk 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 and immunotherapy, the overall prognosis of non-small cell lung cancer patients remain poor, with very low five-year survival rates.
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 our 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 the current standard of care in the first-line non-small cell lung cancer setting, which I will walk you through a little later on. Very importantly, with some of the very important data readout from the phase II studies, we'll be moving very quickly into an earlier line of treatment, including an adjuvant and neoadjuvant setting.
Gilead is in a unique position with a 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 three ongoing phase III registration studies and four ongoing phase II registration study with near-term readouts. In addition, we are planning for two 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 hand, we have a very near-term potential for some registration studies in lung cancer. As you see on the slide here, we have three 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 the 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 represent a unique opportunity to improve outcome for patients over current standard of care. In the second line plus setting, majority of the patients with non-small cell lung cancer progress after initial IO and chemotherapy. The current standard of care in this setting, unfortunately, still remains 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 CITYSCAPE data. For majority of the patients that are PD-L1 low or negative, the current standard of care therapy is IO plus chemotherapy. TIGIT plus standard of care PD-L1 plus chemotherapy is being pursued in ARC trial. We talked 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 you move into an earlier line of treatment, in stage three disease, the current standard of care is immunotherapy after chemoradiation, 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 cover 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 our broader strategy for transformational combination in the future.
Based on some of the readouts from phase II study, we also plan to develop very quick and rational combinations into an earlier line of treatment, including in the adjuvant and neoadjuvant setting. Over the next few minutes, I'll discuss in detail our pivotal registration study, EVOKE-01, as well as provide you with some of the study design details on EVOKE-02 and a newly disclosed 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 median survival only for about nine 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 the U.S. Top two ADCs, like Trodelvy, are seen as the most promising agent in this setting. Some of the early data with the Trodelvy for the IMMU-132-01 study fairly shows that Trodelvy has 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 a third of the patients having some form of clinical benefit. If you look at a waterfall plot, majority of the patients have some shrinkage in the tumor size.
Very importantly, in the subgroup of patients with prior exposure to IO, the median overall survival in this group was about 14.6 months. Very importantly, safety data with Trodelvy in lung cancer is consistent with our established safety profiles in bladder and triple negative breast cancer. With confidence in Trodelvy, as well as looking at the totality of the data from TROPiCS-02 ADCs, we initiated pivotal registration phase III study 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 one 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 a primary endpoint of overall survival and a key secondary endpoint of other efficacy measures as well as safety and patient reported outcome. The study is fully powered for 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 this setting has a response rate around 20% with a progression free survival around four to five months.
Many physicians express 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 four different cohorts. Cohort A and B will enroll patients and treat them with Trodelvy plus Keytruda. Cohort C and D will treat the patient with Trodelvy and Keytruda with four 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 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 cause 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 combinations for Trodelvy in first-line non-small cell lung cancer, as well as other solid tumors. As I have 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 C, we have a very good safety data from the two drugs in the bladder cancer in a fairly good large number of patients. Very importantly, based on the data from cohort B, there's a potential that the 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 a 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 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.
This 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 provide us with a robust portfolio of novel IO agents that are going to be backbone for our non-small cell lung cancer program. Together with that opt-in, we have two ongoing registration studies, ARC-10 and PACIFIC-8, as outlined here, as well as a phase II ARC-7 study with the near-term readout. Very importantly in ARC-7, we'll for the first time see the triplet combination of anti-TIGIT, anti-PD-1, and adenosine axis 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 expressers, 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 segment, including PD-L1 negative and low expressers. 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 zimberelimab 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. It's planned to enroll roughly about 720 subjects in a 4:2:1 randomization into one of these three cohorts. Cohort A is our experimental arm, where patients will be treated with zimberelimab, domvanalimab in combination with platinum doublet.
Cohort B is a control arm, and just a standard of care chemotherapy of pembrolizumab plus platinum doublet. We have a small cohort, 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 zimberelimab as effective and accessible IO backbone to enable novel combination with other Gilead portfolio assets in the future. It's really an exciting time to be here at Gilead. With a scientific framework and build outline with all the assets in our hand, we are in a very unique position to develop very novel combinations that's gonna deliver transformative therapy for lung cancer patients. As you see on the chart here on the right, our current ongoing combinations in the phase I and phase II.
What you see on the left are 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 the space current standard of care with our drugs in our pipeline. Very importantly, I think the future for lung cancer patients is really bright, and we will be able to deliver a very differentiated transformative combination to address unmet medical needs for this disease.
I'd like to move on and walk you through GI and other cancers within the next few slides. Very similar to what you have seen in breast and lung cancer, our opportunities in GI cancers with our expanding portfolio is quite promising. We have multiple phase IIs 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 combinations 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 our future novel combinations that we can make a difference in this disease.
Over the next few minutes, I'm gonna 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 a near-term readout that could lead up to a phase III registration trials. With the Arcus opt-in, with a collaboration with—from Arcus, we've been developing our anti-CD73 molecule, quemliclustat, in patients with pancreatic cancer. Some of you may have seen this data previously. The combination of quemli, zimberelimab, and gemcitabine 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 plot on your right is 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 colorectal cancer is another area where not a lot of major progress has 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 and [inaudible audio], 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 an 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 is conducted with zimberelimab and domvanalimab. There's this impressive response in a patient with metastatic esophageal cancer who had been previously treated with chemotherapy and pembrolizumab. The pictorial that you see on the right, is a sagittal cut of a CAT scan. What you see the arrows are covering is very large metastasis in the liver from esophageal adenocarcinoma.
After six cycles of the treatment with zimberelimab and domvanalimab, there's a significant shrinkage of the tumor. This patient has been under disease control and continuing in treatment for over two years. In collaboration with our colleagues from Arcus, we'll be initiating a phase II study of zimberelimab and tremelimumab combinations in upper GI adenocarcinoma later this year. The ARC-21 study will evaluate tremelimumab and zimberelimab either alone in the second line setting or in combination with chemotherapy FOLFOX in the first line setting with the primary objective of, you know, objective response rate. We'll leverage the data from this study to fairly quickly move into a phase III registration study in this disease. 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 would unlock potential phase III registration studies so that we can definitely impact the life of these patients. Exploring the TIGIT axis 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 gonna pass over to Giri, who's going to go over our heme 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 little over a year and a half. 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. This is the Gilead Kite hematology pipeline. It includes cell therapy, biologics, and small molecule inhibitors. It's a broad pipeline across several indications, including five 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. Its binding to CD47 in cancer cells 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 in 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 hypomethylating agents and monoclonal antibodies. Our clinical development plan reflects this with 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 and AML and MDS. These are our lead indications and our 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, is currently ongoing. DLBCL study was fully enrolled at the time of the partial clinical hold, and multiple myeloma was just getting started. 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 presentations, 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 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 and near-term opportunities in frontline acute myeloid leukemia and myelodysplastic syndrome. 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 indications.
In this presentation, I'll be primarily focusing on the three 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 curable. Transplantation, which is the only curative option, is applicable to a limited few because these patients are typically elderly with many comorbidities. Hence, there's a great need for developing treatments that are efficacious and safer for these patients. 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 has 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 ASH 2020. In combination with azacitidine, the CR rates are almost double that of historical controls with azacitidine alone, as we see on the right side. The blast clearance in 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 a larger sample size and longer follow-up will be presented at ASH coming this year. With a strong proof of concept, we have initiated ENHANCE placebo-controlled phase III study in this patient population, and this will be comparing magrolimab azacitidine to placebo azacitidine.
This study has a dual primary endpoint with complete remission rate and overall survival. The enrollment has been completed for the CR endpoint, and this was not impacted by the partial clinical hold. The data readout is expected in the first half of 2023. This will be the first in-class therapy if 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 non-intensive treatments with a median overall survival of just five to seven months.
The long-term survivors 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. TP53 mutation, as you all know, is one of the most challenging mutations in oncology to target. Venetoclax, which is the most recent and significant advancement in treatment in 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 has 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 five to seven 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 curable, and there has been no meaningful impact on survival in this patient population. Updated data with more patients and longer follow-up will be presented at ASCO this year.
With a 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 non-intensive approaches using triplet or maybe even quartet in future, just like in multiple myeloma. I remember as a medical student seeing multiple myeloma patients being treated with intensive chemotherapy in front line. It's hard to imagine that now.
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. 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. The study could be the first step in replacing intensive chemotherapy. Our third pivotal study is in front line 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.
Again, these patients don't tolerate bone marrow transplantation because of their age and comorbidities. There is a huge need for treatment that is efficacious and tolerable. We have an ongoing investigator-initiated study at MD Anderson with a triplet combination of magrolimab, venetoclax, and azacitidine in this indication, and this data was presented at ASH 2021. The study here shown sort of very impressive CR rate of 64%, which is a significant improvement over the recent standard of care with venetoclax, which is 37%. P53 mutated and wild 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. Under the data like this, we expect to see a survival benefit. The 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 study. Our strategy here is not to replace the existing standard of care like with ENHANCE-2, but to build on it. Magrolimab, the first CD-47 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 a 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 2024. We've known immune system to play a major role in these diseases for decades. 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.
Surprisingly and disappointingly, conventional T-cell immune checkpoint inhibitors have not shown a benefit in these diseases, but showed a benefit in solid 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 benefit in these diseases, and I'm really excited about that possibility and really getting magrolimab to patients very quickly. 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 studies, including several novel combinations, and we hope to bring these to late phase studies in future. With that, I'd like to hand it 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. Kite has had a huge impact on patients' lives in the past, and we plan and we will continue to do so.
I'm glad that you allow me to lead you through a few slides that will tell you more about the how we're gonna 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. 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 Daiichi Sankyo and Fosun Kite partnerships in Asia. Of course, I lead you through our approaches to advance a multimodality next generation pipeline driven by best-in-class research capabilities. Now, let me show you first maybe two examples of how Gilead and Kite has really had a huge impact on patients' lives, has delivered hope to patients.
This is data that we presented last year at ASH, where Yescarta demonstrated impressive and durable survival benefits five years post-treatment in third-line plus relapsed/refractory large B-cell lymphoma. 43% of the patients were alive at five years. Most interestingly, striking to me honestly, is that 92% of these patients were alive at five years, and they did not need any additional cancer therapy after their one-time infusion of Yescarta, which I think is quite impressive. The second example, where we take or 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're 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. It 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, 2.5 x more, two-year 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+ at 2025, and we are on track with that. We have to date treated a little bit over 6,800 patients.
We think we're 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 gonna 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 in a little bit, in more detail. We're 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. As I alluded to, we are planning to treat 25,000 patients by 2025, 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.
Last but definitely not least, rare B-cell malignancies, we're gonna explore Tecartus efficacy. Now, while we are probably or most likely the ones to chase or beat in displacing current CD19 therapies, we're doing this effort on our own. We'll talk about KITE-363, which is already in phase I. We are also exploring next generation CD19 targeting CAR Ts, but dual targeting CAR Ts and novel targets. All of this we're doing with different cell therapy modalities, autologous and allogeneic, and different approaches to improve the speed of manufacturing. Also, we are building, you know, 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.
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. We have 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 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, and 73% of these patients remained in response.
That really prompted us to move forward and have discussions with the agency about a phase III in this difficult to treat patient population, frontline high risk that is about to start in the second half of this year. 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. Together with the new safety management guideline that we have tested in cohort four and cohort six of ZUMA-1, 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 2022, is a great opportunity to go into earlier lines with Yescarta in follicular lymphoma, where we approved in third-line plus. This is really a great opportunity, as I said, to go into second line. The next trial about Tecartus lifecycle management is great and exciting for me because, you know, based on the feedback from the field, based on the feedback from our investigators and patients, we are exploring the effects of Tecartus in four underserved and unmet needs, Richter's transformation, Waldenström and Burkitt's lymphoma, and finally, hairy cell leukemia. This trial is expected to launch in 2023.
Now, if we go away from the lifecycle 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 zero on normal bone marrow cells, making it the perfect target for a CAR T. 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 CD19 approaches, cannibalizing Yescarta and Tecartus, we have 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. 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 scope of cell therapy, where we have KITE-509 that is a GPC3 targeting CAR T. As you know, most patients with liver cancer have elevated serum TGF-beta, and this really correlates with poor disease outcome.
What we haven't disclosed here is the blocking 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 one question, availability, fast availability of cells. We have placed our bets on healthy donor CAR T-cells, iPSC-derived CAR NKs, and healthy donor CAR iNKTs. 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. 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 three approaches, we will be providing an off-the-shelf option. We are looking into opportunities to address the risk of graft versus host disease. 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, you know, generate a situation where patients might have to wait for definitely fewer time 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. 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 three pillars that, you know, our research group and obviously the rest of us, this is the future, are very, very excited about. One is optimizing cell enhancement. So we're working on optimizing the CAR architecture, but at the same time, Francesco 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, and also there too.
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're 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, that's the third pillar, which really excites me and I wanna leave that as my last slide, is what we do extending beyond traditional CAR T-cell therapy and CAR T-cell manufacturing. On the one hand, we are working diligently on non-viral 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 T's.
What I think is really most exciting is our approaches 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. Avoiding to having to apheresis the patient, having to wait, for the success and whether these cells can be delivered, to the patient. We are extremely successful, 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 multimodality next generation pipelines.
We're working on rapid manufacturing and innovation, and we are advancing the science through best-in-class research. With this, I'd like to hand it over to Jackson and Bernard, and thank you very much for your attention.
Great. Thanks, Frank. 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. 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. I really appreciate the opportunity that Jackson and I have to tell you a little bit about early oncology at Gilead. 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. 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 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 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.
As this slide illustrates, right now we have roughly an equal balance of programs that we are executing ourselves, the ones shown on the left, and those that are being executed by our partners, the ones shown on the right. 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. Through both internal and external work, we anticipate that we'll be filing INDs for two to three new programs in the coming year and probably a pace similar to that in the years to follow.
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 MCL-1 inhibitor. MCL-1 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 the human MCL-1 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. These data were just presented at AACR 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. 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 is 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 Tregs, 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, pre-clinically, shown on the right side of this slide, shows the combination activity of this, an anti-CCR8 monoclonal antibody with anti-PD-1, and showing the interesting combination activity. This molecule is currently in an ongoing phase I clinical trial that initiated early in the middle of last year, and this trial does include a 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 that you've heard about in our pipeline. These are two examples of molecules that we are executing, and then two 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. 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 pre-clinical 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. This molecule has already completed dose escalation, both as a monotherapy and in combination with the PD-1 antibody, and is now enrolling in expansion cohorts, both in monotherapy and PD-1 antibody combinations in defined tumor types. The last example to share with you is Arcus' AB521, HIF-2 alpha inhibitor. HIF-2 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 HIF-2 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. 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 on from Arcus.
This molecule started in a phase I healthy volunteer study late last year and is now moving rapidly through that trial. We're looking forward to seeing that continue to advance. Hopefully that gives you a sense of the early clinical development portfolio. Now I'd like to hand it over to Jackson to tell you a little bit about research oncology.
Great. Thank you, Bernard. It's a pleasure to be speaking with you today. 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. 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 cancer patients as well as actually give us some new biological insight into this disease. 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.
That's exactly what I'd like to talk to you about today, by shifting the focus towards our preclinical oncology portfolio. Within research oncology, we are working to build a strong oncology therapeutic development engine that capitalizes on Gilead's existing strengths, while continuing to expand our internal capabilities. This includes developing transformative best-in-class small molecule therapies by leveraging our world-class medicinal chemistry group, expanding our protein engineering capabilities to enable a competitive large molecule portfolio. And finally exploiting the tremendous synergy we have within Gilead research across our three 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.
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. I think similar synergies can be found in our research efforts in inflammation as well as fibrosis. 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. Within the scientific framework that you've heard about today, I've tried to highlight several of the key research areas we are pursuing.
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, 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 resistant 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. Finally, continuing our work to remodel the tumor permissive microenvironment, a continued focus on regulatory T-cell and macrophage biology, as well as targeting immunosuppressive tumor stromal populations.
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. As Bernard mentioned, these programs are expected to give rise to multiple INDs in the coming years, and beyond. 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. GS-9911 is a novel inhibitor of DGK alpha or diacylglycerol kinase alpha, with first-in-class potential. We're not aware of any other DGK alpha inhibitor in the clinic or in advanced preclinical development. How does this inhibitor work?
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. Inhibition of DGK alpha by GS-9911 thereby potentiates T-cell activation and drives enhanced T-cell mediated tumor killing. That's exactly what we see in preclinical.
To dive a bit deeper into this preclinical data, first you can see that GS-9911 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 non-human primates that were treated with this compound. You see the degradation over time. This degradation of DGK alpha is associated with a concomitant increase in T-cell activation, as measured by enhanced cytokine production shown in the middle panel. 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.
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. 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 development 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. With that, I thank you, and I will hand it back to Dan.
Thanks. Thanks a lot, Jackson. Thanks everybody for walking through that. Wow. Every time I see that, I get blown away about the potential for patients. I just wanna thank the team here, the team that's gonna join us for Q&A. I mean, I guess, you know, it's important to note that to get this quality of talent and experience into the organization takes a very promising portfolio and a portfolio that's, you know, playing out already today. I saw the difference dramatically in the past three years outside of Kite, where we already had a world-leading position with these 30 transactions to see the level of talent that has come here, purposely come here because they see the impact they can make upon patients in their career.
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've dug deep into the portfolio. 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. There's a lot of progress now with the scale we have in the organization in terms of what we can do.
We firmly believe we have the right portfolio, partnerships and people to make it all possible. With that, I wanna get right into Q&A. I'll ask Jacquie to help kick us off here, and we look forward to your questions. 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. With that, Jacquie, over to you.
Thank you. As Dan said, we'd now like to invite your questions. You can raise your hand using the Zoom tool and wait to be called on to ask your question live. Or, if you prefer, you can use the Q&A function, and I will ask the question on your behalf. While we let people raise their hands for the audio questions, I have a couple that have 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.
Yeah, thanks, Dan. Thanks, Jacquie. Thanks for the question. It's, I think we're very excited about, you know, our ability to combine the triplet, and, you know, we really look forward to triplet data from ARC-7 to guide us, with our future clinical development plan, in lung cancer. We'll announce this as appropriate dates as we study more data. I mean, for triplet to be, you know, meaningful in lung cancer, definitely have to show better efficacy than what we expect from the doublets to move forward. As you all know, there's also very intriguing data coming out, of course, with the adenosine pathways. But I think overall, you know, this pathway needs to be a little more validated, in the treatment of lung cancer.
I think we are in a very well positioned to look at all these various combination. As I mentioned, you know, in my presentation, we're also planning to launch a platform study that will address some of these novel combination across different segments. That'll be coming a little later. That'll probably, you know, give us more confidence and information to make rational decisions 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-02 result, 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 domvanalimab development.
Bilal, it's you again.
Thanks, Jacquie. I just remind everyone about what CITYSCAPE and SKYSCRAPER is a little bit and then maybe give a couple of my thoughts on it. You know, as you all know, CITYSCAPE is a phase II study in metastatic advanced non-small cell lung cancer in high PD-L1 expressers, where really just look at, you know, Atezo versus Atezo plus Tira in that setting and, you know, show us a very impressive results from this. SKYSCRAPER-02, the one that you're mentioning too, is an extensive stage small cell lung cancer, which is a completely different disease. And as we all know, small cell lung cancers aren't as immunoresponsive as non-small cell lung cancer. Very importantly, getting into SKYSCRAPER-02, there's very little clinical or any data to support.
If you talk to a lot of physicians, they're quite skeptical about activity of TIGIT in small-cell because, you know, this has not really been very studied. I really don't think, you know, the results of SKYSCRAPER-02 have any impact on our confidence in the 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, you know, how this is gonna play out as the data matures.
From the tolerability profile, with the Fc-silent, you get less infusion reactions, you know, which could be a very big deal especially when you're trying to combine with chemotherapy and other agents. We really look forward to, you know. I mean, I think there are a lot of data that's gonna be reading out in TIGIT, and I think we have full confidence in our program for TIGIT in lung cancer.
Thanks, Bilal.
Thank you. Let's go to a live question from Brian Abrahams at RBC. Do we have Brian? All right, we'll come back to Brian once we figure out how we can hear him. Next question-
Can you hear me okay now?
Oh, perfect, Brian. Go ahead.
Great.
Go ahead.
Sorry about that.
No worries.
Oh, thanks. First of all, thanks so much for the really comprehensive overview. Super helpful. Couple questions on magrolimab. What gave you and the FDA comfort that the AEs that led to the partial clinical hold were either 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 more is left to be done to remove the partial clinical hold in the other indications, the LBCL and myeloma? Is it just a matter of logistics since they're different parts of the agency, or are there other considerations for those indications? Thanks.
Thanks very much, Brian. All really good questions to dig into. I think I'm gonna turn it over to Giri and Bill, if you wanna add or Merdad, but let's start with Giri.
Yeah. Thank you for that question. 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 sub-subset of the data. Since then, we've done a comprehensive analysis of the safety data internally. The comprehensive safety data from the ENHANCE phase III study, which is our largest and most mature phase III study, was analyzed by the independent data monitoring committee twice in the last few months. 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 unblinded 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.
We don't anticipate any major safety with magrolimab going forward. With regards to the other indications, 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 hold lift with these indications. Those efforts are ongoing, and we hope to get the hold lifted quickly as well. As you all know, the partial clinical hold did not impact the solid tumor studies, and those studies continue to enroll during this timeframe.
Thanks. [crosstalk] Brian, did we get all your questions?
Sorry.
Oh, sorry. Go ahead, Giri, if you had one more.
The question of interim analysis. The plan for the interim analysis holds. 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.
Thanks so much.
I wanted to reiterate that the diffuse large B-cell lymphoma has completely enrolled before the partial clinical hold was placed and the multiple myeloma was just getting started. The impact on our program has been quite minimal with the partial clinical hold. As you've seen, I mean, the hold was lifted quite fast, even for our pivotal study. I would say the impact has been minimal for us.
Thanks, Giri. Appreciate that.
Sure. Let's go to Matthew Harrison of Morgan Stanley, please.
Great. Appreciate it. Thanks for the information and thanks for taking the question. I was wondering if you'd just comment on Trodelvy in HR positive. You're obviously starting this phase III study in earlier lines. Can you talk about, you know, 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.
Thanks a lot, Matthew. I don't know, Merdad, if you wanna start, and maybe Bill wants to comment as well, or if you just wanna handle it.
Maybe I'll start, and if Bill or See have anything to add, please.
Sure.
As you guys can tell, the smart folks are the people who spoke today. They've been trying to keep me quiet all day. 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. 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 gonna be ongoing in earlier lines of both TNBC and HR positive, and that work is gonna continue to proceed based on everything we've learned so far in the activity of the drug.
Thanks. See, Bill, go ahead.
I'll just basically add on that the totality of the data that you've seen today, you know, continues to give us really high levels of confidence in Trodelvy, you know, to keep on bringing it into earlier lines of therapy, you know, with the positive endpoint readout for TROPiCS-02, along with our approvals in TNBC and bladder cancer. Then you saw many other datasets today in other tumor types, you know, that it continues to add on to our confidence that we can bring that level of efficacy forward to other patients. See, if you wanna add anything else.
Great. Thank you, guys, very much.
Great. 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. Regarding the phase III STAR-121 study exploring zimberelimab and domvanalimab and the platinum doublets and starting 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 were much more heavily pretreated than the DESTINY-Breast04 breast patients. You made the case that patients were much more heavily pretreated than the DESTINY-Breast04 breast patients.
In retrospect, why didn't you or couldn't you enroll less pretreated patients in TROPiCS-02? At ASCO, could you do a subgroup analysis showing data for more or less pretreated patients?
Thank you, Tyler. Really great question. Why don't, Bilal, do you wanna handle STAR-121, Tyler's question, and then See, if you would pick up on the, on the TROPiCS-02 patient population.
Yeah, just to answer your question correctly, we currently have full confidence in the data program, and we're not gating anything to get this started. I think that'd be a short answer to it, and we're still looking for more mature data from ARC-7 for us to evaluate.
Yeah. With respect to the TROPiCS-02 questions. You know, TROPiCS-02 was designed by Immunomedics prior to the acquisition, and the design was based on the earlier data that they saw in the IMMU-132-01 trial. A lot of the design was meant to replicate what we saw in IMMU-132-01. That design involved in the current standard of care for these patients. We had patients who had endocrine therapy and also CDK4/6. It replicates what patients would be getting now in the current landscape. As far as addressing the question of can we look at earlier lines, the eligibility criteria did require two prior treatments. 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. I think Tyler had a question around, you know, expectations for any subset analysis in the future, See.
Yeah. As I said, I think there's just a limited number of patients who, because of the eligibility criteria, the criteria were stricter for TROPiCS-02, so we don't have the same flexibility that we had with ASCENT.
Great. Thank you, See. Tyler, hopefully that handled both of your questions. Thank you.
We'll take one from the Q&A chat. 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. Like with all phase I's, 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, "Well, is it working? What is the efficacy?" 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 I A probably in the second half of next year.
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, you know, not only attacking the blasts, 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. CLL-1 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 this is a standalone treatment.
As I alluded to, you know, we're 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, you know, conquer the huge unmet need in AML.
Thank you.
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?
Oh, yeah. Terrific. We've got Thad here, who's the finance head from Kite. Thad, I think if you can start with the color. Andy, if you wanna add anything, but Thad, go ahead.
Thanks for the question. You know, 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. We have a great deal of confidence in our ability to deliver both growth and profitability in the near term and longer term. Andy.
I think that's great, Thad. I would just add that the business is doing really well, and we've made, as Thad said, 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. It's all consistent with the opportunity that we envisioned for patients and for our shareholders when we did the deal five years ago. I think we're largely on track. The business is really shaping up nicely. 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 operation. We're excited about deploying that technology in that facility and across the network over time.
Thanks, Chuck. Thanks for the add there on the Maryland facility. Appreciate that.
Great. We'll go next to, Robyn at Truist for a live question, please.
Great. Thank you for taking my question and doing this. I guess two quick ones. One, there's a lot of focus on off-the-shelf cell therapy. I was just wanting to see, we have an agreement with Shoreline, where you see that fitting in, to your, you know, as you said, you're the dominant cell therapy platform. Like, at what point do you think that those programs become de-risked enough that, and where do you see them fitting in as far as the, you know, the community versus academic? And then big picture, I mean, you've really outlined, a really aggressive, you know, I think plan for entering, like, the space in very competitive, different disease areas. How do you see yourself fitting in? Are you gonna be more segmented versus big pharma?
You know, how do you see yourself really grabbing, like, a good stronghold within, like, lung, bladder? I mean, these are tough areas where there's very competitive combination strategies already ongoing. Thanks.
Thanks, Robyn. 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. On the second one, I'd love to hear Bill and Merdad's comments on the broader oncology portfolio. Why don't we start? Frank, do you wanna kick us off and call upon 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. You know, quite honestly, we believe it'll take some time before allogeneic, you know, will be converging beyond autologous therapy. Autologous therapy, as I alluded to, will move into early 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. 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 cell, the off-the-shelf situations for patients that can't wait for therapy for a couple of days or longer. With this, I really also would like to turn it over to Chuck because as I alluded to in my presentation, not only we are looking into the allogeneic off-the-shelf opportunities, but also we are trying to improve the manufacturing time and 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 two will have both a role in patient care. Chuck, let me turn it over to you to talk a little bit about the activities we have in streamlining and speeding up the manufacturing.
Oh, I would love to, Frank. 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 that have improved them with autologous cell therapies. That's been a important part of our partnership with those two companies. Regarding autologous manufacturing, we have currently industry-leading 17-day turnaround time from apheresis to product release. We're exploring different 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.
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 eight days down to three to two to one day. We'll just see how that evolves over time. It's gonna 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 the, and support the changes we'd like to make. 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 Chuck. You know, 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. 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. Should we start on the R&D with perhaps Merdad, Bill, or Flavius or Jackson commenting? Who wants to start? Maybe Merdad, do you wanna start, or do you want Bill to start?
I'll do a brief and I'll hand it off to Bill. The main comment I wanna make is, we didn't undertake this, I think, lightly. I mean that, you know, a couple of years ago, when we made the decision to go into oncology, it wasn't, you know, we didn't sort of say, "Let's see how it goes." We wanted to be really committed to being competitive in oncology. 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.
That's been a very deliberate effort on our part because we know this is gonna be hard. I don't think we have any illusions that even when you're Roche versus Merck, it's hard, right? It's difficult for everyone in oncology. For us, it's I think on the R&D side in particular, but in my shop in the medical affairs side, it's really about talent. It's around bringing the people with the experience who are gonna be able to come in and bring that. 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 shotgun 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. I think that allows the medical affairs teams and the commercial teams to continue to grow and get established. 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 three buckets I was gonna cover as well. It's really, you know, the pipeline. I think you hopefully saw, Robyn. It was a great question. You know, 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. Hence, you know, we are, you know, also reaching out to some of those larger pharma companies around continuing to expound on our development opportunities. Then the people, so many people you don't see today, not just this set of experts today on video. A lot of people have been driven to come here by the pipeline, as you heard earlier by many folks, including myself.
We're also trying to look at a balanced approach on how we can, you know, basically do more with less too. 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. I'd say, lastly, I don't think we're done with our pipeline. I think we continue to really look for those combination potentials that we'll as Jackson outlined in his research talk. Thanks for the question.
Yeah, thanks. Thanks so much. Before we go to the customer-facing, maybe any comments, Flavius, from you or from Jackson?
Yeah.
I appreciate that.
Yeah, thanks, Dan. I appreciate the chance before we leave R&D. It's great to see this interest. I just wanted to kind of give an even more high-level answer to the question, and it's what really humbled me when I joined Gilead a year ago, is this company has in their DNA two 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 want against bigger, more resourced players. Two, a very, very robust and thoughtful corporate development strategy, which again, played out in the virology space. You know, I'm 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. Should we pivot to the customer-facing side, Janet? Do you wanna start and then Warner? I mean, obviously two different stages of progress there, but.
Yeah. 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. You know, Bill and the team are just every day making me more excited about the future of our commercial organization. I'd also say it helps attract the right talent, as others have said. You know, when you look at our portfolio today and we just did a build in the U.S. field organization, you can just see that we're able to bring in really great experienced people. I would say, you know, we need to be humble, and we need to be hungry, and we're out there really wanting to build those right relationships.
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 [& Co .] in collaboration with Kite and working with Warner's team, that we can really show up and make a difference with our customers. Warner, I'll pass it over to you if you have a few things to add.
Yeah. Thanks, Janet. Hello, everyone. I think on the Kite side, we're competing in this space in 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 deliver cells consistently, as Chuck 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. We're also looking to expand into smaller markets, into Asia and South America as well.
Finally, I think, Janet, you touched on this, we say this at Kite all the time, cell therapy is a team sport. 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. The customer-facing group, our field teams, our Kite Konnect support systems that really help differentiate Kite as a company that our customers wanna deal with. 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. Jacquie, over to you then.
Thank you. Yeah. We still have plenty of questions, but I know we've been going for a while now, so we'll try and wrap this up within the next ten minutes. We will go to Umer at ISI for the next live question, please.
Hi, guys. Thanks for taking my question. Can you hear me? Sorry.
Yes. Yes. Hi, Umer.
Thank you. 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 endpoint and not PFS. Just curious what your thought process is there. 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? 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 surprise to the upside in that Asian trial? Thank you.
Thanks a lot, Umer. Why don't we go in 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?
Yeah, sure. Thanks for the questions, Umer, and then I'll quickly hand it over to See and Bilal. Yeah. The endpoints are obviously always discussed with health authorities and based upon what is the expectation of delivering clinical efficacy beyond the current standard of care. 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. When you move into earlier lines, then of course you're looking more for overall survival benefit. 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 in HR-positive.
Sure. I think you're referring to the Everest lung trial for HR-positive patients. That trial is designed as a bridge from the TROPiCS-02 for the Chinese population. You noted that there's a difference in the eligibility between that trial and TROPiCS-02. That's a result of access to the CDK4/6. The CDK4/6s are clearly the standard of care now, given all the data that we have, they're in all of 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 will note that you know, 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 ASCENT. We're confident that we'll see similar results with the HR-positive trial.
Great.
Bilal on EVOKE, on EVOKE-1.
Sure. Thanks a lot for that question. Generally, if you see here in the post-IO, post-chemo setting, you know, the standard of care is docetaxel, which I think is still a pretty low bar. In that setting, you know, for you to have a meaningful clinical improvement, you actually need to have an overall survival improvement. I think you know, marginal improvement in PFS in this setting is really not going to be transformative. I think that's why EVOKE-1 is designed as an OS trial in that setting and appropriately powered to look at it. You know, based on all the data we are seeing, we are very confident. I think docetaxel is a pretty low bar to beat in this setting. We are very confident about you know, the success of this trial.
Thank you.
Great. I'm gonna pull two magro questions from the Q&A. For magro, can you comment on your confidence in using CR as a primary endpoint for approval in the phase III ENHANCE-3 trial of the magro triplet with ven and aza in unfit AML? The second question is there any particular step that you need to do to mitigate future risk of clinical hold on magro development in MDS?
Giri, right over to you then.
Thank you for that question. I can address the CR endpoint for the ENHANCE phase III study. I can answer that in two points, in two parts. First, the probability of technical success with the CR. As you've seen the CR data from MD Anderson's triplet data, a CR of 64% compared to what is the standard of care with the venetoclax and HMA combination is 37%. So just from the technical perspective, we are highly confident about the probability of reaching the CR endpoint. The second aspect is with regards to the potential for approval based on CR. We've had conversations with FDA on the endpoints 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 endpoint.
With regards to the second question, as I alluded to before, you know, we have done a comprehensive analysis of the safety data internally, independently through the DMC and recently submitted the data to the FDA, and our program is continuing with no safety signal identified in our program. We feel very confident about our safety data, safety of magrolimab, and we don't anticipate any future risk for magrolimab in MDS or in other indications.
Thank you. I'm gonna sneak in two more. The first one is from the Q&A. It's 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, but.
Sure. Yeah, thanks very much for the question. Maybe to start with, I think the key combination for the CCR8 is really with PD-1 antibody, PD-L1 antibodies, and that we're already have that in the study investigating that. In terms of tumor types, I think, you know, 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. Then I think, you know, potentially to go beyond that to indications where PD-1 in antibodies may have not shown activity if, you know, the presence of Tregs is one of the reasons for lack of activity. I 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, you know, this, 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 gonna 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. As an example, to make a plug for a different molecule, our FLT3 agonist GS-3583 has shown clinical data and has data to be shown at ASCO. 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. Mohit, are you there?
Yeah, I'm unmuted. Yes.
Okay.
Can you hear me now? Perfect.
Yes, we hear you.
Hi, Mohit.
Okay. Thank you very much for doing this. Maybe a question on EVOKE-02 trial, and given that you mentioned that there is 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 benefit. That's the first question. 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? Thank you.
Thanks so much. Over to you, Bilal.
Thanks, Mohit. It's 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. We're really expecting that, you know, moving Trodelvy into an earlier line of treatment, particularly in chemo-naive patients, will have a significant response. It's a little too early to speculate on what type of, you know, subsequent registration study is going to look like. We really wanna see the data from EVOKE-02 trying to help us all make a decision about, you know, how aggressively we wanna go versus, you know, what type of chemo that we want to replace. EVOKE-02 will really give us that flexibility to generate that data a lot across these cohorts. Your question on safety is very, very important.
You know, Trodelvy is approved. It's on the market. I think the safety profile is pretty well defined. You know, a lot of physicians are very familiar with managing some of the side effects like neutropenia and diarrhea. I mean, a lot of physicians have used it in the past. I think when it comes down to, you know, we still have yet to see the data, you know, with the other drugs in combination with IO. I mean, pneumonitis, as you alluded to, is clearly a risk. You know, we are very confident in that combination. I think you have seen the data from bladder cancers. About 40, 50 patients have been treated with Keytruda and Trodelvy. The expected safety profile is fairly consistent with what you expect from Trodelvy or pembro alone.
I think from that aspect, we have a really great advantage, and we feel pretty confident. I think that's why we've been in discussion with Merck to move our registration fairly quickly in that space. Thanks for the question.
That is all we have time for. Dan, anything you wanna share before we wrap it up for the day?
Just wanna 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 gonna continue to make. Thank my colleagues here, but far beyond those colleagues that are just here, I wanna thank them. Please give a special thanks to IR for pulling this off and herding the cats to get us to this stage. Please continue to give Jacquie and the colleagues at IR here at Gilead your feedback on how we can continue to meet your needs in terms of information as well. With that, Jacquie, just a huge thanks.
Oh, yeah, thank you to everyone for attending today. 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 or the others on the IR team. Have a great day. Thank you so much.