Adaptimmune Therapeutics plc (ADAPY) Earnings Call Transcript & Summary

Hi, everybody. Good morning. It's so wonderful to see so many faces, some new faces, some familiar faces, some folks who have been on this journey with us since IPO, and some folks that we've just met. We're so grateful to have you here today. I'm going to take care of a few housekeeping things. I'm Juli Miller. I'm the Head of Investor Relations and Corporate Affairs, here at Adaptimmune. Just, there's the shuttle if you need to go back to the Marriott for any reason and it's raining and you want to use the shuttle, that will be the bus that's out front. And then also, I want to say welcome to the folks online, and I would like to refer you to our forward-looking statements. I would ask you to review the full text of our forward-looking statements from this morning's presentation, which is now posted on the IR tab website and shown here. We anticipate making projections during this day, and actual results could differ materially due to several factors, including those outlined in our filings with the SEC. And with that, I'm going to turn it over to Adrian Rawcliffe.

Thank you, Juli, and thank you, everybody, for coming. I'm Adrian Rawcliffe. I'm the CEO of Adaptimmune, and I'm absolutely delighted and privileged to welcome you to our investor event to discuss the upcoming launch of the first engineered T-cell therapy for a solid tumor, afami-cel for synovial sarcoma with a PDUFA date in 110 days. Today, as well as the opportunity to understand a little bit more about what Adaptimmune is doing to prepare for the commercial launch, we're also going to have the opportunity to hear from the sarcoma community about the unmet medical need, their anticipation for afami-cel and the expectations of Adaptimmune as we seek to launch this groundbreaking product. We'll start the agenda with introduction to where afami-cel is in the approval process by Dr. Dennis Williams, and then Dr. Druta from Moffitt Cancer Center will introduce us to the sarcoma space, the synovial sarcoma space, treatment options of afami-cel in that her experience of treating patients and the unmet need in this space. Plenty of time for Q&A, and we'll have lots of time for questions with Dr. Druta and Dr. Williams. And then we will move into a discussion about Adaptimmune's readiness for that launch. I start with the commercial preparedness led by our Chief Commercial Officer, Cintia Piccina, and also, very importantly, the operational CMC readiness led by our Chief Patient Supply Officer, John Lunger. We have the opportunity then for an extended panel with leadership from Adaptimmune and Philip Leider, the head of Sarcoma Alliance -- the President of Sarcoma Alliance, and then we'll close in about 2 hours' time. These are the people that you'll hear from today. I've referred to some of them on the agenda slide. A couple more. Bill Bertrand, our Chief Operating Officer, will be -- and Dr. Elliot Norry, our Chief Medical Officer, will be moderating the Q&A sessions. There are other seniors available to you, both in the breaks and for Q&A. So before we start talking about a particular product, afami-cel for the treatment of synovial sarcoma. I want to put a bit of context around that, a bit of context about how we got to be here. Because it isn't a coincidence or a chance that Adaptimmune is on the verge of launching the first engineered T-cell therapy for a solid tumor. We were conceived with the ambition that this is exactly where we would be. This is exactly what we would be doing. We were founded on the basis that if you want a different lives of patients with solid tumors with cell therapy, then engineering the T-cell receptor is likely to be a critical component of those therapies. We've also found that on the basis that whilst technology platforms are cool, and we have a world-class cell engineering platform, technology platforms aren't what transform lives, products are what transforms patient lives. And if you want to be successful in the endeavor of actually bringing cell therapy products to market, then you have to invest in the capabilities to discover, develop and deliver those cell therapies. And those of you who are on the manufacturing tour saw this morning, probably the biggest physical manifestation of that investment that spans the entire company. We have built from the ground up as a cell therapy company to do precisely what we are about to do with afami-cel and also those capabilities enable us to do that for the rest of our pipeline, which is coming behind. So although we are here to talk about a particular product, afami-cel for synovial sarcoma is at the same time, the culmination of this and the history of Adaptimmune to this point, and the start of our mission to transform the lives of people with cancer with engineered T-cell therapies. With that, I'm going to hand over to Dennis Williams, who's going to talk about afami-cel's position in the regulatory and approval process.

Thank you, Ad. So hello. Good morning. I'm Dennis Williams. I'm the Senior Vice President of late-stage development at Adaptimmune, and I'm responsible for the afami-cel development program. As you can hear by my ascent, I'm a native of Philadelphia, and as a native of Philadelphia, I'm a fan of underdogs. And I think that's why I spent my entire career developing therapies for rare diseases, diseases with unmet medical needs. Sarcoma is a rare disease, a disease with an unmet medical need, an underdog. I can say I felt this way for a long time that we need more therapies for sarcoma. And in fact, 17 years ago, I had that feeling when I was part of the team that went down to the FDA to discuss the Phase III trial, pazopanib in soft tissue sarcoma. And although pazopanib was ultimately approved, 12 years ago this month, I still feel that way today. We need more therapies for this disease. And you'll hear Dr. Druta speak more about that in a few moments. That's why I'm really happy to talk to you all today about afami-cel, which will be the first -- will be the first therapy available for patients with synovial sarcoma in a very long time. So I want to give an update about where we are with this application. So in December of last year, we completed our rolling submission of this marketing application. And in January of this year, we had what's known as an application orientation meeting with the FDA. So just a few words about what that meeting is about. That's where we present the key findings of the trial, safety and efficacy of the SPEARHEAD-1 trial and give an overview of the application as a whole. This meeting was very well attended by the FDA. There were over 160 FDA participants at this meeting and including very senior people at the FDA. I've personally been to a lot of these meetings in my career. I've never been to a meeting that was this well attended by the FDA, and I consider that to be a very positive sign of their interest in this application. Several days after that meeting, we received the FDA filing letter, okay? So when you submit an application to the FDA, there's a 60-day period where the FDA reviews the content to make sure they can review and then an application gets filed. And that filing letter assigned a priority review to this application. And why is that important? So our priority review is deemed for those products, these medicines that are there to treat a serious disease and represent a substantial improvement over available therapies. Now we felt pretty confident about the data in this application that it would support a party review, but it is very nice to see it in writing, I must say. We actually -- the next month in March, we hosted the FDA for our first FDA regulatory inspection, what's known as a bio-research monitoring inspection or a BIMO inspection as we often say in the industry. And that's -- what happens in a BIMO inspection is the FDA reviews the clinical data. So the data that was submitted in the application, and they also assess our compliance with good clinical practice. So the FDA spent a glorious days with us at the Navy Yard, where you're at, and we're very happy with the outcome there. And a few weeks after that, we had our pre-license inspection with the FDA. So here again in that setting, the FDA got to review our compliance with good manufacturing process. And they had the opportunity to witness several afami-cel manufacturers, both for patients that are in our SPEARHEAD-1 trial as well as our ongoing trial in pediatrics. We also had the mid-cycle review meeting with the FDA. So what is a mid-cycle review meeting? So the mid-cycle review meeting is an opportunity for the FDA to communicate with the sponsor of the status of the review. And when we met with the FDA, they confirm certain details like there are no plans to take this application to advisory committee. And really, the focus of the conversation was areas where the FDA has sent information requests. Let me give you an example. So the FDA was interested to learn more about our strategy for the use of tocilizumab to manage CRS. So for the proposed U.S. prescribing information, we're proposing a management strategy that mirrors what we did in the trial, where we advocate for tocilizumab use for Grade 2 CRS and for Grade 1 CRS under certain conditions. And so it was clear the FDA wanted to learn more about that as it relates to ultimately what we're going to propose for the final label. So what's -- one thing I would say, the key takeaway for me for the mid-cycle meeting is the FDA did not communicate anything that would suggest this application has any major concerns. So there were nothing that the FDA raised to me that would accept -- that would indicate an approvability issue. So that is really the key takeaway from us coming out of that meeting. They also confirm the date of the late-cycle meeting, which is in late May. And what I would expect for that meeting is to discuss -- the forward-looking statements around discussing labeling and any potential post-marketing commitments or post-marketing requirements. Afami-cel is a targeted therapy. So there are 2 important biomarkers. The mechanism of action of afami-cel requires you to have both the correct HLA and your cancer needs to express the MAGE-A4 cancer test these antigen. And as a consequence, we have 2 companion diagnostic allocations that are also in play. And these are in progress, and we are planning for contemporaneous approvals of both companion diagnostics, along with the PDUFA date of afami-cel. Some of my commercial leagues will talk later more about the testing strategies and the launch activities related to these biomarkers. So really, at this point, we're past the midway point in this review cycle, and we're looking very forward towards this August PDUFA date. And I would say from my perspective, there are 2 key takeaways from this is afami-cel has the opportunity to be the first approval in synovial sarcoma in a very long time, too long, to be honest. And at this point in the review, we are very confident about that action date. We have not heard anything during this review that would suggest there are any concerns about approvability of this application. And with that, I'm going to turn it over to Mihaela Druta. Dr. Druta is the Vice Chair of the Sarcoma department at Moffitt Cancer Center. She's a medical oncologist. And I think more important, I would say to me, is her passion for taking care and bettering the lives of people with sarcoma is unparalleled, and I get a little bit more excited and enthusiastic every time we talk. So with that, Dr. Druta.

Thank you so much Dennis. Thank you, Adaptimmune; thank you, Dennis; and thank you, everyone, to give me the opportunity to come here today and share the story of synovial sarcoma treatment and patients and what -- how we can help them with this new therapy. I am a sarcoma medical oncologist. I treat patients with sarcoma, but I'm part of a market disciplinary team of other medical oncologists, surgeons, radiation oncologists, pathologists, radiologists, that we have expertise in treatment of soft tissue sarcomas and synovial sarcoma. I'm practicing at Moffitt Cancer Center in Tampa, Florida. And if you are wondering about my accent, I am originally from Romania. So I'm going to talk today about synovial sarcoma and what -- how we treat these patients. What we have available for them in the treatment paradigm and how much need we have for better therapies. Synovial sarcoma, it's a type of sarcomas that are aggressive. When we talk with the patients, they come and see us, we talk about the treatment challenges, not only due to the rarity of these tumors, also the heterogeneity. We are talking about 100 different sub-types of sarcoma, synovial sarcoma being one of them. It's a tumor that is, contrary to the denominator, is not arising in the intra-articular synovium, but rather from the primitive mesenchymal cells. And it's affecting young patients with the median age of diagnosis being 39 years old, and it's accounting for 5% to 10% of the soft tissue sarcomas. When we talk with the patients and they're coming to us, we talk in the localized setting about the curative intent, and we want to be as aggressive as possible with the treatment with the chemotherapies, with radiation therapies, with surgery. But despite our efforts and a very long journey of these patients to have this treatment, 50% to 70% of them, they will develop metastasis. They will actually die from their disease and outcome in this setting is very poor, with less than 15% of these patients being alive at 5 years. So it's a devastating disease. And when that is -- it's metastasizing and we want to help these patients to live a longer life and a better quality of life. When we talk about the patients about their outcomes, we talk about their tumor characteristics. The larger their tumors are, a more advanced age they have at the time of the diagnosis. When we talk with them about the need for oncologic approach of their resection to not leave any tumor behind, these are all factors that will influence their outcome. The larger the tumors, the more tumor is left behind. The more deep location of these tumors, and frankly, outside the extremities, they will have a poor outcome from their diagnosis. When, patients, they develop this advanced disease, metastatic disease is not really a consensus how we're going to treat in this setting. And we use traditionally and historically this doxorubicin and ifosfamide combination of chemotherapy, which is a tough regimen. We talk with them about the opportunities for this therapy, which we see their not amazing response rate but also these treatments, they are coming with a toxicity that we need to manage in this setting and it's taking that all on the patients. When we are beyond the first line of therapy and we go to the second line treatment, the controversy and the lack of consensus is even more. We are treating with ifosfamide single agent, and then we are going with pazopanib, trabectedin or other modalities. I wanted to pause here because we have a very tough conversation with these patients in our clinics, and we sit down with them and not only that we tell them that you have a disease that eventually is going to take your life. But what we have available for you, to treat you, are these toxic therapies. And you're going to have to, at times, we probably have to manage your infections. Sometimes we need to have you go into the hospital. You're going to have an infection. You might have a sepsis. You're going to have the need for IV antibiotics, sometimes ICU stay. You need to have to come to do transfusions and IV fluids and so forth. So when we talk about the treatment, we try to tell that we are explaining that we keep your disease under control. But we also want to talk what will be the quality. They are asking me, what will be the quality of my life Dr. Druta? I understand. You gave me this devastating news. I'm not going to see my 2 kids going to college, but how is going to be my life going through these therapies. How -- what would the quality of my life. And this is an extremely, extremely tough conversation that we have for the patients. Because what we want to do is to try to extend their life, but with a good quality of life. We use different modalities, right, of treatment, and we have surgery, definitely the main stay of the treatment for these tumors with limb salvage approach, especially in the patients that we have in localized disease. What that means, we try to have the tumors removed in such a fashion that is no disease left behind, but also preserving their limbs. But we have patients, they come to us and they have surgeries done in other places where they don't know how to manage these tumors, and they have disease that is left behind and the risk of developing recurrence at the site of where tumors was located and develop distant disease with metastases, it's even higher in those circumstances. That is where it's very important for these patients to also be treated in a multidisciplinary fashion in a center where they -- we have expertise in treating these patients. We use radiation therapy. We use radiation therapy, neoadjuvant-adjuvant setting prior to the surgery, after to the surgery, in -- especially in localized disease, but often also in metastatic disease if the patients will develop -- they will develop symptoms related to this. We used the radiation in the effort, especially for the large tumors. They are located in close to any joint to save their limb for the patients to be functional. And then this is where is my role. I'm talking with patients about systemic chemotherapies. And while we have standard treatments for pediatric sarcoma such as osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, when we talk about the standard treatment for synovial sarcoma, there are randomized clinical trials, they included all different subtypes of sarcomas. However, we know that doxorubicin and ifosfamide in localized setting when we want to cure these patients is pretty much the standard of care. But how about when these patients develop metastatic disease? We remember that we have over 50% of these patients despite this long journey and going through months of therapy -- months of chemotherapy, months of radiation and surgery, then we're still, despite our efforts, they are still developing metastatic disease. And when we look at the response rate in the first-line chemotherapy to different agents, either the same aggressive doxorubicin and ifosfamide that maybe was used in the localized setting, the anthracycline doxorubicin-based chemotherapy or ifosfamide, we have a wide range of response rates modest at best. So it's clear to us that we want to do better and doxorubicin, frankly, is a drug that is being used for 50-plus years. It's time for us to see if we can have better therapeutic options for these patients. We know that these patients, when they come to us, we talk about these approaches, but they are asking us, "Okay, but I'm willing to embark in this journey, Dr. Druta. And I understand that we will try to manage all these problems. It's anything that any marker, anything that will predict I will benefit from this treatment." And when we talk about the metastatic disease, it's even harder because now we are -- we don't cure these patients, but we actually put them through these aggressive treatments. There are targeted therapies. So then in terms of what we use for the treatment of soft tissue sarcoma and synovial sarcoma, pazopanib is an FDA-approved drugs. But this drug was approved when progression-free survival benefit in the [ clinical ] trial versus placebo was 4.6 months versus 1.6 months. And there are other tyrosine kinase inhibitors that are available. Some of them, they are approved for other indications and some are in the clinical trial arena. When we go to the second line therapies, as I mentioned earlier, we have usually -- we use our oral therapy with pazopanib, because that was FDA approved for soft tissue sarcomas, as I mentioned, with advantage of 4.1 months versus 1.6 in terms of how long these patients they can have before the progression, but was no significant overall survival difference in patients treated with this drug versus placebo. And we have trabectedin, but trabectedin was approved for patients with metastatic leiomyosarcoma and liposarcoma, and then it's used off-label for synovial sarcoma, but the trial was designed for other subtypes of sarcoma. And when we look again at overall response rates, pretty modest at best. All right. So we use therapies that have been available for 50-plus years. Despite of this journey of these patients of months with all these therapies, we are not offering them a long time, and we don't offer them quality of time. So we are in 21st century. We are in the context of explosion of different immunotherapeutic approaches, different ways to treat cancer. We hear every day that with a new therapy, a new immunotherapy, new checkpoint inhibitor, another CAR-T for other cancers. What about sarcoma? Complete silence. So I started my journey as medical oncologist after -- sarcoma medical oncologist after completing my fellowship at MD Anderson Cancer Center, 1 year extra on top of the long, long journey just with focus in sarcoma. And then I joined faculty. I was pretty much the only sarcoma medical oncologist, and kind of managing these patients on my own. And with this therapies, I am trying to help them as much as I was possibly could help, of course, with the team that we have at Moffitt. But in the back of my mind, this is how I want to treat the patients for the rest of my career. This is what I was looking around at my colleagues having all these exciting trials, ZUMA-1 just started with a CAR T therapy, what is that? Can we have something similar ever? Can we dream to have this similar to synovial sarcoma -- to sarcoma patients. And then Adaptimmune is coming with this novel T cell, adoptive T cell therapy. Are we interested for our patients? And that was the first one, absolutely. We can't continue to do this. I don't want to treat these patients. Let's learn, might not be something that is going to help them, but I need to learn. We are obligated for these patients to try something different. So this is how I joined the group that emerged at Moffitt. In that context of the CAR T therapies, the ZUMA-1 was just got up, and I was part of the of that team that was leading to this trial and having our trial with Adaptimmune part of their group. So again, we wanted -- because we know we have surgery. It's been there for hundreds of years and radiation, chemotherapy and treated patients with the same drugs, I wanted to do better. So what we learned so far? We learned that synovial sarcoma, it is an aggressive cancer. Despite all our efforts, these patients will develop metastatic disease. We cannot cure them, can we extend their life with their quality of life. And when we look again and look at what we are using in second line for these patients with pazopanib with not really any overall survival advantage versus placebo, when we look at doxorubicin single agent versus doxorubicin and ifosfamide, an aggressive therapy with a lot of toxicity, still we don't see any difference in overall survival. First-line therapies. I've lived through all of these trials. The biggest disappointment, we had such an excitement at ASCO in 2019. We had Dr. [ Dutt ] from Memorial Sloan Kettering on a plenary session at ASCO, when is the sarcoma on the plenary session? When was the last time? Every -- all the sarcoma medical oncologists we were in audience, was the Oscar night for the sarcoma. And the disappointment, I remember like yesterday, because we were very, very, very excited about this, and there was a negative trial. That was the first time that we heard about the results. And again, we had to go back to doxorubicin, the old drug that we had available. And as we see, we had multiple trials that they try to beat the first-line therapy. And response rates, very low as we've seen. And then when we go to second-line therapies, again, overall survivals, they are very modest across all these trials, different combinations of chemotherapies and targeted therapies. So excitement. I wanted to learn. I started this journey with Adaptimmune with the trials because I felt obligated for the patients to give them the chance to try something different. We wanted to try something that the rest of the cancer treatments were tried, and we didn't have anything better for these patients. So this is where I started the journey with afami-cel. And what is afami-cel? It's this engineered T-cell therapy that is pretty much targeting this tumor-associated antigen, MAGE-A4, that is expressed in the higher -- has a higher expression in synovial sarcoma and frankly in other subtypes of sarcoma, and is requiring one single-dose therapy. The patients, they are in the room and they receive the therapy, it's half hour infusion, and they're done. And then you're seeing what is this -- how they tolerate and how -- what is this doing for their cancer. One single infusion, as opposed to months and months of trips to the infusion center and treatment and aggressive and coming back to the hospital with a lot of problems and side effects. And these are the results of the afami-cel Phase I trial. They were showing durable responses in synovial sarcoma. Not only that, we had responses like partial response, is the most -- I tell to the patients when we sit with them, stable disease, it's a good day in our sarcoma. If we keep this not to grow and spread in other places, this is a good day. Not only that we had partial responses and confirmed responses in 44% of the patients, but these responses were durable after one infusion of afami-cel. These are the results of the SPEARHEAD-1 primary analysis and show this 39% -- 39% overall responses in these patients. And remember, these patients, they were heavily pretreated. These patients, they had lines of other therapies they were included in this trial. When we look at the progression-free survival -- median progression-free survival was 3.8 months. And what is remarkable in the 17 patients on the blue light there with synovial sarcoma, they had response, median progression-free survival was 14.3 months, and 23 -- 24 months progression-free survival probability was 20% of these patients. And when we looked after a single afami-cel infusion, the 24 months probability of being live and additional systemic therapy free was overall 30%. Overall survival in these patients was 16.9 months that are cut off. And estimated overall survival, again, in the patients that responded with synovial sarcoma, 90% -- 90% at 12 months and 70% at 24 months. I don't know for us that -- again, we've been in this field for quite some time and having these results and sharing with the patients, it's something that we were just dreaming for. And we are so excited that we can have these therapies for our patients. Okay. We saw the responses, the durability of responses, but how about how they tolerate these therapies? And I was in the ZUMA-1 trial with the CAR-T inpatients rounding on these patients and going into patients' room that received the CAR T infusion and having the whole constellation of side effects and CRS and neurotoxicity and walking in my patient's room, and they were asking Dr. Druta, when can I go home? But I don't know, do you have any fever, any -- but just a little bit of fever Grade 1. I'm doing well overall day and night in terms of the side effect. And again, primarily where Grade 1 CRS is in these patients and just one patient had some neurotoxicity. So I wanted to come today to share with you the data that we have available, where we are standing with the treatment of the patients with synovial sarcoma. But not only to tell you that, I wanted you to tell a story how we spend our lives and our careers with patients and trying to help them and wanting to do better. But when we define better, it's not only to extend their life, we want them to have a good quality of life. We want them to be able to, whatever time is there, to be able to work or I tell the patient "If you can go back to work, I want to go back and if you exercise and take your kids to a movie and have a good quality of life." So we don't have treatment options -- good treatment options for these patients. And it's a huge, a huge unmet need for these patients. This is the first of its kind and not only that it's in the solid tumor, it is in sarcoma, in synovial sarcoma, it's something that -- how is that possible for something that, we know that it's challenging to treat, we know this is a rare cancer, and this is going to happen for us. And we -- I emphasized how is this looking different from what we have available for these patients. I wanted you to understand what is the journey for what we have available today and what is going to be the journey for these patients when they will have this drug FDA approved. It's going to be -- it's going to make their life looking in a different way. We know that, that might have side of facts, but we learn. I've been with the team in 8 years and manage all the toxicity profile. But frankly, we have them watching in the hospital for a few days. And if they -- this is the critical time when they can develop some toxicity and then they are discharging, they are coming with scans and just living their lives. So I hope that I was able to show you not only that we have -- we don't have good tools to help our patients. And I wanted to tell you that us -- the patient first and us, the ones that we are seeing every day in the patient's room and we hear their story, I cannot tell you how excited we are to have this tool available for us. And I cannot think enough to Adaptimmune to putting their trust in a disease that we don't have options and it's such a challenging disease. Because without having people trusting us and trying to help these patients, is going to be very hard to navigate like this. So thank you so much everyone for being here today and for listening to the story of the synovial sarcoma and the patients and the challenges that we have and the hope that we have. Thank you.

Good morning, everyone. My name is Elliot Norry, and I have the privilege of serving as the Chief Medical Officer at Adaptimmune. I have been at Adaptimmune for 9 years -- almost 9 years now, and you can sort of help it, the level of enthusiasm that these 2 have, and I think we all, in general, have for the delivery of this afami-cel product to the marketplace. It is very gratifying to have seen this product come out of our laboratory, be developed in our clinical programs and be really on the doorstep of making it to the marketplace where we can serve so many more people.

We're going to have questions and answers. A little bit of just housekeeping around that. [Operator Instructions] So I would like to just sort of start with a question for Dr. Druta, as we see the questions come in. Can you give us an idea of where you feel that afami-cel will fit in the treatment paradigm of patients with synovial sarcoma? You gave us a really nice explanation of how these patients sort of start with curative intent treatment and then end up with chemotherapy. But where does afami-cel fit in with the options for treatment?

Thank you for the question. I mean, it will be up to me in metastatic setting, I will start right away to treat the patients with this product, but we have this FDA approved after at least one line of therapy. And usually, we have the doxorubicin-based chemotherapy. But the answer will be very quickly in the paradigm of treatment of the patients. And seeing the response rates that we have in second line with not a consensus in terms of what will be the therapies for these patients and seeing the toxicity profile associated with this, definitely, our community of medical oncologists in sarcoma will favor to try this in very early lines of therapy.

Thank you. And I have a question that's come in for Dennis. Dennis, can you explain a bit about the regulatory pathway for the companion diagnostics?

Yes, sure. So in both cases, the nomenclature is different, but there's a PMA or premarket approval and for the IHC assay, that's the MAGE-A4 IHC assay and essentially undergoes a regulatory review by the FDA, the group called CDRH, that's not dissimilar for what the drug division does. And similarly, for the HLA companion diagnostic, it's under a regulatory application process known as a 510(k). It's a premarket clearance. And that's also reviewed by another division at the FDA, affectionately known by the acronym OBRR, which essentially is a division that deals with blood products. But essentially, it runs through our regulatory process, not dissimilar from what happens with the drug application, albeit the shorter time lines in the case of the 510(k), for example.

I think we have a question from..

Thank you very much both for hosting us and also for your comments today. Ted Tenthoff from Piper Sandler. Dr. Druta, is there a reason to think because of the low response rates with early line first-line therapy? Because patients are maybe healthier before getting chemo, is there any reason to apherese early in order to really get the best possible apheresis sample that could ultimately be used in what you think will be a commonly prescribed second-line refractory product?

Thank you so much for this question. And definitely, we discussed extensively amongst ourselves as treating sarcoma medical oncologists from the big sarcoma centers and it's across the board, it's exactly what you're saying, how we're going to approach these patients. And again, in metastatic setting, clearly, everything that now today will be better in clinical trial rather than using standard therapy. Now we're going to have a better product that if used, definitely, these patients will need to be screened and have apheresis before starting the first line. So I think that is going to be across the board. This is what will be the practice to have for the synovial sarcoma patients.

Gil Blum, Needham & Company. So a couple of questions for you, Dr. Druta. First of all, did PRs allow first surgical intervention. So responding patients, did you have access to the tumor? And secondly, when you did see resistance, was there any understanding of the underpinning of resistance, like heterozygosity or something else?

So again, thank you for your question. So you're saying that to have access to the tumor surgically, that is a completely different approach and strategy that is used for -- now it's approved for other indication and that is under clinical trials for sarcoma. But because we are collecting the T cells and then from the patients, it's an easy access -- IV access. And I don't -- there's not any clinical trial right now looking at the outcomes in [ T cell ] therapy versus adoptive T cell therapy to kind of have an educated answer to that question. In terms of the mechanism of resistance, I think Adaptimmune is doing a lot of correlative studies, and this is what we are definitely looking and to understand what is going to be something that we need to improve in terms for the extent -- increase the response rates and the durability of the responses. Definitely, we are measuring, for instance, persistence of the T cells -- engineered T cells. And we know that the more -- the longer these T cells persist in the patients, definitely, they have a better response. We need to look at the tumor micro environment. It's anything that we can identify that will explain us. So we will look at the better or the worse responders, right? We also look at the tumor burden and it is something that is discussed amongst ourselves. The more disease these patients have, the harder is to treat them, and that is where is the other question coming that, early when the patients they have limited tumor burden will be more definitely, they will have a better response. So definitely, the academic world in collaboration with Adaptimmune definitely looking and understanding better, exactly in the hope to come back with a better product.

There's a -- I have -- we'll go to your question and I have some questions that have come in online.

This is Peter Lawson from Barclays. A question for Dr. Druta. Just what percentage of patients in the second line do you think will be amenable to afami-cel?

What percentage? I mean everybody will be willing to try this in second line. So in that regard, it's 100%. It's just a matter of [ dosing ] for the HLA subtype and the percentage of the MAGE-A4 expression. Again, the advantage that for the MAGE-A4 expression in patients with synovial sarcoma, we probably amongst all other types of tumors, we have the highest expression comparing with other head and neck or other types of tumors. So we have an expression around, I think, 70%, that was made before in these patients. So I think we'll have a high proportion of these patients that will be -- in terms of us drawing this and definitely having these patients, we can screen them upfront, have apheresis and then treat them in second line and will be everyone that will qualify from that perspective.

So I have a couple of questions that have come in online. This one for Dr. Druta. Sarcomas are not typically treated historically outside of the clinical trials that you participated in with cell therapies. Can you give us an idea of what do you think are the most important knowledge gaps for physicians that treat sarcomas across the country for us to try and address as we sort of embark on getting ready for commercializing this product?

So thank you for the question. I think that it's going to be very important to partner with patient advocacy groups. And to have these patients to be aware about this drug that is approved and the importance of these patients to come to a tertiary cancer center, multidisciplinary approach of the treatment for things that are eligible for this trial -- for this therapy when it will be FDA approved or for other clinical trials. So I think going from both us as medical community, educating our colleagues, but empowering the patients and partnering with patient advocacy group, that we together will be successful in this journey.

And we'll have a chance to hear from a leader in the patient advocacy form a little bit later. Do you have another question?

George Farmer from Scotiabank. A couple of questions. Just thinking about the overall opportunity. Of the metastatic patients, how many of those would have had potentially surgeries, whether it be amputation or otherwise that may have had more curative intent. Just thinking about how many patients ultimately would be candidates? And then secondly, I don't know if the company or maybe more appropriate for you, Dr. Druta, how does the company get this therapy into frontline? Is that really necessary to do the trial? Or do you think there are other ways around that?

All right. Thank you for the questions. So I will say that to answer to the first question, even in the most aggressive approach, right, when we treat patients with oncologic intent, when we definitely do wide margins and it's something that is done in our hands. Even in the context of patients having months and months of chemotherapy -- aggressive chemotherapy and radiation, these are the 3 modalities that are pretty much the standard of care. Still, we've seen that more than 50%, so 70% of them, they developed metastatic disease despite of all of these efforts for these patients, that they will -- to cure them, right? This is what we tried upfront. So it's going to be, a big percentage of these patients, they will need this therapy for sure. And we also have patients that with a surgery in the extremities is one approach, but we have patients, for instance, with primary synovial sarcoma of the lung. I have a lot of patients in this context where surgery even in the hands of the most experienced cardiothoracic surgeon, they know with the negative margins, the percentage of these patients developing metastatic disease is even higher, and they have much poor prognosis than extremities. So that is another thing. In terms of going to the to the front line, definitely as an academic world, it's always we wanted frontline, and perhaps we can have a frontline trial to demonstrate that, but also it's going to be important from the payer's perspective to have this addressed in a clinical trial fashion. And I'm hoping that the company in the future will be interested in such a trial. I'm going to defer that...

Yes. I don't know if, Dennis, you want to sort of would be able to save couple of seconds...

I think it's fair to say, I'll just say briefly that we've had this conversation with key opinion leaders often about different settings in the front line, whether it's even in sort of in a consolidation setting after chemo. Or in fact, some have even approached us using it in the neoadjuvant/adjuvant setting, which might also be in certain high-risk patients be an opportunity. So there are certainly some things we've been thinking about.

And frankly -- thank you, Dennis, for this and frankly, what we are missing tremendously, not only in the treatment of synovial sarcoma, in all the different subtypes of sarcoma, can we have something and I would be -- I'm more interested in that setting, where again, the patients, they were -- they went through all of these aggressive treatments, can we consolidate with something that is not as aggressive in terms of toxicity to increase their chance not to develop this metastatic disease. So to me, that is a more appealing frankly, to have a trial in that setting, which is completely missing in -- across the board in all other subtypes of sarcoma.

There are a bunch of other questions. I see hands up, but I also see that my clock says 0:0:0 there for the duration of this. I don't know if we can go on a little bit or I'm also happy to just sort of people can approach Dr. Druta, Dennis during the break, ask additional questions. We do have a break built in right now. And then we'll come back, and you'll see a fantastic presentation from our commercial team. So thank you all very much, and thanks to Dr. Druta and to Dennis, and all the participants for further questions, and enjoy the break.

Thank you. [Break]

I think it's an exciting time in sarcoma because we're seeing more and more investment in sarcoma and treatment options for sarcoma. And for synovial patients, in particular, it's hope that there is a treatment option out there that could potentially save lives. A vital part of our mission is to empower patients to be able to play a more active role in their journey and provide them not only more treatment options, but less toxic and better tolerated treatment options as well. In sarcoma, there's just not a lot of resources. There's not a lot of awareness. The average age of diagnosis in synovial sarcoma is approximately 30 years. It is a younger person's diagnosis. Not only is a sarcoma diagnosis scary for the patient, it's also difficult for the family and the caregiver and the loved ones and family and friends because they also don't know what that means. Since the 1980s, there hasn't been any new innovative treatment options, specifically for synovial sarcoma. And working in sarcoma, you can feel every day like you're failing. But in the last several years, the amount of investment and attention and awareness about sarcoma is exciting to see. And it makes it a little bit easier to think that there could be more treatment options for patients, that there could be a world in which people don't die from synovial sarcoma.

Welcome back, everyone, and this is why we do what we do to help, to create this world where patients have more options and hope is why we work so hard every day to do what do, and in particular, to bring afami-cel to market. So I'm very happy to be here and share with you our commercialization plans for afami-cel. I'm Cintia Piccina, I'm the Chief Commercial Officer for Adaptimmune, and I've been in the biotech and pharma space for over 20 years, but the last 5 of them have been dedicated to cell therapies, bringing cell therapies to market. And so I'm very excited to hear, not only today but to be part of this amazing team that is working to build a sarcoma franchise that has the potential to address up to 1,000 patients in the U.S. per year between lete-cel and afami-cel, and we are starting with afami-cel. So what are some of the things that we need to understand and keep in mind when we think about our commercialization strategy. What is distinctive about what we're trying to do. So first, we're working with synovial sarcoma. We heard a lot today from Dr. Druta that it is an ultra-rare cancer, and we have a very high unmet need, especially after the first-line of systemic therapy. Because it's so rare and so complex, the patients with synovial sarcoma are usually taken care of by physicians and care teams that are specialists and concentrated in sarcoma centers of excellence across the country. So it's a very concentrated space. Second, afami-cel is a TCR T-cell therapy. So we are bringing an unprecedented clinical profile. We saw the data today in an area that has not seen any innovation for several years, and we do this with one single dose. We also heard a lot about it and also from Brandi, how important it is for patients that they don't need to be keeping going back for treatment and also to have to manage the toxicities and the side effect profile of the more traditional medications. We are also a targeted therapy. So we are targeting patients that areMAGE-A4 and HLA-A2 positive. So for that reason, we are also establishing a biomarker testing platform that we heard from Dennis, is going to be approved at the same time as afami-cel is approved, and we're going to hear more about it today on how we're going to make it all work in the commercial setting. Finally, we are Adaptimmune, and so this is a historical milestone for us. This is our first commercial product. So we are going to build for what we need right now and that will be the platform to grow as we continue to reach more merchants and bring more to market. We have strong expertise years working in the clinical development setting. And we brought an amazing team with a lot of experience commercializing and launching products in very specialized areas and a team that is very passionate about our mission. So when we think about this, we thought about a few guiding principles. So these are some things that are going to be shaping our commercial strategy. This is what we want to be known for. So first, we're going to be focused. We are going to focus on the treatment sites that see the majority of the patients. We're going to enable access. We will leverage our proposition in a very targeted patient population. We'll be reliable. We've been manufacturing and delivering afami-cel for years in the clinical trial setting, and we're going to translate all this experience into the commercial setting, and we deliver very high levels of customer support. We will be simple, creating a treatment journey that will be very smooth from the patient identification all the way through the infusion. We know that cell therapies is complex, but we are working very closely with the care teams, and we understand how important simplicity is. So we are working with them to build processes and systems that are going to be as simple as they can be. And finally, we care boldly. We are a very nimble, specialized and integrated team, very passionate and we work relentlessly to find solutions for our patients and our care teams. So now how are we going to make it all happen? We have 5 clear business drivers. These are the things that we need to make happen to make sure that we can identify and treat every patient for which afami-cel can be appropriate for. So starting with educating and informing the patients and the care teams wherever they are, making sure that they can get to the authorized treatment centers by establishing a very effective referral network, getting them tested, by establishing also a platform for testing that is very simple and accessible and making sure that they have access and personalized support each step of the way. So we're going to drill down into each one of these business drivers. You're going to see the entire cross-functional team falls behind one of these 5. And we're going to hear from our medical affairs, commercial and market access team in a little more detail. And to do that, it is my pleasure to introduce you to the commercial and medical affairs leadership team. We have over 20 years of average relevant experience in areas, most importantly, in cell therapies, but also in oncology and in rare diseases. And in combination, we've been part of more than 20 launches. We've been working very closely together with our patients and our care teams in mind. We are very passionate about we're doing. And in fact, we heard a lot today from Dr. Druta already. And we were visiting one other of our trial sites that will become, hopefully, a commercial site as well. And one of the people from their care team, from their clinical team told us, "Thank you for bringing this all the way." And that was very touching to all of us because the care team sees the patients every day. They understand the anticipation and the unmet need for those patients. And she also realizes how complex it is to bring a product like afami-cel all the way from research to clinical development and to commercialization. So that gives us a huge sense of responsibility for making this happen, a really strong sense of commitment. And you're going to see from all the presentations today, we're going to have an opportunity to share the team and the things that we're doing. We are a fairly small team, but we do care boldly. And you will see that, I'm pretty sure. So with that, in order to learn a little bit more about what we're doing, I want to invite Maria Lopes to share the commercialization plan. Maria? Thank you so much.

Thank you, Cintia. Good morning. My name is Maria Lopes, and I have the privilege of working at Adaptimmune for almost to be 2 years in August and helping to support this amazing team, to get this amazing product, to amazing physicians like Dr. Druta. I've spent the last 2.5 years in the health care end, primarily in the bigger pharma space and have now transitioned into the biotech space and really understanding what it means to build something from the ground up. The last 15 years have been my absolute favorite where I got the chance to work on several rare disease products. And the reason why they were my favorite was because you get an opportunity to get really close to the community. You understand the struggles of providers like Dr. Druta, who have limited options and have to get very creative about how they're going to manage their patients. You have an opportunity to get really close to the patient community and understanding what their journey is like and each one is always very different. And most importantly, we got the opportunity to raise their voice, a voice that is often unheard, often not a place where there's patients them to understand their challenges, especially in oncology. Oncology is a highly invested space in terms of patient advocacy, but it's some of the bigger cancers that really get a lot of attention. You'll hear from Philip a little bit later. And we have the responsibility to deliver medicines, to elevate the patient voice and create a community that feels connected to our shared purpose. And that's why I'm here at Adaptimmune. Before we get into some of the details about the launch of afami-cel, I want to talk a little bit about our why. Julie is a patient or a synovial sarcoma patient who we met about a year ago. She was 23 years old when she got the diagnosis of synovial sarcoma and was told she only has 3 months to live. She had an aggressive tumor, about the size of a watermelon in her chest didn't exist 3 months before. I mean it's -- if you imagine for a 23-year-old what that was like for her, that news. She was planning her life thinking about what is her career going to be like? Will she buy a home, will she get married, will she have children. Julie went through several aggressive treatments, and was able to get treated actually quite fast because her mom next to her was not going to let her do or die. So she got herself to an academic center, a sarcoma center of excellence, receive treatment and Julie today is doing really well. She got married. She has a baby named Miles. He's 3 years old. She owns a home, and she's living the life she thought she would never be able to live. Julie, however, is also very realistic and knows that synovial sarcoma has a high rate of recurrence. And what she shared with us a year ago, aside from her remarkable story was that recurrence keeps her up at night or thinks about it every day, but going on chemo equally scares her. So when she learned there is a company in her backyard that's developing a onetime infusion for patients with advanced synovial sarcoma, she -- like Dr. Druta, it was a dream come true about knowing that this is going to come -- could come back, but also knowing that there's a treatment option that is not the journey that she had before in terms of a treatment option, gives her a sense of hope that we are going to do better. You heard from Dr. Druta today, right? I don't think anyone questions her passion for cell therapies and what afami-cel will deliver. And about a year ago, also at ASCO, we had her talk to us a little bit about what this meant for her and the sarcoma community and she told us you had me at hello. She told that actually to Dennis when she was approached to be a clinical trial researcher for SPEARHEAD-1 and enrolled, in fact, the first patient. So memory is very good this morning. There was a slide that was put up about the results of the Phase I trial. And there was one line that kind of shout out all the way that was Dr. Druta's patient who is still responding today. And then there's the treatment. There's an image there of a 53-year-old man who only after 6 months of treatment have a remarkable response in terms of his tumor burden. So we have a responsibility to make sure that every patient has access that's eligible. And we're going to talk a little bit about that in great detail -- to some degree in detail throughout this next session. Then there's Adaptimmune. Our commitment to cell therapies, our commitment to sarcoma, building a sarcoma franchise. And it's an incredible opportunity to give patients options they don't currently have and physicians' tools they don't currently have and continue to build that. But it doesn't stop there. There are so many more products and opportunities for us to continue building our cell therapy platform for many, many, many more patients in the future. And that really is, for me, a dream come true as a possibility and as a job with a high degree of responsibility. So I'm going to focus a little bit on the 2 of the business drivers that Cintia had talked about. So how do we get afami-cel to patients and providers? We need to make sure that we have the right network in place at the time of launch. And Dr. Druta and I often talk about this, what does that network going to look like? How are we going to operationalize ourselves and how do we make it happen on day 1 at the launch. So that's going to take making sure that we identified treatment centers. The treatment centers that have experience of cellular therapy, experience of Adaptimmune and the patient base that is eligible for treatment, so C-sarcoma patients. Those will become our authorized treatment sites, and I'll get a little bit more in detail about that in a bit. Then we have to understand what are those referral networks. We need to drive education. Laura is going to talk a lot about that in a bit about how do we drive education, not only about the treatment, the biomarkers, the disease itself and how the afami-cel fit into that algorithm and then how do we get those patients to these ATCs in an efficient way. And over to the right, the other business driver about delivering customer experience, excellent customer experience. The journey for cell therapy is complex, as Cintia mentioned. We can try to simplify. We can try to remove. We will remove barriers in terms of access and put processes and people in place in order to make this as smooth and seamless of a process for both providers and patients. I'm thrilled. I actually just got the next -- one of the last letter signed in terms of an offer that we -- about 90% of our team is built. We have a very special team that we brought in. And I think you can tell by the way that we care so deeply. That's what we expected the team that we're bringing in as well, of highly skilled professionals that have spent a large part of their career actually in cell therapies. They really understand what it means to operationalize a cell therapy in an individual, highly complex, academic institution. They also come to us with -- most of them a career in oncology and also rare disease. So this team is in place. We're engaging right now so that by the time afami-cel launches, we're going to be prepared to start treating patients. So what does our engagement plan look like? So we're going to do a little bit of math together, okay? There might be a test later. You all have a white book. You can write down the notes so that you can shoot a little bit if I pull you off to the side and ask you the question. About 50% of patients with synovial sarcoma are seen within 100 -- approximately 100 centers of excellence. So that's the top 30 and the second middle [indiscernible] of 70. So that's our 100 sarcoma centers of excellence and 50% of patients are seen in these centers of excellence. Underneath that is the other 50% that's in the community. Of those 50%, 80% are within the 30 top sarcoma centers of excellence in terms of volume like Moffitt where Dr. Druta practices medicine. Those 30 sites have been identified as our future authorized treatment sites. We will not be opening up all 30 on day 1. That's very difficult to do. It's a lot of work, but we will be phasing and try to get to those 30 sites and have them open to treat patients as fast as possible. We will also then work with the community, the rest of the sarcoma community in the sarcoma centers of excellence to make sure that we have identified -- given the ability to identify patents, appropriate patients access to testing and enable referral processes into these authorized treatment sites. To enable this process to happen and this engagement to happen, we have 5 distinct regions right now carved out within the United States. Each of these regions will have a dedicated team to support our not only our authorized treatment sites, but also the referral networks. So there's 2 colors on there. You will not be tested on this, only the other math. So the red dots are our clinical trial sites, our partners, partners that have been with us from the beginning, that have the experience, that have the patients and have the understanding how to treat with afami-cel and can operationalize with us quite quickly. They have expertise in cellular therapy too with their partners on the hematology side. The green dots represent the next wave of clinical trial -- I'm sorry, of authorized treatment sites who are also centers of excellence for sarcoma and in fact, have experience of lete-cel as well. So they will help to set us up for lete-cel. Each of these geographies or each of these territories have a dedicated commercial person. They will also have a dedicated medical director. They also have to be resourced with our market access team as well as our cell therapy navigators that I want to introduce to you on the next slide. So we have our field teams. But in addition to having our field teams, we built Adaptimmune Assist. Adaptimmune Assist is going to be an integrated support program to enable seamless ordering, understanding of where the cells are in their journey and making sure that we get patients their cells back within a timely fashion. But it's not just that. We're going to also have the ability to offer financial assistance, travel, lodging, ensure that we have efficient processes in place to help support referrals. And it's not just a system, there's people behind the system. We've hired 3 cell therapy mitigators that come to us either with experience in cell therapy as health care providers or have worked doing this as a profession. They care boldly about what they do and why they do it. They're the caretakers of these patients' journeys, and we're excited to be able to build not only Adaptimmune Assist, but also bring in exceptional talent that is going to alleviate and making sure that this experience not only for providers, but for patients is as good as we can make it. So in summary, I think that you heard the level of responsibility that we all feel to make sure that our treatment sites are ready, our referral sites also are already, and we have an exceptional team in place. And this deep sense of responsibility comes because time counts. People with cancer need to make sure they have the pathways to the right treatment. And it's because every single patient for us with synovial sarcoma cancer, and we want to help as many of them as we can. Thank you for your time. And I'm thrilled to welcome my colleague, Laura Gunn.

Thank you, Maria. Good morning, everyone. I just wanted to reiterate some of the messages that Maria shared with us about rare disease and synovial sarcoma being a rare disease. Rare diseases don't have the same level of awareness, resources or treatment options. Companies like Adaptimmune that are developing and researching diseases like this play an important role in the treatment ecosystem. And we're thrilled and honored to be working alongside doctors like Dr. Druta and our advocacy partners. With that honor comes great responsibility. And it is our responsibility to make sure that we are doing everything that we can to ensure that afami-cel is accessible to patients who would benefit from this treatment. My name is Laura Gunn, I'm the Head of Medical Affairs at Adaptimmune. I've been in the health care industry also for about 20 years, seems to be a pattern here. And most of that time, I spent in the specialty and rare disease space, and I'm very excited -- oh, one other point is before coming to Adaptimmune, I was actually at TCR2, which, if you remember, was another autologous T-cell therapy company that merged with Adaptimmune last year. It was the best move in my career because I've been able to be part of something so extraordinarily special. So we've built out the medical affairs team, and we've also deployed the field team. And the medical affairs team plays a really important role in this prelaunch space for a few reasons: One is the team is already out there able to engage with physicians and the care team to make sure that they are aware of afami-cel and we're discussing our data. But we also know that clinical trial experience is not the same as real world experience. And it's the medical affairs team that really helps evolve our clinical trial sites to commercial treatment sites. And we do this through a series of steps. We have great deep relationships with our clinical trial sites, and we leverage that deep expertise within those trial sites to broaden the awareness across the multidisciplinary care team. But we also leverage experts like Dr. Druta to educate throughout our referral networks. We want to make sure that we are educating as many physicians that see sarcoma patients on our data and on our biomarkers. We're also establishing a platform to ensure that we have a streamlined way of identifying patients, enabling referrals and accept and safe use with afami-cel. Once we're commercialized and we have real-world experience, we're able to capture real-world data. And that real-world data will feed back into our better understanding of the disease, understanding of afami-cel, and drive our strategy forward for afami-cel and beyond. So you've seen this slide a few times. These are our business drivers. And medical affairs supports all of these business drivers, but I'm going to focus on two. I mentioned education and the importance of education, raising awareness. So as I said, our team is already out there engaging speaking with physicians at our future authorized treatment centers as well as engaging physicians in that referral network. Addition to those direct engagements, we're also publishing our data and attending scientific meetings, which I'll talk about a little more in a moment. But we're also working to incorporate afami-cel associated biomarkers into treatment guidelines like the NCCN guidelines, for example. The second business driver that we're very, very focused on, and you've heard it a number of times already, is the importance of educating and enabling testing for patient identification. Afami-cel is a targeted therapy that requires MAGE-A4 expression and the appropriate HLA allele. We need to make sure that people understand why we need these biomarkers, when they should test for these biomarkers and where they can test for these biomarkers. We know that timely testing is critical for a timely treatment. And we want to make sure that there is a streamlined way of getting patients tested as early as possible and where they are. So that education is not only at our treatment centers, but also in that referral network. I mentioned our scientific meetings and our publications, and we're off to a strong start in 2024. You can see that we presented afami-cel data -- afami-cel quality-of life data at ESMO sarcoma earlier this year. We have a number of conferences that we're planning on attending in the second half of the year. And we're absolutely delighted that we were awarded a platform presentation at ASCO on our lete-cel data, the interim analysis from IGNYTE-ESO. One other thing I want to point out is the fact that our SPEARHEAD-1 data was recently published in The Lancet. There are copies I'm sure everyone's seen on your way in. I'm sure you could get Dr. Druta to autograph on if you wanted. But this is just a testament to our efforts to get our data out there to raise awareness, to increase the understanding of the clinical profile of afami-cel and the need for early and timely testing. This spectrum of conferences is also multidiscipline. We're not just focusing on the medical oncology conferences. We're focusing on cell therapy conferences, hem-onc conferences because we understand that there are many, many players in the multidisciplinary care team that we want to make sure that, that education is as widespread as possible. So in summary, the medical affairs team is out there. We are engaging. We're making sure that there are no barriers to understanding our clinical data, our biomarkers because patients need this option now. We want to make sure that we are able to provide access as quickly and as seamlessly as possible. And with that, I'm going to turn it over to my colleague, Tam, now.

Good morning, everybody. My name is Tam as Laura mentioned, I'm Head of Market Access here at Adaptimmune, and similar to colleagues on the panel with me. I've had the opportunity to launch multiple products within my pharmaceutical career. I've also held multiple commercial positions, but probably the most relevant for today's conversation is my time at Novartis. Where back in 2017, I was part of the team that launched the first CAR T team to the marketplace. Since then, I've had a chance to launch other complex therapies. Antibody-drug conjugates, radioligand therapies. I was also responsible for the pricing and contracting strategy for the hematology portfolio during my time in Novartis. And for the past 2 years, we've been building the same capabilities here within Adaptimmune. And we're doing this to help the organization get themself to the finish line. And to us, the finish line doesn't stop at the FDA approval of afami-cel. The finishes line is ensuring that every patient that's prescribed our product has access to our treatment. And we think about access, the 3 key stakeholders that we engage with. It's a payer, the provider and the patient. And oftentimes, when you think about access, payers come to mind, whether they're a public payer, such as Medicare or Medicaid or a commercial payer. And payers are both cautious as well as curious when it comes to cellular therapies. Because cellular therapies don't fit into a traditional box. They're not used chronically. They're not used in cycles as chemotherapy often is. But as you heard, they administrators a onetime single dose, and they've been shown to be clinically effective in certain tumor types. They also have a high price point. And so because of that payers are trying to evaluate the cost persisted value for their members. And so they're curious. And especially for a product like afami-cel in a space like synovial sarcoma, where there hasn't been any new treatment in over a decade. They haven't heard about synovial sarcoma. So they're trying to understand what are the treatment options? And how does afami-cel self help them in this space above and beyond what the standard care currently does. They also want to understand their budget impact. And as you heard, this is not the size of lung cancer. It's not the size of breast cancer. It's a targeted patient population, about 400 patients a year, and that's important for payers to know. We would love to be able to share all the information and passion that Dr. Druta has with every single payer because that's what they need to understand in this space. Providers are also an equally important stakeholder when you think about access, and cell therapies are unique in the sense that providers are part of the supply chain much earlier in the process. You have nurses and staff collecting a patient's blood cells to help develop afami-cel. And so Maria mentioned onboarding sites. And oftentimes, when we're onboarding sites will be in the first meeting, and there will be 20 or more hospital person now in the room with us, either in the room or on Zoom. And they probably represent half a dozen, if not more, functions within an institution. And I think this speaks to the fact of the commitment of our authorized treatment centers to really onboard our products. But I think it underscores the level of resources that are required with an institution. And so providers want to understand that the care that they provide for patients along that journey will be covered and reimbursed. And the last stakeholders are patients. And our U.S. health care system is very complex. I think it's an understatement. I mean I have parents who are Medicare Vantage. And I get phone calls from them every month asking about prescription drugs, if their new provider is going to be in or out of network. And to me, these are routine types of questions about health care, and we're talking about patients with cancer who had multiple lines of therapy, who have probably seen different specialists. Looking at a therapy and wondering if this new therapy, this new cellular therapy is going to work for them. But they want also to know if their insurance is going to cover the product. And how do they get to a treatment center if they live in a state where that one doesn't exist and the cost of the product, what's the out-of-pocket cost for them going to be. And so this is the work that we do to engage with stakeholders really to help remove these access barriers for our patients. And the 2 points that we'll highlight that I haven't touched on just yet is first is the testing, enabling simple and efficient testing. And one way we're looking to do that is provide sponsored testing. So patients get tested where they are. Maria mentioned that every day matters for these patients. And this will help in that respect. They can get tested within a authorized treatment center or with their diagnosing oncologists. It also makes it simple and efficient for payers and providers because there's one lab that payers and providers know can do the testing for them. The next point I'll talk about is pricing. And I think pricing is always that elephant in the room before a drug gets approved. And at this point in time, there's no pricing guidance that we can share. But what we can share is the fact that we've been doing a lot of work talking to payers and talking to our providers. We first and foremost look at the clinical value that our product provides. Secondly, we're benchmarking against other analogs. We do look at cell therapies. There are good analog. They're very similar in terms of the mechanistically versus what we're looking to do with TCR T-cell therapies. But this is different with afami-cel because we're also treating a smaller, rare patient population. And so we're also then looking at analogs that treat rare diseases as well. And so these are the factors and what they were doing, and there's more work ahead. But we believe there's a clear access -- clear path to access for our patients, and we're confident in this because of 3 reasons: First, there's a favorable payer mix. 55% of patients will be covered by commercial insurance. And what that allows our providers to have more liability in terms of negotiating case rates for their patients. Second is established reimbursement pathway. Back in 2017, when I launched KYMRIAH, there wasn't a bundled payment for Medicare inpatient patients at all. It was a struggle. It took over a year to get a single billing code for your drug. On day 1, we didn't think our plan will get approved on August 4. We'd be automatically linked to that CAR-T cellular therapy reimbursement code. We're also -- we'll also be the seventh cellular therapy approved in 7 years. So there's a little bit of familiarity that payers are having with cellular therapies. And so we feel confident that the coverage reimbursement for afami-cel will look very much like the other 6 before us. And we feel that way because we've been having early positive engagements with providers as well as payers. And our value propositions resonate with them. And the value proposition goes beyond the cost of the therapy. The value proposition speaks to what Dr. Druta mentioned that there's a high unmet need in this space, but these are young patients and the prime of their life being impacted, being told they have metastatic disease that 4 out of 5 of them will succumb to their disease in 5 years. And so you can't help us mile to be part of a company that's going to launch a product in this space with such a high unmet need with a product that's specifically studied it will be approved, hopefully, for synovial sarcoma. And this is what we do. This is Adaptimmune sur commitment. You heard Adrian mentioned it upfront. Our goal here is to design, develop and deliver cellular therapies, and we're looking forward to doing that. Thank you. With that, I'll pass it over to our Chief Patient Supply officer, John Lunger.

Thank you. Thank you, Tam. My clock is already at 0, I see here. So thank you very much, I was a little bit behind. For those of you I didn't meet this morning on the tour, my name is John Lunger, I'm the Chief Patient Supply Officer here at Adaptimmune, and that means I'm responsible for process analytical development, manufacturing supply of all of our platforms. I joined Adaptimmune a little over 7 years ago. And when I did the building across the street was empty. We were running one Phase I trial in the U.S. only. We had no internal manufacturing capabilities at all and about 19 people in CMC. So to be here today talking about our first commercial product from our own facility to have 2 additional late-stage products in the clinic, to have our own internal capabilities is really a professional and personal highlight for me and I'm very excited to be at this stage of the evolution of the company to lead into commercial. So as you can imagine, I'm proud of the CMC organization that we have here at Adaptimmune, not just the 7 leaders that you see on the screen here, but approximately 200 people that we have in CMC spread across 2 countries and 4 geographies covering the entirety of our platforms, autologous allogeneic and antiviral vector. I want to call your attention to the 24 years of Adaptimmune experience. You often see in biotech these slides and you see all the logos on the side because people tend to have 1 or 2 years of experience. The group on this screen has been here, myself included, all the way from first-in-human studies now through BLA for afami-cel. And I think it's the depth of experience in cell therapy that is so powerful. I think a year in cell therapy is kind of like dog years, right? It's like 5 years in a more mature organization. So those years, you can multiply by 5 to get there. So -- that said, commercial experience is important. And these folks here all spent their time early in their careers in commercial life science companies. They've run cell therapies, supply chains. They've managed global regulatory filings. They've led quality for commercial autologous cell therapy facility. So the combination of cell therapy experience, Adaptimmune history and commercial experience makes it the best team to support the afami-cel we head toward commercial. A bit more numbers on why I'm so confident. I mentioned we have 3 manufacturing facilities that we've developed over the last 7 years, the autologous drug product manufacturing across the street. In the U.K., we have 2 additional facilities, one focused on the allogeneic platform and a second in the cell and gene therapy, Catapult facility in Stevenage, where we produce antiviral vector. Our drug product history goes back more than a decade back to 2013 when we transferred the manufacturing process for lete-cel, the Phase I trial at the time from Penn to a contract manufacturer. And 2 years later with some of the funding from the IPO, we started down the journey of creating as our Chairman once called out a CMC tower of strength that is really necessary to be successful in cell therapy. We moved into the facility next door in beginning of 2017. And by the end of 2017, we harvested the first patient log, which we shipped to a patient in early 2018. So since then, we've kidded out 15,000 square feet of the facility. We've invested in the digital infrastructure that is really necessary if you're going to put yourself in a position to scale. And by that, I mean, electronic batch records, electronic QC monitoring systems. The chain of custody and chain of identity tools that are necessary for autologous. All of these are investments we've already made and are ready to scale to the kind of numbers that we are talking about here in the future. And we've used these capabilities to produce more than 350 [ lots ] out of the facility that you walked through this morning. That facility has the ability to go up to nearly 700 patients a year which is enough capacity for afami-cel, both the clinical as well as the commercial supply. Uza-cel was also produced in that building. And lete-cel, which is a product that is currently manufactured to the third party, we're examining the opportunity to add the Navy Yard facility to that supply chain for lete-cel. I don't want to forget the bottom right corner here, the lentiviral vector as well. Similar to the early days of the story, we were getting vector from academic centers in 2013. We recognized the need that we had to control that lentiviral vector. That's the critical drug substance that we use for engineering our T cells. And we began to develop our own process for that as well. And as we sit here today, we actually have 3 lentiviral vector suppliers for our late-stage assets. We have AGC, based in Milan, Italy, that provides the vector for lete-cel. We have [ Inomagen ], which is the supplier for afami-cel, and then our own facility supplying the uza-cel vector. And this base of 3 vector suppliers gives us an opportunity for some redundancy for some scale and the opportunity to really leverage that network for our future uses and that we're in lentiviral vectors. I'll close talking about the manufacturing processes and the capabilities that we have to continue to improve how we make autologous cell therapy products. We actually have 3 manufacturing processes in the clinic at the moment. What you see here is the afami-cel process that you saw as we walked around the building in the 4 to 6 weeks turnaround time that we have for afami-cel. And while we had a 90% success rate in SPEARHEAD-1 with this manufacturing process, and it's absolutely appropriate for afami-cel. We're not done and we're relentless in our ability to continue to improve the process. The uza-cel product, that's the one that's being run in SURPASS trial at the moment. We manufacture that also in the Navy Yard, but we use a different bioreactor and improved bioreactor, and we've made some changes to the process to shorten the manufacturing time, improve the product and reduce the cost of goods. The lete-cel product, that's the one that recently came back to us from GSK, that is produced by a contract manufacturer called Miltenyi on a device called the Prodigy device, which is a fully integrated manufacturing device, which we're actually using our allogeneic platform, and we're looking at the opportunity to potentially use that here in the Navy Yard as well. So I often get when I showed this question, well, that seems very complex. Why don't you standardize on something? And the short answer is, I think the ability to manage multiple processes in multiple trials, multiple geographies is a huge strategic advantage for us. There's the cell therapies that are out there, the CAR-Ts have demonstrated that the autologous platform can be used and you can build a business off of an autologous platform. And there's a lot of innovation that's coming into the space. They're centralized and decentralized manufacturing. There's fully automated manufacturing. There's fresh in, there's fresh out. There's bedside manufacturing. All of these are rapidly changing and you need process and analytical expertise to be able to assess them, understand what to put into the clinic, actually get them into the clinic and test them in the real world. And it's that process and analytical development expertise that we have created over the last decade that will put us in a fantastic position to be able to leverage the changes that are coming in autologous and use them in future products. So I'll leave you with a couple of comments. We have the capacity for afami-cel. We have the capability to make it, and we're in a great position to be able to support the afami-cel launch. So I think with that, we're heading to a short break, and we'll have Q&A when we come back. [Break]

I think the lights are a sign that we're ready to go with this panel. So welcome back, everyone, after the break. Thank you for continuing on this journey through the morning, and we are in the home stretch. We have brought a panel up here, which I will introduce in a second. But first, let me say, I'm Bill Bertrand, I'm the Chief Operating Officer at Adaptimmune. I've been here about 7 years. It's been a phenomenally interesting and emotional and passionate journey over the last 7 years to get to this point where we are right now. I've been with the biopharmaceutical industry, like many of our colleagues for over 25 years. And I've been at companies that have commercialized products. I've been at companies that have launched products and it is so amazing to be on the cusp of that here at Adaptimmune. It's amazing not only for the company, for the journey we've been on over the last 15 years or so, but it's also even more amazing for the patients that will be able to benefit when afami-cel comes to market. So I want to welcome back Cintia, John and Laura to the panel, but it's also my extreme pleasure to introduce our new panel member up here, Philip Leider. So Philip is the Board President of the Sarcoma Alliance. The Sarcoma Alliance is celebrating its 25th year in 2024, and its mission is to improve the lives of people affected by sarcoma through accurate diagnosis, improved access to care, guidance, education and support. So Philip has served on the inaugural Board of Director of the Sarcoma Alliance starting in 1999. He took over as President when unfortunately, his sister, Suzanne Leider passed away from synovial sarcoma in 2002. He served as the President until 2012. He returned as the President again in 2022. And as a man after my own heart, he is also a practicing attorney with a lifelong interest in the intersection of law and medicine. So thank you for joining us, Philip.

Why don't I share the first question for you. Can you share a bit about your family's experience with synovial sarcoma? And maybe sprinkle in what a person might experience in that emotional journey as they deal with sarcoma?

Thank you, Bill, and thank you, everyone, at Adaptimmune and Dr. Druta. It's great to be here. I want to talk to you today in two roles: One is first just as the brother of somebody who died of synovial sarcoma and was treated for synovial sarcoma for 10 years. And then my sister Suzanne, who is less than a year younger than me, she founded the Sarcoma Alliance in 1999. She was a registered nurse at UC San Francisco, and she was diagnosed with synovial sarcoma. And I got to watch her journey over 10 years as a health care professional, not as an ordinary person, most of the people we help. And I have a lot to share with you. I'll try my best to be brief, and I'm also interested in answering your questions. It is a brutal that's the word Dr. Druta used, a brutal thing to be diagnosed with this disease to be a family member of somebody diagnosed to this disease, a friend of somebody diagnosed with this disease. And it usually comes as a total shock. My little sister had a bump on her knee and she was in terrific shape, great health, ran, hiked, swam. She was a nurse right at the beginning of her career, she was 25 years old. She had this little kind of pain just above her knee, it kept bothering her. So she went to the doctor and the doctor saying, maybe you need to go see somebody, let's see what it is. And there was a bump in there and they thought maybe it's a cyst. So they usually think, it's just a cyst, something benign. And they decided, well, let's try to take some fluid from that, couldn't get any fluid out of it to figure out what it was. So they just cut it out and send it off to the labs. And this happens all the time. Dr. Druta will know this. They don't know it's a cancer. They don't know it's a sarcoma. It's just a mass that's causing pain in this region, often in this region, some here very common in these places. And the lab results came back and it was this just lightning bolt from the sky. She thought she had a tumor -- I mean she thought she had a cyst, and it had been removed. It was a synovial sarcoma. And as a nurse, she had no idea what that was. Imagine just being a lay person and hearing that and not knowing what it is. And I remember the day as clear as it can be I went to the UCSF library with my sister, she worked at UCSF as a nurse. And we walked across the street on Parnassus looking over the beautiful San Francisco area. And so we went into the library and we opened this giant book, soft tissue tumors, huge book and she turn to the page that was about synovial sarcoma and it she had 5 years to live. And this is my 25-year-old sister, perfect health nurse, just absolutely devastating. And she knew that there were people out there in the world that would not know the first thing when they were diagnosed with this disease about what it meant for them. And she -- this is before the Internet. This is before the information that's so available to all of us now was available. And so she founded this organization Sarcoma Alliance and she became its President. And I want to speak a little bit about her journey. Sorry to go on and on. First, she had to have a second surgery because when they took out this, what they thought was a cyst, they didn't take broad enough margins when you have a sarcoma it can travel metastasizes quite easily, and so you can't leave any cells or any tissue with the disease in it in the surgical site. So they had to go back in and [ resurgerize ] the site. And then they also radiated her. So she had a -- beautiful year 25-year-old girl. She had an incision from her knee to about here, probably 10 inches. We called it the zipper and we were a little morbidly, and then actually have this radiation and it formed a kind of rectangle on her leg and it got redder and redder and redder, as she went through the -- and she had to do it day after day after day. And so that was the start of it. We thought we were done, all looked good. And 5 years later, she was told they were after scans every 6 months to make sure that the disease hasn't recurred. They found some tiny little dots in her lung, which is very common. And from then on, really just absolutely brutal, that's the right way to explain what happens. She had to have -- I think she had 5 thoracotomies, which are these incredibly invasive chest surgeries where they go in and they take not just again the cancer, but they take tissue around the cancer. And unbelievably painful, unbelievably hard to recover from. And then on top of that, it became a therapy that Dr. Druta was talking about, which makes you violently ill. You have to have a transfusion eventually because your blood has just lost all the things that are necessary to it. You can't eat, you vomit. All the food you do eat tastes terrible afterwards, mean just all these horrible things that happen, recurrently, and my sister was fortunate. She was a medical professional with tremendous support at UCSF. And she had a family, a loving family that cared for her. We were united each time she had a thoracotomy at a dinner that she morbidly called the last supper each time. And we would all join together have dinner with her before the surgery, hoping she survived the surgery itself, but the recovery from the surgeries was just is brutal for somebody who's healthy and as strong as she was, imagine for somebody who's not. Then imagine for somebody who's not in San Francisco and who's not a health care professional, somebody who's in Alaska or fisher person or it's just she was fortunate as you can be for somebody with this diagnosis and still, it was brutal for her, very hard on our family. And that's why we're so passionate now, and I'm so passionate as the President of the organization. I want to make sure that people are supported through this and its array of light, quite honestly, to see that there's some hope for a mode of treatment that isn't as brutal as this, and that offers even just a speck of hope to people that they might have some prospects of a normal life for a longer period of time. So that's a long answer to but...

Thank you very much for sharing that. Again, I'm a grizzled lawyer, all of that in this pharmaceutical field. And you hear stories like that. You understand and Cintia talked about caring boldly and every one of the folks that has been up on this panel presenting today has been driving why we do what we do at Adaptimmune, and that's just a real-world example of that. So why don't I -- Cintia, maybe a question for you and a bit of a follow-up on that. So given some of the challenges that Philip's sister may have experienced in terms of finding out about the disease, given some of the challenges that the physicians in the community settings might feel, how are we planning to try to help them ensure that patients are referred to, where they need to go?

Yes. Thank you, and thank you so much for sharing the story. It is very touching. And we are very aware and as Bill said, care a lot about understanding the journey that patients go through and also working very closely with the care teams because Dr. Druta mentioned, and Tam mentioned as well, it's not just one physician. It's a whole group of professions that are around that patient and family going through this journey. So we've been doing a lot of listening, first of all, an understanding from the family's perspective, from the patient perspective but also from our sites, not only the trial sites but also the treatment sites that will go beyond that and the referral sites. So each one of them are going to need and require a different type of approach and education depending on where they are. And we also already put it all in place to make sure that we can, across the community, let people know that we are coming and it will be available and explaining that now there is a biomarker that is actionable for synovial sarcoma. So if you have this condition, and if you're positive for MAGE-A4 and you are HLA-A2 that it is something that it's now actionable that it wasn't before. And making sure that we communicate not only where all the sarcoma centers of excellence are but very clearly where the treatment centers are. And then working closely with them to understand each step of the journey. We talked about having the sponsored testing. So then it goes very smoothly for people that want to get tested, but also getting them efficiently through the treatment sites in terms of travel, logistical support, if they need support to talk to payers as well. So all of that support to the patients and the families we're going to make available.

Perfect. Laura, I think you mentioned that the medical affairs team is out in the field. So what is some of the reaction and interactions your team is having with physicians?

So overall, the reaction is excitement, and I think we heard that very clearly from Dr. Druta. In our treatment centers, there's a pretty wide awareness of our data. The investigators for our studies are literally wrote the book on this. They are authors on the paper, and they have a great awareness of the clinical profile of afami-cel. When you get out a little bit further, as Cintia was saying, we're talking about our referral networks the educational needs are a little bit different. And that's where we really need to be focusing on the awareness of the biomarker testing because we know that, that is absolutely essential to get patients treated and done in a timely way. I think we have a number of questions more on the logistical side of things and some of the things that Cintia was just talking about. We've had some questions about whether or not we'll have a REMS program or what our process for nonconforming product is. But overall, I think what we're really hearing is overwhelming excitement urgency for this therapy. And as I said, the biomarker testing and the timeliness of that.

Great. I do want to remind everyone online if you have additional questions, please use the chat feature in the Zoom button or the zoom feature. I've got a couple of more questions here. We've got one then I'm going to direct to John. Philip, I'm going to come back to you in a second, and then we'll obviously go to the audience if there are questions out there. So John, you mentioned that you've been on this manufacturing CMC journey for the last 7 years or so at Adaptimmune. Dennis referred to remarkably successful inspections we had gone through. How does that make you feel having been on this journey for the last 7 years with Adaptimmune?

Great. Actually I think the things that I think I'm most proud of are the most impressive, it is our first FDA infection. We just got through that a couple of weeks ago, and Dennis mentioned that there's nothing there that's going to prevent this therapy from moving forward. I've been through a couple of BLA inspections like that before. Wanted a big company wanted a similar biotech with their first one, and we're as ready as anybody for that. The second is the experience that we have. Usually, in a biotech, you've -- when it's not autologous, you've done maybe 1 or 2 batches, you've done your PPQs, the 3 runs you have to do. We have done hundreds and hundreds of batches in the facility for afami-cel. And that gives us a breadth of experience we're on version 2, version 3, version 4 of our processes and precision in control. So I am absolutely confident that we're not going to have any issues as we head toward the launch and we're staffing up now to make sure we have the capacity to handle the patients that are going to come.

And then maybe a follow-up, John, a question that came in. So what are your specs and how do you think you will avoid the out-of-spec pitfalls other companies have faced in cell-therapy?

Right. So there's 17 specifications, just to be clear, there's actually 17 QC tests that are done on each [ lot ] that range from safety to potency to identity. So when people talk about out of spec. Non-conforming is a better way to think about it. The specifications that we ran for the trial were actually wider than what we had on many of those than we have for the commercial specifications that are not approved yet, right? These are part of the BLA but the specifications that we put in there would cover 99% of the outcomes of the manufacturing runs we did in the clinic. So I don't expect to see much difference in terms of the results that we get commercially than we had from a clinical perspective.

Are there questions in the audience?

This is Yuan from B. Riley. Great to participate in this event here and see the innovation in the cell therapy space is better in the sarcoma tumor. And maybe one question to Cintia. So just curious about this process to get doctors engaged with this new therapy. Laura mentioned earlier that you guys are already talking to the doctors. I'm just curious how long does this process take to get this novel therapy into the formulary once it's approved? Because we already have so many touching points like KOLs are writing the books or writing the papers and then you're talking to doctors already. I'm just curious about this timing process, how long can -- once it's approved, when can the first patient get this commercial product ?

We are working to make it as fast as possible. We certainly understand the urgency. So we have basically 3 main teams in place in the field right now that are working with medical affairs. So medical affairs is working a lot not only with the physicians, but also with the treatment guidelines to make sure that everything is in place. We have Maria's team that is also engaging with the referral sites and with the treatment sites through an onboarding process. So then they are ready to go at approval. So the sites will be everything that can be done before the approval that will be done. We're already signing all of the technical agreements, quality agreements and the IT because there are systems that need to in place, all their IT technology, check-ins are starting to happen right now and market access as well. So not only the engagement with payers, we have several conversations with payers already, but also all the background work that needs to be done from a coding perspective, end type applications. So all of that and also translated that into what does it mean like coding guides and things for the providers to be able to be ready to use afami-cel as soon as it's approved. Now what we need to keep in mind is that the patients are going to be tested, right, which is a little different than CAR Ts in sales. And the testing -- commercial testing will be approved at the time of the launch. So in terms of we're going to be ready to go day 1, we're working towards that. And so hopefully, we can get patients tested and already into their journey as fast as they possibly can.

Matt Cowper, Leerink Partners. So as you're approaching a potential U.S. launch, this is obviously an unmet, the transcend borders. So how are you thinking about positioning of afami-cel ex U.S.? And thoughts on time lines, any potential partnering discussions and manufacturing consideration?

Yes, I can start and maybe then John can talk about manufacturing considerations. We certainly want to make a afami-cel available for any patient that can benefit from afami-cel. We are starting with the U.S., and we've been focused in the U.S. From a commercial perspective, we do have clinical trial sites across the globe. So we have experience with afami-cel, manufacturing and delivering afami-cel when we have data across the globe. So right now, we have been -- I don't know, maybe Dennis can comment also on the regulatory, but -- we have been in initial conversations with European authorities to understand what they will require for us to potentially be able to get to Europe, but it is certainly part of our plan. John, I don't know if you want to comment on that...

I mean we supply Europe from this facility here for the clinical program. So It is logistically possible to supply afami-cel into Europe from the U.S. facility. We also have I mentioned 2 other facilities, 1 of those being colocated with our research group in South for Oxford which has got a lot of extra space in it, and we thought of that as a potential European source should we have to go there. So I think we have a lot of flexibility, but at least initially, if we choose to go through Europe through partners or otherwise, the opportunity to supply it from Navy Yard is probably where we would start.

So we have one question that had come in during the prior panel that we felt might be better directed to this panel. So -- and we did commit to answer that one. So probably Cintia to you. I have read this new therapy could cost upwards of $400,000, which initially sounds high, but after hearing the alternative, which are the current range of therapies, it could save the system money in the long run. Any thoughts on that?

Yes, absolutely. And so I think Tam mentioned a little bit earlier as well that the way that we are looking into pricing for afami-cel takes into consideration first, what we call the value proposition, but really the benefit that afami-cel can bring not only to patients from a clinical perspective that we saw but also to the entire health care system because the patients do need to keep getting back for treatment, they get complications. They many times need ICU. So the entire cost of care for that patient is very high. And in addition to that, we talked about the fact that, unfortunately, this cancer also impacts patients in earlier life and are patients that are very active. So also in terms of patients and families because if a patient needs to travel for treatment, it needs to be available, usually, you need to have a caregiver that can go along with them and the disruption that, that causes for the family ability to work and things like that. So all of those elements are taking into consideration as we are decided how to price of afami-cel.

And since you mentioned probably something that maybe makes me think of directing this next question to Philip, given we heard the story I've experienced your sister, unfortunately went through. But -- and we also heard Dr. Druta talk about the importance of advocacy in this relationship between patients and companies and providers. So what is an advocacy organization such as the Sarcoma Alliance work to support with patients?

Thanks for the question. The key -- we have 2 mantras at the Sarcoma Alliance. The first one should be obvious, a disease this rare people spread all over the globe. You don't know if somebody who has synovial sarcoma and you're diagnosed with it. Suzanne didn't know somebody with sarcoma, there are several other subtypes, she was a nurse for many years. So people are spread all over. And the first thing when we did a questionnaire of the community we serve, the screaming need was we feel isolated and alone we don't know -- feel like a spotted Zebra. And I want to meet somebody that's like me. I just want to share my experience with somebody who knows what I'm going through. So our first, mantra is you are not alone. There are other people out there who have this disease and are sharing these experience as you have with the families, caregivers, they've gone through this, reach out to them through us. We have a Facebook support group with over 13,000 people participating, which with the disease this is remarkable, very active, very supportive, an amazing, amazing thing that social media has made possible for us. The second mantra of the organization is go to a sarcoma center once you are diagnosed with this disease you maybe in a place that's nowhere near a sarcoma center and maybe going to a great hospital or a tiny little hospital or just a doctor's office somewhere, but you need to get somewhere where people understand this disease. It's tremendously different than other cancers, it's tremendously different than lots of other diseases. And you need somebody with the expertise that Dr. Druta has and her team has multidisciplinary center to really get optimal care, and once afami-cel is a reality, which in a commercial reality and is out there for people, they need to know that's available to them and then they get to get tested so they can see if they're eligible to receive it. So we want to be part of that. We're constantly -- we have a grant program. Alison Muse, my fellows board directors here with us today. We have a grant that we named after my sister Suzanne. It's the Suzanne Renée Leider Memorial Assistance Fund. And what we do with that grant is give people money when they're first diagnosed to get to a sarcoma center and get expert care. And they might not get their care there. They might just make sure it's a sarcoma and really make sure the grade is identified the type make sure that the plan that their oncologist has to treat it makes sense and coordinate with that physician when they go home. But it's just absolutely important to get them to the sarcoma center. If they're going to the sarcoma center to get infused, Great. Just any way we can get them to the people who really know how to treat them is in our view the key to all of it.

Perfect. Thank you very much. Cintia, a couple of questions for you and the Dennis, one has come in for you as well. You thought you're off the hook on it, but you're not. So Cintia, you used the word focus, as you talked about launching afami-cel. What is the size of the commercial and medical affairs teams? And do you feel this is sufficient to do what we need to do?

Yes. We feel very confident that this is a good size because of what we shared earlier also that it is a fairly concentrated space, and it is a rare disease that is treated by the specialists. So if you look across our commercial and medical affairs organization in total, it's about 30 people, half of them more or less are in the field, meaning that they are seeing customers every day. We have the 5 regions that Maria shared. So we have pretty much one commercial person that will be a coordinator of that site in each one of those regions. It's 5 people, 5 medical affairs. It's a mirror team. They will work very closely together, a couple of between market access that will support reimbursement and talk to the payers. And we have also the great team that Maria referred to earlier, part of Adaptimmune Assist. They are also adopting new employees that are allocated to specific sites. We have 3 of them. There are navigators that will help the patient and the care teams go through the entire treatment journey. And then us and we feel very confident that it's a good sized team.

Perfect. Turning back to the audience questions?

Marc Frahm from TD Cowen. Maybe from the Adaptimmune team but also maybe a little bit for Philip. Just what -- in the earlier slides, you can implied maybe 400 patients are actually -- are going to major sarcoma centers like Dr. Druta where the treatment decision seems pretty clear. How many -- and being cared for there? How many more do you think are actually going to those centers? And then going home to get their infused therapy somewhere else and maybe aren't being captured in the treatment data at those centers?

Yes, it is possible that not all the patients kind of are captured and we are estimating more or less what the distribution in the each one of the sites of care are today. One other thing that we were commenting earlier is that, that's the current picture. And when there's -- we just talked that there are not a lot of immune treatments available. We believe that by the time that afami-cel gets through commercialization and people know that there is a new product available and that is a new treatment and there is a new option. And that those are the sites in which the care will be provided that the referral will increase. And so then we estimate that, that referral and the percentage of patients that you end up in those treatment centers are being significantly higher.

Just related to that is just kind of what's the process of getting kind of the testing implemented at those much more broader the community centers, where the initial -- like Philip laid out, that initial surgery is happening because they think it's a cyst so that they actually know they need to get to a place that has cell therapy?

Right. Several things that we're doing to make sure that, that happens. One is a lot of communication and informing that now there is an actionable myomarker, if you have some of the sarcoma that's what needs to happen through what we call nonpersonal efforts, online digital platforms and other types of media in addition to our team. A lot of work with societies in terms of treatment guidelines. So incorporating that as part of a routine process that it's what's considered standard of care for the treatment of synovial sarcoma. And then finally, from a testing perspective, anybody that is interested in afami-cel hears about MAGE-A4 or synovial sarcoma that will look us up online or when what you do, we will have the testing available in a very simple way. We are partnering with the lab that we'll be able to do a very simple form. Any physician could order the MAGE-A4 and the HLA test with no costs. And they can do that from wherever they are. It's just like a simple form. They can either download or fill online and that whole process will be taken care by the lab that we're partnering with.

I would like to add one quick note. Even identifying that these people are synovial sarcoma patients in the first place is a huge thing. So our organization, 1 of the things that's just so frustrating my sister, taking as an example, that surgeon could have just taken out the mass and not send it off for testing. Just thought it was a cyst or an odd-looking cyst because it came back and they said it looked like a big pink blob. So we thought it was a little odd and wanted to have a test. Thank God, and went to for different diagnostic places and it came back that she had synovial sarcoma, but that's not happening everywhere. People are walking around with bumps or pains in their body or they're going in, having them taken out, and they don't even know that it's a cancer, let alone a synovial sarcoma. So one of our big efforts is to make sure this exact same thing, but in an advocacy kind of role. We're trying to make sure people don't just take masses out and say, "Hey, you're done." Test it, find out what it is. And when you find out that it's a sarcoma, there's a -- like you said, there should be a standard of care for this. There should be a roadmap for every surgeon, every physician so they know what they're supposed to do with these very, very important decisions.

It's the importance of education really continuing to drive that deep into the field.

Rosy Liao with Guggenheim Securities. I guess you kind of touched upon this earlier, but do you have any more line of sight into NCCN revisions and potentially getting afami-cel into the updated recommendations? And then also more specifically, I guess, like how the category of recommendation might affect your commercial trajectory?

Laura?

So we're currently working right now to establish what our recommendation for the NCCN guidelines are. The NCCN guidelines that exist right now are for soft tissue sarcoma. There is not a specific recommendation for synovial sarcoma. So one of the things that we'll aim to do is actually pull out a piece of those soft tissue sarcoma guidelines to focus on synovial sarcoma. So then what that will look like, it will include the biomarker testing, our recommendations for when testing should occur, how that fits into the current kind of work up that they currently do and then also obviously include a afami-cel in the treatment paradigm. So our plan is to be working with NCCN between now and approval and get that integrated. So we can have a much broader recommendation for physicians to understand how to manage patients with synovial sarcoma.

Tony Butler, Rodman & Renshaw. Phil, I wanted to ask, I checked out the site very quickly. It's incredibly insightful and very detailed. But let's say, for example, I'm a farmer in Cleveland, Mississippi. I've got 5 hours to drive to Nashville for one ATC site, 5 hours roughly to Tampa. There's a grant, but I don't really like the time to read through all this. I want to know if I can call you or call somebody. So teach me about what kind of information I can get from you. And more importantly, even we have this grant, that's great, you could say that. But it's important for me to talk to somebody as opposed to flip through the website to some degree because, again, I'm going to have limited time. And then is there any way that you can help me with that referral. I mean you could maybe call Dr. Druta, she or some permutation of that so that there is a time which I can get there. I could see this as being a very real-world situation.

Thank you for your question. And it's just directly on point, that's exactly what we do day in, day out. The website is obviously our first connection with people quite often. But we have a traditional phone line and we get phone calls each week. Alison responds to many of them from people who are a mother with a young child crying who has some form of sarcoma very often synovial sarcoma. And we walked them through to the whole process. We connect them with our support group. Some of them are in person and local. We have an online support group, which hopefully, if they have Internet access, they'll join because it's absolutely fantastic. We connect them definitely with local, and the closest local sarcoma expert that they can consult with. We provide financial assistance for them to get a consultation with a sarcoma expert. And we just make every effort we can possibly do. Obviously, we accept e-mails and get inquiries and all sorts of other ways than those. But this poor guy who's trying to just do his job and keep going in his life aside from just dealing with this disease. He does not want his whole life to be about this disease. He needs support. He needs to connect with people. And not just the support group, some people don't like to join a support group they're kind of shy and private. We partner with a terrific organization called Imerman Angels. And what they do is they pair you with somebody who's similar to you, and you can just a one on one with them on the phone or if they're nearby if you're lucky enough to have somebody in your buy, you can meet them. And you decide what you want, somebody this old has this diagnosis, this situation. And you get to meet somebody that's similar to you. It's just remarkable how that's so important and those people usually have terrific information. They've been through it themselves and they can help guide somebody like the support fellow out in the middle of nowhere about what he can do to take care of himself and his family.

Great. Thank you very much. Question for Dennis has come in. How are you thinking about labeling for afami-cel? Specifically, any baseline expectations for prior therapy requirements that are included in the label or potential safety warnings in line with historical cell therapy approvals?

So if I just come up here it would be easier. Thanks. So I would say for labeling, like many therapies that come before, like I gave this example of pazopanib in my previous life. We're looking to be placed after frontline chemotherapy. In other words, anthracycline-based chemotherapy. So if you have received anthracycline-base chemotherapy plus or minus ifosfamide, our goal is that you would be eligible to receive afami-cel. As far as management of toxicities, as I mentioned, right, so cytokine release syndrome is -- you saw Dr. Druta present the data. It is the most common adverse event that we see with this therapy. It is generally low grade, but we certainly make recommendations about how that should be managed with supportive care and the use of tocilizumab, which is a standard of care treatment for that. So we do not see neurotoxicity or ICANS for the most part. And I don't expect to have the same type of labeling around that, that some of the CAR Ts have for hematologic malignancies. But in general, there probably will be some similarities of the types of things that we would describe in our label that you would also see for CAR-T and hematologic malignancies.

Dr. Druta, did you want to say something?

I wanted to add actually, I did not have a mic, and that's why we -- in terms of the -- yes, in terms of the recommendations for the management, we already have all of these in bigger centers where we manage these patients. There are -- we have the standard approach from the institution how to approach these patients. But I wanted to also add to your question, and it is a passion of mine, and then I'm trying to -- this is where we will need to partner with patient advocacy groups and change some of these legislations. In terms of the -- especially in the terms of the rare disease, we need to try to have access for these patients despite of limitations of our licensing on the virtual platforms. Again, we are living in a 24th century where we need to be able to communicate with these patients and to evaluate them from distance to start to kind of break some of these barriers and for patients to drive I don't know how many hours or to have all this financial burden, just to figure out because that will be extremely important to figure out if it's the right diagnosis, just to begin with that. And then us as a center of excellence to have a plan in place before the patient is even committed to all this journey to come to have this. So this is something that I'm very passionate. This is something that we should be able with the patient advocacy groups, with the support of the pharma companies to be able to. Especially to start, especially in the rare diseases, where these patients, they will need access for the right diagnosis, a treatment plan and to make it as easier and cost-effective for them and not to put them through this burden. So thank you.

Thank you very much. We have time for a question here in the audience.

Arthur He from H.C. Wainwright. Thanks for hosting us here. I just had two questions for John. You have things you being here for many years. Could you tell us more about the prong headcount for keep the manufacturing in-house? And do you have a backup plan to internalize the lete-cel manufacturing in-house? Second question is regarding the afami-cel. At what capacity do you think you can reach the optimal COGS for afami-cel?

Okay. So internal manufacturing to begin with, autologous cell therapy, you've heard about the patient journey. It's very complex, very hard to schedule patients work around a patient's schedule, certainly for the apheresis side as well as for the manufacturing. So I think one of the advantages, just from a flexibility perspective and having our own internal manufacturing, it's hard to do to a third party, right? Third parties are trying to firmly schedule things what the assets they make money off of how many batches they run, whereas that's not our case. So that's an advantage in autologous. You asked about lete-cel. So lete-cel is with a third party at the moment. So GSK chose to go down that path with a third party. And our intention is to maintain that third-party network as we progress towards BLA because our primary goal is to get that product to market. However, we are looking at the maybe as a potential source, we're doing the work right now. It's a third platform. I mentioned on my tour. So it is done on a different device, so we have to physically see if that will work. And we're going through that exercise now. But for the purpose of launch, speeding toward BLA is going to mean we look at the existing supply chain that they have. And I guess the last bit about the optimal COGS. Our cost structure is not that much different from what the CAR-Ts are out there, somewhere between that 100,000 and 300,000 number is kind of what's expected out there in COGS. A lot of levers to pull on that. There's volume levers, which are obvious, right? This facility can get up to about 700 patients. That's our maximum capacity, physical capacity of that particular facility. So that will help. But there's a lot of other things that we can do, frankly, that don't require comparability and clinical comparability. When we change the process, we can do automated QC methods. We can do all the things that any operational person does in terms of Lean and Six Sigma. We can negotiate better discounts on things we buy as our volume gets higher. So the margins that we talked about, the 70% gross margin is based on our current structure. And I still think we have a lot of levers we can pull to improve that and help provide more access there.

Great. Thank you, John. Time for one more question in the audience, and then I'm going to end with a question for Cintia.

In terms of, I guess, market access, right, what are your thinking in terms of like patient support or systems programs? How quickly do you think this afami-cel can get added to the formulary lists overall?

So in terms of patient support, Maria shared Adaptimmune Assist, which is the -- it's going to be like a centralized place that we'll have people that will be also answering the phone, not only available online to provide financial support, support working with insurance and getting any type of pre approvals that are necessary and also working with the providers to make sure that they have the information that they need to be able to get reimbursed because this afami-cel is a product that is health care administered. So the sites actually have a big role to play in the access for this product and financial support. So if a patient has larger of pocket or has challenges in not being sure all those types of financial support for travel, partnering with patient support groups a lot as well, we heard a couple of times today how that is important and work that we've been doing. I'm very passionate about the amazing work that these organizations are doing, it's also very high on our priority list.

Great. Wonderful. And finally, we have the joy of welcoming you back to our executive team recently after a short stint away. Anything you'd like to folks to take away from your experience coming back into Adaptimmune? And how we are ready to commercialize this product upon approval?

Thank you, Bill. Yes, I'm very excited to be able to be back. And I was away for about a year, and it was very exciting to see the progress that the organization has done in bringing afami-cel to patients. It was great to be reunited to all of my colleagues and see the alignment and the excitement to get this done. And I think the other thing too is that it's very concrete and very real right now. So it's one thing, like when I first started, we were putting together the plans on paper and imagining scenario, infinite number of scenarios, what if this and what is that and how can we get resources and allocate and prioritize, so a lot of mental exercise, right? And now we're getting to the site and we're like, all right. So this is the system that we're going to be implementing. This is what we need to do. Who is the person that is going to be picking up the phone and bringing people like my first day we had a training meeting. So I was able to meet part of the team that had already been hired by them or 90% of the way now. So it feels very real, very concrete, and I think we've talked about today. Huge sense of responsibility. And it is a very humbling to be part of something so big that can have such an impact in the lives of patients. So really grateful to be here.

Thank you. So I'd like to thank my colleagues who have joined the panel up here, and I especially like to thank Philip for joining us and providing some of that insight. So thank you very much. And with that, I will turn it over to Adrian.

So as we wrap up, I just want to say thank you. I want to say thank you to everybody who came down to Philadelphia, undertook the manufacturing tour and participated in this event today. I want to say thank you to the 100-or-so people online who also participated throughout this session. But most of all, I want to say thank you to the sarcoma community that has enabled afami-cel get to where it is today on the verge of approval and being a reality for people with synovial sarcoma. We are inspired by the resilience of the patients that participated in our trial. We are, I think, inspired by the passion of the patient advocacy that we see in this space, and we are inspired by the relentless determination of the care providers and the whole care team for their -- to bring the best available to their patients. And that is something that I think from Adaptimmune, we are committed to mirror that resilience that dedication, that passion as we bring the first engineered T cell therapy in the world for a solid tumor to market. So with that, thank you ever so much for being here. There's lunch for people who are physically here in the site back over Adaptimmune. Thank you.