Good morning, and welcome to Adaptimmune's Conference Call to discuss our first quarter 2021 financial results and business updates. I would ask you to please review the full text of our forward-looking statements from this morning's press release. We anticipate making projections during this call, and actual results could differ materially due to several factors, including those outlined in our latest filings with the SEC. Adrian Rawcliffe, our Chief Executive Officer, and Karen Miller, our SVP of pipeline research, are with me for the prepared portion of this call. Other members of our management team will be available for Q&A. With that, I'll turn the call over to Adrian Rawcliffe. Ad? Thank you, Juli, and thank you, everyone, for joining us. Kicking off this year's conference season, May will be a busy month for us. We will present our first preclinical data for our mesothelin-targeted HLA-independent TCR, or HiT, at ASGCT on May the 11th. Dr. Karen Miller is here to talk more about this platform and the potential of our deep preclinical pipeline. Abstracts came out last week, and data will be updated in the poster. On May the 19th, ASCO abstracts will be out, and we will issue a full press release with an update of our initial data from our SPEARHEAD-1 trial with afamitresgene autoleucel, or afami-cel, for people with synovial sarcoma or MRCLS. Data from SPEARHEAD-1 will form the basis of our first BLA filing later next year. We completed enrollment in the 45-patient registrational cohort of SPEARHEAD-1 last year in about 12 months, and we recently treated the last of these patients. At the time of the data cut-off for the abstract, which was in early February, 32 patients had received afami-cel. The oral presentation at ASCO will include initial data on these and additional patients, but not all of the 45 patients in the registrational cohort. We will issue a press release on May 19th summarizing these results. We plan to update these data later in the year at CTOS, and at that point, the vast majority of patients should have at least six months follow-up. We're incredibly motivated to bring afami-cel to market. When you compare the phase I data with afami-cel to what can be achieved with available treatment options, this product clearly has the potential to change the lives of people living with synovial sarcoma. Moving on to our next -generation SPEAR T-cell targeting MAGE-A4 and our program targeting AFP. 2021 is off to a good start. In Q1 2021, as the pressures of COVID lifted, we've been able to enroll and treat more patients in Q1 in our SURPASS and AFP trials than we did throughout the whole of 2020. I believe this recruitment will continue, and I'm optimistic that we'll be able to present meaningful updates from both trials later in the year. We continue to treat patients in the SURPASS trial, focusing on indications where we have seen signs of efficacy with our MAGE-A4 targeted products, namely lung, head and neck, gastroesophageal, and bladder cancers. Given the increased enrollment we've seen during Q1, we aim to share a robust data update in the fall with the aim of identifying further indications to take into the late phase. We also plan to present updated data from our Phase I ADP-A2AFP trial for people with liver cancer at ILCA in September. We're planning to identify the next steps for this program also based on these data. One of our key commitments since I became CEO has been speed and quality of execution. With these upcoming data updates, this is what we're doing. Financially, we've again confirmed we're funded into 2023 and equipped to deliver on our ambitions. A critical component of realizing these ambitions relies on developing cell therapies that are both curative, meaning people don't die from their cancers, and mainstream, reaching a large number of people with cancer. We have a deep preclinical pipeline that I believe will move us meaningfully towards these goals. To talk more about the exciting data emerging from our HiT platform, I'll turn it over to Dr. Karen Miller, who leads our pipeline research team. Karen? Thanks, Ad. Next week at ASGCT, we're going to present preclinical data from our HLA-independent TCR, or HiT, platform. These are proof of concept data from the first HiT candidate targeting mesothelin, which is now being co-developed with Astellas. We're really excited about HiT, as this platform enables us to target solid and hematological cancers without the need to select patients based on HLA type. The work we've done with this first candidate establishes a preclinical testing strategy to evaluate HiTs against additional targets. I'd like to take a few minutes to put HiTs in perspective, though, and explain why we think there is such a tremendous opportunity here. First of all, the HiT platform leverages our vast experience in TCR engineering and affinity optimization. It opens a whole new range of targets for us that don't depend on HLA and have to date been targeted by CARs or other cell therapies that use antibody moieties to engage with antigen. There are many options for cell therapies to target cancer, each comes with distinct advantages and disadvantages. To date, Adaptimmune has focused on T- cell receptor, or TCR therapies, for which we have proprietary technology enabling us to engineer TCRs to target cancer antigens presented by HLA. TCRs have the advantage of giving us access to basically any protein processed by a cancer cell, which is important when targeting solid tumors, as they often lack unique cell surface antigens. We've seen success in the clinic with our TCR therapies. As Ad has laid out, further meaningful data updates are planned throughout the year. However, a limitation of our current therapies is that they are restricted to certain HLA types. There has also been great success with CAR T-cell therapies that use an antibody to target large cell surface proteins, which are broadly expressed in hematological malignancies. However, CAR T-cell therapies come with some well-publicized challenges. These include the need for engineered intracellular signaling domains to mimic what the TCR does naturally that can result in tonic signaling, potentially leading to toxicities. Furthermore, the CARs need a relatively large amount of antigen or target, which is not a limitation in most hematological malignancies but does limit the number of solid tumor indications available. More recently, there have been next-generation advancements that attempt to overcome the limitations of CAR T-cell therapies, one of which includes coupling antibody moieties to TCRs. These are known as TRuCs. The TRuCs have the distinct advantage of using the TCR's native signaling machinery. One potential drawback, however, that will not be overcome by this approach is that antibodies have been shown to be neutralized by soluble protein. This is especially important because there are many cancer targets, such as mesothelin, that are both cell surface bound and secreted as soluble proteins. At ASGCT next week, we will demonstrate that we have developed a TCR that can recognize and kill target cancer cells expressing mesothelin independent of HLA. I can't discuss the full data update as it's under embargo until May the 11th, but I can say that this data is very exciting. We demonstrate that our HiT candidate is effective at killing tumor cells expressing mesothelin both in vitro and in vivo. We also show that our HiT targeting mesothelin has advantages in our experimental system over a comparative TRuC construct that we developed in-house. Beyond HiTs, we are working to expand our cell therapy capabilities with new targets, new modalities, broader HLAs, and our allogeneic platform. All of these are designed to make our arsenal against cancer better and accessible to more people. This deep preclinical pipeline supports our ambition to bring five new products to the clinic by 2025. I'm truly pleased with the rapid progress we have made with our first HiT program, and I look forward to further updates on this and the rest of the pipeline. With that, I'd like to turn it over to the operator for the Q&A. Thank you. Ladies and gentlemen, as a reminder, to ask a question, you need to press the star, then one, on your telephone. To withdraw your question, press the pound key. Again, that is the star one to ask the question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Marc Frahm with Cowen and Company. Your line is open. Thanks for taking my questions, and congrats on all the progress. Maybe Ad or someone else on the line might also want to chime in. Just with the fall update for SURPASS, given the enrollment increase you've seen recently, do you expect that update to mark the transition of that program from the basket signal-finding approach into an exclusively tumor-specific development program? Or do you think it still won't be quite able to fully determine the range of tumor types that justify advancement? That's an innovative way of trying to ask how many patients have we dosed and what indications are they in. You're to be congratulated for that. We've avoided giving that type of information because it's not been useful. I think, though, that's one of the options. I think we want to understand the breadth of indications where we see activity for this treatment and therefore what the consequential development program will be. Obviously, you pointed out a couple of potential outcomes, and those are within the spectrum that we're considering, and we'll have more information in the fall. Okay, fair enough. Figured I'd try. Then maybe on the comments on the HiT program that's going to be able to pitch you, thanks for that kind of overview and kind of contrast from your approach versus the traditional CAR approach. There's also a competitor out there, particularly for mesothelin, who kind of already has a hybrid approach already. Can you maybe speak to the differences between that approach and how you guys are going about it? Yeah. Absolutely. I presume you're referring to the TRuC constructs that TCR2 is producing. Exactly. I'll ask Karen to comment on the difference between that and our approach. Sure. For our preclinical evaluation, our intent was to test how our mesothelin HiT performs in vitro and in vivo. We wanted to do this relative to a valid comparator. For this, we've chosen a mesothelin TRuC, as well as emerging positive clinical data from TCR2 Therapeutics's TRuC that's currently in the clinic. For our experiments there, we synthesized the mesothelin TRuC from a publicly available sequence, then obviously used our own vector and cell manufacturing process to test it alongside the HiT in vitro and in vivo. This is the data that we're going to share with you on the 11th of May. In terms of the differences between the TRuC and our HiT, our HiT is a natural TCR that binds in the normal way for a TCR and has normal TCR signaling. The TRuC, I'm sure you're aware, has an antibody moiety tagged to each epsilon chain of the CD3 part of the TCR. This is a higher affinity interaction than a standard TCR. The kind of advantages that we see here are that the TRuC will actually bind to soluble cleaved forms of the target antigen, like mesothelin. This acts as a sink for things like both CAR-T and TRuCs and affects their ability to migrate to the tumor and inhibit their function. Because HiT cells have a lower affinity for antigen, which is in the natural range for TCR, they have high functional avidity. Our HiT T-cells are not inhibited in the same way. Okay, great. Thank you. Thanks, Marc. Thank you. Our next question comes from the line of Nick Abbott with Wells Fargo. Your line is open. Oh, good morning, everyone, and thanks for taking my questions. Hi, Nick. First question on SPEARHEAD-1: we noticed that a second synovial sarcoma cohort has been added to the trial, and the trial size increased from 45 - 90 patients. Can you talk about this second cohort and what the differences are, perhaps to the first cohort? Certainly. I'll ask Elliot to comment on that. Elliot? Hi. Thanks for the question. Really, cohort two was opened to strengthen the efficacy and safety database that we'll have and will aid in subgroup analysis of the patient population. That's really the primary intent. Great. Elliot, are you able to elaborate a little bit more on what these subgroups are or might be? Well, I think that it would be a typical subgroup analysis of looking at differences in age, differences in tumor size, et cetera. Just having a broader database helps to look at smaller numbers of patients that fall into specific subgroups. Okay. I'm not sure I can provide more specific detail than that. Yeah. That's okay. I just want to confirm that this does not affect the overall timing for the registration component. Hypothesis testing will be based on cohort one. Okay It should not introduce a delay. Okay. We said that we dosed the 45th patient just recently. It's that group of 45 patients that will provide the basis for registration and the hypothesis testing and registration. That will be available for analysis later on this year. I think the initial data is coming up at ASCO. We're optimistic about the opportunity to present that initial data and to show what afami-cel can do in patients with synovial sarcoma. Terrific. All on track. Maybe just following that, afami-cel has RMAT and PRIME. Can you remind us how these potentially assist in accelerating the approval process and timeline, and are there any strategies that you're considering to further accelerate your registration and approval of afami-cel? Elliot? Yeah. Both of those designations are associated with accelerated review capabilities and provide us with increased access prior to submission with both agencies for planning purposes. They also, I just will mention, are based on preliminary data that demonstrate promising efficacy. Neither of those designations is provided just based on sort of the rarity of the tumor. They both provide us with an advantage from that standpoint. The other pathways that you're describing are generally already included in the RMAT and PRIME accessibility options and capabilities. There's really no need to seek additional designations. Perfect. Thanks, Elliot. I look forward to the data update next week. We're looking forward to providing it. Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim. Your line is open. Hey, this is Kelsey on for Michael. Thanks for taking our question. Hi, Kelsey. Hey. Just building actually on that question a bit, preparing for the upcoming launch, I guess maybe could you provide some color on what that entails and maybe remind us what needs to get done to get sites online to eventually treat commercial patients for those that maybe weren't included in the initial trial? Thanks so much. Sorry, I'm not sure I fully got the last part of your question. Patients that weren't included in the initial trial? Sorry. For sites that weren't included, I guess just getting them online — Right ... potential launch, and yep, exactly. Thanks. Maybe I'll comment generally, and then I'll ask John to pick up on one aspect that we feel is particularly important, which is the ability to actually service patients in a commercial setting. We've obviously begun building our commercial team, and that includes a lot of mostly internally facing roles at the moment, such as market access, marketing, et cetera. Looking forward, we are planning on the more externally facing roles, and obviously we're initiating the interactions externally, as you'd expect, on discussions about thinking about pricing, etc. I think the thing that we are also paying a lot of attention to as a fully integrated cell therapy company is the opportunity to enhance the patient experience by optimizing the whole process from identification of the patients all the way through to the infusion and subsequent follow-up. That patient services activity, I think, is a key demarcation of successful autologous cell therapy companies. John, do you just want to touch on our activities in that space and our thinking in that space? Sure. Thanks, Adrian. From a capacity and supply chain perspective, we will be commercializing out of the facility that we've been running our clinical trials out of, and we have the capacity to do so. We feel very good about the fact that we're already in a position to serve the markets we'll be launching into for sarcoma next year. To Ad's point, we're well underway with digitizing the patient journey. As everybody knows, this autologous treatment is a challenging one, and we spent the last couple of years putting systems in place and getting ready to launch one that will be what I think is a really important part of execution of the patient journey. Finally, to Ad's point, we're focused on this thing we're calling I-to-I. I think everyone in this space is familiar with V2V, which is that vein -to-vein part of the patient journey from apheresis to infusion. The fact of the matter is, the patient journey starts well before that. We're putting in place people, processes, and technology to start from the very beginning of the process, which is the identification of the cancer and the ability to screen into this particular therapy. Great. Thanks so much. Looking forward to the data. Thanks, Kelsey. Thank you. Our next question comes from the line of Tony Butler with ROTH Capital Partners. Your line is open. Thanks very much. Elliot and Karen, you've spent some time this morning having some discussion about the HiT program. Elliot, I just wondered if you could just spend a minute on the relationship with Astellas. Given what I think you're seeing pre-clinically, it would stand to reason that you would want to move this program fairly rapidly into the clinic. Does Astellas make that decision? Do you make that decision? Can you just give us some idea of next steps in that program, importantly, next steps with Astellas? That's question one, if I may. Question two, Karen, I just wanted to ask, if one did not have a cleavable soluble target for which a TCR, a construct, needed to be directed toward, would a TRuC be useful then? Is the advantage here really this notion of having an antibody sticking out of the epsilon receptor and it being bound by antigen and therefore no longer available as a therapeutic? Thank you. Fantastic. Thanks, Tony. I'm actually going to ask Helen to comment on the Astellas relationship and the next steps with Astellas on this. Then, Karen, you can talk about the advantages of TCR or CAR targeting. Helen? Thanks, Ad, and thanks, Tony, for the question. You're absolutely right. This is a co-development program with Astellas on the mesothelin HiTs, and we are working very closely with them in the optimal way to advance it as quickly as we possibly can to, first of all, de-risk the target and then accelerate it within our allogeneic program of work. We can't say any more about that at this point in time, but rest assured that we are actually working very closely with them to accelerate it based on the promising results that Karen's outlined today. Karen? Okay. To answer your question about whether or not a TRuC targeted a non-cleavable protein, would that be better? I think the best way I can answer that is to say that that truly depends on the actual constructs that are being compared. What I can say is, with our TCR products, including the HiTs, we go through a process of affinity optimization of those TCRs, and we also optimize the expression of the TCRs on the cell surface in order to develop a product that is highly effective, which is very different, of course, from a TRuC, which is an antibody moiety bound to the epsilon chain of the CD3 portion of the receptor. That being generally a high-affinity binding will not be so easy, I think, to optimize in the same way that we can with the TCR products. I think at the end of the day, what we need to do is to compare them in the clinic. Karen, thanks very much. Helen, appreciate it. Thanks, Tony. Thank you. Our next question comes from the line of Jonathan Chang with SVB Leerink. Your line is open. Good morning. Thanks for taking my questions. Yes. I just want to clarify something that I heard in the beginning and what I'm reading in the footnote of the press release, and that is, will the press release on the 19th describe the full ASCO data, or will the press release just describe the data from the abstract? The press release on the 19th will describe the full ASCO data. Got it. Okay. Second question: I'm curious if you could just help set investor expectations ahead of the SURPASS next-gen MAGE-A4 update at ESMO. I think the expectations that we have of that dataset are that it will represent the patients that we have recruited across a range of tumor types. We've been focused on lung, bladder, head and neck, and gastroesophageal. Although I will point out that that focus has not historically precluded other tumor types from being in that patient group. It'll be a broad set of tumor types. The objective that we have for that dataset is that we will be able to understand the breadth of activity that we're seeing and start to think about what the development pathways might be going forward for that agent in those tumor types, individually or generally. I'm just going to point out, given that we're obviously recruiting those patients now and over the course of the recruitment in Q1, which has, as I said, gone very well, that that dataset will not have the most durability data that you might expect, given that it will be coming out in a few months' time. Got it. Thank you. Thank you. Thank you. As a reminder ladies and gentlemen, press star one to ask a question. Our next question comes from the line of Mara Goldstein with Mizuho. Great. Thanks for taking that question. Firstly, on the SURPASS-2 trial that'll initiate this year, I'm wondering if you could give us just a forward look at what the enrollment and the size and scope are and when we can begin to see some clinical data out of that program. Secondarily, appreciate the color on the HiTS program. I'm curious about the TIL program, given that at least on the pipeline chart, it certainly looks a little bit more advanced, and I'm wondering where and when you think we'll get some more information on that program. Certainly. Thanks. Thanks, Mara. Thank you. I'm going to ask Elliot to comment on the status of the SPEARHEAD-2 program. I'm going to ask Karen to comment on the status of the TIL program. Elliot? First of all, Mara, I just want to clarify: you said SURPASS-2, right? Correct. Oh, SURPASS-2. Sorry. Yeah, no, I just want to make sure. No problem. I want to make sure I am answering the right question. I'm happy to take any additional info on SPEARHEAD-2 as well, if you want to do that. Of course. Yeah. I'll answer your question. With respect to SURPASS-2, we really haven't guided as to the protocol specifics and size of the trial. It will take into account the recent changes in the treatment paradigm for those types of cancers, that is, esophageal gastric junction cancer and esophageal cancer. There have been some recent approvals for combination first-line therapy. The patient population that we're trying to address will take that into account. With respect to when you'll see data out of that trial, it will be designed as a potentially registrational trial, and we won't be providing regular updates with respect to data as the trial unfolds. It will probably follow sort of a similar pattern to what we've done with SPEARHEAD-1, and the approach that we've taken with respect to data in the sarcoma population. Okay. Thank you. I'm happy to answer a question on TIL. Our collaboration with Inge Marie Svane and her team at CCIT is going extremely well. As you know, they're experts in TIL therapy, we're working with them to develop a next generation for patients with melanoma. Our first product that we've chosen to progress is a TIL product with IL-7. This is progressing well, we'll be giving you further updates later on in the year. Thank you. Appreciate it. Thank you. I'm not showing any further questions in the queue. I would now like to turn the call back over to Adrian Rawcliffe for closing remarks. Thanks. Thank you, everyone, for your questions and for your continued interest in Adaptimmune and our progress. As is apparent from the discussion today, we are heading into a period of significant data updates, beginning with ASGCT, which will showcase the potential of an element of our preclinical pipeline, and then ASCO, which shows the first pivotal clinical trial data from our most advanced cell therapy. You'll get insight on both ends of the pipeline. Look forward to discussing those data and continuing to make progress to bring our cell therapies to people with cancer. Thanks again. Have a great day. Ladies and gentlemen, this concludes today's conference call.