Adaptimmune Therapeutics plc

Ladies and gentlemen, thank you for standing by, and welcome to the ADAPT Immune Conference Call. With that, I'd like to turn the call over to Julie Miller. And you may begin.

Good morning, and welcome to ADAPT Immune's conference call to discuss our full year and fourth quarter 2020 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 a number of factors. including those outlined in our latest filings with the SEC. Adrian Rockliffe, our Chief Executive Officer, is 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.

Thanks, Julie, and thank you, everyone, for joining us. Three months ago, during our Investor Day, I laid out plans to deliver transformative value for patients and for investors over the course of the next five years, our 2252 plan. In concrete terms, this means two products on the market targeting MAGE A4, two additional BLAs from our clinical pipeline, as well as five autologous and two other generic products entering the clinic in the next five years. All this is based on an integrated cell therapy company with the intent and capabilities to discover, develop, and deliver products that are both curative and mainstream. At the JP Morgan conference last month, we outlined the key catalysts for 2021 and beyond, which will be the mile markers on the road to our 2252 ambition. And I'm absolutely delighted every time I say this. We aim to launch our first product next year. As you know, not many biotechs get to this stage, and it is hugely motivating. for our research and development teams to know that ADPA2M4, the treatment they discovered and developed through clinical trials, may soon be delivered to transform the lives of people with sarcoma. The launch is our first building block of our 2252 plan. The next key dates when we aim to release data at ASCO and CTOS, and these data will be used to support the registration and approval of ADPA2M4. In 2021, beyond our BLA and launch readiness, we will also focus on, firstly, initiating a Phase II trial with our next-generation MAGE-A4 targeted product for people with either esophageal or esophagogastric junction cancers in the first half of this year. Secondly, treating patients in the ongoing Phase I SURPASS trial that also uses our next-generation MAGE-A4 targeted product. We're focused on indications where we've seen signs of efficacy with our MAI-J4 program, namely lung, head and neck, gastroesophageal, and bladder cancer. And we aim to report updated data from the SUPASS trial at ESMO this year. Thirdly, treating patients in our Phase I ADP A2 AFT trial, we planned to report data at ILCA. We will also determine the next steps for this product. And lastly, continuing our research work to bring new products to the clinic, including HLA-independent TCRs, next-generation TILs, and next-generation spear T-cells targeting additional HLAs. Looking back at 2020, you'll find a summary of our key achievements in our press release. I just want to pick up on a few points. When I became CEO, I committed to increasing our focus on speed and quality of execution. And last year, we demonstrated clear progress by completing enrollment in our Spearhead 1 trial in about 12 months, even with the challenges of the COVID-19 pandemic. Whilst we wait for data from Spearhead 1, we're working towards filing a BLA for ADPA2 and 4 for people with synovial sarcoma in the U.S. next year and shortly after that in Europe. The U.S. and EU regulatory designations granted based on compelling and durable response data from our Phase I trial, will help us with this approval process. We've also started to grow our commercial organization and plan for the launch of a companion diagnostic. When you compare our Phase I data to what can be achieved with available treatment options, ADPA2 and 4 has the potential to truly change the lives of people living with synovial sarcoma. And the synovial sarcoma community is incredibly excited about these data. We confirmed in 2020 that sarcoma is only the beginning for our MAGE-A4 targeted products. Last year, we reported responses from spear T-cells targeting MAGE-A4 in four different tumor types, including melanoma, esophagogastric junction, head and neck, and lung cancers. There were also meaningful tumor reductions in other indications. We also completed dose escalation in the surpassed trial with our next generation ADP A2 M4 CD8 product. We're recruiting in the expansion cohort of this trial. And as I said, we plan to report data at ESMO this year. 2020 was also the year where we showed we're building the cell therapy company in the future with our deep preclinical pipeline. Our research team has made great progress on multiple fronts, including identifying the first candidate, mesothelin, to take forward with our HLA-independent TCR platform in co-development with Astellas, products targeting HLAs beyond HLA-A2, and strengthening our toolkit of next-generation options, including a TIL therapy with IL-7 in collaboration with CCIT. This preclinical pipeline supports our ambition to bring five new products to the clinic by 2025. Finally, I want to bring up the progress with our allogeneic platform. We signed a major co-development and co-commercialization agreement with Astellas in 2020 and showed we could generate functional T cells from stem cells. We also demonstrated these T cells can kill cancer targets in vitro. And financially, we've confirmed that we are funded into 2023 and equipped to deliver on our ambition. With that, I'll open it up for questions. Operator?

Thank you. Ladies and gentlemen, if you wish to ask a question at this time, please press star then 1 on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Our first question comes from the line of Tony Butler with Roth Capital. Your line is open. Please go ahead.

Good morning. Thank you very much for taking the question. Elliot, Adrienne, I wanted to actually touch on commercial readiness, given that you were moving forward with Spearhead 1. And then I have one follow-up on the clinical program. Thanks a lot, Adrienne.

Okay, thanks, Tony. Thanks for the question. As we're preparing to be able to launch ADPA24 for synovial sarcoma on approval, which we anticipate to be next year, and clearly we've been in the process of planning for that for some time. And 2021 is the year where we are committing to both the BLA filing which will happen in 2022, and starting to build the commercial presence. And I think I've said before, this is a perfectly sized opportunity for a company like Adaptamude because of the very concentrated nature of the patient and physician treating footprint here. And we are obviously talking to many of those centers and sites as part of the clinical development. So it's important that we build something that is focused on delivering for the synovial sarcoma community, but also critically scalable for the other indications that will be coming down the pipe in due course, obviously starting with esophageal and gastroesophageal junction, for which we're starting the Phase II trial now. And I think the scope for... commercialization for a cell therapy is obviously quite broad and it covers you know all of the usual things that you would anticipate for a normal commercialization of a product and the payer and patient and physician research and all of that's been ongoing for a while and then but it also covers I think the importance of patient services aspects from our supply chain organization and we think about how to develop those from the clinical state, whether we've been operating to date, including for the pivotal trial, through to something that is fit for purpose for commercial. And we'll have more to say about that and other aspects of it as we go through the year. It's such a diverse set of stuff that you have to do. I mean, from the large things that I've just mentioned, but all the way through to relatively small things. I mean, just a couple of days ago, we got the generic naming confirmed for ADPA2M4 for synovial sarcoma, which will be called a famitrogen autoleucel or a famicel. And it's just accumulation of lots of activity and lots of small and large milestones along the way that's going to ensure that we're able to get there. And I want to just say that I think our ability to do that will be largely based on the fact that we are specialized in this space, knowledgeable in this space, and we've built the integrated capabilities to enable us to be able to do this.

Thanks very much. I did want to follow up on two short clinical questions. Number one is, are patients still being dosed with the AFP Spear T cells, that's one. And number two, on the phase two, Surpass 2 study, which starts the first half of this year, in Surpass 1, correct me if I'm wrong, you already have 17 sites, at least according to clinicaltrials.gov. Are all those 17 sites going to then switch over to dose for Surpass 2? How will those be split up, or will there be new sites that have already been recruited for Surpass 2? Thank you.

Thanks, Tony. I'm going to ask Elliot to answer both of those questions. Please, Elliot.

Yeah, so the first question, thank you, Tony. The first question was around whether we're still dosing patients in the ADP, A2FP liver cancer-directed trial, and the answer is yes. We're dosing patients in the expansion phase of that trial, and there's an intent to provide an update with respect to patients' dose and direction at the International Liver Cancer Association conference in the third quarter. With respect to Surpass sites and Surpass 2, many of the sites that are in the the SURPASS trial will be engaged in the SURPASS 2 trial as well, but there will be differences as well. We're going to be adding new sites and also expanding geographies as well. I don't think that we've guided specifically to the exact number, but those will be specifically gastrointestinal-focused sites, while the SURPASS trial also includes sites that are focused on a broader range of tumor types. But we're going to leverage our experience from phase one into phase two. Those centers that are enrolling well, we certainly would want to have in phase two. And we will have to make that transition for those tumor types from enrolling in the Phase 1 trial into the Phase 2 trial. That will be the intention once that trial is open is to enroll the Phase 2 trial.

Thank you, Adrian. Appreciate it. Thanks, Tony.

Thank you. And our next question comes from the line of Kenneth Atkins with Cowan & Company. Your line is open. Please go ahead.

Hi, guys. Thanks for taking my question. Could you comment on the breakdown of the enrolled patients in Spearhead 1 between synovial sarcoma and MR-CLS, and how many patients in each category do you think you would ultimately need to support licensure in each indication?

So I'll take that just to say that we haven't guided as to patients in either in category and how that allocation split out other than to say that we believe that there will be significantly more synovial sarcoma patients than MR-CLS patients.

Got it. Okay. And then assuming that ADPA2 and 4 is successfully developed for refractory sarcoma, how much of a priority is moving that product into the frontline setting? Do you think ADPA2 and 4 has the right profile, or would you want to explore a next-gen product for frontline use?

Elliot, do you want to comment on that?

Sure. So I think that it certainly could be, you know, used in a frontline setting, either in sequence with chemotherapy or up front. It will never be for every patient with sarcoma because of the HLA restriction and the patient's need to express the target. So even if in the frontline setting it won't be sort of, you know, across the board for all patients with the disease type. It would be those that qualify. I don't think that we've made, you know, sort of a final decision as to, you know, as we might pursue a first-line setting, whether that would be the first or the second-generation product. I think that we would have to sort of evaluate that closer to the time of us really implementing the studies that would support that.

Got it. Okay. Thank you. Thanks, Kevin.

Thank you. And our next question comes from the line of Mohit Bansal with Citigroup. Your line is open. Please go ahead.

Good. Thanks for taking my question and congrats on the progress. One question I have is regarding the use of AKT inhibitor. You have talked about that on your R&D day. Could you please help us understand the rationale there, what it does, and how it actually improves the manufacturing aspect of the TCR manufacturing? And the other second part related to that is that you are using that in your CD8, the second generation program at this point. Would we be able to see any comparative data in clinical setting that use of AKT inhibitor is actually doing something to these patients either in terms of responses or durability? Any color there. Thank you.

Sorry, just coming off mute. So as you say, we use the AKT inhibitor in the manufacturing process. So I just want to be clear that the comparison, and there's no AKT inhibitor in the final product that's administered to patients. So I just want to make that clear. And then I was wondering, Helen, do you want to talk about use of the AKT from a mechanistic perspective and what it does?

Sure. Just coming off mute. Sorry about that. I think that the use of kinase inhibitors and their impact on T cells has sort of been known for some time. And bluntly, I think, you know, probably a number of dimensions to the mechanism, but sort of simplest said, I think it seems to increase the overall potency of the cells. And there's probably a number of pathways involved in that but it's certainly something that we and others have seen and are using and I think it's been a relatively straightforward adjustment to sort of make in our process for a potential increase in the potency of the cell product that we make. I don't think we probably won't go into more details on that. I think we've published on quite a bit of this and we've certainly put it into posters and John may also have commentary on the ease with which we brought that into our process.

Do you think it could help you from the patent point of view? Can you patent it, this particular part of the manufacturing that you are using equity inhibitors in there?

We haven't commented on our patenting strategy as regards our manufacturing process, this aspect of our manufacturing process. Got it. Thank you very much.

Thank you. Thanks, Mahood.

Thank you. And our next question comes from the line of Michael Schmidt with Guggenheim. Your line is open. Please go ahead.

Hey, this is Kelsey on for Michael. Thanks for taking our question. Hi, Kelsey. Hey, how's it going? In, I guess, first question in the SURPASS trial, what efficacy signal, I guess, would you need to see in order to kind of make that go-no-go decision? And how many patients in a given indication would you feel comfortable basing that on? And then separately, if I could, maybe bigger picture, maybe could you just remind us of your strategy for developing HLA-independent T cell receptors and maybe to what extent that might broaden the opportunity for your platform kind of longer term? Thanks so much.

Certainly. Thanks, Cassie. So I'm going to ask Elliot to comment on the signals in Surpass, just to say that the focus areas for Surpass are obviously lung, bladder, head and neck, and gastroesophageal. That doesn't mean we'll only recruit patients in those settings, but that's what we're focusing the trial on, and we plan on putting data out at ESMO.org. on the first set of patients in the expansion cohort. Elliot, do you want to comment on that? And then we'll move to the other question on TILs.

Sure. So thank you. With respect to, you know, what efficacy signal would we look to see to drive a go-no-go decision to a later stage development program, there's nuance here. It's not a specific, I can't quote you a specific cutoff with a specific number of patients where we would say, if we see this, we will go, and if we don't, we will not. There are several parameters, and we like to think of it along the lines of when we see it, we'll know that we're seeing it. And I think that you could use the example of synovial sarcoma as a great example, where we saw a 44% response rate in the Phase I study, which is clearly advantageous as compared to the other treatments available for second-line treatment. We've typically used a threshold of a 30% response rate with a six-month duration of response as a as a guidepost, but not as a definitive marker. And the reason that I say that is that there are other factors beyond just response rate. And it really depends on each tumor type as well. And you can use the gastroesophageal cancer example to look at that, where these patients have, you know, very limited treatment options and very short very short time of survival even with, you know, after first-line treatment. I think that, you know, with the data that was published at ESMO last year showed that even in best circumstances, the median overall survival was approximately 15 months in this patient population with first-line treatment. So coming into the later line of treatment, it's obviously going to be, you know, the expected survival is less than that. If you determine that a patient, if we're able to show that there's 25% response rate, but some of those are durable, or that we really improve the quality of life in patients with prolonged stable disease, those are things that need to be factored in as well. And you start to look at progression-free survival as well as just overall response rates. to look at the benefit of a treatment. So if you look at the gastroesophageal scenario, you know, we saw that three patients out of three with the first, in the first six, three out of the first six patients in the phase two, the SURPASS trial had esophagogastric junction or esophageal cancer, and all three demonstrated meaningful antitumor response. Well, you know, that was enough for us to say that we ought to be planning a phase two trial, especially when some of those patients have been treated with lower cell doses than we had seen previously. So I think that, again, it takes nuance. We have some guideposts and that we're going to, you know, work around that. But we're really looking for relatively clear indications of advantage over current treatment. You shouldn't have to squint at it to say, hmm, maybe that's going to be advantageous, maybe it's not. You know, you're going to need, you know, 500 patients to show a very narrow marginal difference. It has to be visible.

Thanks, Elias. On the HIT question, which was sort of how it works and how it works to expand applicability of our platform, maybe I'll ask Helen to touch on that.

Yeah, thanks, Ed. I'd be very happy to talk about the HLA-independent TCR platform, the HIT platform. It is exactly sort of what it says it is. It's actually a T cell receptor that can bind an epitope on a cell surface protein. So the target protein, the whole protein, could be the same as... as a car or an antibody, but it's actually a TCR that's binding to a specific peptide or a specific epitope on that cell surface protein. So there are two aspects of that. One is that there is no HLA restriction, so we don't have to screen out for HLA for the treatment of patients with an HLA-targeted T cell therapy, so that obviously increases the number of patients by removing a specific criteria that segments our population with HLA-restricted T cell receptors. The other aspect of this which is very exciting for us is this is a functional T cell receptor. It functions and behaves like our other optimized T cell receptors, and we also have the ability to test that for specificity and sensitivity, affinity, really leveraging all of the capabilities we've built up over many years to safely bring T cell receptors through to the clinic. So very excited that we've got a T cell receptor platform that can broadly increase the number of patients that we can access with a T cell receptor that can bind to a cell surface protein and that broadens out the patient pool for specific targets and Mesothelin, I think, is a validated target now. We're very excited about that program with our collaborator, Estelis, in which we are co-developing. And we also mentioned another one that we've started to bring through, targeting GPC3, which is a hepatic cancer-specific target. And obviously for us, it will be very important to continue to bring and validate this platform alongside the HLA-dependent programs that we have, like MAJ4 and AFP. to increase the numbers of targeted products that we can bring through. I hope that's a useful overview of the platform and its applicability.

Yeah, great. Thank you so much.

Thank you. And our next question comes from the line of Nick Abbott with Wells Fargo. Your line is open. Please go ahead.

Good morning, and thank you for taking our questions. Ed, can you provide some additional guidance on when in 2022 you plan to file on the Spearhead 1 data?

Short answer to that is no. We haven't provided additional guidance, and we won't. There's a whole swathe of moving parts, as you can imagine, that affect the timing of that, and we'll update as we have more certainty as to the specific filing timeframe.

Okay.

I would just mention we've got the RMAC designation and therefore the opportunity to have more rapid approval on that.

Right. The goal is to file and launch in 2022.

That is certainly our goal.

Yeah. So in preparation for the filing, obviously this would be the first TCR engineered product to be reviewed and clearly there's no established path so how confident are you you have alignment with the agency on cmc given issues that have delayed filing or approval of other cell therapy products so uh so i think the the

challenges that have been faced by people who have sought to bring cell therapies to the market, uh, are significant and, and nobody should ever think that this is easy. Um, yeah, we do it because it's hard. Um, but, uh, but I think we do have, we do have some advantages, uh, for us, uh, in, in, in thinking about this. Uh, number one, uh, we have, uh, the advantage that others have taken not exactly the same products and not a TCR, but an autologous cell therapy, autologous cell therapies in the hematological space. And I think there are likely to be at least four of those approved by the time we get there, four or five of those approved by the time we get there. And then secondly, I think there's the opportunity to learn from the experience in TILs and the first TIL product is likely to have been approved there. So there are precedents for this and obviously in the interactions with the agencies they get to see that and we get the benefit of that in terms of understanding their evolving thinking in this space. I think the second thing that I'd point out is that we have RMAC designation in the in the US and prime designation in the EU. And that gives us, I think, the opportunity to have enhanced interactions with the regulators in both of those jurisdictions and to ensure that insofar as possible, there is alignment there. Now, you will never find anybody at this company tell you what the regulators think that's going to be for them to speak to. But at the same time, we are having what we believe is constructive discussions with both of those. And I think we are, we certainly believe that we understand what we need to do. Then lastly, I'd say that we are using from a CMC perspective, same facilities and the same process in the phase two that we will use for launch. And I think our processes and our assays, et cetera, are in an appropriate place relative to where we want to be for our BLA goals. And I'd say, you know, we have not got some of the challenges that some other types of therapies have, for example, you know, the potency assay as it relates to a till therapy. which is obviously quite different to the discussions that we've had. So, you know, this isn't easy. And there are, as I said, there are a number of moving parts. But because we've sort of been focused on this, because of the capabilities and the insight that we've built up over a long period of time and a lot of interactions with the regulators, I think we're confident that we've got the process and the requirements gripped.

All right, thank you. And then you recently listed the phase two esophagogastric trial, which I believe you have, you consider as potentially registration enabling and like to be ahead one, plans to roll 45 patients. So can you explain, you know, how you get to, how you got to that number? And then also, I know this is being studied in other tumors, but, you know, clearly, perhaps a unique concern here is for on-target off-tumor toxicity. What do you need to do to assure the regulators that this is not an issue? How many patients do you need really to treat in order to ensure that it's not an issue?

So, Elliot, do you want to speak to the thinking around the surpassed two trial design a little bit and in terms of what we've said publicly and how we're thinking about the toxicity or the safety profile that will be required to register products in this place. Elliot, I think you're on mute.

Sorry about that. I'll start over. I don't think that we've guided with respect to the powering and statistical methodology for the trial. I will say that it is designed very similarly to Spearhead 1. So while the statistical considerations are not exactly the same, the the study is powered to demonstrate, you know, benefit as compared to what would be the sort of historical control as it relates to, you know, line of treatment. So I don't want to provide specific numbers around that at this juncture. With respect to the off tumor on target toxicity, it's, important to remember that the T-cell receptor is the same as the first-generation T-cell receptor. And we have, you know, it's not a huge amount of experience as compared to like, you know, a diabetes or cardiovascular trial. But, you know, we have a pretty good accumulating experience of patients that we've treated with a MAEJ4-directed T-cell receptor at this point. and really have not seen any indication of off-tumor expression of MAGE-A4 or, you know, off-target reactivity of the TCR against other tissues. So, look, I think that ultimately, you know, the benefit-risk ratio is what will drive the day. the T cell receptor in this patient population or in others, it'll have to come with a safety profile that is acceptable. And the safety information that we put out along with the six patients that were reported at FITC showed that, at least in early days, that the safety profile for the second-generation product is very similar to the first-generation product. Now, you can't compare six patients to over 70 patients, but that will come with time. At this point, it's our anticipation that if the drug is more potent, that we may see some of the more common effects toxicities associated with the potency of the product, like cytokine release syndrome. That has not been the case to date, but we'll have to see that over time. But I think we're feeling reasonably confident around the specificity of the T cell receptor in that we haven't seen off-tumor or off-target toxicity to date with MAJ4. Great.

And then Thanks, Elliot. That's very comprehensive. And would you expect to communicate to us data from this trial as it's going along or only when it's complete?

I wouldn't want to promise to provide data should we think of this, as you said, as potentially registrational. So if we're to make the decision that this trial, you know, would be a registrational trial, then we would be unlikely to provide patient data along the way. If it were to be, you know, determined to the contrary, then, you know, we would, I would certainly, we would reserve the right to provide interim data along the course of the trial if that were, you know, helpful from a communication standpoint. So I think it, we just, I can't, In general, for registrational trials, we would not do that. But if it turns out to not be a registrational trial, then we certainly could.

Great. Thank you very much.

Thanks. Thank you. And our next question comes from the line of Mark Goldstein with Mazuho. Your line is open. Please go ahead.

Great. Thanks for sending the question. I have two questions. The first just is on the spearhead one. And can you just clarify for us the scope of what you anticipate for the preliminary update in June versus the full update later in the year? And then secondarily, I'm just curious about the status of the TIL program. It certainly appears within your pipeline chart, advanced from a preclinical perspective, and I know it appears in your corporate deck, you know, almost as a crossover in the graphic that you have between the cure versus mainstream therapy. So can you talk a little bit about what's going on in that program?

Certainly. Thanks, Mara. So I'm going to ask Elliot to talk about the updates, what's likely to be happening at ASCO and CTOS. And then I'm going to ask Helen to talk about the IL-7 TIL program. So Elliot, do you want to touch on Spearhead first?

Sure. So good question. First of all, I want to just say that the update at ASCO is based on the information being accepted by ASCO. And you raised, I think, the point of this being a registrational trial, how is it that we're presenting interim data? The reason for we believe that being allowed is that all the patients will have been dosed by the time this information would would come out. So it would have no effect on the recruitment and enrollment of the trial. But it is ultimately up to ASCO as to whether they will allow the presentation of data in an interim fashion. So if we were to present it, it would be based on a data cut that will be ultimately approximately six months prior to the final data cut for the trial. So the level of durability of response across the whole population will be less robust than the final information. We'll also have to provide some interpretation along the lines of patients who have been treated but have not yet completed their series of assessments as to whether they represent responses or stable disease or There are some patients who have stable disease at one juncture who then go on to have a response. So we'll have to interpret it with some clarity as it relates to who's been dosed, who's had the right number of assessments to make a determination around efficacy. And then, of course, there will be safety information as well. We will provide duration of response information as is available at the time of the data cut, but just recognize that, for example, if the data cut is sometime in, let's say, March, then a patient treated in February, we won't be able to provide real meaningful duration of response information. So I hope that clarifies what we expect to present at ASCO, later in the year we would anticipate providing the data that would essentially be similar to what we would present to agencies for registration. The study is set to read out six months after the last patient is dosed, provided that patient remains on study. If you go six months from, we've said that we plan to finish dosing in this study by the end of the first quarter, so that data cut would be around the end of the third quarter, and then we would be able to provide information at the CTAS conference that uses that data. So that will be a more complete look at the data that will also be shared with regulatory authorities for the purpose of registration.

Okay, thank you. That's really helpful.

Thanks, Elliot. And Helen?

Yeah, sure. Great question. It's a pleasure to talk about the TIL program that we have on our pipeline. So we have executed a collaboration with CCIT in Denmark, which is the Center for Cancer Immunotherapy, which is a leading center for TIL trials in Europe, a group that we've known for some time. And there are two aspects to this. I think the TIL strategy feeds into two things. It feeds into our integrated cell therapy approach. capabilities which we believe really enable us to sort of read across and apply in a relatively straightforward way. The same sorts of approaches from the science through to the CMC, optimization, execution of the clinical programs, regulatory interactions, et cetera, as we do with our SPIR T cells. We can apply an awful lot of those capabilities to TILs. And we have a TIL IL-7 program, currently in preclinical, but expecting to move quite quickly towards the clinical stage in collaboration with the CCIT, where we're bringing in our own second-generation capabilities and expertise and knowledge from the spare T cells into a second-generation TIL product, which we think will improve the proliferation and penetration of TILs in other solid tumors, because I think that there's great promise with TILs, and we believe that There's more promise in other tumor indications to be had. So TILs don't require HLA restriction testing. They don't require target testing. So it's another one of our strategies that enables us to reach more patients without segmenting for HLA type or target type. And it adds and complements. I mean, our in-house capabilities in cell therapy broadly, in T cell therapy broadly. So hopefully that gives a bit more color to where the TIL-IL-7 program fits within our overall strategy of bringing further products. It's in the five of our 2252, so hopefully that helps.

And do you have a sense of which indications would be prioritized?

We do, but we're not commenting on that at this point, I'm afraid. Okay. Thank you. I appreciate it.

Yeah.

Thanks a lot.

Thank you. And our next question comes from the line of Jonathan Chang with SBB . Your line is open. Please go ahead.

Hi, team. This is John Barrett on for Jonathan. I realize it's still early in the year, but for the second-gen MAE-J4 program, can you talk about the current status of the SURPASS study? any color on the progress of that study since the last update and help set expectations for the data readout at ESMO, including any potential or hopeful number of patients or a breakdown of what tumor types you expect?

Thanks, Joe. So you asked for color on the study. It's a very colorful study. It was enrolling a basket of patients, nine nine different tumor types. As you know, we've focused it down onto four different tumor types. I do just want to be really clear about that. That doesn't mean we're only going to have patients in those four tumor types, which are lung, bladder, head and neck, and gastroesophageal cancers. But that in our recruitment, we are focusing on those centers that are recruiting those patients. But we will have others. Recruitment is going well. Last year we had a biphasic recruitment driven off the COVID pandemic increase in cases and decrease in people being recruited into early stage oncology and cell therapy trials in the second and third quarter, but we've reestablished and rebuilt the pipeline as we talked about in the fourth quarter of last year. And I think the recruitment and dosing of those patients is going well as we're headed into 2021. We have explicitly not commented on numbers of patients, but all of these patients are being recruited in the expansion cohort of that trial, and we will update at ESMO on all of the patients that we have dosed and have access to. I think the objective of that is to be able to gather a sufficient cohort of patients to say meaningful things about the development of that therapy going forward. And beyond that, we aren't commenting until we put out the data.

Got it. Makes sense. And quickly on Spearhead 2, could you talk about the current status of that study? And just conceptually, is this still viewed as a learning study? type of study that you might eventually move forward with the second gen, and what is the bar for success of that trial?

Elliot, do you want to talk to those points?

Yes, so thank you. I don't, we haven't really guided as to sort of, you know, numbers of patients screened, enrolled, dosed, etc., The study is open and enrolling. We do still look at it as a, I mean, every study should be looked at as a learning opportunity. But this one in particular is the first scenario in which we'll be combining the MAJ4-directed TCR program with PD-1 inhibitor. So based on the sort of natural potential synergy of those products, will certainly be paying attention. I don't want to say that we wouldn't take the combination of those two products in head and neck cancer forward if we were to see the right kind of responses. And again, I'll go back to the go, no go comments that I made before. But I also do think that this is the learning here is really more about the potential of this type of combination across programs. And the benefits will certainly see, you know, how the patients do from a response and toxicity standpoint. That will be really important. But there will also be important translational information about, you know, what happens to you know, up-regulation or down-regulation of certain, you know, genes that control cancer growth, T-cell exhaustion, tumor microenvironment, et cetera. So I think that it is a learning trial, as you've indicated, but it does have the potential to really, you know, with T-cell therapy for solid tumors. I want to add that the way that we've organized and designed the trial also is an example of how cell therapy could fit into a first-line sequence with approved therapy. That is that one, leukapheresis and obtained cells prior to treatment, so no impact of the treatment on the bone marrow that would produce the cells that we would use to manufacture. The patient gets their first-line treatment while the manufacturing is ongoing so that the product is ready at the time that they're no longer either seeing continued benefit or additional benefit from the first-line treatment and it provides an opportunity to use cell therapy you know, right in sequence with another treatment. And that's a paradigm that is not simple to organize from a patient standpoint, but we feel this is, again, our first toe in the water as it relates to that as well.

That's very helpful. Thank you. Thanks, Joe.

Thank you. And this does conclude today's question and answer session, and I would like to turn the conference back over to Adrian Rockler for any further remarks.

Thanks, and thanks, everyone, for joining us. I want to, before we close the call, acknowledge the incredibly hard work and commitment of everybody here at Adaptimmune, who, despite the challenges of the COVID-19 pandemic over the last year, have remained focused on our mission and our vision and delivery of the results that we've just put out of the press release and everything that we accomplished last year. I also want to thank our investors who continue to have confidence in the opportunity presented by adapt to me. I think we're all here looking forward to 2021 and I'm looking forward to being able to update you all on the key mile markers on the road. to delivering that 2252 strategy that I talked about at the beginning of this call, and ultimately the opportunity to create significant value for people with cancer and for the company. And with that, thank you, and speak soon.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.