Ladies and gentlemen, thank you for standing by and welcome to Q1 2021 Adaptimmune Earnings Conference Call. At this time all participants are in a listen-only mode. I will now like to hand the conference over to your speaker for today, Juli Miller. You may begin..

Good morning and welcome to Adaptimmune's conference call to discuss our first quarter 2021 financial results and business update. 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..

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'll present our first preclinical data from Mesothelin targeted HLA independent TCR or HiT at ASGCT on May the 11. And 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.

Then on May the 19, 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 data cutter for the abstract, which was in early February, 32 patients had received the 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 and we will issue a press release on May the 19 summarizing these results.

We plan to update these data later in the year and at that point, the vast majority of patients should have at least six months follow up. We're incredibly motivated to bring a afami-cel to market.

When you compare the phase one data with a 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 cancer.

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 late phase..

Thanks Ad. Next week at ASGCT are 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 and we're really excited about HiTs , as this platform enables us to target solid anti-hematological cancers without the need to select patients based on HLA type.

And the work we've done with this first candidate establishes a preclinical testing strategy to evaluate HiT against additional targets. I'd like to take a few minutes to put HiT 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 today 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 and each comes with distinct advantages and disadvantages. To-date Adaptimmune is focused on T-cell receptor or TCR therapies for which we have proprietary technology enabling us to engineer T-cells 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. And we've seen success in the clinic with our TCR therapies. And as Ad has laid out further meaningful data updates are found throughout the year.

However, a limitation of our current therapies is that they are restricted to certain HLA types..

Thank you. Our first question comes from Marc Frahm with Cowen and Company. Your line is open..

Thanks for taking my questions and congrats on all the progress. Ad or someone else on the line may also want to turn in the fall update for SURPASS.

You can expect given the enrollment increase you've seen recently you set that update to kind of mark the transition of that program from the basket signal finding approach into kind of 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 a innovative way of trying to ask how many patients that we don't want indications whether you want to be congratulated for that and we've avoided giving that information because it's not been useful. I think, though that 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 and 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. And then maybe on the comments on the HiT thanks for that kind of overview and kind of contrast for your approach versus a traditional CAR approach.

But there's also a competitor out there particularly for me to feeling who kind of already has like a hybrid approach already can even be the differences between how you guys are going about?.

Yes. Absolutely. I presume you're referring to the TRUCK constructs. The TCR squares produce, I’ll ask Karen to comment on the difference between that and our approach..

Sure. So for our preclinical evaluation, our intent was to test how our moves are feeling HiT performs in Vitro and in vivo. We wanted to do this relative to a valid comparison, for this we have chosen mesothelin TRUCK as well as emerging positive clinical data from TCR square TRUCK that's currently in the clinic.

And so for our experiments where we synthesize the mesothelin TRUCK from a publicly available sequence and then obviously use our own vector and cell manufacturing process to test it alongside the HiT in vitro and in vivo. And this is the data that we're going to share with you on the May 11.

In terms of the differences between the TRUCK and our HiT our HiT is a natural TCR that binds in the normal way for a TCR and has normal TCR signaling whereas the TRUCK.

I'm sure you're aware has an antibody moiety tagged to reach actually long chain of the CD-3 part of the TCR and this higher affinity interaction than a standard TCR and so, the kind of advantages that we see here are that the TRUCK will actually bind to soluble cleaved forms of the target antigens, like mesothelin.

And this acts as a sink for things like both CART and TRUCK and affects your ability to migrate to the tumor and inhibit their function. So because of HiT cells having a lower affinity for antigen which is in their natural range for TCR and it has high functional avidity 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..

Hey good morning everyone and thanks for taking my questions. 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 to 90 patients.

So can you talk about the second cohort and what the differences are after the first cohort?.

Certainly. I'll ask Elliott's to comment on that.

Elliot?.

Hi, thanks for the question. Really cohort two was opened to strengthen the efficacy and safety database that will have and will aid in subgroup analysis of the patient population. That's really the primary intent..

Great and are you able to elaborate a little bit more on what these subgroups are or might be?.

Well, I think that it would be typical subgroup analysis of looking at differences in age, differences in tumor size, etc. And just having a broader database helps to look at smaller numbers of patients that fall into specific subgroups. I am not sure, I can provide more specific details than that..

Yeah. And I guess now, I just want to confirm that this does not affect the overall timing for the registration component..

In our hypothesis testing will be based on Cohort 1 and it shouldn't matter introduce the delay..

Okay. .

We said that we dosed the 45th patient just recently and there's that group of 45 patients that will provide the basis for registration and the hypothesis testing and registration. And so that will be available for analysis later on this year.

And I think the initial data is coming up at ASCO and we're optimistic about the opportunity to present that initial data and to show what afami-cel can do and patients with synovial sarcoma --.

Maybe just following that afami-cel has on that and prime reminders how these potentially assist and accelerating approval process and timeline and are there any other strategies that you're considering to further accelerate registration and approval for afami-cel?.

Elliott?.

Yes. So 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. So they also, I just will mention are based on preliminary data that demonstrate promising efficacy.

Those designations, neither of those designations are provided just based on sort of the rarity of the tumor. So they both provide us with advantage from that standpoint. The other pathways that you're describing are generally already included in the and prime accessibility options and capabilities.

So there is really no need to seek additional designations..

Okay. Thanks Elliot. I look forward to the data update next week..

We are looking forward to providing it..

Thank you. Our next question comes from the line of Michael Smith with Guggenheim. Your line is open..

Hey, this is Kelsey on for Michael. Thanks for taking our questions..

Hi Kasey..

Hey.

Just kind of building actually on that question a bit kind of preparing for the upcoming launch, I guess maybe could you provide some color on what that entails and maybe what reminders what needs to get done to get sites online to kind of 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 kind of getting them online for potential launch and yeah, exactly. Thanks..

Yes. So maybe I'll comment generally and d 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.

So we've obviously begun building our commercial team and that includes a lot of mostly internally facing roles at the moment, market access, marketing, etc. Looking forward we are planning on the more externally facing roles and obviously, were 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 as others will follow up and that patient services activity I think is a key demarcation of successful autologous cell therapy companies.

And John do you 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 that we have the capacity to do so. 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 were 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.

And finally, to Ad's point, we were focused on this thing we're calling I think everyone in this space is familiar with, with V2V, which is that vein to vein part of the patient journey from a free resource to infusion, but the fact of the matter is the patient journey starts well before that.

So 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 Kasey..

Thank you. Our next question comes from the line of Tony Butler with Roth Capital. Your line is open..

Thanks very much. Elliot, Karen, you've spent some time this morning having some discussion about the HiT program.

Adrian, I just wondered if you could just spend a minute on the relationship with the Astellas importantly, given what you've been, what I think you're seeing preclinically it would stand to reason that you would want to move this program fairly rapidly into the clinic.

Does Astellas make that decision? Did you make that decision? Can you just give us some idea of next steps in that program importantly next steps with the cells? That's question one, if I may.

The question to Karen, I just wanted to ask if one did not have a cleavable soluble target for which a TCR construct needed to be directed towards would a TRUCK 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..

Thanks Tony. I'm actually going to ask Helen to comment on the on the Astellas relationship and the next steps with a Astellas on this and then Karen, you can talk to the advantages of TCR CAR targeting.

Helen?.

Yes. Thanks Ad. And thanks Tony for the question. You're absolutely right. This is a co-development program with Astellas on the mesothelin HiT 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 allergenic program of work.

So 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 and to answer your question about whether or not if a TRUCK 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 construct 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 TCR is on the cell surface in order to develop a product that is highly effective which is very different of course, to a TRUCK which is an antibody moiety bound to the actual onchange of the CD-3 portion of the receptor and that being generally a high affinity binding will not be so easily, I think optimized in the same way that we can with the TCR products.

But 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. First question, 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 the press release just describe the data from the abstract..

The press release on the 19th will describe the full ASCO data..

Got it. And, okay. The second question, I'm curious if you could just help set investor expectations ahead of the SURPASS next gen MAGE-A4 update at ASMO..

I think the expectations that we have of that data set is that it will represent the patients that we have recruited across a range of tumor types and we've been focused on lung bladder, head and neck and gastroesophageal, although I will point out that that focus does not, that has not historically precluded of tumor types from being in that patient group.

So it will be a broad set of tumor types. And the objective that we have for that data set 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.

However, I'm just going to point out, given that we have, we're obviously recruiting those patients now and over the course of the recruitment in Q1, which has, as you say, as I said, gone very well, that data set 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. Our next question comes from the line of Mara Goldstein with Mizuho. Your line is open..

Great. Thanks for taking that question. Firstly on those SURPASS-2 trial that will initiate this year, I'm wondering if you could give us kind of just a forward look of what the enrollment and the size and scope and when we can begin to see some clinical data of that program and then secondarily, appreciate the color on the HiTs program.

I'm curious about the program, given that, at least on the pipeline charted it certainly looks a little bit more advanced and where and when you think we'll get some more information on that program?.

Certainly. Thanks, Mara..

Thank you..

So I'm going to ask Elliot to comment on the status of the SPREAHEAD-2 program and then I'm going to ask Karen to comment on the status of the TIL program, Elliot. .

So first of all, Mara, just want to clarify you said SURPASS-2 right?.

Correct, correct?.

SURPASS-2. Sorry..

No. I want to make sure I was answering the right question..

But I'm happy to take any additional info on SPEARHEAD-2 as well if you wanted..

Of course. Yes. With respect, I'll answer your question. So 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 esophagogastric junction cancer and esophageal cancer that has, there have been some recent approvals for combination first line therapy and the patient population that we're trying to address we'll take that into account.

With respect to when you will 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 the data as the trial unfolds.

It will probably follow sort of similar pattern as 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..

And I'm happy to answer a question on TILS, our collaboration with is going extremely well. As you know, they're experts in TILS therapy and we're working with them to develop a next generation for patients with melanoma. Our first product that we've chosen to aggress is a TIL product with IL-7.

This is progressing well and we'll be giving you several updates later on in the year..

Thank you. Appreciate it..

Thank you. I'm not showing any further questions in the queue. I will now like to turn the call back over to Adrian Rawcliffe for closing remarks..

Thanks. And thank you, everyone for your questions and for your continued interest in Adaptimmune and our progress.

As 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 therapies. So you'll get an insight on both ends of the pipeline.

We 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. Thank you for your participation. You may now disconnect..