Ladies and gentlemen, thank you for standing by. And welcome to the Adaptimmune Q1 2020 Earnings Conference Call. At this time, all participants' lines are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. [Operator Instructions]I would now like to hand the conference over to your speaker today Ms.

Juli Miller. Thank you. Please go ahead ma'am..

Good morning, and welcome to Adaptimmune's conference call to discuss our first quarter 2020 financial results.

We issued a press release earlier this morning, and I would ask you to please review the full text of our forward-looking statements there.We anticipate making projections during this call an actual results could differ materially due to a number of factors, including those outlined in our latest filings with the SEC.Adrian Rawcliffe, our CEO is with me for the prepared portion of this call and 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. Before I get started, I'd like to officially welcome Gavin Wood to his first Adaptimmune's earnings call. Gavin joined us as Chief Financial Officer in early April. Looking back at the first quarter, the year began strongly for us.In January, we announced responses in four new tumor indications.

These are early responses, but they are a validation of our SPEAR T-cell platform for people with cancer.

We are funded into the second half of 2021, having added close to $140 million to the balance sheet from our deal with Astellas and the public offering in January.The January clinical data announcement was followed by increases in screening during the first quarter across all our clinical trials before the inevitable slowdown associated with COVID-19.

The impact of COVID-19 still evolving, including its impact on our R&D programs. And the full extent is likely to vary across sites.As a company, we've implemented new ways of working together to reduce the risk of disease spread. We want to ensure the safety of our colleagues.

So we're working on-site, manufacturing SPEAR T-cells for patients enrolled in our clinical trials, all conducting time critical research activities.I want to thank all our employees, both those who have been working from home and those who have been working in our facilities to make sure that we can hit the ground running as the situation improves.

Manufacturing of our SPEAR T-cells has continued with our facilities operating at close to full capacity throughout March. We are still manufacturing for patients in April and May, will be at a reduced level.

And we're optimistic the patients screened and patients for whom we've manufactured cells during the pandemic will be able to participate in our trials as clinical sites resume non-COVID-19 related care.Although many scientific and medical meetings have been delayed or switched to virtual formats we will continue to communicate our data at these meetings.

In a press release issued on April 29th, we laid out expectations for when you would see updates between now and August at ASGCT, ASCO and the International Liver Congress.Earlier this week, we presented data from an allogeneic program at ASGCT.

We've made great strides in the engineering required to make T-cells from stem cells, including the location and timing of edits to get our T-cells receptor into progenitor cells for the generation of T-cell banks.We have also been able to produce functional engineered T-cells from stem cells that can kill cancer targets in vitro as effectively as engineered control cells from our autologous products.

These are significant steps in progressing our allogeneic platform towards the clinic.At ASCO, Dr. David Hong of MD Anderson Cancer Center will give an oral presentation with data from the Phase 1 trial ADP-A2M4, our first generation SPEAR T-cells targeting MAGE-A4.

This presentation will provide a full summary of the trial, including more mature data from patients with synovial sarcoma, as well as data from a broad range of other indications.The acceptance of this abstract as an oral presentation by ASCO is validation of the strength of our ADP-A2M4 program.

The full ASCO content will be available online the morning of May 29th. And we will issue a press release with a clinical update that same day. We will also be available in a virtual ASCO boot throughout the day of the 29th for Q&A.We've learned a lot from the Phase 1 ADP-A2M4 trial.

We have learned that MAGE-A4 is a viable target expressed in a broader range of tumors at levels high enough to go on responses.

We've learned that the TCR against MAGE-A4 successfully targets MAGE-A4 expressing cancer cells and can results in T-cell trafficking and responses in multiple tumor types.We've used this information to build out our program of assets targeting MAGE-A4 these include, our next generation ADP-A2M4 CD8 cells which we are testing against a broad range of cancers in our SURPASS trial as well as the radiation sub study of our Phase 1 trial.

And we're on track to present data from both these trials at medical conference since in the second half of 2020.This program also includes the Phase 2 combination trial with ADPA-A2M4 and a PD-1 inhibitor for patients with head and neck cancer. This trial will be called SPEARHEAD-2.

All clinical sites will be activated as soon as possible.Our SPEARHEAD-1 trial in sarcoma was recently acknowledged by the EMA's Committee for Orphan Medicinal Products with this adoption of a positive opinion for orphan drug designation, the ADP-A2M4 for the treatment of soft tissue sarcomas.In Q4 2019 we announced that the FDA had granted orphan drug designation and then RMAT designation for this program.

ADP-A2M4 has clearly demonstrated the potential to offer substantial improvements over current standard of care for the treatment of advanced soft tissue sarcomas.With these three designations, we believe we're in a strong position to achieve our goal of launching our first product in the U.S. in 2022.

Our commercial preparation is ramping up as we add key staff and develop our capabilities towards commercial scale.Finally, we are progressing our ADP-A2AFP program in liver cancer. And we are delighted that Dr.

Bruno Sangro from Navarra University Clinic in Spain will present data from the third dose cohort at the International Liver Conference in August, which was delayed from April.We continue to enroll this trial having progressed to the expansion cohort doses of up to 10 billion SPEAR T-cell.

As I said earlier, 2020 started strong for us with the validation of our SPEAR T-cell platform in multiple solid tumors and our most significant deal in the past five years.Now I'll open the call up to questions. Operator?[Operator Instructions] Our first question comes from Marc Frahm with Cowen and Company. Your line is now open..

Yes. Thanks for taking my questions. Just to start off, you mentioned counterbalancing, the added interest in the program based on the updates in January, but then of course COVID slowed things down.

Can you maybe quantify that as to how much did you see screening increased maybe in February versus what you'd been seeing in the back half of 2019?And then when we get the update on the press release on the 29th, would it be restricted to MAGE-A4 or should we be thinking that that's a broader clinical update of whatever you have across all the programs, like you've done some other times..

Okay. So I'll take the second question first.

And then I will ask Elliott to comment on the first question and progress on the screening on the clinical trials in the first quarter of this year.So I think the -- in terms of what we will give as a clinical update, I think it's just worth putting the whole thing in context of what's going to be presented at ASCO.

David Hong's presentation will be on all of the data we have to-date on the patients enrolled in the ADP-A2M4 Phase 1 trial.You incorrectly stated, this is the first generation SPEAR T-cells targeting MAGE-A4 and that trial has been ongoing for some time. It's just worth noting Dr.

Hong and the team at MD Anderson have been key partners for us across the range of approaches that we're targeting MAGE-A4 including the radiation sub study, the SURPASS second generation trial.And you will recall that we had a strategic Alliance with MD Anderson as well.

So they are instrumental in treating patients across the range of these studies. The first generation Phase 1 trial of ADP-A2M4 was recruiting across nine different tumor types expressing MAGE-A4, including synovial sarcoma, where we clearly recruited the most patients.Last year, no, actually two years ago at ESMO 2018, we showed safety from this.

You might remember the first two dose cohorts were full of ovarian patients, six ovarian patients posted 100 million and 3 billion cells. In May 2019, we showed some initial responses in a few sarcoma patients and we showed signs of antitumor activity and other tumor types.We updated ESMO and CTOS last year on the sarcoma patients.

And roughly half of those patients were responding over that time course. Durability at that point was relatively immature. The data cutoff for CTOS was 23rd of October.

And we basically use that data cut off to submit the ASCO abstract.And then subsequently, we announced that we had seen a response in a head and neck patient alongside other responses in our other trials, including those targeting MAGE-A4, the radiation sub study and the SURPASS study, which is the second generation study.We have continued to recruit patients through Q4 and into Q1 2020.

Overall, we have dosed 38 patients in that study. The six ovarian patients in the first two dose escalation cohorts, followed by 16 synovial sarcoma patients, and 16 non-sarcoma patients. Those non-sarcoma patients are split over a wide range of tumors, including ovarian, head and neck, bladder, lung.

And so you can be clear that there will be relatively small ends in each tumor type.Dr. Hong's presentation basically will provide a full update on both sarcoma patients, including durability of those responses and also what we've seen outside of sarcoma. And we're quite excited for that presentation.

Following on from that presentation, we will give an update on the various trials targeting MAGE-A4.So just to confirm this includes an update on progress on SPEARHEAD-1 which is the Phase 2 trial targeting within synovial sarcoma myxoid/round cell liposarcoma and update i.e. more details on the design of the SPEARHEAD-2 trial.

This is our Phase 2 trial in head and neck cancer in combination with Pembrolizumab.As I mentioned above, we have seen a response in head and neck cancer in the first generation program as a monotherapy. So we know that the SPEAR T-cells active in the setting and we're excited to initiate this trial this year.

An update also will be provided on SURPASS our second generation ADP-A2M4 CD8 where we announced in January that the very first patient of this trial at the lowest dose cohort had responded.Now, I want to remind everyone that we do plan to stick to our practice of supplying data updates at major medical and scientific meetings.

But I think we'll give an overview of progress on our entire MAGE-A4 targeting program on the 29th.And just to point out, we have previously said that the AFP program will be updated at the International Liver Conference which has moved from April to August and Dr.

Sangro will give that update on those cohorts.So with that, I'll just ask Elliot, to comment on the screening -- the increase that we saw in the early part of this year. Obviously, I don't want to -- we're not going to give specific details on how many patients et cetera. But generally speaking across our trials.

Elliot, what color could you add there?.

Good morning. Thank you, Ad. I would just say that there was a very palpable increase in interest in our studies from our investigators in conversations that we had with them.

And that really translated into an increase in the actual number of screen patients.As Adrian said, I'm not prepared to or don't think we should provide specific screening numbers as it relates to individual trials.

But I don't think, it's surprising that following the announcement of the responses that we had seen across tumor types and across our platforms that there was an increase in interest..

Okay, great. Thank you..

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

Good morning, Adrian. I just wanted to ask pacifically about SPEARHEAD-1 and enrollment in SPEARHEAD-1. So there's really two parts to the question.

One is, has enrollment continued at a pace that doesn't necessarily protracts the outcome of the finality of the trial, presumably?And then number two, with respect to your comments Elliot back in January, as it relates to an increased interest in clinical sites and investigators.

Was that skewed toward synovial sarcoma, and just given the fact that you're enrolling a substantial number of patients within that particular disease setting, as it relates to SPEARHEAD-1? Thanks..

Thanks, Tony.

So, in regards to the pace of recruitment of SPEARHEAD-1, I would not dispute your statement that what we're seeing continues to give us confidence that we'll be in a position to meet our objective of launching ADP-A2M4 for patients with sarcoma in 2022.There obviously has been some impact in the sort of mid-March onwards as it relates to screening for the SPEARHEAD-1 trial.

But it is encouraging that we continue to screen [indiscernible] manufacture for patients. And we will give an update on that in the May 29 clinical update.With regards to the balance of screening and interest, I would just say this. I think it's worth, yes.

And lot of the patients that we have seen this year are for the SPEARHEAD-1 trial, not surprising, that is a 60 patient trial. It's much larger than our other trials.

It's opening close to 20 centers at this point in time, across Europe and North America.And it's on the back of compelling data, I believe regarding the efficacy of ADP-A2M4 in synovial sarcoma.

However, I think -- I just click the Elliot, to confirm that we also saw on the back of the efficacy data, the response data that we put out in January, we also saw an uptick across other trials and indications as well.

Elliot, anything to add to that?.

Yeah, I would just confirm that, Adrian that we saw robust interest in enrollment really across the programs in the early part of the year.

And as you said, I think that the interest in synovial sarcoma really, mostly came from the data that was presented at ESMO and CTOS last year, and just the general knowledge in the sarcoma community about the promise of this therapy.And we expected to have robust enrollment in that study at the beginning of the year, as the centers were really opening, where we really saw a change was in the other studies where it was on the back of the data we presented in January, across other tumor types, that generated sort of a different type of interest in those programs.So in summary, the answer to the question is that it really was not restricted to synovial sarcoma, but seen across the program..

Thank you, Elliot, Adrian..

Thank you. Our next question comes from Mohit Bansal with Citigroup. Your line is now open..

Great, thanks for taking my question and very good morning. Hope everyone is staying safe at team Adaptimmune..

Thanks, Mohit..

Thanks. Just wanted to understand -- so thanks for providing all the colors on the ASCO data.

Is it possible to put the ILC data the Liver Meeting data as well in context and set expectations there? What should we expect? How many patients are there already? Anything you could provide to help us understand how to how to feed those data?.

Elliot, would you like to comment on what will be presented at ILC..

So as at the International Lever Congress, we will present the data for cohort three.

I'm not going to announce any of that data in advance of that, beyond what has already been communicated, which is the 100% reduction in target lesions seen in the first patient treated in cohort three with the approximately 5 billion cell dose.We also do have a poster presentation at the International Liver Congress discussing cohorts one and two in summary, which they hadn't been updated in total.

So they're really two presentations. One on cohort one and two. And then the presentation by Dr. Sangro on cohort three..

Got it. Really helpful. Thank you..

Thanks Mohit..

Thank you. And our next question comes from Jim Birchenough with Wells Fargo. Your line is now open..

Good morning. It is Nick for Jim this morning. A couple of questions. The first one is I know that you're going to be reviewing designer add to virtual ASCO.

But is there a reason that PD1 dosing would just not follow its label for head and neck cancer? Is there I mean, I guess I'm trying to get at is there some way you think you can optimize the function of spear T-cells, perhaps at different dosing paradigm or modify just some paradigm?.

So I think I would just say on that, that if we were going to give more details on the design of that now, we're going to give more details on the design of that on the 29th. And I'll defer that question until that if that's okay. Anything else I can help you with something..

Hope I get to ask it again?.

Absolutely..

And then I noticed that you have [indiscernible] in both HLA independent target? Can you give us an example of what an HLA independent target is? And are these too small to be targeted by a CAR? How do you decide on a CAR versus HLA independent TCR strategy?.

That’s a very good question. I will hand -- I'll ask Helen Tayton-Martin to answer that for us..

Thanks, Ad. Thanks, Jim. So, I think the simplest way to answer that is the HLA independent targets, the TCR targets that we've been focused on are effectively CAR targets.

So these are cell surface proteins with obviously look at the candidates that are well validators as well as others that are less well validated but emerging.I think really an HLA independent TCR is a TCR that can recognize specifically a cell surface protein. And really then signal through the TCR, it behaves like a TCR on a T-cell.

But what we've been able to do is find these very, very rare TCR that then put them through our internal proprietary processes for specificity testing, and potency and efficacy.And at that's really the basis of the targets that we're going after in that platform. So it's very exciting, it leverages all of the TCR capability and functional behavior.

But it is obviously not HLA restricted. So we haven't disclosed the first target that we have agreed with Astellas obviously, but we it will be a hit target.I hope that I answered the question..

Certainly, partially.

So you are selecting something you go head to head with the CAR or is this just a way target HLA independent proteins without having to develop on using CAR technology? I guess the point is we always hear that CAR-T cells and blind targets was lower antigen density then a numb SPEAR matured TCR, but CAR-T sort of positioned to being more potent to like TCR based therapies..

So actually I think that the TCR based targets normally had actually it's usually very low frequency. So, further levels and therefore having appraisal specific TCR is critical. I think you can apply similar sort of dynamics.

So cell surface proteins, typically many more proteins and the CAR is seeing much more surface antigen.But the idea of a finely tuned specific TCR that can see the fragment of that cell surface protein is really the design behind a functional TCR that can recognize the cell surface proteins.

So we think that there are advantages in our preclinical testing. You wouldn't be surprised to know that we do head to head comparisons and I think that's what's given us a huge amount of compare of enthusiasm and excitement around this program.So we've been able to generate them. We tested in comparison to publish CARs on well-known targets.

And we've been able to fine tune them in terms of their potency and specificity..

Great. It's very helpful. Then just the last on for me on ASP. Obviously you started this program with a healthy degree of trepidation.

Now that your very high doses of cells, is there a concern that there is enough variability in healthy tissue potentially that there are rare events, safety events that you're not really going to be able to discount until you've treated tens or hundreds of patients.

So how confident are you now than you got passed this concerned about on target of tissue toxicity?.

I'll ask Elliot to take a step on that..

Yes, thanks for the question. I mean, I think that I would say that we have increasing confidence with each patient that we treat and see that there's an absence of liver toxicity associated with the TCR. So I think your point's well taken.

Could there be a rare patient that has a level of expression that's high enough to generate such a response? And will we know that without treating many, many more patients.I think that, in the world of clinical safety, until you've treated that number, it's hard to make assumptions about that.

But to-date we haven't seen liver toxicity that would be of that type of concern to us. So we're gaining increasing confidence in the product and actually just the number of patients that we've treated to-date and seeing safety at the highest cell dose does give us increasing confidence..

Great. Thanks a lot. I'll share my questions and I'm trying to picture on your virtual ASCO booth will look like that. You'll have to send me a picture..

Thanks, Nick..

Thank you. [Operator Instructions] Our next question comes from Jonathan Chang with SVB Leerink. Your line is now open..

Hey guys, this is David Rush on for Jonathan. Thanks for taking our questions and congratulations on the progress. Just to go back to that last question a little bit, you mentioned the AFC program had progressed to the 10 billion cell expansion cohort. And you've talked about the safety profile already.

But I was wondering how you think about dose escalation from here and when do you think we might see updates from these later cohorts?.

So I’ll just put out in terms of the timing for later updates and then I’ll ask Elliot to comment on the dose ranging that we’re seeing and what our thoughts are about that? So we previously guided that we would provide a update on cohorts on the dose escalation at the International Liver Conference, that was subsequently moves from April to August.

And as Elliot talked about earlier that would be the case.Also at the same time that we provided that guidance, we provided guidance that we would update on the expansion cohorts patients that we recruited in the second half 2020. And we think remains a reasonable goal for us at this point in time.And so that’s when you should anticipate.

I will point out, I just want to in the abundance of caution, we -- small numbers of patients are very meaningful for us. This trial is now recruiting at the expansion level. The advantage of that is a lack of stagger between patients. However, this is still early Phase 1 trial and we're still evaluating safety at this level, et cetera.

And so we, I would now anticipate hundreds of patients in the updating in the second half of this year. But I think we hope to give a meaningful update on patients enrolled into the expansion cohort there.Elliott, thoughts on dose escalation..

I would just say that the study is designed at this point to as Adrian mentioned to treat patients with doses up to 10 billion cells in the expansion phase without a stagger. And we don’t -- there's no plan to dose escalate beyond that.

We're really looking to accumulate a number of patients experience with that cell dose and to make further decisions from there..

Got it. Thank you. That's helpful. And you mentioned, the durability data from the sarcoma patients, from the ADP-A2M4 study would be presented at ASCO.

How are you thinking about competitive benchmarks in the sarcoma space? And could you help set expectations here?.

Elliot, would you like to talk to that..

Sure.

So from the standpoint of competitive benchmarks, in the second line setting, after a systemic chemotherapy for the treatment of sarcomas, the second line therapies that are currently approved and/or used regularly are typically associated with response rates in 5% to 15% range and are associated with a degree of toxicity depending on the treatment.

And the treatments are generally ongoing treatments where patients have to return for time for therapy.So, when we're seeing 50% response rates and the durability will be discussed. And as of CTAS we are seeing durability out to nine months. That represents we believe an advantage to those patients as compared to what's currently available.

And the advantage of a single therapy that allows patients to go through a treatment with that does have a degree of tact, but once resolved can enjoy a period of time without further ongoing week to week or month to month treatments. Also is part of the advantage to the patients. So I'll leave it at that, but I think that's really how we see it..

Got it..

And I would just … Thanks Nick..

Thank you. Our next question comes from Mara [ph] Goldstein with Mizuho. Your line is now open..

Hi, thank you. This is Mara actually. Just a question on the allogeneic TCRT program.

And can you just outline for us, how we should anticipate that that would progress and what are the milestones we should look for into? In addition to which, on the approach that you're taking are there ways in which as you look to develop therapeutically that you can somehow also an antigen presentation on HLA are there approaches that allow you to do that, and would you consider that?.

So, thanks. Thanks, Mara. I will ask Helen to talk to the allogeneic base..

Hey Mara, thanks for the question. So as you will have seen our approaches is focused on developing T-cells from IPSC stem cells.

And that's been a focus for some time and that's where we've made the most progress with the recent presentation this week at ASGBT where we actually were able to determine the right location to put in a TCR into those edited, then differentiated stem cells to T-cells.So there's a lot of research that's going on been performed to get to that stage.

And it's important to generate a cell where we are basically removing class one and the endogenous TCR and putting in a cell side gene that enables those cells to be stopped if we need to. So the last step for us was actually getting a TCR into a functional location from editing and differentiating into a functional cell.

So huge -- that's a huge step forward to produce a T-cell in that setting.And then we're, the next steps are really around confirming any other final edits. We may need to and then beginning the process development work into, to get cell banks that can go into the clinic. And we know we started all of those processes.

And so the next in terms of the question terms of milestones that will be obviously IND filing and heading to the clinic.And we haven't -- there are a number of new really steps on that which we haven't bottomed out yet. So we're not talking about specifics of the timelines, but that is on our horizon.

And obviously, we have our own programs which leverage that for MAGE-A4 and then we have new programs through the Astellas collaboration, which will be coming along behind.And the second question, I'm sorry, perhaps, if that's repeated? I'm not sure what do you want me to answer that or whether that's another member of the team?.

Mara, can you clarify your second question about driving HLA presentation?.

So I'm just wondering within the context of the discussion around CAR versus TCR. I'm just wondering around sort of approaches, where you could increase the amount of expression or neo antigen expression cells, so that you could use that in combination with existing TCR T program? That's all..

So, what I will say is we have looked at approaches whereby you might increase presentation of HLA and antigen on cells. That's not the current preferred approach to driving for increased efficacy.We've referred to a number of other approaches, as sort of next generation approaches, including the approach that we're currently in the clinic with CDA.

In terms of converting our T-cells. And the overall rationale for that, I just want to be clear. Is a well-designed T-cell receptor should in its normal state with right ability, be able to track down cells with very low expression.As Helen referred to earlier, I think it's a bit of a mix that TCRs are less potent than a CAR-T for themselves.

I think the antigen presentation of a typical surface antigen on a cell, particularly in the context of something that's floating around in the bloodstream and therefore, immediately available for a CAR-T in the hematological setting and is orders of magnitude higher. And is typically seen by HLA presentation.

And yet in the natural system, the T-cell receptor is naturally able to find normal antigen presentation for viral antigens, et cetera.And so -- and indeed our TCRs, we've managed -- we believe that they can track down very low -- relatively low levels of HLA presentation of cells.

So the question therefore for our perspective is not necessarily how do you drive HLA an antigen presentation with the associated risks of that that would come with, but rather how did you improve the functionality of the T-cell through a number of our next second generation approaches in order to enable it to either be more potent to traffic to the tumor or to overcome to the microenvironment..

Okay, thank you..

Thanks Mara..

Thank you. And our next question is a follow up from Jim Birchenough with Wells Fargo. Your line is now open..

Hey, just one more on the IPSC T-cell. And that is, are you just able to make CD8 T-cells at the moment or you able to make CD4 T-cells as well and given what you've done with second generation A2M4. Are you putting CD8 into those CD4 T-cells? Thanks..

This is with respect to our allogeneic program?.

Yes, correct..

Yes.

Helen, would you like to comment on that?.

Sure. So, the answer is yes, we can make CD4 and CD8 double positive, and we also get into single positive CD8. So, that's all through differentiation of the stem cell to a T-cell. So, it's not true, adding in CD8 in that sense that that's a specific element that we have used in our autologous second gen programs.

So, in the ally space, we have focused on differentiating the IPC to a functional CD4 and CD8 positive and CD8 T-cell. We have still some work to do but that's basically the phenotype we've been driving for and that's the functionality we've been starting to show in most recently in this week's poster..

Okay, thank you..

Thank you. I'm not showing any further questions at this time. I'd now like to turn the call back over to Adrian Rawcliffe for any closing remarks..

Thank you. We've made real progress in the first part of 2020, pushing forward with our product in sarcoma, and generating encouraging responses across a broad range of solid tumors. And I'm looking forward to sharing more data on May the 29th at the beginning of ASCO.

I'm more confident than ever the work we do is making and we'll continue to make a difference for people with cancer. And with that, we'll close the call. Thanks a lot..

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect..