Q4 2020 Adaptimmune Therapeutics PLC Earnings Call

Ladies and gentlemen, please standby your conference call will begin momentarily once again, ladies and gentlemen, thank you for your patience and please standby.

Operator: Ladies and gentlemen, please stand by. Your conference call will begin momentarily. Once again, ladies and gentlemen, thank you for your patience, and please stand by. (inaudible) The Bulletproof Executive 2013, Ladies and gentlemen, thank you for standing by, and welcome to the Adaptive Immunococcus Call. With that, I'll turn the call over to Juli 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.

[music].

Okay.

Ladies and gentlemen, thank you for standing by him off of what you said the afternoon conference call with that ought to turn the call over to Julie Mellor Ma'am you may begin.

Good morning.

Welcome to adapt minions conference call to discuss our full year and fourth quarter 'twenty 'twenty 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 a number of factors.

Operator: I would ask you to please review the full text of our forward-looking statements in 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.

Those outlined in our latest filings with the SEC Adrian rock with 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 <unk>.

Juli P. Miller: Adrian Rawcliffe, 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.

Adrian G. Rawcliffe: Thanks, Judy, 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 MAJ-A4, two additional BLAs from our clinical pipeline, as well as five autologous and two allogeneic products entering the clinic in the next five years.

Okay.

Thanks Judy.

Thank you everyone for joining us.

Three months ago during our Investor day, I laid out plan, the labor transformative value for patients and for investors over the course of over the next five years.

2252 plots.

In concrete terms. This means two products on the market targeting MAGE a pool.

Two additional BLA east from our clinical pipeline as well as five autologous to allogeneic products entering the clinic in the next five years.

Adrian G. Rawcliffe: 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 mainstay. At the J.P. 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.

All of this just based on the integrated cell therapy company with the intent and capabilities to discover develop and deliver products that the both the curative and main stream.

The J P Morgan conference last month.

Outlined the key catalysts for 2021, and beyond which will be the mile markers on the road to a 2252 ambitions.

And I'm absolutely delighted every time I say this we aim to launch our first product next year.

Adrian G. Rawcliffe: 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 the first building block of our 225-227 project.

As you know not many biotechs get to the stage entities hugely motivating for our research and development teams to know that ADP, a two of them for the treatment. They discovered and developed through clinical trials may soon be delivered to transform the lives of people with Sakai.

The launch is off the first building block of about 225 to plan.

Adrian G. Rawcliffe: 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 two trial with our next generation MAI-J4 targeted product for people with either esophageal or esophagogastric junction in the first half of this year, and secondly, treating patients in the ongoing Phase 1 SURPASS trial that also uses our next generation MAJ-A4 targeted product.

The next key dates when we aim to release data at the <unk> and Sito and these data will be used to support the registration and approval of a tpa two of them Paul.

In 2021 of them beyond the BLA of launch readiness. We will also focus on firstly initiating a phase II trial with our next generation, maybe Jay for targeted product, but people without the esophageal or Suffolk of gastric junction cancers in the first half of this year.

Secondly.

Treating patients in the ongoing phase one so pulse trial, but also uses all of next generation Magi for targeted product.

We're focused on indications, where we've seen signs of efficacy with a matrix of all program, namely lung head and neck, gastroesophageal and blood accounts.

Adrian G. Rawcliffe: We're focused on indications where we've seen signs of efficacy with our MAYJ4 program, namely lung, head and neck, gastroesophageal, and bladder, and we aim to report updated data from the SURPASS trial at ESMO this year. Thirdly, treating patients in our Phase 1 ADPA2-AFP trial with plans to report data at ILCA. We will also determine the next steps of this product. And lastly, continuing our research work to bring new products to the clinic, including HLA-independent TCRs, next-generation pills, and next-generation SPIR T-cells targeting additional HLA classes.

Aim to report updated data from the support of style.

This year.

Thirdly treating patients in our phase one ADP a two I S. T trial with plans to report data Ilkka.

Also the turbine in the next steps for this product.

And lastly, continuing our research work to bring new products to the clinic, including HLA Independent TCR next generation pills and next generation spear T cells targeting additional HLA.

Looking back of 2020, you'll find the summary of our key achievements in our press release, well I just want to pick up on a few points.

Adrian G. Rawcliffe: Looking back at 2020, you'll find a summary of our key achievements in our press... 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.

When I became CEO of I committed to increasing our focus on speed and quality of execution.

Adrian G. Rawcliffe: Last year we demonstrated clear progress by completing enrolment 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 spina bifida or sarcoma in the US next year and shortly after that in Europe. The US and EU regulatory designations, granted based on compelling and durable response data from our Phase 1 trial, will help us with this approval process.

The last year, we demonstrated clear progress by completing enrollment in our spearhead one trial in about 12 months, even with the challenges of the <unk>.

COVID-19 pandemic.

Whilst we wait for data from the spearhead one we're working towards filing of BLA for ADP I too am pool, the people with the ideal sarcoma in the U S next year and shortly after that in Europe.

The U S and EU regulatory designations granted based on compelling a durable response data from our phase one trial will help us with this approval process.

Adrian G. Rawcliffe: We've also started to grow our commercial organization and plan for the launch of a companion diagnosis. When you compare our Phase 1 data to what can be achieved with available treatment, ADPA2 and 4 have the potential to truly change the lives of people living with synovial sarcoma.

We've also started the Gras commercial organization and planning for the launch of a companion diagnostic.

When you compare all of phase one data to what can be achieved with available treatment options.

<unk> two of them pool has the potential to truly change the lives of people living with synovial sarcoma.

Adrian G. Rawcliffe: And the synovial sarcoma community is incredibly excited about these data. We confirmed in 2020 that sarcoma is only the beginning for our May J4 targeted product. Last year, we reported responses from SPIRT cells targeting MAJ-A4 in four different tumors, including melanoma, esophagogastric junction, head and neck, and lung cancer.

And then so I know you saw kind of of communities incredibly excited about these data.

We confirmed in 2020, the sarcoma is only the beginning for all of them AJ for targeted products.

Last year, we reported responses from spear T cells targeting by Jay for and for different tumor types, including melanoma of Suffolk of gastric junction head and neck and lung cancers.

Adrian G. Rawcliffe: There were also meaningful tumor reductions in other indications. We also completed dose escalation in the SURPASS trial with our next generation ADP A2 M4 CD8. 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 of 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.

Also meaningful tumor reductions in other indications.

We also completed dose escalation in the supposed trial with our next generation ADP <unk> and for CDI 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 of the year, where we showed were building the cell therapy company of the future without deep preclinical pipeline.

Our research team has made great progress on multiple fronts, including identifying the first candidate meets the ceded to take board without HLA independent TCR platform in co development with Astellas.

Products targeting each of life beyond HLA, a two and strengthening of toolkit of next generation options, including of til therapy with IL seven in collaboration with CCI team.

This preclinical pipeline supports our ambition to bring five new products to the clinic.

Adrian G. Rawcliffe: 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 part. 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 B tests.

The 25.

Finally, I want to bring up the progress with our other generic part thoughtful.

We started the 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.

Okay.

Operator: And financially, we've confirmed that we are funded until 2023 and equipped to deliver on our ambitions. With that, I'll open it up to questions. Operator?

Financially we've confirmed that we are funding the 2023 and equipped to deliver on our ambition with that I'll open up for questions operator.

Thank you, ladies and gentlemen, if you wish to ask a question at this time. Please press Star then one on your Touchtone telephone. If your question has been answered for you wish to remove yourself from the queue. Please press the pound key.

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.

Tony Butler: 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 Ross Capital. Your line is open. Please go ahead. Good morning.

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.

Adrian G. Rawcliffe: Thank you very much for taking the question. Elliot, Adrian, I wanted to actually touch on commercial readiness, given that you are moving forward with Spearhead 1, and then I have one follow-up on the clinical program. Thanks a lot, Adrian. Okay. Thanks, Tony.

All of it.

For Adrian I wanted to.

Actually touch on commercial readiness.

Given that you were.

Moving forward.

And the spearhead one and then I have one follow up on the clinical program. Thanks, a lot of it.

Okay. Thanks, Tony Thanks for the question as.

Adrian G. Rawcliffe: Thanks for the question. We're preparing to be able to launch ADP A2M4 for synovial sarcoma on approval, which we anticipate will 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 a commercial presence.

We're preparing to be able to launch <unk> in full for synovial sarcoma.

On approval, which we anticipate the next year.

Clearly would be in the process of.

Planning for that for some time.

And 2021 is the year, where we we.

Committing to the both the BLA filing.

And which.

Which will happen in 2022.

And starting to build the commercial presence and I think I've said before this is the perfectly sized opportunity for the company like that to me because of the the very concentrated nature of the patients and physicians, who treat them footprint here.

Adrian G. Rawcliffe: And I think I've said before, this is a perfectly sized opportunity for a company like Adaptimmune 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.

We Oh, obviously talks.

Talking to many of those centers and the sites it doesn't 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.

Of course, obviously, starting with cash.

I felt the GI line Gastroesophageal junction for which Youre, starting the phase II trial now.

Adrian G. Rawcliffe: And I think that the scope for commercialization of cell therapy is obviously quite broad, and it covers all of the usual things that you'd anticipate for a normal commercialization of a product, and payer, patient, and physician research, and all of that has 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 think that the scope for.

Commercialization for cell therapy is obviously quite broad and it.

Covers all of the usual things that you would anticipate for the normal commercialization of our products.

The the payer and patient and physician research and all of that has been ongoing for a while.

And then but it also covers I think the importance of patient services aspects from a supply chain organization and we think about how to develop those from the clinical stage, whether it would be the operating to date, including for the pivotal trial through to something that is picked up.

Purpose for commercial and we'll have more to say about that and other aspects of it.

As we go through the year.

Okay.

It's such a.

Diverse set of stuff the way you have to do I mean, the from the large things of that just mentioned, but all the way through to relatively small things I mean, just just a couple of days ago, We got the the generic naming come from.

Adrian G. Rawcliffe: I mean, just a couple of days ago, we got the generic naming confirmed for ADPA2M4 for synovial sarcoma, which will be called afamotrigine autolucel or afamacel, and it's just the 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 that. Thanks very much.

For.

<unk> two of them for for synovial sarcoma, which will be cool.

The <unk> ultra looser law of found myself at least just the accumulation of a lots of lots of activity and lots of small and large milestones along the way that's kind of ensure that we are able to.

Get the.

I wanted to just say I think our ability to do that will be largely based on the fact that we all we are specialized in this space are knowledgeable in the 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 on two clinical short clinical questions.

Tony Butler: I did want to follow up on two short clinical questions. Number one is, are patients still being dosed with the AFP SPIR T cells? That's one.

One it is our patients still being dosed with the AFP spear T cells, that's one of <unk>.

Tony Butler: And number two, on the phase two, surpass two study, which starts in the first half of this year. And surpass one, 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?

Number two on the phase to surpass two study.

Which starts the first half of this year.

And surpassed one correct me if I'm wrong, you already have 17 sites.

At least according to clinical trials start Carl.

For all of those 17 sites going to the switch over to dose for surpassed two.

How will those be split up or will there be new sites that have already been recruited for surpass two thank you.

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

Elliot Norry: 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.

Yes. So the first question. Thank you Tony.

The first question was around whether we're still dosing patients in the ADP <unk> S. P.

Liver cancer directed trial and the answer is yes.

We're dosing patients in the expansion phase of that trial and there is an intent to provide an update.

With respect to patients dosed and direction at the International Liver Cancer Association conference in the third quarter.

With respect to.

Elliot Norry: With respect to... Surpass sites and Surpass II. Many of the sites that are in the Surpass trial will be engaged in the Surpass II trial as well, but there will be differences as well. We're going to be adding new sites and also expanding geographies as well.

Surpass sites and surpassed two.

Many of the sites will that are in the the.

The surpass trial will be engaged in the surpassed two.

The trial as well, but there.

There will be there will be differences as well, we will be 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.

Elliot Norry: 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 I into Phase II. Those centers that are enrolling well, we certainly would want to have in Phase II. We will have to make that transition for those tumor types from enrolling in a Phase I trial into a Phase II trial. That will be the intention once that trial is open to enroll in the Phase II trial. Elliot, thank you. Adrian, I appreciate it.

But those will be specifically.

Castro intestinal.

Focused sites, while the surpass trial also includes sites that are focused and.

Focused on a broader range of tumor types.

But we're going to leverage our experience from phase one.

Into phase two of those centers that are enrolling well.

We certainly would want to have in phase II and then we will have to make that transition.

For those tumor types from enrolling in the phase one trial into the phase II trial that will be the intention once that trial is openness to enroll the phase II trial.

Thank you Adrian appreciate it.

Kenneth Atkins: 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, Tony.

Thank you and our next question comes from the line of Kenneth Atkins with Cowen <unk> 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 the spearhead one between.

Adrian G. Rawcliffe: Thanks for taking my questions. 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? So I'll take that just to say that we haven't guided us to patients in either category and how that allocation splits out, other than to say that we believe that there will be significantly more synovial sarcoma patients than MRCLS patients. I got it.

Some of Youll sarcoma, and MRC of life and how many patients in each category do you think you would ultimately need to support licensure in each of indication.

So I'll take that just to say that we haven't guided as to patients in the end.

The category on how that the allocation split out other than to say that we believe the there will be.

Significantly more synovial sarcoma patients the MLC all of those patients.

Got it Okay, and then assuming the ADP <unk> for has successfully developed for refractory sarcoma how.

Elliot Norry: Okay. And then, assuming that ADPA2M4 is successfully developed for refractory sarcoma, how much of a priority is moving that product into the frontline setting? Do you think ADPA2M4 has the right profile, or would you want to explore a next-gen product for frontline use?

How much of a priority is moving that product into the frontline setting do you think ADP HCM for has the right profile or would you want it for a next gen product for frontline use.

Elliot do you want to comment on them.

Elliot Norry: Elliot, do you want to comment on that? Sure, so I think that it certainly could be used in a front-line 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 across the board for all patients with the disease type, it would be those that qualify.

Sure so.

I think that.

It certainly could be used in the frontline setting either.

In the.

Sequence with chemotherapy or upfront it will never be for every patient with sarcoma because of the HLA restriction and and and the patients need to express the target. So even if in the frontline setting it wont be sort of across the board for all patients with the disease type of would be the.

Those that qualify.

I don't think that we have.

Elliot Norry: I don't think that we've made sort of a final decision as to whether or not we might pursue a first-line setting, whether that would be the first or the second-generation product. I would, I think that we would have to sort of evaluate it closer to the time of us really implementing the studies that would support that. Got it.

Made sort of a final decision as to as we might pursue a first line setting.

Whether that would be the first for the second generation product that I would I would.

I think that we would have to sort of evaluate.

Closer to the time of us really implementing the the studies that would support that.

Got it okay. Thank you.

Kenneth Atkins: Okay. Thank you. Thanks, Kim.

Thanks, Kevin.

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

Mohit Bansal: Thank you. And our next question comes from the line on Mohit Bansal with Citigroup. Your line is open.

Mohit Bansal: Please go ahead. Great, thanks for taking my question and congratulations on the progress. One question I have is regarding the use of the AKT inhibitor. You 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?

Great. Thanks for taking my question and congrats on the progress.

But the question I have is regarding the use of EQT and EBITDA you have talked about that on your R&D day.

Could you please help us understand the rationale there.

What it does.

Holly to actually boost the the manufacturing the aspect of the Dci.

<unk> manufacturing.

And the.

Adrian G. Rawcliffe: The other 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 a clinical setting that the use of AKT inhibitors is actually doing something to these patients, either in terms of responses or durability? Any color there.

The second part related to that is the U S. Using that in your CD eight the second generation program at this point.

Would we be able to see any competitor data at the clinical setting that use of <unk> inhibitor is actually doing something to these patients either in terms of responses the durability.

Any any color there. Thank you.

Helen Katrina Tayton: Sorry, just coming off the mute. As you say, we use an AKT inhibitor in the manufacturing process. So I just want to be clear about 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 the use of the AKT from a mechanistic perspective and what it does? Sure, just coming off mute. Sorry about that.

Sorry, just coming off mute.

So as you say, we use the <unk> inhibitor in the manufacturing process. So I just wanted to be clear of that.

The comparison than the <unk> inhibitor in the final product that's administered to patients. So I just wanted to make that clear and then.

I was wondering how long do you want to talk about the use of the <unk>.

From a mechanistic perspective, and what it does.

Sure just coming off of the niche sorry about that.

Helen Katrina Tayton: The use of kinase inhibitors and their impact on T-cells has sort of been known for some time. And bluntly, I think there are probably a number of dimensions to the mechanism, but that sort of simplest said, I think it increases the, seems to increase the overall potency of the cells and probably a number of pathways involved in that. But it's certainly something that we and others have seen and are using.

Hmm.

The use of kinase inhibitor from the impact from T cells of sort of benign for some not.

For some time.

The bluntly.

Probably the number of donations for the mechanism that the sort of Sims.

As I said I think it in PCC.

The April patency of the sales.

The number is.

Pathway involved in that but it is certainly something that we and others have seen.

And I think value.

Helen Katrina Tayton: 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 than that; I think we've published on quite a bit of this, or we've certainly put it on posters, and John may also have commentary on the years with which we've brought that into our process. Do you think it could help you from the patent point of view? Can you patent it?

Relatively straightforward adjustments, it just sort of making a price that pool of potential.

The increase in net.

The cell product that we make.

Other than we probably won't go into more details on that I think from published on quite a bit of the clinical data.

In pesos.

Also have commentary on the.

Just switching for adding key into a price.

Do you think it could help you in the from the pattern point of Zucchini patented.

Mohit Bansal: This particular part of the manufacturing process 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. Thank you very much. Thank you. Thanks, Marit.

This particular part of the manufacturing that you are using the DNA, but isn't there.

We haven't commented on.

Patenting strategy as regards the manufacturing process of this aspect of our manufacturing process.

Got it thank you very much.

Thank you thanks, Mike.

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

Michael Schmidt: 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 behalf of Michael.

This is kelsey on for Michael Thanks for taking our hydro assets.

Kelsey Beatrice Goodwin: Thanks for taking our questions. Hey, how's it going? In, I guess, the first question, in the SURPASS trial, what efficacy signal would you need to see in order to kind of make that go or 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.

Hey, How's it going.

And I guess first question and Mr paths 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 of when do you feel comfortable basing that on and the.

And then separately if I could maybe bigger picture maybe.

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 and kind of longer term. Thanks. So much.

Suddenly thanks Betsy.

Adrian G. Rawcliffe: Certainly. Thanks, Kelsey. 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 on the first set of patients in the expansion cohort. Elliot, do you want to comment on that?

So I'm going to ask Elliot to comment on the signals in the past just to say the for.

Because the areas force of POS are obviously, the lung bladder head and neck and gastroesophageal that doesn't mean, we'll only recruit patients in those settings, but thats what were focusing of the trial and we plan on putting data out of it.

At ESMO.

The first set of patients in the expansion cohorts Elliot do you want to comment on lots of them will move to the other question on sales.

Elliot Norry: And then we'll move to the other question. Sure. So, thank you.

Sure. So thank you and the with respect to what efficacy signal would we look to see to drive a go no go decision to a later stage development program.

Elliot Norry: With respect to what efficacy signal we would look to see to drive a go-no-go decision for a later stage development program, there's nuance here. It's not 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, you know, when we see it, we'll know that we're seeing it.

Yeah.

There is a nuance here and it's not the 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 there are several parameters and we like.

To think of it along the lines of when we see it we will know that we're seeing it.

The and I think that you could use the the.

Elliot Norry: 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 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.

The example of.

Synovial sarcoma as is a great example.

Where we saw a 44% response rate in the phase one study, which is clearly advantageous as compared to the other treatments available for second line treatment.

The.

We've typically used a threshold of of 30% response rate.

With a six month duration of response as the as a guidepost, but not as a.

The 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.

Elliot Norry: And you can use the gastroesophageal cancer example to look at that, where these patients have very limited treatment options and a very short time of survival, even after first-line treatment. I think that the data that was published at CMO last year showed that even in the 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.

And you can use the gastroesophageal cancer example.

To look at that where.

These patients have <unk>.

Very limited treatment options.

And very short.

At very short time of survival, even with after first line treatment I think that with the the data that was published it.

All of last year showed that even in the best circumstances. The median overall survival was approximately 15 months.

In this patient population with first line treatment so coming in at a later line of treatment, it's obviously going to be the expected survival.

Less than that so.

Elliot Norry: So, If you determine that a patient, if we're able to show that there's a 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 rate to look at the benefit of a treatment. If you look at the gastroesophageal scenario, you know, we saw that three patients out of three with the first, with the first six, three out of the first six patients in phase two of the SURPASS trial had esophagogastric junction or esophageal cancer, and all three demonstrated meaningful anti-tumor responses.

If you determine that.

Patient if we're able to show that there is 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 rate.

To look at the benefit of of of treatment. So.

If you look at the gastro esophageal scenario, we saw the three patients out of three.

With the first with the in the first six.

Three out of the first six patients in the phase III the.

The surpassed.

The surpass trial had us Africa, gastric junction or esophageal cancer and all three demonstrated.

Meaningful antitumor response.

Elliot Norry: 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 had been treated with lower cell doses than we had seen previously. So, I think that, again, it takes nuance. We have some guideposts that we're going to work around, 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.

That was enough for us to say that we ought to be planning of phase II trial.

Especially when some of those patients in between with lower cell doses than we had seen previously.

And so I think that again it takes nuance.

We have some guideposts and that the that we're going to 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 the same hmm, maybe that's going to be.

Advantageous maybe its not youre going to need 500 patients to show a very narrow marginal difference it has to be it has to be visible.

Elliot Norry: You're going to need 500 patients to show a very narrow marginal difference, but it has to be visible. Thanks Elliot. And on the HIT question, which was sort of how it works and how it works to expand the applicability of our platform, maybe I'll ask Helen to touch on that. Yes, 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.

Alright.

Thanks, a lot of yet.

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

Yeah, Thanks, Brad you're very happy to talk about the the HLA independent.

Tcl Plex on the hip platform. It is exactly the sort of what it says it is it.

Elliot Norry: 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 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.

T cell receptors that can find an appetite on the sales such as pricing side of the target pricing how pricing could be the same as.

As a car or an antibody, but it's actually the TCR the binding team of specific peptide or specifics at the type on that cell surface pricing.

Helen Katrina Tayton: So there are two aspects of that. One is that there are no HLA restrictions. So we don't have to screen out for HLA for the treatment of patients with an HLA-targeted T-cell therapy. And 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, sensitivity, and affinity, really leveraging all of the capabilities we've built up over many years to safely bring T cell receptors through to the clinic.

The two aspects of that one is the there is no HLA restriction. So we don't have to screen out the.

<unk> for for the treatment of patients with an HLA targeted T cell therapy, so that obviously increases the.

The number of patients by removing them.

It does.

The specific criteria that the.

The segment saw a population with HLA <unk> mismatch of T cell receptors, but the.

The other aspect of this which is very exciting for all of this is a function of T cell receptor of it functions and behaves like a roster of optimize T cell receptors and we also have the ability to.

The test that the specificity and sensitivity of affinity really leveraging all of the capabilities with the also pay for many years to safely bring T cell receptor range to the clinic. So very excited that we put up of T cell receptor platform that can broadly.

Helen Katrina Tayton: 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, and we're very excited about that program with our collaborator, Estellas, 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.

The increase the number of patients so we can access with the.

T cell receptor that combines two of the cell surface protein and that broadens out the <unk>.

Patient pool, the specific targets and maybe the state and I think it's the validated target now very excited about that program the backdrop of richa.

The status in which we are kind of developing.

And we also mentioned another one that we started to bring trained targeting GPC three which is the hepatic cancer specific target and obviously for us it will be very important to continue to bring in validate the platform alongside the the HLA.

Helen Katrina Tayton: 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 NAJ4 and AFP, to increase the number 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.

HLA <unk>.

Dependent programs that we have let me Jay for NSP.

To increase the numbers of targeted products that we can bring true.

That's useful.

You have the platform and its applicability.

Yeah, great. Thank you so much.

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

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

Adrian G. Rawcliffe: 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 the Spearhead 1 data? short short answer 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 times. Okay, I would just I would just I just mentioned we've got the arm at designation and therefore the opportunity to have rapid, more rapid approval. The goal is That is certainly our goal.

Good morning, and thank you for taking our questions.

And can you provide some additional guidance on when in 2022.

You plan to file of the spearhead one data.

Sure sure thoughts with us is no.

We haven't provided additional guidance and we won't.

Our sways of moving parts as you can imagine.

Of that affect the timing of lots and we'll update as we have more certainty as to the specific filing timeframe.

Okay.

I would just I would just I'll just mentioned we've got the all of that designation of therefore the opportunity to have.

The rapid more rapid approval on that.

Alright.

For the goal is to file and launch in 2022.

As suddenly all go.

Adrian G. Rawcliffe: 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 that you have alignment with the agency on CMC given issues that have delayed the filing or approval of other self-therapy products? So I think the challenges that have been faced by people who have sought to bring cell therapies to the market are significant, and nobody should ever think that this is easy. We do it even though it's hard.

Sure.

So in preparation for the filing obviously this would be the Cta.

Engineered product to be reviewed and clearly there is no established Paul.

So how confident are you you have alignment with the agency on CMC given the issues that are delayed filing or approval of the other cell therapy.

Products.

Yeah.

So.

So I think the the challenges being faced by people, who have sort of to bring cell therapies to the market.

All significant and nobody should ever think of this is easy.

Yes.

Do it because it's hard.

But.

But I.

I think we do have we do have some advantages for us.

Adrian G. Rawcliffe: But I think we do have some advantages in thinking about it. Number one, we have 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.

In thinking about this.

Number one.

We have.

The advantage that others have taken not.

It won't be exactly the same products in all of the TCR, but its an autologous cell therapy, the whole topic of cell therapies in the Hematological space and I think there were likely to be.

At least for those approved.

By the time, we get the four of five of those approved by the time, we get there.

Adrian G. Rawcliffe: And then secondly, I think there's the opportunity to learn from the experience in TILS, and the first TILS 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 ARMAC designation 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, as far as possible, there is alignment there.

And then secondly, I think the does the opportunity to learn from the experience.

Pills.

And the first drop for us too.

Product is likely to of being approved that so there a precedent for this.

And obviously in the interactions with the agencies.

We get to see that and we get the benefit of thoughts in terms of understanding the revolving thinking.

The space I think the <unk>.

Second thing the thought.

I'd point out is that we have all of my designation in the in the U S.

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.

Two.

Ensure the insofar as possible. There is alignment now you will never find anybody at this company tells you what the regulators think thats going to be for them too.

Adrian G. Rawcliffe: 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 certainly believe that we understand what we need to do. And 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 we have not got some of the challenges that some other types of therapies have, for example, the potency assay as it relates to a pill therapy, which is obviously quite different to the discussions that we've had.

Speak to but at the same time.

We are having what we believe is constructive.

Constructive discussions with both of those and I think we are we certainly believe that we understand what we need to do the lastly, I'd say that we are using from a CMC perspective.

Same facility using the same process in the phase two that we will use for launch.

And I think all the processes and our assays et cetera, and an appropriate place relative to where we want to be for all BLA goals.

And and.

Yeah, we have we have not got the some of the challenges that some other types of therapies have for example.

Potency assay as it relates to of til therapy.

Which is obviously quite different to the discussions that we've had so this isn't easy.

Adrian G. Rawcliffe: So this isn't easy, and there are, as I said, 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 correct. Thank you.

The raw as I said, there are a number of moving parts, but be close with sort of be focused on this because of all 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 processing.

The the requirement script.

Alright.

Thank you.

Elliot Norry: And then you recently listed the Phase 2 esophagogastric trial, which I believe you consider as potentially registration-enabling. And Spike Spearhead 1 plans to enroll 45 patients. So can you explain how you got to that number?

And then you recently listed the phase two of sulfur go gastric trial.

Which I believe you have you considered potentially registration enabling in price.

The head one plants the role 45 patients so.

Can you explain.

How you get to how you got to that number and then also I know this is being studied in other tumors.

Elliot Norry: Also, I know this was being studied in other tumors, but... You know, clearly, perhaps a unique concern here is for on target off tumor causes. What, what, what do you need to do to assure the regulators that this is not? How Many Patients Do You Know? really need to treat in order to ensure the safety. So, Elliot, do you want to speak to the thinking around the Surpass 2 trial design a little bit and in terms of what we've said publicly and then and then and how we're thinking about the toxicity or the safety profile that will be required to register products. Elliot, I think you're on mute.

Clearly perhaps of unique concern here is for.

On target off tumor toxicity.

What do you need to do to for sure. The regulators. The this is not an issue how many patients do you need.

The to treat in order to ensure the midst of non issue.

So the Elliot do you want to speak to the.

The thinking around the <unk> two trial design, the little bit and in terms of what we've said publicly and then and then how we're thinking about.

The toxicity of all of the safety profile that will be required to register products in the splits.

Elliot I think you're on mute.

Yes.

Sorry about that.

Elliot Norry: Sorry about that. I'll start over. I don't think that we've gotten very far with respect to the powering and statistical methodology for the trial, but I will say that it is designed very similarly to Spearhead-1.

Yeah.

I'll start over the.

The I don't think that we've guided with respect to the powering and statistical methodology for the for the trial I will say that it is designed very similarly to spearhead one.

Hum.

Elliot Norry: So while the statistical considerations are not exactly the same, the study is powered to demonstrate benefit as compared to what would be the sort of historical control as it relates to the line of treatment. 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

While the while the statistical considerations are not exactly the same.

The.

The.

The.

Study is powered to demonstrate benefit as compared to.

What would be the sort of historical control.

As it relates to 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.

Important to remember that the T cell receptor is the same as the first generation T cell receptor.

Elliot Norry: And we have, you know, it's not a huge amount of experience as compared to, 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 MAGE-A4-directed T-cell receptor at this point and really have not seen any indication of off-tumor expression of NAGEA-4 or off-target reactivity of the TCR So, look, I think that, ultimately, you know, the benefit-risk ratio is what will drive the day.

And we have.

It's not a huge amount of experience as compared to like of diabetes or cardiovascular trial, but we have.

Pretty good accumulating experience of patients that we've treated with the major for directed T cell receptor at this point and really have not seen.

Any ad.

Any indication of off tumor expression of major for or.

Off target reactivity of the TCR against other tissues.

Look I think that ultimately the benefit risk ratio is what will drive the day.

Elliot Norry: You know, as we're able to further demonstrate the benefit of the T cell receptor in this patient population or in others, it'll have to come with a safety profile that is... that is acceptable, and the safety information that we put out, along with the six patients that were reported at CITSE, showed that, at least in the early days, that the safety profile for the second generation product is, you know, very similar to the first generation product. Now, you can't compare six patients to over 70 patients, but, you know, that will come with time.

As we're able to further demonstrate the <unk>.

Benefit of the T cell receptor in this patient population or in others.

It will have to come with the safety profile that is.

That is acceptable.

And.

The safety information that we put out.

Along with the six patients that were.

The reported it fits the show.

So that at least in early days that the <unk>.

Safety profile for the second generation product is very similar to the first generation product.

You can't compare six patients to over 70 patients but.

That will come with time.

Elliot Norry: And we, at this point, it's our anticipation that if the drug is more potent, we may see some of the more common 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.

<unk>.

<unk>.

At this point, it's our anticipation that if.

If the drug is more potent the we may see some of the more common.

At <unk>.

Toxicities associated with the potency of the product like cytokine release syndrome that has not been the case the date, but we'll have to see that over time.

<unk>.

Elliot Norry: But I think we're feeling reasonably confident around the specificity of the T-cell receptor in that we haven't seen any off-tumor or off-target toxicity to date with MAGE-A4. Good. And then, thanks, Elliot.

But.

I think we're feeling reasonably confident around the specificity.

Of the T cell receptor and that we haven't seen off tumor for.

Our off target toxicity to date with May Jay for.

Great and then.

Thanks, Elliot that's very comprehensive.

Elliot Norry: 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 completed? I wouldn't want to promise to provide data should we think of this, as you said, as potentially registrational. So if we were 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, reserve the right to provide interim data along the course of the trial if that were helpful from a communication standpoint. So I think we just, I can't.

Would you expect to communicate to us.

Data from this trial as it going alone.

Only when it's complete.

I Wouldnt want to promise to provide data should we think of this as you said, it's potentially registrational.

So if we were to make the decision that this trial.

Would be of Registrational trial, then we would be unlikely to provide patient data along the way if it were to be.

<unk>.

Determined to the contrary then we would I would certainly we would reserve the right to provide interim data along the course of the trial if that were helpful from a communication standpoint, So I think we did it.

I can't.

Elliot Norry: In general, for registrational trials, we would not do that, but if it turns out to not be a registrational trial, then... and we certainly could. Great, thank you very much. Thank you. And our next question comes from the line of Mara Goldstein with Mizuho. Your line is open.

In general for Registrational trials, we would not do that but if it turns out to not be of Registrational trial then.

And then.

We certainly could.

Great. Thank you very much.

Thanks, Nick Thanks, Thank you and our next question comes from the line of Mara Goldstein with Mizuho. Your line is open. Please go ahead.

Mara Goldstein: Please go ahead. Great. Thanks for sending that question. I have two questions.

Thanks for taking the question.

Two questions. The first is on the head one and can you just clarify for us the scope of them.

Mara Goldstein: The first is on 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.

What you anticipate for the plant.

And any update in June version of that well update later in the year and then secondarily I'm just curious about the status of the <unk>.

The program.

It certainly appears within your pipeline chart advance from preclinical perspective, and I know it appears in your corporate deck.

Since the crossover in the graphic that you have between the share versus mainstream therapy. So can you talk a little bit about what's going on in that program.

Mara Goldstein: So can you talk a little bit about what's going on in that program? Thanks Mara. So I'm going to ask Elliot to talk about the updates, what's likely to be happening at ASCO and CETOS, and then I'm going to ask Helen to talk about the IL-7 PIL program. So Elliot, do you want to touch on Spearhead first?

Certainly thanks, Bob.

So I'm going to ask Elliott to talk about the update what's likely to happen and get US go on sito's.

And then I'm going to ask Helena to talk about the IL <unk> program, sorry, Elliot do you want to touch on spearhead first.

Sure so.

Elliot Norry: Sure. So. Good question.

Good question first of all I wanted to just say that the update at <unk> is based on the information being accepted by <unk> and you raised I think the point of this being a registrational trial, how is it that we're presenting interim data.

Elliot Norry: 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 why we believe that it should be allowed is that all the patients will have been dosed by the time this information would come out, so it would have no effect on the recruitment and enrollment of the trial.

The reason for we believe that being allowed us at all of the patients who had been dosed by the time. This information would would come out. So it will have no effect on the recruitment and enrollment of the trial.

But it is ultimately up to ask though as to whether they will allow the presentation of data in an interim fashion. So.

Elliot Norry: 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. Hence, the level of durability of response across the whole population will be, you know, less robust than the final information.

If we were to presented it would be based on a data cut.

Ah.

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.

The whole population will be.

Less robust than the final information. We will also have to provide some interpretation of along the lines of patients who had been treated but have not yet completed their series of assessments as to whether they represent responses or stable disease more.

Elliot Norry: We'll also have to, you know, provide some interpretation along the lines of patients who have been treated but have not yet completed their series of assessments as to whether, you know, they represent responses or stable disease. Or, you know, 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 and who's had the right number of assessments to make a determination about efficacy. And then, of course, there will be, you know, safety information as well.

There are some patients who had 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 has been dosed who's had the right number of assessments to make the determination around efficacy and then of course, there will be safety information as well, we will provide duration of response information.

Elliot Norry: We will provide duration of response information, you know, as available at the time of the data cut, but just recognize that, you know, 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, you know, really meaningful duration of response information. And so I hope that Clarifies what we expect to present at ASCO. Later in the year, we would anticipate providing data that would essentially be similar to what we would present to agencies for registration.

As is available at the time of the data cut but just recognize that for example of the data cut is sometime in let's say in March.

And then and a patient treated in February.

We won't be able to provide real meaningful duration of response information.

So I hope that <unk>.

Clarifies, what we expect the present at <unk>.

Later in the year, we would we would anticipate providing the data that would essentially be similar to what we would present two agencies for registration.

Elliot Norry: The study is set to read out six months after the last patient is dosed, provided that patient remains on study. So, if you go, you know, six months from now, we've said that we plan to finish dosing in the study by the end of the first quarter, so that data cut would be around the end of the third quarter, and then, you know, 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. Thank you, that's really helpful. Thanks Elliot. And Helen?

Studies set to read out six months after the last patient.

Is dose provided that patient remains on study so if you'd go six months from <unk>.

<unk> said that we plan to finish.

Dosing in the 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 <unk> 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.

Helen Katrina Tayton: Yeah, sure. Great question. It's a pleasure to talk about the TIL program that we have in 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 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 SPIRT cells. We can apply an awful lot of those capabilities to TILs.

Yeah sure Great question, the pleasure to talk about the the total program that we have on <unk>.

On our pipeline.

We have from <unk>.

Executed a collaboration.

With the <unk> in Denmark, which is that the the extent of the cancer immune therapy, which is the leading center for til.

Till trials in.

Europe.

The weekly nine for some time and the two aspects to this I think the tail strategy feeds into two things it feeds into our integrated cell therapy capabilities, which we believe really enable us to sort of read across and apply in.

In the relatively straightforward of right of way the same.

The price shifts from the science rates for the CMC optimization.

Execution of the clinical programs regulatory interactions et cetera is meeting with our spear T cells. We can apply an awful lot of day capabilities to.

The tills.

Helen Katrina Tayton: And we have a TIL-IL-7 program currently in pre-clinical, but we expect 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 into other solid tumors. Because I think that there's great promise with 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 our in-house capabilities in cell therapy broadly, and T-cell therapy broadly.

We.

How the tail of IL seven program.

It kind of in preclinical book.

Expecting to move quite quickly towards the clinical stage in collaboration with the CCI T, where we're bringing in a range of second generation capabilities and expertise and knowledge from.

The spare T cells into the second generation til product, which we think will improve.

The proliferation and penetration of the of Tilden and other solid achievements, because I think that there's great promise. The tails. We believe that there is more promise and other other tumor indications.

I'd say till date requirements from a restriction.

The testing they don't require target testing some of it's another one of our strategies.

That enabled us to reach more patients.

<unk>.

<unk> for it.

HLA type of what will target type and it adds and compliments.

Our in house capabilities and cell therapy broadly in T cell therapy broadly.

Helen Katrina Tayton: 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 225. 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.

All of that gives a bit more color to where the <unk> program fits within our April of strategy, bringing for the products.

In the the.

The pie the <unk> five K, so hopefully that helps.

And do you have a sense of.

Which indications with the prioritize.

We do but we're not commenting on that at this point I'm sorry.

Mara Goldstein: Okay, thank you. I appreciate it. Yep. Thanks, Lois.

Okay. Thank you I appreciate it.

Yes.

Thanks, Paul.

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

Wei Ji Chang: Thank you. And our next question comes from the line of Jonathan Chang with SBB Lyrinc. Your line is open. Please go ahead. Hi team, this is John Barrett on behalf of Jonathan.

The team this is John Barrett on for Jonathan I realize it's still early in the year, but for the second Gen May Jay for program can you talk about the current status of the surpass study any color on the progress of the study since the last update and help set expectations for.

Wei Ji Chang: I realize it's still early in the year, but for the second-gen MAYJ4 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? Ah, thanks, Joe.

For the data readout of at ESMO.

Including any potential or hopeful number of patients or a breakdown of what tumor types you expect.

Thanks, Joe.

Adrian G. Rawcliffe: All right. So. So you asked for color in the study. It's a very colorful study. It was enrolling a basket of patients, nine different tumor types. As you know, we've focused it down on 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, but in our recruitment, we are focusing on those centers that are recruiting those patients. But we will have others.

So.

So you asked the color of the studies the very colorful study.

The rolling a basket of patients nine non should the across nine different tumor types. As you know were focused it down onto for different tumor types I do just want to be really clear about that that doesn't mean, we're only going to of patients in those four tumor types, which are lung bladder head and neck and gastroesophageal Kansas.

But the.

In all of recruitment we are focusing on those centers.

The.

The recruiting those patients, but we will have all this.

Adrian G. Rawcliffe: The recruitment and dosing of those patients is going well. Last year, we had a biphasic recruitment driven by the COVID-19 pandemic increase in cases and decrease in people being recruited into early stage oncology and cell therapy trials in the second and third quarters, but we've re-established 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

<unk> is going well.

We had the last year, we had the biphasic.

Recruitment driven off the COVID-19.

Pandemic increase in the <unk>.

This is a 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 headed into 2021.

Adrian G. Rawcliffe: 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 number 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 a letter. Got it. It makes sense.

We have no explicitly not commented on the numbers of patients.

But all of these patients are being recruited in the expansion cohort of that trial and we will 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 sufficient cohort of patients to say meaningful things about the development of that therapy going forward beyond that where we are we aren't commenting until we put appetite.

Got it makes sense.

Elliot Norry: 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 type of study that you might eventually move forward with the second gen? And what is the bar for success of that trial?

And quickly on spearhead two.

Could you talk about the current status of that study and just conceptually is this still viewed as a learning.

The type of study that you might eventually move forward with the second Gen.

And what is the bar for success of that trial.

Elliot Norry: Elliot, do you want to talk about those points? Yes. So, thank you. We haven't really been guided as to sort of, you know, numbers of patients screened, enrolled, dosed, etc. The study is open and enrolling now. 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 MAE-J4-directed TCR program with PD-1 inhibitors.

Elliot do you want to talk to those.

<unk>.

Yes so.

Thank you I don't we haven't really guided as to sort of you know.

Numbers of patients screened enrolled dose et cetera.

The study is open and enrolling we do still look at it as a.

I mean every study should be looked at as of learning opportunity.

But this one in particular is the first scenario in which we will be combining.

The the major for corrected TCR program with.

The PD one inhibitor so.

Elliot Norry: So, based on the sort of natural potential synergy of those products, we'll certainly be paying attention. But I don't want to say that, you know, 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 would comment on, I'll go back to the go, no go comments that I made before. But I also do think that the learning here is really more about the potential of this type of combination across programs.

Based on the sort of natural potential synergy of those products will certainly be paying attention.

On the.

I don't want to say that we wouldn't.

Take the.

The the combination of of those two products in head and neck cancer forward. If we were to see the right.

Kind of responses and again I would comment on I will go back because of the go no go comp.

Comments that I made before.

But I also do think that this is.

The learning here is really more about.

The the.

Potential of this type of combination across programs.

Elliot Norry: And the benefits, we'll certainly see 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 genes that control cancer growth, T-cell exhaustion, tumor microenvironment, etc. So I think that...

And the the benefits, we'll certainly see.

How the patients due from our response and toxicity standpoint that will be really important but there will also be important translational information about what happens to upregulation.

Upregulation of downregulation of certain genes that control.

Cancer growth T cell exhaustion tumor microenvironment et cetera.

No.

I think that.

The the.

Elliot Norry: It is a learning trial, as you've indicated, but it does have the potential to really demonstrate the advantage of this combination with T-cell therapy for solid tumors. I want to add that the way that we 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, leukophoresis in obtains cells prior to treatment, so there is no impact of the treatment on the bone marrow that would be, you know, that would produce the cells that we would use to manufacture.

It is it is a learning trial as you've indicated.

But it does have the potential to really demonstrate the.

Vantage of this combination.

With T cell therapy for solid tumors.

I wanted to add that the way that we.

Organized and design the trial also.

Is an example of how cell therapy could fit into a first line sequence with approved therapy that is that.

One Luca for Reese's and obtained cells prior to treatment so no no.

No impact of the treatment on the.

The bone marrow that would be.

That would produce the cells that we would use to manufacture the patient gets there first line treatment. While the manufacturing is ongoing for the product is ready at the time that they're no longer either seeing continued benefit or additional benefit from.

Elliot Norry: 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, it's not simple to organize from a patient standpoint, but we feel this is, you know, again, our first toe in the water as it relates to that as well.

From the first line treatment in the.

It provides an opportunity to use cell therapy.

Right in the sequence with which.

In other treatment and that's a paradigm that is it's not simple to organize from a patient standpoint, but we feel this is again our first.

First the.

Total in the water as it relates to that as well.

Elliot Norry: That's very helpful. Thank you, Thank you, Thank you, and this does conclude today's question and answer session, and I would like to turn the conference back over to Adrian Rawcliffe for any further remarks. Thanks, and thanks to 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 in the press release and everything that we accomplished last year.

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 for any further remarks.

Thanks, and thanks, everyone for joining us I want to before we close the call acknowledged the incredibly hard work and commitment of everybody here at the at that to me and who.

Despite the challenges of the COVID-19 pandemic over the last year have remained focused on our mission and our vision and the delivery of the results that we've just put out the press release of everything that we accomplished last year I also want to thank our investors who continue to have confidence in the opportune.

Elliot Norry: I also want to thank our investors who continue to have confidence in the opportunity presented by Adaptimmune. 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. 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!

The presented by adopt to be I think we're all here looking forward to 2021 and I'm looking forward to being able to update you on the key mile markers on the road to delivering that 2252 strategy that I talked about at the beginning of the school and ultimately the opportunity too.

Great significant value for people with accounts and for the company.

Thank you and speaks of it.

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.

Yes.

[music].