Adaptimmune Therapeutics PLC (ADAP) 2016 Q4 法說會逐字稿

Good day and welcome to the Adaptimmune Fourth Quarter Financial Results Conference Call. Today's conference is being recorded. And at this time, I would like to turn the conference over to Mr. Will Roberts. Please go ahead, sir.

Thank you, Alison. Good morning and welcome to Adaptimmune's conference call to discuss our fourth quarter and full year 2016 financial results and other business updates.

As a reminder, today's conference call will contain forward-looking statements. These statements relate to future events or the company's financial performance and the listener is cautioned to not rely solely on these forward-looking statements. Such statements is always are subject to certain risk and uncertainties which could cause actual results to differ and events to differ materially from any future results expressed in or implied by such statements, especially those inherent in the process of discovering and developing our therapeutic candidates and those set out in our filings with the SEC.

With me on the call this morning and participating in the prepared section of the call are James Noble, our Chief Executive Officer; and Adrian Rawcliffe, our Chief Financial Officer; Gwen Binder-Scholl, our Chief Technology Officer; Rafael Amado, our Chief Medical Officer; and Helen Tayton-Martin, our Chief Operating Officer, will be available for the Q&A after the prepared portion of the call. This call is expected to last approximately one hour including Q&A.

And with that, I'll turn the call over to James Noble. James?

Thanks, Will. Good morning, everyone, and thank you for joining us. We plan to cover a number of topics on the call today, including a summary of our 2016 corporate and clinical achievements, our expectations for 2017 and beyond, as well as our financial results for the full year 2016.

2016 was an important year for Adaptimmune during which we established substantial clinical momentum that we believe has positioned us for important data delivery through 2017 and 2018 from our wholly owned assets as well as our NY-ESO program.

First and foremost during the second half of 2016, we implemented a number of important enhancements, including a strategic align with the MD Anderson Cancer Center, significant increases in the number of clinical price and laying the foundation for expansion to European clinical sites, as well as implementation of a centralized screening procedure. All specifically designed to address the delays we experienced last year.

We are already seeing the benefits of these changes. We are delighted with the improved screening rate over the last three months and we have identified patients for each of our open trials. For example, overall core of our NY-ESO synovial sarcoma study, which opened in later October of 2015 has already enrolled 10 patients and we are amending the protocol to enable enrolment of up to 15 patients. And we intend to present the initial data on this cohort at ASCO this year.

Furthermore, over the last 12 months, we opened two new INDs for our wholly owned AFP and MAGE-A4 SPEAR T-cell which gives us three open INDs with wholly-owned assets. Not unexpectedly this indicates increased focus from our wholly-owned pipeline and we intend to deliver initial data from our MAGE-A10 and MAGE-A4 studies later this year.

During 2016, we initiated two new clinical trials the multi-tumor study with MAGE-A10 and a pilot study of NY-ESO in myxoid/round cell liposarcoma or MRCLS, which also actively occurring. All together, our four open INDs enable nine studies across 11 indications in contrast to the end of 2015 where we had two open INDs and studies ongoing in four indications.

In addition to the significant momentum I've just described, we also presented important foundational clinical data during the last 12 months among them. First, we have observed responses among low expressers of NY-ESO in Cohort 2 of the synovial sarcoma study and these data will inform the design of future trials with respect to expression cut-off for our planned synovial sarcoma registration study.

Secondly, based on the results seen in Cohort 3, we believe that Fludarabine is a necessary component of our preconditioning regimen. Subsequently, we opened Cohort 4 as well as an amendment to the ovarian cancer protocol both of which utilize a modified less intent cyclophosphamide Fludarabine preconditioning regimen. If this modified regimen proves effective, we plan to incorporate it in the upcoming registration study.

Thirdly, additional follow-up on synovial sarcoma Cohort 1 yielded an increased median survival of 18 months or 80 weeks as of November 2016 compared to 13 months or 56 weeks as previously reported.

Fourthly, we described key translation data including demonstrating persistence SPEAR T-cells and that these cells retained tumoricidal activity 28 months post infusion. And finally, we continue to observe important differences in the tolerability of our SPEAR T-cells versus that reported in the CAR-T.

While there are differences in the patient population, the incidence of cytokine release syndrome with NY-ESO SPEAR T-cell therapy is the -- of lower frequency and severity and reported with CD19 CAR-T. Furthermore, we have not observed the type and severity of neurotoxicity with NY-ESO SPEAR T-cells as reported with CAR-Ts.

As it's true with all novel treatment modalities partnerships with other industry and academic leaders are essential. In our case, these relationships have the potential to strengthen our industry leading technology platform and operational capabilities and we will continue to identify and evaluate new partnerships as business needs warrant.

To this end, we executed several key collaboration agreements during 2016. First, our clinical agreements included the previously discussed strategic alliance with MD Anderson Cancer Center. Secondly, we entered a clinical trial collaboration with Merck, through which Merck will provide its PD-1 Inhibitor KEYTRUDA for an upcoming Adaptimmune sponsored combination study with NY-ESO SPEAR T-cells in patients with multiple myeloma. We anticipate that the first type will be initiated to this study in the first half of 2017.

Thirdly, regarding the assessment of new technologies for our next generation effort, we entered into a stage collaboration agreement with Bellicum to evaluate the potential of its GoTCR technology, which complements our existing portfolio of next generation approaches. We expect to complete preclinical proof-of-concept work this year and depending on the results we may enter into a two target co-development and co-commercialization phase.

And finally, in February in 2016, we announced that we had expanded our strategic collaboration with GSK to accelerate NY-ESO towards registration study in synovial sarcoma. More recently, we announced earlier this year that GSK had nominated PRAME as its second target reflecting its continued commitment to developing novel immunotherapies. Adaptimmune will be responsible for preclinical testing of PRAME and delivery of the IND package to GSK.

We share the view of the investment community that secure and efficient manufacturing is a key step to success. During our last quarterly call, we highlighted the importance of transitioning to a commercial ready manufacturing process that includes cryopreservation at both ends, a streamlined T-cell enrichment procedure utilizing Thermo Fisher's efficiency CD3/CD28 Dynabeads and optimize media with serum-free expansion. These changes allow for more manufacturing flexibility and a potential reduction in manufacturing cost.

Late last year, we submitted a data package to the FDA detailing these changes in the context by NY-ESO program for review and I am delighted to say today that the FDA has recently approved the implementation of this process into our ongoing Phase 1/2 NY-ESO SPEAR T-cell trial. We will begin transitioning this process during the 2017.

Furthermore, we formed several manufacturing alliances and met additional milestones during 2016 including, first, we executed a 10-year commercial development and supply agreement with Thermo Fisher for use of the CD3/CD28 Dynabeads and the manufacturer of our SPEAR T-cell therapies. Secondly, we agreed a strategic manufacturing agreement with our contract manufacturer PCT. Thirdly, we have initiated a relationship with a manufacturing partner for Europe, namely MaSTherCell. And finally, we moved to our new U.S. headquarters in the Philadelphia Navy Yard and continue to expect the manufacturing facility to be online later this year.

As we look forward into 2017 and beyond, we' will continue to use our proprietary technology platform to develop multiple distinct approaches for novel TCR therapies for cancer. First, we will continue to focus on our current pipeline for cancer-testis antigen or TTAs, which are almost exclusive for tumor tissues and have been shown to be good targets.

We are developing a franchise for TTA with overlapping expression profile in specific cancers, which will ultimately have the potential to offer our patients multiple SPEAR T-cell treatment options. For example, data indicate that between NY-ESO, MAGE-A10 and MAGE-A4, 65% of squamous lung cancers are covered.

Secondly, we will develop SPEAR T-cells against non-TTA antigens such as [onco-fecal] proteins or differentiation markets, which are closely associated with single tumor types. Our AFP SPEAR T-cell therapy for hepatocellular cancer is our first therapy with an open IND directed against a non-TTA antigen.

Thirdly, we will continue to expand our subject with the target multiple HLA beyond our foundational work in HLA-A2. And finally, we will continue to develop next generation SPEAR T-cell therapies and we are also actively evaluating combination approaches, first of which is the randomized study of our NY-ESO T-cells with KEYTRUDA. So overall, we expect 2018 to be data and milestone rich period for us.

And with that, I'll turn the call over to Adrian for his review of our fourth quarter and full year 2016 financial results. Adrian?

Thanks, James. And good morning. As you saw from this morning's release, I'm pleased to say that we closed 2016 with over $180 million in total liquidity, which as a reminder is a non-GAAP measure comprising cash, cash equivalents and short-term investments. We remained therefore well-capitalized and our guidance has not changed in that we believe this cash should last us through to at least mid-2018.

Let's touch briefly on the financial highlights for the full year 2016. Revenue represents upfront of milestone payments, which are recognized over the period that the company delivers services to GSK. Revenue for the full 2016, of $14.2 million was similar to the $14.5 million recognized during full year 2015.

For the fourth quarter of 2016 specifically, revenue was $8.5 million compared $4 million for the same quarter in 2015. This increase was driven by the receipt of $17.4 million in milestone payments from GSK during the quarter.

Regarding Research and Development expenses, as James discussed, we are in a period of significant pipeline momentum. R&D expenses for the full year 2016 was $63.8 million compared to $40.5 million for the full year 2015. The increase in full year costs reflects the fact that throughout 2016, we have invested in clinical trials of our NY-ESO and MAGE-A10 SPEAR T-cell therapies, preparation for studies with our SPEAR T-cell therapies targeting AFP and MAGE-A4 and in development of our manufacturing processes including increased personnel expenses.

General and administrative expenses for the full year 2016 were $23.2 million compared to $17.2 million for the same period in 2015. The increase was largely due to increased personnel cost.

Overall for the full year 2016, we reported a net loss attributable to the holders of the company's ordinary shares of $71.6 million, which translates to a loss of $0.17 per ordinary share or $1.01 per American depositary share.

Looking forward at 2017, we will prioritize our expenditure to focus our efforts on one, delivering data from our wholly owned non-NY-ESO non-sarcoma assets; and two, completing our first commercial ready manufacturing efforts including finalization of comparability studies to enable initiation of the first registration study of NY-ESO SPEAR T-cells in synovial sarcoma.

Coming back to where I started, Adaptimmune has a total liquidity position of a $181.5 million at the end of 2016, which the company believes will fund operations through to mid-2018 excluding of course the effect of any potential new business development activities.

With that, I'll turn the call back over to James for some closing comments. James?

Thanks, Adrian. Adaptimmune is in a period of significant clinical momentum, with data expected in 2017 and 2018 for multiple clinical trials in up to 11 indication. We have built a strong clinical foundation with our NY-ESO SPEAR T-cell therapy and we will continue to develop this key asset.

More exciting for us however is that we are moving beyond our NY-ESO program and are expecting data from clinical trials using our wholly-owned asset MAGE-A10, AFP and MAGE-A4, as well as developing and delivering new next-generation SPEAR T-cell therapies within it.

We believe that TCR T-cell therapies are now of great interest in the industry due to the limited target and tolerability issues that have been reported in the CAR-T phase. We are firmly positioned as a leader in TCR T-cell development and are the pioneers in TCR innovation with over two decades of direct research and development experience. Ours is an unmatched SPEAR T-cell pipeline with four open INDs and our talented researchers and scientists continue to evaluate next generation improvement and combination approaches. We are one of the few companies with the TCR therapy that has been clinically shown to have an effect in solid tumors and we anticipate that we will be the first to initiate a registration trial.

We have made very good progress with FDA towards this registration program, including agreement on the protocol. FDA has also agreed that we can introduce manufacturing process 1.5 into our ongoing NY-ESO studies and we have an agreed comparability plan. Subject to regulatory and direction comparability data we plan to initiate our registration study around the end of this year.

We continue to work to address the unmet medical needs of cancer patients and remain committed to bringing them to most effective immunotherapeutic options possible. In that regard, 2017 is an important year for us.

With that, I'd like to open the call up for questions. Operator?

Thank you, sir. (Operator Instructions) And we will take our first question from Mr. Peter Lawson from SunTrust Robinson. Please go ahead, sir.

Hi. Just wondering if you could give us an update on the SPA for synovial sarcoma?

I'll ask Rafael to answer that.

Hi, Peter. So we were asked by FDA to submit special protocol assessment. We have received a lot of comments from them before the context of the MRCLS study in the past. We've submitted before the end of the year last year and we've received additional comments, which essentially have led to us agreeing in the design of the protocol. As you know it's a single arm study with response rate of the primary endpoints. The agency has indicated that they wanted to review the protocol even if they were not to grant the special protocol assessment given that it's a single arm trial.

And I think the comments have been quite useful and for the most part, we have an agreed upon protocol with the agency. We're in the process now of doing the same thing with EMA, and we expect to complete that process of protocol review in the context of our Priority Medicines designation by the end of May.

Perfect, thank you. And then the commercial ready manufacturing process, James, is that going to be used across the entire pipeline or is it just kind of the new studies, where it's going to be used?

Gwen?

Hi, this is Gwen. We're planning on implementing this process across all of our studies in time. And this applies beyond NY-ESO. So we will be implementing this and also importantly gaining some information on this process prior to entering into the pivotal study as well.

Thank you. And then just finally on the KEYTRUDA-NY-ESO combo study, is that -- so in multiple myeloma is that kind of a second half 2017 data event or do you think it's more likely to be at first half 2018?

Yes, Peter, I think it will be the latter. It's a randomized trial with the TCR alone versus the TCR plus KEYTRUDA, it's unlikely that we will get significant data this year. Obviously, if we do have meaningful clinical or safety or efficacy data, we'll report it, but I think you're right and the early readouts will be next year.

We'll take our next question from Michael Schmidt from Leerink Partners. Please go ahead.

Hey, good morning thanks for taking my questions. I had a follow-up regarding the NY-ESO program in synovial sarcoma and I guess my question is the -- was the protocol design and discussion with the agency the main gating factor or is there additional information you need from the ongoing Cohort 4 trial? And I'm asking in the context of your decision to add additional patients to this cohort.

So Michael, there is clinical design, which as I said before has included a lot of feedback from FDA and obviously a lot of discussions with our partner, GSK, is nearly complete. And as I said, we're still awaiting the feedback from EMA, that they know that study is a single arm design and it will be a sort of discussion about some key inclusion criteria, how we analyze the endpoints, et cetera.

So it's not really the critical path for the implementation of this study, we will probably may have a fully finalized protocol. Our experience with MRCLS study, it is sort of a bias here as well, FDA wants to see comparability between the process that we use in the early study, the pilot sarcoma study, and to the marketed process, which we call Process 1.5. And Process 1.5 is approved but the comparability is not complete.

We have agreed on the terms of the comparability that we yet have to execute, the comparability and obviously when we do comparability, there may be results that we'll need some review from FDA in terms of whether or not the criteria are met. So that's really what's going to take us for the next couple of quarters to complete. And meanwhile, we will engage the sites and progress the trials through the review committees, et cetera, until we get the go ahead from the agency that we can proceed.

So the additional 15 patients in Cohort 4, will they be treated using the new manufacturing process?

Yes, that's a good question. So we plan to transition to [P 1.5] quite soon. The decision exactly when is being reviewed now, but the approval is relatively recent. But we do want to get some clinical experience with P 1.5 in the pilot sarcoma trial and the MRCLS trial which really started recently. And so the idea is to get as much clinical experience as possible, which would be very helpful in addition to the comparability data.

Okay.

It's just five extra patients by the way. It's (multiple speakers) from 10 to 15. Yes, it's not an extra 15, it's 5 extra from 10 to 15.

Yes, that struck me as a little high. Okay. And I guess regarding the ASCO update, will you be able to present data from all 10 patients that have been treated so far in Cohort 4?

So we will present as much mature data as we have. We accrue very quickly since it's still very early and not all of them have been treated. So some have been treated and are having scanned and are awaiting confirmation, others have been treated and are waiting scanning and some are [A4Es] and will be treated in the next few weeks. So we will do a data cut as close to the ASCO timeline as possible and present what we have.

And just in terms of the potential of 1.5 testing in synovial, it's five additional patients in Cohort 4, but we're also adding five additional patients to Cohort 2, which is the low expressers. So we have an opportunity to again have 1.5 in potentially 10 patients in the pilot and seven or eight patients in the MRCLS.

Okay. And can you update us on the enrollment status of the MAGE-A10 trials in lung cancer and the Basket study?

So we have made quite a bit of progress on this round and you heard from James all the measures that we implemented throughout last year. And you may recall that the reason for the delay enrollment was primarily we overestimated the expression of MAGE-A10 in tumor type and that's just following historical literature data. And so therefore, we have planned for an expression rate that was much higher than what we were finding with our immunohistochemistry assay.

So, the lung cancer study has been open for some time. We added towards the end of the year the Triple Tumor Study, the Basket Trial and we did a number of things including adding more sites but the most important contribution to the increase in screening is signing the alliance with MD Anderson, which has been quite effective in terms of screening patients.

So, to give you an example, we were screening 30 patients a month or so early in 2016, up to 2017, we're now closer to 150 patients per month. So we are identifying patients, we've enrolled patients in all these cohorts. And we're very confident now that we will be treating and completing enrollment this year. That's essentially where we are, as soon as we get meaningful safety or efficacy data, we'll report it throughout the year.

We'll take our next question from Eric Schmidt from Cowen and Company.

Thanks for taking my questions. Just maybe one on timelines now that you have interest in enrolling a few patients at least in the synovial sarcoma manufacturing 1.5 process. Are we thinking that the pivotal trial will start just before year-end or what's the timing update?

I think it's totally difficult because it depends on individual piece of the data and obviously regulatory induction. So, the -- it's around the end of the year is the -- where we anticipate the first time experience into that pivotal.

Okay. And then with your FDA discussions on trial design, is there a response rate that you've agreed upon that you need to hit in that single arm study?

We've discussed with the agency historical response rate that it would be -- as we surpassed that rate, that would be of interest and we've agreed on that, on what that number would be. Obviously, that's the way we power the study and we've received comments from FDA on a couple of meetings with agreements on what they would consider a response rate of interest for a potential BLA in the future.

I assume that's multiples of the historical response rate?

Correct.

And then, Adrian, the milestone from GSK or milestone from GSK in Q4 was there anything particular associated with those achievements?

So, those represents a number of milestones, you'll recall that as part of the collaboration they pay us relatively small milestones as we complete and work for them. And that represented multiple milestones that happen to occur in quarter four and I think it represents the progress that we're making in the NY-ESO program as a whole and we were able to achieve multiple milestones there.

We'll take our next question from Reni Benjamin from Raymond James.

Hi, good morning, guys. Thanks for taking my questions. Maybe just starting off on the manufacturing process again and this comparability plan. Am I thinking about this correctly in that maybe you don't have to use the comparability plan for all the studies? You start implementing this across the different indications and targets? Or do you have to implement this plan for every single one of those studies that you already have ongoing?

Yes, that's a great question. So, we just have to do the comparability study once, because we're basically comparing the old process to the new process independent of a target. And actually with some of our future -- some of our studies, we will start those studies with new process, so comparability won't even be relevant.

Got it. Okay, that makes sense. And then just regarding the modified conditioning regimen, can you just review for us what you've decided on? And is there any way to compare -- I mean I hate cross comparison between studies, but is there any way to compare this with the regimens established at other companies and maybe glean some insights?

So, the original regimen with Fludarabine cyclophosphamide is very similar to what used to condition patients for more tumor-infiltrating lymphocytes and was pioneer of the NCI surgical branch. So they're relatively high doses of [hypoxin] and full doses of Fludarabine. So 1.8 grams per meter square times two to cyclophosphamide which is quite a high dose, it's almost a transplant dose and Fludarabine 30 milligrams per meter daily times four which is [full dose] Fludarabine. That causes myelosuppression and lymphopenia for quite some time but the synovial sarcoma patients we were treating earlier on were very young adults or adolescents. So very healthy patients otherwise.

So as we expanded sites and we're now treating older patients and we are moving into other programs that include diseases of older adults, we wanted to modify their regimen into something that would be more tolerable. First, we tried to remove Fludarabine all together. In the case of synovial sarcoma, we saw sub-optimal outcomes there, so we closed that cohort, our Cohort 3.

And Cohort 4 that you're referring to uses regimen that's very similar to what is used in the CAR-T studies. So it's 600 milligram per meter square times three. So it's about half the dose of cyclophosphamide and it's three days of Fludarabine instead of four. So we have treated patients already, the tolerability seems quite good as you would expect. But we are still in the early days of understanding activity.

And as we think about this going forward, are there going to be -- are you looking at maybe biomarkers that can help you determine, which dosing regimen you want to use or will it more or less be determined by age and other criteria such as that?

Ultimately, I think the determinant of whether this is an effective condition and it's going to be clinical outcomes, initially response rates that are comparable to what we saw in Cohort 1. But also importantly, durability because it's possible that we see responses at similar rates, but if the patient endogenous immune system returns quicker we may see responses lasting shorter time, potentially you get Tregs replenishing the immune system quicker.

So we're interested in both. Probably the best biomarker there is, is persistence, so it's the peak of expansion in modified cells as well as persistence. We'll look at other things like degree of cytokine release and other potential biomarkers, degree of lymphopenia, how long it last. But I would say persistence and clinical outcomes are really what will determine where we go in the future.

Got it. And just one final question from me, we talked about as James mentioned in the prepared remarks, a lot of data coming out between 2017 and 2018. Can we just kind of talk through what studies and then kind of approximately when over the next 12 months or so? And whether it will have data at ACR and some of the other conferences that are typically available for oncology companies?

So that's really tricky to answer exactly. We hope to present whatever data we've got, we'll give a formal update as we can as we said on the synovial sarcoma Cohort 4 at ASCO. And the way we look at it is that we want to wait until we've got meaningful data from each of the cohorts, which probably means two or three patients followed for two or three months. Because as you probably know, you often don't get as an immediate response in patients with these T-cell therapies, they need to wait two or three months for individual patients.

So I can't be more specific than that, but I can say that we expect to have data showing at least the first cohort in MAGE-A10 and we hope MAGE-A4 this year. And then of course, we will be updating -- we should be able to update on MRCLS this year as well because that's NY-ESO cohort.

So I think we will have reasonable update, but it's very difficult to be precise without knowing exactly which patients are recruited into which cohort and as we said earlier, we're not commenting on individual enrollment.

(Operator Instructions) And we will take our next question from Ying Huang from Bank of America Merrill Lynch.

Hi, this is Jenny Leeds on for Ying Huang. Thank you for taking our questions. We just had a quick question kind of about this your strategic review of your wholly owned pipeline. So when we think of that MAGE-A4 and MAGE-A10 kind of what indications do they overlap and are there expression levels comparable? And then if so, how would you think about moving forward with either MAGE-A4 and MAGE-A10 in these indications?

That's a really good question. So, we do have -- so in terms of the indications for MAGE-A10, we are in four cancers. So non-small cell lung cancer and then in three other conditions, your pivotal bladder cancer, melanoma and head and neck. Whereas with MAGE-A4, wherein we will start in a Basket study of seven cancers. So there's bladder, melanoma, head and neck, ovarian, non-small cell lung cancer, esophageal and gastric.

Now that's -- so strategically the way the two overlap is in -- is that what we are hoping to do is to increase the percentage of patients who turn up to a clinical study or later for commercialization by having a range of these cancer testis antigen.

Now in terms of the expression level and I'm pretty sure we can send slide out, it should be on the website somewhere. MAGE-A4 is a much more highly expressed cancer antigen than either MAGE-A10 or NY-ESO. And in terms of strategically, if one looks forward at the company, I would say MAGE-A4 is not the most important product in our whole portfolio for value creation purposes over the next few years.

Just to give you an example, if you took squamous cell lung cancer, NY-ESO is in 22% of patients; with MAGE-A10, maybe in 33%; MAGE-A4 in 60%. If you take head and neck, the figures are 10% for NY-ESO, 14% for MAGE-A10 and 42% for MAGE-A4. So MAGE-A4 is in more diseases at a higher percentage than almost any of the other cancer testis antigens, but has a similar clean tox profile, obviously not tested in man yet, but we anticipate a similar profile.

So strategically, I think your questions is incredibly important, because we have to create the optimum portfolio and the optimum portfolio we think will comprise a set of cancer testis antigens on the one hand to increase the expression level. So that means that any given patient coming in will be tested with the HLA and then will have a very good chance of being positive to one of the cancer testis antigen.

And the second portfolio we are creating is outside the cancer testis antigens where they tend to be higher presentation in an individual cancer, but not across a broad set of cancers. So we're very keen on finding targets across the given set of diseases, which we put out in the Analyst Day last year. But for example, prostrate is something we are very keen on and we found targets which are actually on 99% of prostate cancer patients, but not on any other disease, those targets. So that's how we're looking at it going forward. Does that answer your question?

Yes, great. Thank you so much.

Our next question comes from Tony Butler from Guggenheim Securities.

Thanks very much. Perhaps when will we get an update on survival in Cohort 1 from what we saw in 2016? Question one. And then number two, Rafael, on the discussions on SPA for synovial sarcoma, is it independent of the amount of expression with -- of NY-ESO in the sarcoma patients? Thank you very much.

On the first question, we will do an update on survival for the ASCO presentation. And so we should have updated numbers at that time. And on the pivotal trial and discussions with the agency, we decided to include patients with slightly lower expression than the Cohort 1 patients. So will come down 30% of cells at least [two plus]. And Cohort 2 is studying any range of expression that's less than 40% of the cells two plus; that in synovial sarcoma, NY-ESO expression is quite common and it's not easy to find patients that express a very low level.

We are treating some, but because we don't have good representation of the very low expressing tumors, we've decided to draw the cut off at 30% for now and that's what we presented to FDA. And that's based on data from Cohort 2 showing that patients that express at least 30% were just as likely to respond. We may in the future include lower expression patients if we get more evidence from Cohort 2, but for now that's the data we have.

Our next question comes from Kripa Devarakonda from Citigroup.

Hey, guys, thank you so much for taking my question. Now that GSK has nominated a second target. I was just wondering if you can talk a little bit about the timelines, when you do expect to handover the IND package to them? And also would you be able to give any further guidance on upfront? Is there an upfront payment and milestone payments from GSK? Thank you so much.

So, that's a good question. So the PRAME -- so all we have to do on PRAME, it's very different from NY-ESO in the context of GSK deal. We simply complete the preclinical testing and then handover package suitable for an IND to GSK and we would expect to do that towards the end of this year, that's our timing. Because our preclinical package normally takes between 9 months and 12 months, obviously, assuming nothing goes wrong because a lot of it is safety testing. So that's the timing for that to be around the end of the year.

There is -- there was a small, very small milestone as Adrian explained that the whole deal is sort of predicated on lots of small milestones. There was a very small milestone paid on the nomination of the target and there will be another one when they file the IND, but obviously we've got -- and that would be much larger, but we can't control the filing time. So we can just simply control the time at which we handover the package.

So the package roughly the end of this year and then when they file and we will get a better indication. And from my point of view, the reason that I think the PRAME nomination is significant is actually not really to do with individual milestones, but the strategic commitment of GSK to this area. Because of course they will have to put in place manufacturing of both the vector and the cells, the agreements with all the hospitals, the agreement with Thermo Fisher for the Dynabeads. This is now, instead of just paying the small milestones to complete individual cohorts for them, this they will have to gear up for very significantly internally and I think that is an important reflection particularly since it comes at a point of changing CEOs for GSK to have that commitment for us was very important. It obviously comes with the endorsement of the top management of GSK.

It appears there are no further questions at this time, Mr. Noble. I'd like to turn the conference back to you for any additional or closing remarks.

Thank you very much and thank you everybody for attending and for asking actually some really interesting questions today, so that was really good. This is a really important year for us. I feel like I spent since 1999 looking at T-cell receptors and finally we actually have four very, very good T-cell receptors with open-INDs and the clinical data because of the screening and enrollment that we are now seeing from the trial -- across all of the trials.

We are going to find out whether we have effective molecules in the clinic, I think that's very, very exciting time. This is an important year, and 2017 and 2018, I think we will see a wrath of data across wholly owned assets. And also we should be into our first ever registration study. So I'd like to thank you all for listening and I feel very excited about potential for the company over the next year or 18 months. Thank you.

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