Adaptimmune Therapeutics PLC (ADAP) 2015 Q4 法說會逐字稿

Good day and welcome to the Adaptimmune full fiscal year financial conference call and other business updates. Today's conference is being recorded.

At this time I would like to turn the conference over to Mr. Will Roberts. Please go ahead, sir.

Thank you. Good morning and welcome to Adaptimmune's fiscal year 2015 conference call to discuss our 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 are subject to risks and uncertainties which could cause actual results 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 prepared section of the call are James Noble, our Chief Executive Officer, and Adrian Rawcliffe, our Chief Financial Officer. Also available for Q&A after the prepared comments are Helen Tayton-Martin, our Chief Operating Officer; Bent Jakobsen, our Scientific Co-Founder; Rafael Amado, our Chief Medical Officer; and Gwen Binder-Scholl, EVP and Head of Translational Sciences. This call is expected to last approximately one hour.

With that I'll turn the call over to James Noble. James?

Thanks, Will, and good morning to everyone. I'm very pleased to be holding this call today and to be sharing the progress we've made in the last few months. This call marks our first for Adaptimmune as a public Company as we only completed our IPO in May.

For those of you who are shareholders or cover our stock thank you for your continued interest in the Company. And for those of you who are learning about us I hope that this call will help you in that regard.

I'll first make a few comments on the recent progress within the Company and on our corporate priorities through 2016. Adrian will then speak briefly about our financial results and I'll return for some closing comments.

Our vision at Adaptimmune is clear: to be the world's leading T-cell receptor cell therapy Company with a pipeline of exquisitely engineered T-cell therapies targeting numerous cancers. We have a deep pipeline of validated targets and our aim is to build a portfolio of affinity enhanced T-cells to cover most tumors in the years to come.

If we look at that from the perspective of a cancer patient seeking treatment it would mean that once their HLA type has been determined and the tumor assessed to identify the antigens presented on the surface of the tumor cells our goal will be to have the relevant affinity enhanced T-cell product available to specifically target that tumor.

What we are doing at Adaptimmune has the potential to revolutionize cancer therapy. We have the potential to change the way cancer is treated by modifying the body's natural immune system.

Cancer exists because the body's immune system doesn't naturally recognize tumor cells. The tumor is recognized as being self and as such the immune system and specifically the T-cell ignores it or is silenced if activation occurs.

With our proprietary technology we can modify T-cells so they no longer ignore the tumor. Instead our T-cells target the tumor and kill the cancer.

Furthermore because of our proprietary technology platform we have the capability to make numerous T-cell receptors against most tumor targets from which we can select the ones we believe have not only the optimum potency but also the right specificity so that we minimize the risk of cross-reactivity. Our technology is also capable of delivering TCRs to different HLA types which is essential for worldwide patient population coverage. We have already demonstrated the validity of our technology with encouraging preliminary data in both hematologic and solid cancers and there are no other TCR data that show this degree of anticancer activity and durability.

Since our IPO in May we've been aggressively moving this Company forward. We've built an unparalleled pipeline of TCR therapeutic candidates targeting multiple cancers.

For example we initiated dosing in two new cohorts in the sarcoma trial with our T-cells targeting NY-ESO, one cohort in low expressive NY-ESO and the other assessing the removal of fludarabine as part of the lymphodepletion regimen. Although I won't go into details here we will present clinical updates on the NY-ESO synovial sarcoma first cohort at the upcoming SITC Conference at the beginning of November.

Because of the promising data that's seen thus far we're also working with GSK to look at accelerating the synovial sarcoma program. We've made good progress towards our NY-ESO study in non-small cell lung cancer which we expect to initiate this quarter.

In addition to the significant amount of data presented at various medical meetings in the spring at our various clinical studies data were published in Nature Medicine on our clinical study of NY-ESO T-cells in multiple myeloma patients describing durable persistence, clinical activity and tolerability. We successfully opened our IND for our MAGE-A10 T-cell candidate and expect to initiate a study with this target in non-small cell lung cancer later this quarter.

We've largely completed our preclinical assessment of our AFP T-cell receptor which we expect to be our next IND. And from our growing preclinical pipeline of over 30 validated targets we've expanded the number of ongoing research programs from 9 to 12, giving us preeminent pipeline of opportunities. These targets expand beyond previous cancer tested antigens and we hope that this will allow us to address unique tumors that represent serious unmet needs.

In addition we're building the organization to ensure that we can execute on our business plan. We've almost doubled the size of our global team from 105 employees at the time of the IPO to 190 today. We believe that our scientific team is elite in the industry, having developed multiple cancer drugs in the past and is uniquely capable of executing on our aggressive plan to develop a pipeline of affinity enhanced T-cells and bring them to market.

To this end we have significantly increased our clinical trial site footprint which now includes top academic centers in the United States and have plans to expand European sites in the first half of 2016. To support this growth we are building two new facilities: one in Philadelphia, a 47,000 square foot state-of-the-art office laboratory and GMP manufacturing facility designed to support clinical development and manufacturing for initial commercialization of our TCR products; and the other, a 67,000 square foot laboratory and office facility in the UK designed to support our innovation and growth of our research and development operations.

As a result of all this activity we are now very well-placed to execute on our corporate priorities from now through to the end of the calendar year 2016. And in summary these are the first we will generate a significant amount of data in a variety of solid and hematologic cancers. We expect to generate and present new clinical data from our multiple ongoing studies of our NY-ESO affinity enhanced T-cell therapy in melanoma, myeloma, ovarian, non-small cell lung cancer and all three ongoing cohorts of the sarcoma study in 2016. In addition we will present the first data from the MAGE-A10 non-small cell lung cancer study.

Secondly, we will continue to focus on delivering clinical evidence with the new TCRs in new indications. We expect to initiate the two non-small cell lung cancer studies this quarter, one with NY-ESO and one with MAGE-A10 as well as an additional multi-tumor basket study with MAGE-A10 in 2016.

Our focus will also remain on rapidly moving new affinity enhanced T-cell candidates towards IND. On that topic we expect to file our IND for our AFP therapeutic candidate in the first half of 2016 and initiate dosing in a hepatocellular cancer study later in the year.

And thanks to the efforts of our research and development team we have a broad pipeline of validated targets in a variety of cancer types. From 2017 onward we expect to file multiple INDs for new affinity enhanced T-cell candidates to target multiple tumors each year.

Third, our ongoing efforts include exploring ways to further enhance the rate, depth and durability of responses to our T-cell therapies. One potential strategy in which we are engaged to enhance the activity of our affinity enhanced T-cell therapies is to combine them with checkpoint inhibitors. We intend to move forward with partnerships to conduct these combination studies in 2016.

In addition a significant effort is already underway internally towards developing generation 2 T-cell receptors. These are TCR constructs containing other elements to enhance the TCR's ability to kill a cancer cell either by making the TCR more active against targets or by preventing other parts of the immune system from suppressing the T-cell response. These generation 2 TCRs will become an important focus for us in 2016 with the first IND currently expected in early 2017.

And fourth, our affinity enhanced T-cells have potential utility in areas other than oncology and efforts are already underway to expand beyond this setting. There is already a significant body of work that supports this expansion and I look forward to speaking about it in detail once it's announced.

Before I hand this off to Adrian I want to comment on the tolerability profile of our clinical candidates thus far. In our company-sponsored studies we have observed adverse events but consistent with that observed in other cancer gene therapy clinical trials but we've reduced toxicity from cytokine release syndrome-related events. The risk-benefit ratio to date support development for our NY-ESO candidate across cancer indications.

However, you may be aware of an investigator initiated study through the Attack consortium in patients with esophageal cancer but with important differences compared to our Company initiated studies including patient characteristics, pretreatment history, cell manufacturing, conditioning chemotherapy and other protocol features such as the inclusion of IL2 which we don't use in our own studies. Unfortunately, a patient died at day 46 in this investigator initiated study which caused the investigators to voluntarily pause enrollment in the study.

Together with the investigators we are currently investigating the cause of death and are working with them to restart enrollment as soon as practicable. Any patient's death in a study is a sad event and we absolutely feel for the patient's family. While we generally wouldn't comment on preliminary data, particularly from a study that was not company-sponsored, there has been a lot of market noise on this topic and as such I wanted to provide some additional clarification.

So our NY-ESO T-cell candidate has been administered to patients in multiple company-sponsored studies in multiple tumor types. We have not observed this pattern of toxicity in relation to the NY-ESO TCR construct or to the entire procedure including chemotherapy conditioning and cell infusion. In particular, neither the timing or pattern of toxicity seen in the esophageal study suggests any off-target crosscheck activity like we saw with our MAGE-A3 T-cell receptor in 2011 and 2012.

Critically for these reasons and others this event does not impact our confidence in our affinity enhanced T-cells or our ongoing efforts. As you have already heard since that unfortunate event we have initiated two new cohorts in sarcoma and are nearing initiation of new studies in non-small cell lung cancer.

Our TCR targeting NY-ESO is clearly active, potent and selective and has a promising risk-benefit profile thus far. And we continue to see good responses in patients receiving the cells in clinical studies.

However, NY-ESO is only a start. Our proprietary technology is unique in that we could make numerous T-cell receptors against most tumor targets from which we can select the ones that we believe have not only the optimum potency but also the right specificity. And we have a deep preeminent pipeline of validated targets.

There is much to do and we look forward to providing continued updates as our clinical progress continues.

I'll now turn the call over to Adrian for an overview of our financial results for the full fiscal year 2015. Adrian?

Thanks, James, and good morning everyone. As James mentioned one of the highlights of the most recent financial period was the completion of our IPO. This closed in May and raised $176 million net which as you've heard we're actively putting to work to accelerate our pipeline of affinity enhanced T-cells.

Regarding our current cash position as you saw from this morning's release we've closed the 2015 fiscal year with $284 million in cash, cash equivalents and asset investments. We are therefore well-capitalized and we believe that at current forecast spend levels this cash should last us approximately three years.

Touching briefly on the financial highlights for fiscal 2015, regarding revenue in fiscal 2015 we had a full year of revenue recognition relating to upfront payments under the collaboration and licensing agreement with our partner GSK as well as triggering additional milestones as we have progressed our NY-ESO T-cell program. As a result our revenue in this period was $10.7 million compared to $0.6 million for the full fiscal year 2014. We expect our revenue in the coming 12 months to be significantly higher as based on our current plan we expect to hit a number of additional development milestones during the period.

Regarding our research and development expenses, we have significantly increased our clinical resources to support our ongoing studies and our preclinical resources to deliver new INDs. We have therefore seen an increase in personnel expenses and other costs relating to our growing R&D operations in the US and the UK. As such our R&D expenses were $23.2 million for fiscal year 2015 compared to $7.4 million for 2014.

We expect that our total research and development expenses in the current fiscal year will be significantly higher again as we continue to invest in our pipeline of affinity enhanced T-cells, our technology platform and manufacturing optimization activities. Our general and administrative expenses related to expanded organization managing our R&D programs and to the requirements of being a public Company were $11.3 million for the fiscal year 2015 compared to $1.6 million for fiscal year 2014.

All of this adds up to an operating loss for the period of $23.6 million which after other expenses and taxes gets us to a net loss of $21.9 million. On a per ordinary share basis, this translates to a loss of $0.07 per ordinary share for fiscal year 2015.

As you saw from our press release this morning, we are in the process of transitioning our fiscal year end from June 30 to December 31. This is primarily to facilitate more direct comparison to our peer group and indeed to the majority of NASDAQ listed companies.

In addition and for the same reason we will transition from the IFRS accounting standards to US GAAP starting again in January 2016. So what will this look like to you? Later today the Company will file its Form 20-F containing audited financial statements prepared under IFRS and covering the period from July 1, 2014 to June 30, 2015.

In mid-November we will present on Form 6-K, our quarterly results prepared under IFRS, for the quarter from the first of July to the 30th of September 2015. And given the proximity to these full-year results we don't anticipate doing a conference call at that time.

We will subsequently file Form 20-F containing audited six-month financial statements again prepared under IFRS covering the six months from July 1, 2015 to December 31, 2015. And then in 2016 we will begin filing quarterly results under US GAAP on Form 10-Q and our year-end 2016 financial results also under US GAAP on Form 10-K.

As a result of this change in our fiscal year end the Company is providing cash burn guidance as follows. For the six months from July 1, 2015 to December 31, 2015 the Company expects cash burn to be between $20 million and $30 million, excluding of course cash burn associated with new business development activities. For the full year 2016, the Company expects its cash burn to be between $80 million and $100 million, again excluding cash burn associated with new business development activities.

Therefore the Company expects that its cash position at December 31, 2016 including cash, cash equivalents and asset investments will be at least $150 million.

Finally, James mentioned the buildout of our US manufacturing and UK R&D facilities. In the US we remain committed to securing our current and future supply chain. Our first step is the construction of our new Philadelphia facility which will include a state-of-the-art GMP manufacturing facility designed to support the clinical development and potentially the initial commercialization of our affinity enhanced T-cells.

In Oxfordshire, UK, our new laboratory building will support our expanding R&D operation. Both of these are scheduled for delivery in late 2016. And once we have taken delivery of these newbuildings we will have annual lease expenses of approximately $3.2 million.

Capital cash expenditure for these facilities is estimated at approximately $25 million which will show in our financial statements as investing activities. And all this is included in the guidance just given.

In summary, and given our stage of development, we are financially quite sound with approximately three years of cash runway. Since the IPO we have invested in a disciplined fashion, building our organizational capabilities and accelerating our pipeline.

This is a very exciting time for us as over the next 18 months we will deploy our financial resources carefully to deliver the critical milestones previously discussed including multiple clinical trial starts and data readouts, new INDs and the opportunity to continue to expand the utility of our affinity enhanced T-cells treating patients with advanced solid and hematological cancers.

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

Thanks, Adrian. As I hope you've heard during this call we are making excellent progress towards delivering on all of our corporate goals. We're generating significant new data in multiple tumor types, building clinical experience by initiating studies with new constructs and aggressively bringing new INDs towards the clinic and exploring the possibility of enhancing the rate, depth and durability of our affinity enhanced T-cell therapies.

We're generating important data in both solid and hematological tumors including antitumor activity, persistence, tumor trafficking and tolerability data and at the same time building an industry-leading pipeline of targets and TCR candidates. Of course our goal is to create value for our shareholders and I believe that by continuing to execute on this plan and by hitting the myriad of upcoming key milestones we will do just that.

I mentioned at the start of the call the journey a cancer patient would follow as we match them with the right individualized therapy for them based on the antigens expressed on their tumor at any stage of the disease and their HLA type. We're the only Company in the field with pipeline technology that can address the challenges of target heterogeneity in cancer and to deliver on this goal.

I'll end it where I started. Our vision is clear, to be the world's leading TCR, cell therapy Company with a pipeline of exquisitely engineered T-cell receptors targeting numerous solid tumor cancers and other targets, delivering on the promise of our proprietary optimized T-cell receptor technology in standalone therapies and in combination with other options. In doing so we're well-placed to potentially revolutionize cancer therapy and radically change patient outcomes.

So with that I'd like to open up the call for any questions. Operator, are there any questions?

(Operator Instructions) Michael Schmidt, Leerink Partners.

Good morning and thanks for taking my questions and congrats for your first earnings call. So my question is for CAR T-cells a few theoretical challenges have been discussed, specifically when targeting solid tumors including potentially the need to overcome an (inaudible) microenvironment and target selection and also the ability of T-cells to actually penetrate a solid tumor. I was wondering if you could compare the TCR approach to CAR T, especially with regards to targeting solid tumors and what learnings you could apply from the CAR T (technical difficulty)

So Michael, your phone was breaking up a little bit. But as I understand the question it's to compare and contrast the ability of a T-cell receptor T-cell to a CAR T-cell in addressing solid tumors. And I'll ask Bent Jakobsen, our cofounding CSO, to answer that question.

So, Michael, only a little is known as yet. But I think if you look at the natural function of a T-cell one of the really important aspects of it in order to be able to penetrate tissues is that there are very few targets on each cell, maybe less than 100 typically. And the T-cell receptor is compared to an antibody, very low affinity.

This allows the cells not to get stuck on the outside of a tissue, in this case a tumor, but to penetrate deep into them. This may be a challenge for CAR T-cells because they use antibodies which are always a magnitude higher affinity and there are thousands of targets on each cancer cell.

So it is possible that the penetration of CAR T-cells could be more problematic. And if they are to destroy solid tumors they would have to do it from the outside and work their way in. I think the initial clinical results indicate that CAR T-cells are at least the ones that are around right now are maybe not so good at penetrating.

It should not be a problem for T-cells that are guided by T-cell receptors because of although we engineer them to high affinity they are still in the natural range of for example an antiviral response. And so those T-cells we know have no problem penetrating into solid tumors.

Yes, great. Thank you. Then I guess I had a question on your you mentioned you're working on a second-generation T-cell receptor and I was wondering if you could share some more information on that?

Yes, so we are working on two aspects of that. One is for making the engineered T-cells overcome the suppressive environment that is present in the tumor. This can both be through soluble factors but it can also be self-serve receptors and co-receptors that the cancer cells express on the surface.

And you can engineer functions into the T-cells that make them less sensitive to this. Clearly the most important and interesting ones are the ones that generally apply to almost all cancers. It's not entirely generic in all cancers but there are functions that are present in most of them.

And we are working on a number of those that show that the T-cells become insensitive to these inhibitory mechanisms. But we also are working on a slightly different aspect and that is where we try to make the T-cell communicate with the rest of the T-cell system and indeed the whole immune system in order to break tolerance to the tumor in a more broad fashion.

So because tumors mutate so much you can hardly hope to eradicate every single cancer cell by targeting one single antigen. So therefore to get a sort of radical response for the tumor it would be highly beneficial if one can get, if one can ease the path for the rest of the immune system to recognize the cancer and so we're working on such functions as well and have some very promising results in the lab at this stage.

Okay, great. Then lastly, I mean you mentioned your path data on this and most of your programs in 2016 and I was just wondering if you had some more granularity in terms of timing, will you have something at ASCO potentially and which of the cohorts are most advanced at this point in terms of enrollment?

Ask Rafael Amado our CMO to comment on that and to just dimension SITC en passant.

Hi Michael, this is Rafael. So as James mentioned we are updating the results of the post cohort in the synovial sarcoma study and we plan to present that at SITC soon.

It will include response and duration but also time to event endpoints that we have not reported on up to now. With regards to the rest of the year a lot of work is either begun or about to begin. So for instance we have two sarcoma cohorts that just started.

We hope to complete that within the year and report towards the end of the year. We will wrap up our myeloma, ovarian and melanoma studies and again report towards the end of the year on all those indications. And we're starting the MAGE-A10 first-in-human study which is in non-small cell lung cancer.

It goes through a dose escalation phase and then we will expand to characterize activity and safety. So we hope that at least the dose escalation will be ready again for presentation in a congress. So it looks to us like the bulk of data will come more towards ESMO rather than ASCO which is too early for a lot of these studies.

Okay great. Thank you so much and congrats on the progress.

Tony Butler, Guggenheim Partners.

Yes, good morning and thanks very much for taking the question. James, you alluded to and as did Rafael on two new cohorts for NY-ESO, one in low expressers and one in no fludarabine.

And I'd love for you to expand. How do you actually define a low expresser? Is it a cutoff of X or how do you actually attract that population?

And number two in the cyclophosphamide-only arm, what's the rationale leaving out fludarabine? There was some studies certainly in [cartezagen] different where that did not manifest well, at least in the one study that was presented at ASCO this past year. So that's one question if you will.

Then my last question is around your comments on combining with checkpoint inhibitors. Is that limited to anti-PD-1 and anti-PD-L1 or would you consider other if you will checkpoint inhibitors like IDO, etc.? Thanks very much.

Hi, Tony, it is Rafael. So your first question was the low expresser cohort. And you're absolutely right, it is very difficult to actually characterize what low expression means with regards to a threshold for activity with our TCR.

In synovial sarcoma the majority of patients express at high level, so about 70%. And we define that as either 2 to 3-plus in at least half the cells.

Now the question is what happens to the rest of the spectrum? And we actually have actually had patients that have not been able to enroll because of lower expression than that cut-off I just mentioned.

So it goes from zero all the way to perhaps 2 to 3-plus in 30% or 1-plus in 100%. So the whole spectrum is available. And we are starting to study the 2 to 3-plus in less than 50%. So we are actually enrolling as we speak patients and we want at least to have five patients in that group.

And then we will try to characterize as well the more diffuse pain in that low level as well. And we think this is important because it will allow us to make decisions, for instance when we move into the non-synovial NY-ESO positive sarcoma and as well as to a potential pivotal trial. So its work in progress and we will march methodically to try to understand it.

With regards to fludarabine, fludarabine has been employed and it's become traditionally part of the conditioning, I think because it started that way it's really a lymphocyte toxic drug. And it actually causes immunosuppression inpatients that receive it that actually goes well beyond the recovery of neutrophil.

So as we expand into other indications where patients may be less fit, for instance lung cancer and others, it would be desirable to not use fludarabine. And so we thought that we would study that cohort, the results that you mention notwithstanding. Those results actually we've looked at them carefully from June on.

The most I think compelling piece of information that came out is potentially a longer disease-free survival in patients that were conditioned with fludarabine. But I think those results are very difficult to extrapolate to solid tumors. And those patients have really bulky disease and maybe that the conditioning also has an important antitumor effect that may not be required in our indications.

In particular fludarabine is inactive in sarcoma. So it's only being used for lymphodepletion. So if we really think that in the end it shows that we need fludarabine that we will revert to the use of it but we're hopeful that the results would allow us to remove it from the conditioning.

I think the last question was the combination with other either checkpoint inhibitors and whether we will go beyond that. So we definitely the logical combination is PD-1 and PD-L1 inhibitors. And we are generating preclinical and also translational data that support these combinations.

There is also a strong rationale to use CTLA4 inhibitors. And Bent referred to that in his previous answer relating to (inaudible) spread which is probably going to be a required phenomenon for these treatments. But there are other compelling combinations that may include as you say IDO inhibitors by specifics and others that we're looking very carefully, we saw their external partners as well.

Ying Huang, Bank of America.

Hi, good morning, thanks for taking my questions. First question is related to manufacturing.

I haven't heard any update on this call about manufacturing. Can you provide an update where you are in terms of your next-generation manufacturing and what is the goal you're trying to achieve in 2016?

Secondly, I have a question on your cash burn. Apparently your guidance for 2016 cash burn is a step up from 2015. Can you maybe provide a bit more color where your investment is going to?

Is it your proprietary program? Is it going to the GSK collaboration program in the clinic?

And the last question is about your second-gen TCR program. In terms of the target is it any different from your first-gen?

For example are you targeting more hematology indications or still more likely into the solid tumor indications? And is it going to be monotherapy or a combination approach for the second-gen? Thank you.

Okay. I will ask three different people. I will ask Gwen to answer manufacturing and then I will ask Adrian to answer the cash burn and then Rafael will comment on the second-generation programs.

Gwen, can you comment on manufacturing?

Yes, sure. Absolutely.

So the question was about next-generation manufacturing. And so back in 2014 we took a careful look at both our vector manufacturing process and our cell manufacturing process and evaluated the aspects that would need to be updated in order to support commercial manufacturing.

We then submitted a dossier to the FDA reviewing proposed changes and got a sense from the FDA that these changes would indeed support commercial manufacture. And we also discussed how to introduce these changes into our clinical programs. We've now implemented our own vector packaging plasmids, our vector backbone and also our own vector manufacturing process and purification process.

We've transferred that to a contract manufacturer, SAFC, and we've completed our first engineering run and we're just completing our first GMP run now. And so we expect to implement that into clinical studies in the first quarter of 2016.

The cell manufacturing process we've also updated. We have simplified the upstream purification step. We've also streamlined the media through the serum and we are in the process of transferring this to our CMO now and expect that to also be live in the first quarter of 2016.

Thanks, Gwen. And it's Adrian here answering your second question on the cash burn.

So you correctly stated that our cash burn is expected to increase in 2016 to $80 million to $100 million. The most important thing to realize is that the GSK collaboration around NY-ESO and other targets is essentially self-funding and therefore essentially cash neutral over long-term.

Now it is paid for by milestones, so in any individual month or quarter it might not be exactly cash neutral. But the vast majority of the cash burn in 2016 will go on our proprietary pipeline of products, specifically MAGE-A10 and the non-small cell lung cancer dose escalation study followed by the basket study that Rafael referred to earlier and moving AFP into the clinic as well and the progression, significant progression of the preclinical work such that we're able to meet our goal of delivering multiple INDs per year from 2017 onwards.

In addition to that we've got the investment in our manufacturing capabilities that I referred to as well. And all of that is basically to develop our proprietary pipeline.

I'd just comment on your question on the second-generation, so the strategies were described by Bent before. And I think in order to really prove in the clinic whether they will be superior we have to use the same antigen as we have from our [intel] TCRs and also ideally use the same indications and the same patient so that we have a historical benchmark with which to compare the new strategy. So our goal is to start with both NY-ESO and MAGE-A10 and then march on with other antigens as our pipeline expands.

That's helpful. Thank you.

(Operator Instructions) Eric Schmidt, Cowen and Company.

Good morning, thanks for taking my questions. One, just a quick follow-up on NY-ESO 1. Do you think you'll have enough information from these three ongoing cohorts to be in position to make a go/no go decision on a pivotal trial in 2016?

So our hope is that we will. I think we are actually gaining more information as we are accruing this trial to increase our efficacy database but also our safety database.

These are very rare tumor types so we need to check with regulators as well in terms of what would it take in terms of clinical evidence to get registration. This is a pioneer program so we have lots at discussions with GSK our partner as well as to how this could be moved forward. But we're hopeful that the data that we're going to gain as you heard we want to standardize on key aspects such as expression of fludarabine will be sufficient for us to move on to pivotal.

Okay, and then second question just on MAGE-A10, it sounds like you will be starting the trials in non-small cell lung cancer shortly. Could you give a little bit more color on the trial design Rafael, like the selection criteria in terms of expression levels, preconditioning regimen, if there will be a dose escalation procedure, what sort of cell count you might be starting at, etc.?

Yes, sure. So we're starting in lung because it's one of the highest expressing tumors. We will use three dose levels and it's sort of a modified 3 plus 3 design.

We've agreed with the agency on the cell dose, on the definition of TLT and how we're going to march on between patients and then across dose levels. In terms of the eligibility the expression of MAGE is going to be the same sort of cut-off that we been using thus far that I mentioned before for NY-ESO. And it will be patients that essentially have failed platinum containing therapy and if they had mutations or translocations for EGFR they need to have failed those respective agents.

We are trying to cut down the timing between the patient's consent and infusion by getting patients apheresed ahead of progression so that we have cells ready to treat these patients given that this is a different disease that can progress very fast.

Okay. And then on maybe James mentioned potential collaborations or partnerships around checkpoint inhibitors in 2016. Is there an ideal form of such a partnership? What would you hope to get other than just access to a checkpoint inhibitor and what kind of structure might those deals take ideally from an Adaptimmune perspective?

Well, this is James here, I think really we're just keen to see them in combination and to see the clinical data. Some of the programs are approved drug, some are not approved drugs and that has big implications of how you structure a deal. I'll let Helen say a few words I think about the partnership strategy.

Yes, thanks James. I think that just sort of echoing that I think what we're aiming to do is a very simple proof-of-concept type study, initial study and that is certainly very much the way that potential collaborators are happy to engage with us. I think at this point in time we are learning a lot about how the technology works from our oncologist data as well as what we might find out from a combination approach.

Great, thanks for taking my questions.

As there are no further questions in the queue I'd like to turn the call back over to you Mr. Noble for any additional comments.

Yes, I just like to say thank you very much to everybody for attending. I hope that you found it interesting.

We are certainly very proud of the progress we've made since the IPO. And we're looking forward to reporting a lot more progress and many more milestones over the next three to six months. Thank you very much.

Thank you. That will conclude today's conference call.

Thank you for your participation ladies and gentlemen. You may now disconnect.