Juli Miller - Director, IR James Noble - CEO Helen Tayton-Martin - Chief Business Officer Adrian Rawcliffe - CFO Rafael Amado - Chief Medical Officer Gwen Binder - Chief Technology Officer.

Jonathan Chang - Leerink Partners Tony Butler - Guggenheim Securities Robyn Karnauskas - Citi Peter Lawson - SunTrust Reni Benjamin - Raymond James Eric Schmidt - Cowen and Company Nick Abbott - Wells Fargo Jenny Leeds - Bank of America.

Good day, ladies and gentlemen. And welcome to the Adaptimmune Q1 2018 Earnings Call and Business Update. [Operator Instructions] As a reminder, this call is being recorded. I would now like to turn the call over to Juli Miller. You may begin..

Good morning, and welcome to Adaptimmune’s conference call to discuss our first quarter 2018 financial results and other business updates. We issued a press release earlier this morning, and I would ask you to please refer to the full text of our forward-looking statements there.

As a brief reminder, 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. James Noble, our Chief Executive Officer is with me for the prepared portion of this call.

Helen Tayton-Martin, our Chief Business Officer; Adrian Rawcliffe, Chief Financial Officer; Rafael Amado, our Chief Medical Officer; Gwen Binder, our Chief Technology Officer; and Bill Bertrand, our Chief Operating Officer will be available for Q&A after the prepared portion. With that, I will turn the call over to James Noble.

James?.

Thank you, Juli. Good morning, everyone and thank you for joining us. Today’s call will be brief and the two messages are the first, 2018 is off to a great start for Adaptimmune; and secondly, we are on track to deliver data from our wholly owned SPEAR T-cells throughout 2018.

Earlier this year, we observed responses in a second solid tumor with NY-ESO and myxoid round/cell liposarcoma or MRCLS. And one of our investigators will present the first clinical report and an oral presentation at ASCO in June. These data in MRCLS strengthen our conviction that we have a pipeline capable of treating solid tumors.

We will also be presenting updated safety data from our ongoing MAGE-A10 studies in poster at ASCO. Based on the first quarter, we remain confident that 2018 will be a transformational year for us. And this conviction is reinforced by the positive clinical momentum across trials with our wholly owned assets.

We announced in January this year that the safety review committee recommended dose escalation to 1 billion transduced cells in the MAGE-A10 triple tumor study in bladder, melanoma, and head & neck cancers.

And today, we are pleased to announce that the safety review committee has also recommended dose escalation to 1 billion transduced cells in the MAGE-A10 non-small cell lung cancer study, and we are now dosing in this cohort. This keeps us on track to deliver response data from our MAGE-A10 SPEAR T-cells later this year.

Our MAGE-A4 basket study across seven solid tumor indications including bladder, melanoma, head & neck, ovarian, non-small cell lung, esophageal, and gastric cancers is also dosing patients. And we remain on track to deliver initial safety data from this study in the second quarter of 2018 with response data anticipated later in 2018.

I would also like to mention that preclinical data from MAGE-A4 and MAGE-A10 SPEAR T-cells recently presented at AACR. We have two posters to summarizing the discovery process and extensive preclinical validation work performed by Adaptimmune to characterize the specificity, affinity and potency of the SPEAR T-cells.

There is also news from our next generation program. Recently, Adaptimmune’s granted a U.S. patent covering one of our approaches to help our SPEAR T-cells overcome resistance to immunosuppressive elements in the tumor microenvironment, and this enhancement is likely to be used in some with our upcoming clinical trials.

Our proprietary preclinical development and validation program for our SPEAR T-cells is unique, and one of the main reasons that we believe we have the industry-leading pipeline at TCRs to address solid tumors.

We generate TCRs that have the right level of specificity, affinity and overall ability for cancer cells expressing specific targets, while minimizing the risk of off-target toxicity.

Our proprietary preclinical methods combined with our compelling foundational clinical data with NY-ESO in synovial sarcoma and results in the second solid tumor, MRCLS, make us very optimistic for the remainder of 2018.

To summarize, anticipated data readouts of 2018 include, first, additional safety and initial response data from the MAGE-A10 pilot studies; secondly, the initial safety data in the MAGE-A4 basket study to support dose escalation to 1 billion cells; thirdly, initial response data in the MAGE-A4 basket study as well as additional response data from the MAGE-A10 studies throughout the second half of 2018; and lastly, we anticipate initial safety data to support dose escalation in our AFP study in hepatocellular carcinoma later in 2018 with response readouts in 2019.

As we have stated before, our focus on MAGE-A4, MAGE-A10 and AFP has been greater since GSK exercised its option over NY-ESO program and we plan to complete the transition later this year.

Until then, we are continuing to execute on the studies in MRCLS, synovial sarcoma, non-small cell lung cancer and the multiple myeloma combination study with Merck’s PD-1 inhibitor KEYTRUDA or pembrolizumab. Turning to manufacturing. We continue to make great progress to becoming a fully integrated cell therapy company.

We are routinely manufacturing SPEAR T-cells at our Philadelphia Navy Yard facility and have received regulatory clearance to manufacture SPEAR T-cells for all three of our wholly owned clinical programs.

We announced in January this year that we executed an agreement with Cell and Gene Therapy Catapult in the UK to provide our own dedicated manufacturing space to secure vector supply for the medium term. Now, I’m pleased to say our vector manufacturing site is now officially opened. We also on the manufacturing site had a U.S.

patent granted covering a WPR-free vector system that will further optimize the vector system used in manufacture of our SPEAR T-cell. To conclude, we have demonstrated compelling results in synovial sarcoma and additional responses in a second solid tumor MRCLS.

These data combined with the encouraging initial safety in our MAGE-A10 pilot studies, the first with one of our wholly owned assets, along with our unmatched proprietary preclinical development methods reaffirm the potential of our SPEAR T-cell platform in solid tumors.

Further, our strides towards becoming a fully integrated cell therapy company will put us in the best position to conduct future clinical studies to support approval and ultimately deliver products and value for our patients and investors.

In 2018, we are on track to deliver data from our wholly owned pipeline in upto eight different solid tumor sites. With more than a $161 million in total liquidity, we are funded to deliver these data and through to early 2020.

We are confident that we will achieve our goal to be the first to market with an engineered TCR T-cell therapy in solid tumors. With that, I’d like to open up the call for questions.

Operator?.

Thank you. [Operator Instructions] Our first question comes from Jonathan Chang of Leerink Partners. Your line is open..

Hi, guys. Thank you for taking my questions.

First, can you help set investor expectations ahead of the NY-ESO myxoid round/cell liposarcoma data coming out at ASCO? How many ore patients worth of data can we expect to see versus what you’ve already disclosed?.

So, I think it’s very difficult to be precise about things and we tend not to comment on individual patient numbers. It would be a handful of patients. And obviously, the more recently they’ve been treated, the less data we have on them, if you like.

So, there will be an update on the patients who we’ve already given the data out on, but essentially we’re embargoed from giving you exact numbers at this point..

Got it.

And second question, as you dose patients at the 1 billion cell dose with MAGE-A10, can you talk about the implications of the safety data that’s been generated at the 100 million cell dose?.

I’ll let Rafael Amado, our CMO take that one..

I mean, I think there are different ways to answer that question. I think, if there is a clear cut cross-reactivity, it is possible to see that with a handful of millions of cell. So, I think 100 million cells is reassuring with regard to major cross-reactivity.

I think, obviously the more -- the higher disposals, the more sort of confident we can be that will lead to an obvious cross-reactivity either on target or off target is not present.

And so, we were pretty pleased to see absence of cross-reactivity in the first cohort but I think the definitive proof will come as we start treating as we are now patients that are 1 billion cells. .

Thanks..

Yes. Just a reminder, the 1 billion cells is really -- the reason that 1 billion cells we think is important is that approximately the level of cells with NY-ESO that led to major cell expansion within the patients and there is a correlation between expansion in vivo and the response rate.

So that’s obviously -- we hope it will work in the same as it did with NY-ESO..

Okay. That’s helpful. And just one last one for me.

Can you talk about the manufacturing turnaround time at the 1 billion cell dose?.

Yes, I’ll let Ad Rawcliffe, [indiscernible] manufacturing to talk about that?.

Certainly. So, there’s essentially no difference between the manufacturing time at the 1 billion cell dose or 5 billion cells, which is the target dose for the top cohort in our pilot studies and the 100 million cells.

As we’ve discussed before, we are operating on around about 30 to 35 days from start to finish for the manufacturing process and release itself. .

Yes. The actual manufacturing itself is around 10 to 12 days whether it’s 100 million cells or 1 billion. We routinely -- when we say we’ve had routine success at the Navy Yard, we mean we’ve had routine success of achieving at least 1 billion cell, transduced cells out of the run because that’s essentially the lowest level for the higher state.

It’s a mid dose and it’s also lowest level permitted at the highest dose. So that’s successful run. But it doesn’t take any longer. We just have a lot of cells left over for the people in a 100 million cohort..

Our next question comes from Tony Butler of Guggenheim Securities. Your line is open..

I have three questions if I may. James, when -- as you’re handing off NY-ESO to GSK, question is, are you -- could you characterize that as being in the 8th inning, or you’re closer to the fourth inning, if you will? As it relates to FTEs at Adaptimmune, they’re actually spending more time on that hand off or less time? That’s number one.

Number two is, you alluded to 1 billion cell dose that was now in non-small cell lung cancer according to the data safety monitoring board.

What is it that they are specifically looking at that says that is successful and you can dose up? Is it simply a duration of time plus toxicity or is there another parameter? And then, finally, is there a goal even beyond 1 billion to look at 5 billion or 2.5 billion or some other number greater than 1 billion? Thank you..

Okay. I will answer questions one and three. As to the 8th inning, I don’t play American football. That was a joke. Remember that. So, the answer is….

It was baseball, James. .

Yes. I couldn’t resist that as a player. So, the answer on the GSK is that it’s a multiple modular transition. There are programs that have to be transferred -- there are written up programs, the reports, those mostly are finished. There are trials that are ongoing where you have to agree which patients we will dose before it gets handed over.

That’s more or less agreed with the plan, one or two patients discussing that. And then as a multiple, there’s a data base transfers, agreements that they have to set up, a lot of that’s done and absolutely going well. I would say, we are right at the cusp of deciding whether we can hand it over.

The most difficult thing to hand over as you’d probably realize is manufacturing because it’s not something that GSK has done before. It is a very big company, but it hasn’t actually got in-house vector manufacturer or in-house cell manufacturing. So, I think we’re in the sort of penultimate round if it was a boxing match.

I don’t know what innings that would be in baseball.

Helen, do you want to add anything to that?.

No. I think that that’s pretty much spot on. I would say, we’re near the 8th innings, but it’s not done till it’s done. Manufacturing is a challenge..

Yes. And we still work very constructively with the GSK team. So, I don’t think there is any issue, it’s just timing issue, it does take quite a long time to set these things up. And I’ll answer your third question.

Yes, on the number of cells, or the trial to set up to go 100 million, 1 billion and then 5 billion that’s the intended number of cells with minor variations. But essentially that is the program. But, it was -- the reason that 1 billion we think is significant is that that’s the sort of threshold level with NY-ESO.

So, we have the same the threshold with MAGE-A10 or MAGE-A4. You wouldn’t expect to see responses below that, but you might get them above that. That would be the hope. And I’ll let Rafael answer the middle question..

Yes. Tony, so, the question was essentially how do they adjudicate whether or not to dose escalate. So, we made this decision based on recommendation from a safety review committee which essentially is data monitoring committee for safety.

And it’s composed of three individuals with expertise in cell and gene therapy, external to the company and external to the trial that they are not investigators as well as safety physicians from inside the company. There is a charter that sort of stipulates what they look at.

But essentially, they focus on dose limiting toxicities, whether any have been declared, in which case, there are rules for expansion of the cohort or safety events that don’t meet criteria for DLT, but they could be concerning. So, they are essentially evaluated and discussed. And so, in general, dose escalation follows the protocol rules.

And if there are no DLTs, then after three patients move on to the next dose. If there are DLTs, we follow the rules, which essentially add an additional three patients. You may recall that’s what happened within non-small cell lung cancer MAGE-A10 study. So that’s essentially the process that we follow. And just to conclude, the DLT window is 30 days.

So, we have to wait 30 days from the dose infusion and we space out patients about 30 days apart. So, every cohort takes 30 days in between patients..

Thank you very much. .

And that’s the other significance of going up in the dose by the way, is that window reduces. So we don’t have to wait so long in between the patients..

And just to add to what James said in regard to your third question. The third dose cohort of 5 billion, but every cohort has a window of cells. So, the upper bound of the cell dose in the third cohort has been increased to 10 billion. So, we can dose after that with a target of 5..

Our next question comes from Robyn Karnauskas of Citi. Your line is open..

So, you mentioned that the window gets shorter as you dose up.

So, is it shorter than 30 days? Can you elaborate a little bit on that? And then, as far as when you think you might want to present this data in the second half of the year, do we expect the press release or a presentation? And then lastly, what plans are underway? Did you have any discussions as you are going to getting a manufacturing process approved about maybe reducing QT time to reduce to 30 or 30 to 35 days from start to finish? Thanks..

I’ll answer the first question. So, after the first cohort, the decisions on accrual between patients are made if there are no DLTs during that seven-day observation period. So, in essence, we need seven days following the lymphodepletion.

So, we make the decision to lymphodeplete seven days after the previous patient has been dosed, provided that there are now DLTs, which means that in between patients we have to wait a total of two weeks, seven days of observation and then seven days to lymphodeplete the subsequent patients.

So that assumes there have not been any DLTs in the previous cohort. If there are DLTs in the previous cohort, then -- and we do dose escalate, we still maintain a wide space in between patients..

In terms of when we actually announced data, I mean, obviously these are all open label studies and equally obvious is that they’re very price sensitive, whether we do or don’t get responses and we are keenly conscious of that. I think it’s very unlikely that we will therefore be able to hold off announcing data until conferences.

What we prefer to do and I think what we’ll end up doing is what we’ve done with the MRCLS data which is giving an outline sketch of response data at some form of earnings release or press release and then following it up as soon as we can with a presentation let’s say at a medical conference to give more objective.

Obviously, it’s not us who’ll be speaking and on top of that there will be far more data. I don’t think it’s really possible to just hang on to data. There are patients and doctors out there who actually go on social media as we’ve already discovered about various things.

So, I think it’s bound to happen as we get a few patients -- we wouldn’t go on single patient, but once we get a few patients, then, I think we’ll put it in the next either quarterly or put a press release and then follow it up at a medical conference. And I’ll let Adrian talk about the manufacturing time table..

Certainly. So, yes, we are working on shortening the release time. The critical step, the largest critical step on that is sterility testing, currently takes 14 days. Obviously, there are ways of shortening that and we’re working on introducing rapid sterility, which would take a week of that timeframe, take seven days of that timeframe.

The theoretical minimum of the current process is similar to that Novartis has sort of in the 22 to 23 days. And obviously as we push towards commercialization, that would be a more acceptable target for us..

And just one follow-up. So, does that mean like within the next three months, it sounds like we could get data from one or two patients or would you wait to release it from you when get all three patients in the cohort completed from your billion dollar -- sorry, billion cell cohort. Sorry about that. Give me the price.

And then the second is, how short do you think over time you can get the turnaround time? You said for commercial 22 to 23 days. Do you think you actually could build beyond that over time or is that sort of the peak? Thanks..

I’ll take that second question. So, with our current process, which has a 12 to 14-day manufacturing time and using rapid sterility of seven days, let’s say that obviously gives you a theoretical minimum. One can go beyond that but that’s sort of where we’re targeting with the existing process.

Alternative processes could reduce it below that but that’s not where we are at the moment..

So, I think, it’s very difficult to answer other question. What I do know is that in -- we have a large number of patients sitting and waiting for treatment across MAGE-A4, MAGE-A10 programs. And therefore, as long as nothing goes wrong with those patients, we will have data on a significant number of patients over the next few months.

It’s very helpful. [Ph] So, patients do drop out, number one, for any number of reasons. And so, it’s actually quite difficult to predict the exact timelines of those. But I think, we do have a very good pipeline further on, a very good number of patients awaiting treatment.

And so, it’s -- what’s relevant is actually more to do with that gap between patients and actually finding in that with both MAGE-A10 and MAGE-A4..

Our next question comes from Peter Lawson of SunTrust. Your line is open..

Just on the transition of NY-ESO over to GSK.

Is there any way to quantify the number of FTEs that have kind of been freed up in that transition?.

Well, we have obviously internal data on all of that. I mean, I would say that -- I don’t know if I want to give you the exact number. But I think NY-ESO at the end of last year was using at least half the clinical regulatory resources of the U.S. office overall.

So, it has -- it’s making a very significant difference in terms of recruiting patients, being able to amend protocols, deal with the FDA, recruit -- add additional sites and the general maintenance of the clinical trial.

So, I would say, yes, it’s probably -- we would have had to add -- it’s probably a function that we’d have had to add enormous numbers of people to get the same resource, as we get the same resources, it’s actually freed up I would say at least half of the -- I am sitting at the Navy Yard, sitting at least half of the resources here being used on the NY-ESO program, so they are all now being freed up to work in our own stuff..

And then, on the vector manufacturing in the UK, when you’re going to start using that in clinical trial work?.

Yes. So, as you probably know when you set up a new manufacturing facility, you do something called an engineering run, those are set for early in the second half of this year. And it depends on how this goes, to when we can actually go to GMP run.

I should say that we have -- because I know vector manufacturing is a key topic in the industry, we have a lot of slots booked at a lot of different places other than Catapult as well to make sure that we have covered for all emergencies, both companies and academic institutions in USA.

The reason that the Catapult is so important to us is that if in an ideal world that is where you would make vector for a pivotal trial, because it’s best to make vector in a single location on your own control, and that’s what we would like to do, and if possible that’s what we would do.

But, I would hope, they’d be up and running completely by the end of this year, around the end of the year..

And then for both A10 and A4, when you release efficacy data, it sounds like it’s going to be three, four patients; it won’t be single patients when you get to the first PR or DPR et cetera?.

I would hope that the MRCLS is the sort of perfect model that when we have enough patients to see whether it is sort of convincing ourselves and they have -- that we had a reasonable time that we could actually release something.

And as I say immediately then try and get into the next sort of high ranked conference for a presentation with obviously more detail given the potential dose for longer. And as I said earlier, there may be another 1 or 2 patients in the data at ASCO from the original. It is very difficult to be more precise.

And actually I don’t think as to giving too much detail away before ASCO either..

Our next question comes from Reni Benjamin of Raymond James. Your line is open. .

I guess, maybe just starting off, as we move from 100 million cells to 1 billion cells, do you see any additional -- or when you’re doing the work, do you see any correlation between expression levels of antigens and potential AEs? I guess, trying to get a sense of the higher levels of antigen expression lead to more potential AEs?.

I think it is a really good assumption. It’s difficult for us to make that correlation right now because of the sample size. But, all I can say is that when patients come into the study with bulky diseases and high expression levels, we obviously are very attune into the potential for toxicity.

But, I cannot say that right now we are seeing appreciable differences based on antigen. Maybe in the future as we treat clean more patients that will be the case. But so far, the numbers don’t bear them [ph] out..

Got it. And then, I guess just switching gears kind of back to Philadelphia Navy Yard.

Can you talk a little bit about what the current manufacturing capacity is? And what it potentially could be as you get closer to the commercialization?.

Yes. So, right now, the capacity -- we also still retain our contact with HCATS, Hitachi, usually called PCT by the way. And that capacity is roughly 8 to 10 patients a month. And we expect to be at that level in the Navy Yard within a short period from now. So, we quite adequately deal with the pilot studies. So that’s okay.

The Navy Yard is actually designed to get much, much bigger. Initially it can go to around 300 patients a year and then three times now that we build out the second half of it. So, it’s a modular building.

So, what we physically build out, we could get out and we put into more equipment and obviously trade -- to those more people, we get up to around 300 patients a year. If we go to the second half, you can settle that. And actually we have an option of the land next door this building to put another one, if we needed.

And so, it’s a modular approach to -- which will follow the trials, basically we have success, we will obviously go to the Board and ask for permission to build out the other half of building and then we will be quite well advanced..

And then, just sticking with manufacturing.

Can you talk a little bit about the next generation approach? And is that already being worked on at the Philadelphia Navy Yard or is that still kind of very early in development? And maybe just some thoughts as to when, you think that next generation approach could get to the clinic?.

So, we have a very substantial process development team actually in the UK and the second team here in the Navy Yard looking at everything from vector all the way through to cell manufacturing. So, you can do a lot more incremental things on both vector and cell manufacturing, which we’re doing. So, things change all the time.

And in fact, one of the biggest advantages I would say, -- I would hate to be in a position without my own facility because I think one of the biggest advantages having our own facility is that you can implement incremental changes very, very quickly and effectively.

You can see in real time what needs to be changed and change it, which is incredibly helpful. So, the version 2 in the vector side is what is designed to be used in the Catapult. And in fact, we have one commercial supply of vector other than the Catapult where also going to develop that. And that has been -- that is being developed in-house.

On the cell manufacturing it’s a continuous process. As Ad mentioned, the next step is to get sterility testing down from two weeks to one week which automatically we just chop week off the manufacturing time. But there are a lot of other things that we are doing in terms of -- in terms of whole load of things internally to do that.

So, it’s a bit of -- piece of string, I don’t think we’d ever give up progress development in cell manufacturing for the next at least 10 years..

Got it. And then just one final one for me. I think you mentioned, James, in the prepared remarks about combination with checkpoint inhibitors.

Can you talk a little bit more about how you guys are viewing that program? Will it be patients who have already been treated with checkpoint inhibitors and now you’re trying to potentially desensitize them, do they need to be naïve? And I guess I’m really interested also in hearing yours and Rafael’s thoughts on the idea of genetically deleting PD-1 from these T-cells.

What you think is in terms of advantages and disadvantages of that strategy? Because I think one of your paths -- there is next generation that tackles the immunosuppressive micro environment?.

So, just to be clear what we are doing now, we are running a multiple myeloma study which is a randomized 28-patient study, half of who will get our cells alone and the other half will get our cells and then four weeks later they get KEYTRUDA or pembrolizumab. So that is a trial in going.

That’s one of the trials that we just carry on recruiting and when GSK takes over the program, they will just finish off that trial. So, we call that in flight. We are as a company, extremely interested in running combination studies with our own programs once we have understood, both the responses and the safety profile of our own programs.

I’m a great believer in not altering two variables at once. You don’t really know what is happening. So, what we’re trying to do is if we get a response but it’s not enough, we’ll be very keen to do combination studies. I’ll let Rafael take over from there..

Yes. So, I think, we are learning a lot actually on how to operationalize the combination of PD-1 and SPEAR T-cells from multiple myeloma study. The study is going pretty well. It has an interim safety path to look at potential toxicity of the combination. And then it will continue on to accrue.

It will be obviously transferred to GSK in due course after the transition takes effect. But, it’s been a very good learning experience for us as we prepare for potential combinations with our own proprietary pipeline. And I can say, those discussions are already ongoing with the right companies.

With regards to whether doing genetic editing for PD-1 or any other checkpoint receptors or ligands, [ph] obviously there are groups doing that externally. We have the opinion that it’s probably best to use the pharmaceutical first to sort of be able to titrate potential toxicities, remove the product if the tolerability is not there.

But, then, once we establish benefit read, then consider whether that is something that could be incorporating to a second generation program. That’s true particularly for things like PD-1 receptors or other checkpoint receptors where you -- the potential toxicity is there.

With regards to other ways to interdict the tumor microenvironment to affect epitope setting et cetera, those are part of our second generation strategies which we are by definition building them into our constructs together with the parental TCR..

I think we’re quite nervous about introducing immediately into the new trial -- into the new product, a PD-1 knockout into the cell because it’s not reversible.

And so, we must key -- as Raphael said on the pharmaceutical combination because obviously we can titrate the dose and the pharmaceutical product itself has a known toxicity and obviously PK profile et cetera. I’d let Gwen comment later on the second generation program, on the tumor program, that’s not a PD-1..

Thanks, Jim. I would also add to the PD-1 discussion there. By using PD-1 blockhead systematically, you are not just affecting the SPEAR T-cells but also the other T-cells in the body to maybe rejuvenate some endogenous immune responses against other tumor antigens such as neo-antigens and other cancer testis antigens that might be expressed.

So, there could be advantages. So, the combination that may be preferred over engineering and the PD-1 knockout. And in particular with our cells, we don’t see a massive up-regulation of PD-1 as well. So, it might not actually be effective in all of our cells.

Instead, we have -- we focused on four approaches, second generation approaches, all of which are going through preclinical testing right now for us, so that we are able to select one or more to go into our MAGE-A4 programs next year. And they are meant to address three areas.

The is two programs that are meant to address the immunosuppressive effect of the tumor microenvironment. I mean, actually the phosphodiesterase patent that was just issued is one of those two approaches. The other approach, we’ve previously publicly disclosed, it’s expression of the dominant negative TGF-Beta receptor.

The second approach is to have inducible expression of cytokine with the T-cells to help promote expansion of those T-cells in vivo. And the third approach is to express the gene that helps to improve the function of the CD4 component of our SPEAR T product.

And that’s important because the CD4 T-cell helps to the cytotoxic T-cells components of products, will actually help to drive antigen spreading in the patients and also can mediate direct anti-tumor toxicity. So, overall that would improve potency of the product..

And just as a quick follow-up on the multiple myeloma study because I’ve totally forgotten about that. Can you just give us an update as to -- I mean, it seems like from Rafael’s comments that you’ve already treated patients with KEYTRUDA. And so, there are some learnings from that. And I think you mentioned an interim look, maybe I heard that wrong.

Can you just give us status update on what’s happening with that study and when we might see some results?.

The study is designed so that patients have been treated with a combination of KEYTRUDA and SPEAR T-cells. There would a pause to look at safety. And because it’s a randomized trial, that would be approximately after six patients have been enrolled. We are enrolling in the pre-interim analyzing phase of the study.

And we have -- and the screening has been quite good and there has been quite a bit of excitement around that trial. But we anticipate that the trial will be transferred to GSK, obviously upon transition.

And whether or not the interim analysis will be done, and then our oversight or GSK’s oversight obviously depends on when that transition takes place..

Our next question comes from Eric Schmidt of Cowen and Company. Your line is open..

It was a little unclear to me from the prior discussion whether or not you’ve actually dosed the patient at 1 billion cells with the A10 and in the triple tumor trial, maybe Rafael could clarify?.

So, I think the statement that was made in the prepared remarks is that we are dosing at a 1 billion cells..

Yes..

Okay. And then in terms of the ASCO poster on MAGE-A10 safety update, I know we saw 8 patients earlier in the year.

Roughly, how many more should we expect there?.

I think the poster will cover those eight patients actually and there will be much more detailed examination of what happened and what didn’t happen with them..

And when should we start thinking about sort of the next generation of SPEARs of say new IND cadet, when might that be disclosed?.

So, as Gwen said, we’re going through pre-clinical testing. I think, there are multiple -- there are actually some which are at least one, so maybe 10, which is clinically ready. And there are several MAGE-A4, which will be clinically ready, i.e. ready for an IND, sometime this year.

But actually what’s much more likely to determine the timing of filing an IND is, which one do we need and why.

In other words, based on the data from the initial pilot studies of MAGE-A4, we wouldn’t just launch an IND with a new -- second generation candidate, if we were doing really well, particularly -- if the evidence for the relapse is X and we’ve got something to do with X, then we would obviously launch that one as soon as we could.

But it could be next year, but it certainly won’t be this year. But we really need to get much more data on generation 1 before we select the generation 2. Because it may be appropriate to continue generation 1 in a given disease and generation 2 in something else.

So it’s a bit of complicated metrics, but the programs themselves will be ready to go into the clinic sometime next year, if we so choose..

That all makes sense, James.

Are there other late-stage pre-clinical programs that are looking at different antigen targets?.

Yes. Yes. And again, we would -- our target would be to have one of those ready for the clinic next year, one for the year after..

Our next question comes from Jim Birchenough of Wells Fargo. Your line is open..

Good morning. It’s Nick in for Jim this morning. Thanks for a lot of detail and not dropping the ball, James. Well done on the sports question. So, in terms of transitioning to 5 billion cells, it sounds like if everything taking along well, it’s approximately 2 weeks between patients.

So, within a quarter, should we be expecting the transition to 5 billion from 1 billion?.

As I said earlier, it’s very difficult to be precise. So, to go to 5 billion, you have to have three patients with the gap. You don’t have to have a safety review committee. You have to have no DLTs, because if you have a DLT, you have to expand the cohort. And also some cohorts recruit much more quickly than others.

So, it’s very difficult, but if things go well, we will definitely be in the 5 billion later this year with both MAGE-A4 and MAGE-A10. It is -- I am not being difficult. It’s just -- it is very difficult to be precise about that..

So, I guess, I’m not -- if you have patients waiting to get cells, where is the delay?.

Well, patients -- as I mentioned earlier, patients do drop out or their doctors can decide they are not well enough or they can simply pull out of the study, any patient can pull out of the study, the doctor could turn around and say, well, actually I advise you to have something else first et cetera.

There are whole host of reasons why patients drop out. They may not feel well. They may have -- they may have some other -- they can track new manuals, something. Patients are -- obviously a lot of them are very unwell that for any number of reason people drop out. And if you have someone drop out, the next person won’t immediately be ready.

There may not be manufacturers; their doctor may be waiting for them to wash out from chemotherapy. In other words, the next patient who we’re scheduled for month away may not be able to be brought forward. So that’s why at a practical level, it’s extremely difficult to get the timing exactly right; I’m not trying escape.

But all I could say is that we’ve got a better line up of patients than we’ve ever had before..

Okay. So have you had the situation where you’ve manufactured product but then lost the patient between the decision of manufacturing….

Yes. Actually on a number of occasions, we know that patients won’t be ready. So, we categorize patients and for those you could take the product immediately if the product is available. But there are number of patients who we know are going to go off and have some other treatment. So, we often manufacture sort of prospectively for patients.

Because as I said we’ve got a certain number of slots. So, we use those manufacturing slots. And sometimes, those patients go on something else and do very well or do very badly and never become available. So, any number of reasons, we do occasionally lose patients because they progress too much during the manufacturing.

But I wouldn’t say that’s the largest cause of loss of patients by any means. .

Okay. And then, in terms of these newer generation of sales -- sorry, SPEAR products such as the dominant negative TGF-Beta as previously described.

Would you have to start from scratch with a product like that or would you be able to say, target at a billion cells, or does it depend on the characteristics of the cell?.

That’s a very good question. So, I’m going to let Rafael answer that..

Yes. So, we have been thinking our approach to what doses to start with, with SPEAR T-cells, whether that’s first or second generation, based on our current experience.

Our hope -- and obviously this is without having had the proper regulatory discussions, just how we could start if we have clear, the top dose in the program, the uses of parental TCR, then we can start with at least 1 billon sales. And that will like be our proposal going forward.

Based on the fact that the parental TCR host has already -- we’ve already been able to exclude cross-reactivity and also if the secondary gene is not thought to add any further toxicity and we’re completing the preclinical safety assessment in all these strategies that Gwen just outlined during the call. So, the answer is yes.

We would try to start with the higher dose than we do with branded TCRs..

And then, maybe just last one for me, a lot of questions answered.

Can you sort of give us an update on where you are with Universal Cells and also the Bellicum collaboration?.

So, Universal Cells continues to make the progress, it’s still a long way from the clinic. I don’t think we really can update you on anything very significant. I mean, it’s a long-term -- it’s a complex and quite a long-term project.

I am delighted to say it will takeover by Astellas has made no difference at all to the extent which Universal Cell wants to indulge and collaborate with. So I think that’s going very well. And I don’t think we anything on the Bellicum front to say.

We’ve done some preclinical work and we’ll probably be -- I think we aim to say much more towards the end of the year..

Our next question comes from Ying Huang of Bank of America. Your line is open..

Hi, guys. This is Jenny on for Ying. Thanks so much for taking our question.

I just wanted to ask about the competitive landscape, now that you are talking more about KITE-718, MAGE-A3, MAGE-A6, just wondering how you guys differentiate and definitely what indications do you think A4 and A10 have an advantage over A3, A6? And then, also with your relatively clean safety profile, have you guys thought about dosing patients in outpatient rather than in the hospital setting?.

So, on the competitive situation, I think, it’s inevitable that given the interest in achieving data in solid tumors that there will be a lot of people trying to get into the space. I mean, the CAR-T’s got wonderful data in hematological tumors and two approvals and more to come obviously in BCM [ph] data.

So, there’s no question in hematological tumors, there’s been fantastic data. It’s very difficult for us to comment on competitive programs, until got a sort of dataset that’s significant and using the same set of patients. But we are very careful on the NY-ESO programs, do four different cohorts with very specific entry criteria.

So, you can actually look at them and they are each of reasonable size, 10, 12 patients. You can actually look at the response rate. It’s very difficult to find data for other companies, which you’ve gone through 40 or 50 patients, like that and given stratified data on response rate and safety. So, that’s the first thing.

In terms of competitors, I can’t remember the HLAs, the MAGE-A3 or MAGE-A6, but it’s not A2, I think it’s DPO4 [ph] from memory. So, it’s a different HLA type. The way the cancer testis antigens work is that they tend to be present on 20% or 30% of many of the tumors.

Now, MAGE-A4 we consider to be our sort of priced project because it happens to be on a higher percentage of quite a lot of tumors. And that’s why we are in seven different tumors because it’s highly presented.

So, MAGE-A3 or MAGE-A6, it would depend on exactly the way individual patients over that and I don’t have that in my head at the moment because it won’t be the same patients who present MAGE-A3 and MAGE-A6 as a DPO4 [ph] as our A2, A1 represent MAGE-A4. So, I think it’s very difficult.

I think that, first of all, I think, we need to see quite significant bodies. We are very conscious. We know the other people come here with data. As it happens, we do think that the affinity maturation is the key to getting responses. It’s certainly the key preclinical programs that we run.

And I’ll let Rafael talk about whether we think that these are going to be patient programs..

Well, I think on the second question, it’s pretty mature to really make a prediction on that. I mean, certainly we’re not at a point where we’re able to say that this could be give as an outpatient. I know that in the CAR space, everything is being sort of very prescribed with predetermined centers that are qualified to administer this product.

But there’s already efforts out there to make this more community setting based if the safety and tolerability of the CAR warranted. I think in the TCR space a bit earlier than in the CAR space to be able to say that. But certainly, our goal will be to make this available to as many patients as possible.

And to the extent that training and physicians and understanding the safety and tolerability allows us to streamline the process, we will work to do that as we commercialize the product. But right now, it’s difficult to say much more than that..

There are no further questions. I’d like to turn the call back over to James Noble for any closing remarks..

Well, thank you everyone for the question. They certainly covered a wide range of things today, and I think really represent the stage the Company is at. It is really, really exciting moment for us, getting through the safety cohorts and then getting towards the response data and programs that we own ourselves.

At the same time, as retaining our emphasis on innovation, which is why we talked about the two new patents today, at the same time, as making sure that people have really understood progress that we’ve been making on manufacturing, both in facilities and people, but also in innovation on the manufacturing side.

So, this is -- as I said, we had a really outstanding first quarter, moving everything forward. And I am very excited about the rest of the year. So, thank you very much..

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..