Greetings, and welcome to the Cellectis Q3 2020 Earnings Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Simon Harnest, Senior Vice President, Strategy and Finance.

Thank you, and welcome, everyone, to Cellectis third quarter 2020 corporate update and financial results conference call. Joining me on the call today with prepared remarks are Dr. André Choulika, our Chief Executive Officer; Dr. Carrie Brownstein, our Chief Medical Officer; and Eric Dutang, our Chief Financial Officer. Yesterday evening, Cellectis issued a press release reporting our financial results for the second quarter ended September 30, 2020. The press release is available on our website at cellectis.com. As a reminder, we will make forward-looking statements regarding financial outlook in addition to regulatory and product development plans. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent Form 20-F filed with the SEC and the financial report, including the management report for the year ended December 31, 2019, and subsequent filings Cellectis makes with the Securities and Exchange Commission from time to time. I would now like to turn the call over to André. André, please go ahead. André Choulika: Thank you, Simon. Good morning, and thank you, everyone, for joining us today. Yesterday, Cellectis as well as our sub-licensee, Allogene announced a series of clinical updates in the form of abstracts selected for oral presentations at the upcoming ASH conference. These abstracts will be the main subject of today's call and our Chief Medical Officer, Dr. Carrie Brownstein will summarize these data in detail, followed by an update on our financials from our Chief Financial Officer, Eric Dutang. As a quick overview, Cellectis yesterday announced an abstract on an early interim clinical data readout of BALLI-01 study investigating UCART22, one of our wholly-controlled allogeneic CAR T-cell program. This dataset has been selected for an oral presentation at the upcoming ASH…

Thank you, André. I would first like to go into more detail on BALLI-01, which is a Phase 1 open-label dose escalation study designed to assess the safety, the maximum tolerated dose and preliminary anti-leukemia activity for UCART22, our first proprietary program in patients with relapsed/refractory B-cell acute lymphoblastic leukemia, which will be presented in an oral presentation at the upcoming virtual ASH meeting in December. As of July 1, 2020, six patients were enrolled on the trial. One patient discontinued prior to UCART22 administration, after developing hypoxia related to the lymphodepletion and five patients received UCART22 infusions. Three patients were administered at Dose Level 1 of 100,000 cells per kilo. And two patients were administered at Dose Level 2 of 1 million cells per kilo. All five patients received the standard lymphodepletion regimen, the cyclophosphamide and fludarabine, which we refer to as FC. Patients were heavily pretreated having received between two and four prior lines of therapy, including one patient with prior CD19 CAR-T and one patient with prior CD22 ADC therapy. And all presented with high baseline bone marrow blasts prior to lymphodepletion with a median of 35%. We are encouraged by the initial anti-leukemia activity observed; two or three patients in Dose Level 1 achieved an objective response, one with the best response of complete remission or CR and the second patient with a CR with incomplete count recovery or CRi. Of note, the patient with the CRi at Dose Level 1 had previously been unsuccessfully treated with inotuzumab, an antibody-drug conjugate targeting C22. One or two patients at Dose Level 2 achieved a significant reduction in bone marrow blasts from 40% on day minus one to 13% at day 28 post-UCART22 infusion. Notably, this patient was unsuccessfully previously treated with a CD19-targeted CAR T-cell therapy. We…

Thank you, Carrie. Cellectis third quarter 2020 were driven by robust financials. The cash, cash equivalents, current financial assets and restricted cash position of Cellectis excluding Calyxt as of September 30, 2020, was at $278 million compared to $304 million as of December 31, 2019. That reflects $28 million of proceeds received from Servier in the first quarter of 2020 and $21 million that guaranteed loan received from the bank syndicate, which was offset by $79 million of other net cash flows using operating, investing and lease financing activities. These cash position is expected to be sufficient to fund Cellectis standard on operation into 2022. The consolidated cash, cash equivalent, current financial assets and restricted cash position of Cellectis including Calyxt was $308 million as of September 30, 2020, compared to $364 million as of December 31, 2019. The net cash flows used in operating capital expenditure and debt financing activities were $29 million at Cellectis and $31 million at Calyxt over the first nine months of 2020. The net loss attributable to shareholders of Cellectis excluding Calyxt was $21 million in the first nine months of 2020, compared to a net loss of $46 million in 2019. This $25 million increase in the next result between 2020 and 2019 was primarily driven by a significant increase in revenues and other income of $44 million, which was partially offset by an increase in R&D expenses of $4 million and a decrease in financial gains of $15 million. The consolidated net loss attributable to shareholders of Cellectis, including Calyxt was $42 million or $0.98 per share in the first nine months of 2020, compared to $65 million or $1.52 per share in 2019. The consolidated adjusted net loss attributable to shareholders of Cellectis excluding non-cash stock-based compensation expenses was $30 million…

Thank you, sir. At this time, we'll be conducting a question-and-answer session. [Operator Instructions] Our first question today is from Gena Wang of Barclays. Please proceed with your question.

Thank you for taking my questions. I have a few regarding the UCART22. Just wondering, it seems dose level one and dose level two, I understand a small number patient, but we didn't see a very clear dose response in terms of CR rate. And the related question is why the dose level one, two achieve pretty high CR rate? So what is the reason to adding alemtuzumab? Is that because the durability from the dose level 1 was not very good? And at the ASH full presentation, just wondering how many more patients, we will see for presentation.

Thank you, Gena, that’s a very, very good question and thank you first of all for taking the time to be on our call today. We're very excited to give you the first updates on our first proprietary program, although it being very early. The question I'd like to delegate it to Carrie, who can best answer the questions from alemtuzumab et cetera and doses.

Yes. Hi, Gena, thanks so much for the question. You're absolutely right, I mean, I think it was interesting that we saw more response in dose level one and dose level two, again, these are very early dose levels, and again, without the incorporation of alemtuzumab. And therefore it's really hard to say whether you would necessarily see a dose response at this time given the low dose levels. We're looking forward to continuing to enroll, to see these cohorts with alemtuzumab as well as higher dose levels, and see where that takes us. We've decided that we think the alemtuzumab is important, particularly given the data we've seen with B-cell NHL, as well as from Allogene and from our other partners, Servier and ALLO and we think that’s an important part of the puzzle to ensure that, we're giving new to the patients the best chance for success.

Okay. And how many more patients should we expect at the ASH?

Yes, I mean, we're not – we can't disclose what the data is going to be at ASH until ASH, because the abstract is the only thing that's been out yet. So we'll see where that is.

Okay. That's fair. And my last question was regarding the partner ALLO Allogene, BCMA allo-CAR-T. Just wondering, like from there, data so far seems like safety little bit worse than the CD19 allo-CAR-T, we would see more infection, and they have a one Grade 5 infection. Just any thoughts there, why the safety profile could be so different between these two programs,

I'm sorry, between which two programs you're saying Allogene and which one?

The Allogene’s BCMA CAR-T versus Allogene’s CD19 CAR-T program.

Yes. I mean, I don't want to speak to their programs and I think there are better people to ask that, but I would say that they are two very different indications. So I think it's hard to compare, it’s how I would answer, but they would know better than I, given it's their programs.

Okay, great. Thank you.

[Operator Instructions] Our next question is from Yigal Nochomovitz of Citigroup. Please proceed with your question.

Hi, great. Thank you very much for taking the question. For the patient in the BALLI-01 011 trial, at those level two that had the bone marrow blast reduction from 40% to 13%. I'm just wondering, is there still an opportunity for this patient to show a CR or CRi with more time on study? Or is that bone marrow blast reduction the best response that we can expect from this patient?

Thank you Yigal, that's a very good question. So I mean, given it’s leukemia, and it's not NHL where patients can just sit and wait and get rescanned and things like that, which is what you would do in a lymphoma and leukemia, because it's a much more proliferative and progressive disease, they need to move on to other therapy. I think that this is the kind of patient where additional doses would make sense. And that's something we're going to continue to look at as we move forward in the development plan, because clearly the patient had some – had a response and had some activity, and therefore, would have been a good patient for something like that. And we're looking forward to getting that data together.

Okay, great. And then for the patient that had the CRi, after failing the CD22 target at ABC, could you just talk a bit about whether this patient remained CD22 positive at enrollment? And what was your expectation for targeting patients that failed prior CD22 targeted therapies with expectations for success with UCART22 prior to seeing the CRi in this particular patient?

Yes. So in order to get enrolled in this part of the trial, the patients do require to have a significant CD22 expression. So that wasn't an issue in terms of having previous CD22, though I do think it's very promising and encouraging that after having a prior CD22, that didn't work out so well for the patients, that we were able to show some activity. What was the second part of the question again? I feel like there was…

Just wondering what your expectations were for success with UCART22 in patients that have failed prior CD22 targeted therapies?

Yes. I mean I think as one that they're expressing the CD22, we expect that there is a good chance of activity.

Okay. And then just… André Choulika: Yigal, one thing I'd like to say it's like very often some failure with T-cell engagers is sometimes due to the fact that the T-cell of the patient are not super fit at the time of the injection. And therefore the respond of the engager needs to have T-cells off the patient like autologous T-cell that are fit. It's the same thing like in autologous CAR T-cell product. So when they fail, it doesn't mean that when you inject allogeneic T-cells that don't have the same fitness would not respond differently, and that's why we can see...

Okay. Thank you. And just one technical question. Is there any particular reason why in the BALLI-011 trial you're exploring three dose levels, whereas an AMELI-01, you're testing four those levels? Is there some reason for that?

Yes, that's a good question. The reason is that in the UCART123 program, we are actually – we were based on dose escalation of three doses, but there is one split though, so to speak between the second and the third dose built into the study, that's why there is four dose levels.

Got it. Okay. Thanks, Simon.

The next question is from Jim Birchenough of Wells Fargo. Please proceed with your question.

Yes. Hi guys. Congrats on the data. I guess just following up on the theme of durability of response, and what we might expect that ASH. Will you have data on CAR persistence, Antigen expression? And just in terms of durability overall, do you think it's more a function of gaps of initial response or persistence of the CAR? And then I've got follow-up.

Good question for Carrie.

Yes. Thanks, Jim for the question. And I think it's a little bit – well, part one is in terms of what we're going to present in terms of additional data, I'm not going to speak to today. That said, I think that the answer to a lot of the questions you're asking now are going to hold with the alemtuzumab cohorts. And we're looking forward to collecting that data and showing that when we have it, so that's really where we are with that data.

And maybe I can add to Carrie, and Jim, thank you so much for the question. Just to clarify, we are in the middle of enrollment for UCART22 and BALLI and for AMELI with 123, without the – alemtuzumab addition. And we're now starting enrollment with the alemtuzumab addition. For the UCART123 program, this will probably be two cohorts, one with alemtuzumab and one without and for the 22 program, because it's very similar to the 19 program, that's driven by Allogene, ALLO-501, where probably quitting over to the usage in the lymphodepletion with alemtuzumab. And that's why right now the number of patients that we're announcing is limited. And we are – the next real big data update for us will be the addition with alemtuzumab. And we are waiting to have a cohort completed to then show that difference in the durability of response.

And maybe just… André Choulika: Go ahead. Okay. So one thing that has to be kept in mind here, like the data, for example for DL1 is like two patients out of three to test – like CRs. Like the dose is 100,000 cells per case, which is time on the cell for an adult, approximately, when you compare this to – for example 19 data without alemtuzumab, without anything, without these types of micro level and knockout, et cetera. This is the kind of response you have the distract of prologue, which is quite interesting to assess in the condition, when you compare, for example, with other data where you go, for example, 30 million cells per kg with no responses for different type of preconditioning, it's a total different type of set. So that's why I think it's also interesting to analyze it through this angle and that's why we've made with or without cohorts – with or without alemtuzumab cohorts.

Yes. Just maybe just a follow-up on the beta 2-microglobulin knocked and congrats on the IP. When does that – when would you move into clinic, B2M knockout, sort of a follow-on effort, hitting both the TCR and the B2M? André Choulika: Well, today I'm not sure that I'm like fully convinced with the data we've seen with this. I think that definitely a combo between knockout of B2M and replace them with HLA-E blocking NK and T might be really interesting and might be interesting for repeat dosing strategy for example in the solid tumor setting. But now like the strategy with alemtuzumab is way more flexibility the – in the way we're going for this. So it's something that has been in the papers of the company for more than 10 years now and like this would come probably after we are entering the solid tumor space, which is something we are envisaging.

And just maybe finally on CS1, any sense of when – what the time might – timeline might be to hear back from FDA and how you communicate that to the street? André Choulika: Carrie, do you want to answer this one?

Sure. So I mean the second part Simon can answer about how you want to communicate, but at this point we've submitted everything we can. And we hopefully have a very straightforward path forward with FDA to have it reopened. I think the FDA's a lot on the plate right now. So we're just waiting to hear back. And once we have a path forward, that's final. We're happy to share how we're reopening and more information on that.

And maybe I can add to that. So CS1 is an excellent product and we are very excited by the early start of the trial as we've seen patient enrollments in the beginning of this year and there is a lot of patients that need for this product and we think the this will be a fantastic alternative to a BCMA target. And as Carrie said, we've submitted everything to the FDA already weeks ago and we're just waiting to hear back. We think the questions from the FDA were pretty straightforward and we answered in a very clear way and we have a plan that we think is acceptable and as soon as we hear back, obviously we will let the street known does this exciting for us to get this product back on track.

Great. Thanks for taking the questions guys.

Thanks, Jim.

Thank you, Jim.

The next question is from Michael Schmidt of Guggenheim. Please proceed with your question.

Hey, this is Kelsey on for Michael. Thanks for taking our question. I guess maybe just to start off with UCART22, maybe just could you maybe help us guide to what the efficacy bar is that you're thinking about as we kind of assess this initial look at ASH? And then bigger picture, did you say you would be pursuing repeat dosing for your programs? And if so, I guess what patients would get retreatment? Thank you.

Yes. Thanks, Kelsey. That's a good question for Carrie, sorry.

Yes, hi. I can take it. No problem. Thanks, Simon. So, I'm sorry, so the first part of the question about the efficacy bar. So what we're looking at, in particular, and why we love our target of CD22 is that it gives us multiple shots on goal for a regulatory strategy. And so you can foresee that going forward a very fast to market. Lower bar for an approval would be in patients who have already failed the CD19 directed treatment, whether it'd be A, any of the options, whether it'd be a CAR-T or otherwise. And so looking at prior approvals for very refractory relapse patient populations in All the bar is not terribly high. So FDA has President for approving on single-arm trials, CR rates that are reasonably durable with MRD negativity in the 30% to 35% range. So that's not – so in that group, that would be where we were looking. Obviously a upside for this program would be if the activity is better than that, we could easily move it up in the treatment paradigm to get earlier patients. So that's one of the important factors are for this program. And then as far as redosing, I think we have said before, one of the mean improvements in allo-CAR-Ts over auto is the fact that it can be treated like a pharmaceutical product and can be dosed more than once. And we are actively pursuing how and in which patients we would potentially be redosing. In All in particular, we know that in the normal treatment, when we treat with chemo in these patients, they typically get an induction type of therapy where you try to get them into remission and then they get another slug of high dose therapy to consolidate that remission. So we can envision a treatment strategy similar to that that we could use with our products. So that's the kind of things that we're going to be looking at as we move forward in the development.

Okay, great. Thank you so much.

The next question is from Salveen Richter of Goldman Sachs. Please proceed with your question.

Good morning. And I'm just curious here, as you look at the other allogeneic CAR-T players like Allogene, CRISPR and Precision, provide data and really layout their thesis right on the purchase, whether it's B2M knockout or knock down or adding alemtuzumab and playing with multi-doses or refractory to CAR-T. How are you adopting that in addition to the other leverage? You're playing with into your trial design just so you can optimize one aspect before kind of moving to the next. And I'm just curious if you have any takeaways from what we're seeing from the landscape to date?

Hey, Salveen, it's Simon. Thank you for the question. Really appreciate it. So as you see the landscape come together to us it's very rewarding because honestly and you can see this in the publications, we were the first with all these approaches. We were the first with the B2M knockout. We presented that at the Keystone Conference in the spring of 2016. We were the first to file patents in the gene editing space on these approaches. We're actually the first to use the alemtuzumab approach that's the patent that Cellectis owns with the CD52 knockout and the concurrent administration of alemtuzumab. So now it's interesting that a lot of people are echoing what we pioneered and implementing that in their programs. So far the CD19 and BCMA targets are the most advanced ones. And what we're trying to show with our proprietary pipeline is that we are actually giving alternatives to these very crowded targets like CD19 or BCMA. We think from our strategy from that point of view, we have the best partner in the space with Allogene and the most advanced partner to bring forward an allogeneic first CD19 off the shelf CAR, as well as the first BCMA CAR that's off the shelf. And we think with alemtuzumab, you have a great way of actually dialing in window of persistence, because you have modality that you can dose in different levels, which is alemtuzumab. And with the B2M knockout, you just have to knockout on the cells as if without any modality there, but it's a very interesting alternative for sure. For our trial, we have learned from what we've done over the last five years in the clinic and we are optimizing the lymphodepletion and we will give all those details with completed cohort, because we think it's more important to show full completed cohorts then make too many forward-looking statements, while not having the clinical data yet. So the alemtuzumab trials are ongoing with UCART22 and 123. CS1 is a different mechanism of action, because the knockout of CS1 in the CAR T-cell and targeting CS1 actually help these T-cells lymphodeplete on their own, which is very interesting as well in the setting, but we're excited that we show already responses in patients with 22 for example without alemtuzumab at the lowest dose of 100,000 cells per kilogram, which is pretty comparable to the early CD19 approaches and we're seeing responses in patients that have been treated with a CAR-T targeting CD19 before. So that's kind of showing two proofs of concepts that we wanted to confirm and with this data set we have it, although being very early. But Carrie, sorry, that was a long answer already, but if you want to add anything, please go ahead.

No, I think you got it all there, Simon. Thank you. And I think Andre had something to say. André Choulika: Yes. Like the thing is – thank you very much for these great questions, Salveen. I really appreciate it. Like the position of the company is quite simple. Like we have two of our very important assets, like a series of our important assets in the hands of our partners, particularly the CD19 target that I think is going to be the first one to be – to file a BLA as an allogeneic CAR-T. When you compare, for example, an allogeneic within autologous, you see real interest in bringing allogeneic CAR-T because there are a lot of patients that are excluded as part of the therapy for a number of reasons, sometimes lack or the poor quality of the T-cells, et cetera. So, the proof of superiority or the expansion of the market access on these type of product makes it approvable. When you come with another CD19 CAR, you have allogeneic CD19 CAR, then you have to prove something different that it shows better. And I'm not sure that it's going to be that much easy when you look for example at the data from Legend on the BCMA and the toxicity induced by BCMA or the 19 data of competitors that induce – that has also induced toxicity that the alternative CAR-T on 19 and BCMA shows a better index. With this, we have a very strong IP that comes behind this and that can protect our assets for their commercialized – during their commercialization step within the hands of our partner, and that's why IP is for. If you have a protection during, for example, all the clinical trials that is called the safe harbor, once you go out into commercialization, then this safe harbor disappears and the IP comes full-fledged. Now, on our side, we have alternatives to these two overloaded targets 19 and BCMA, which is 22, CS1 or an unencumbered targets such as 123. And that's where the company has a very clear path to the registration with a strong IP behind it and also you see that the quality of the product that we produce, even a 100,000 cell per kg finally, 6 time less than others we have better results even without any kind of to precautioning angle B2M knockout et cetera. and give a clear path to where the company is heading at in the coming months.

Thank you.

The next question is from Hartaj Singh of Oppenheimer & Company. Please proceed with your question.

Great. Really nice update all. Thank you. Just a couple of questions. One is with the addition of alemtuzumab as a lymphodepleting regimen to 22 and 123, from your modeling and just experience with your partner programs also, how much of a boost could you get from that? I mean, trying to understand, what additional sort of efficacy would be able to offset any safety and how are you thinking about that? If you can give us some color there. Secondly, on manufacturing, the way you're integrating your clinical and commercial manufacturing, I think actually is something that here competitors are doing. So if you could just give us an update there and help and you will move to your programs into mid and late stage. And then lastly, could you actually detail for us what are some of the specific milestones as much as possible that you could receive based on the milestones that your partners have disclosed over the next 12 to 24 months? Thank you.

Hey, Hartaj. Thank you so much. And I can take the second part of the question first and then I'll hand it over to Carrie for the clinical part. So in terms of milestones, this is becoming very relevant for us because our partners are making a lot of progress in our collaborative targets. So, for the CD19 alliance, that's an alliance, just as a reminder, between Cellectis and Servier for the U.S. and European rights, and Servier sub-license the U.S. rights to Allogene, so – just to know that framework. And all of those CD19 CARs, if it's ALLO-501, 501A, UCART19 et cetera. are basically bundled in one alliance. And for this alliance, we are entitled to receive up to $410 million in outstanding milestone payments, plus a low double-digit royalty on worldwide sales. And these milestone payments are obviously tied to whichever product makes it into the market first and in whichever indication, and then any further would apply as well. That is the CD19 alliance. For the other targets, there are 15 targets that are directly licensed to Allogene. So essentially, Allogene’s pipeline is up on Cellectis license targets and Cellectis is entitled to receive up to $185 million per target in development and commercial milestones, plus a low – plus a high single-digit royalty on worldwide sales of any product out of this alliance. So in those targets are BCMA, et cetera, what Allogene has already disclosed. And Carrie, sorry to the clinical part of that question.

Back to the – yes, so the alemtuzumab question, I mean, I think that the key here, there's not too much to say is that, I can't quantify per se how much more efficacy we should see, but the key is that the alemtuzumab should allow for deeper and more prolonged lymphodepletion, which would only benefit the cells to have more time to expand. And I don't – the point of our trial is we really want to see, how much additional expansion. And therefore – and how that then correlates or translates into improved and more prolonged efficacy in these patients. So we’re like you looking forward to seeing what that data looks like.

Just any updates from the manufacturing, just on the clinical and commercial and how that could help with the – as you move your trials from early to mid and then to late stage in the next 12, 24 months? Thank you.

André, do you want to take the manufacturing question? André Choulika: Yes, hi, Hartaj. Actually, the manufacturing is currently on track. So we'll have the Paris site construction finished, the production started and that's like producing all the raw materials. We think we're on track also on the construction for the Raleigh site. And we probably start producing next year for all the clinical supplies, but also the commercial supply for the pivotal version is currently on track to be produced for the three products themselves. And we have backups with CMOs on, with MolMed and Lonza. I think the company has a tremendous amount of experience in the field of production of CAR-Ts. I think the quality of the product we produce, and that's why low doses get interesting results because of the quality of the product we're producing at the end. And also probably the gene editing technology itself and it gives you more fit cells to expand in the patient at the end and like proportion technologies that we master. So I think that this step is fully mastered by the company and is on track to move on. What I think was the key decision inside the company is the ability to in-house manufacture from clinical supplies up to commercial supplies. And we have a good view on this. And I think that next year is going to be a big year with the kickoff of the production of the first batches at Raleigh – at our Raleigh facility. And I hope that we'll be able if we get out from all the situation to organize the visits and see where like the high standard of the company, where we are – where we are right now.

Great. Thank you, André. Thank you, everyone.

Sure. Thank you.

The next question is from Wangzhi Li of Ladenburg Thalmann. Please proceed with your question.

Hi, thanks for taking my question. I noticed a difference between the UCART22 and UCART19 trial, when you have no alemtuzumab basically there is not much CAR T-cell expression and no response, but in your current ASH abstract, out of the three dose one patients, you have two CRi responses. I think – and you may already mention this, but I want to see if any further color on the potential reason for the difference. Do you think that the manufacturer, the later manufacturer of UCART22 have some improvements over the initial UCART19 that may enable more protein expression or efficacy even without alemtuzumab or any color on the improvement in manufacturing, may be related to that difference?

Hey, Wangzhi, it’s Simon. Thank you so much for the question. Really appreciate that you dialing in. So it's a little too early to tell exactly obviously, and the patient set up just three. But we have certainly always made improvements to our manufacturing at something that we quietly make. We don't think too much of a big deal about it for competitive purposes, but we continuously improve our manufacturing. And we have a lot of know-how in terms of selecting the best cells and to fit the cells for these trials. What we do know, and, Carrie can elaborate a little more on this is the alemtuzumab addition certainly increases the window of persistence for these CARs. So it is something that is, we think important for the durability of response. That's also why we're adding this to our trials right now. And therefore, while we're super excited about these early CRs, and these are in patients that have been extremely difficult to treat, and they have failed basically all other therapies. We're also very excited about the significant reduction in blast in the patient on DL2 because that was a patient that was previously treated with a CD19 CAR. And so we do show that we have a very powerful product already at low doses, and it may be the only option for these patients. But Carrie, maybe talk a little bit about our vision with alemtuzumab going forward.

Yes, sure. Thanks. So, yes, to that question and I can't speak to why there's a difference. And again, as Simon clearly pointed out with only treating five patients at this point, it's very hard to draw any conclusions. That said, we're obviously incredibly encouraged that without the alemtuzumab in that dose cohort, we weren't able to see some response. So we're very excited about that. And we think that when we add in the alemtuzumab, it should only improve the responses that we see, because it will give significantly more time for cell expansion at room for them to expand and do their thing in the patients. So we're looking forward to continuing to enroll those cohorts and gathering that data and presenting that in the future. But I can't speak necessarily to why, it wasn't seen in that, in those on CD19 early cohorts without alemtuzumab. André Choulika: Hi, Wangzhi, how are you? Like maybe one thing I would like to add is like the manufacturing process has evolved of course over the time and every version of the process development. That is becoming a real trade secret among old companies around. It's like so difficult to elaborate on this and we will not. However, I think – seriously, I was surprised that like without alemtuzumab, it didn't work with CD19 because like when you look at our data or for example, other companies that don't use alemtuzumab, of preconditioning such as like Precision BioSciences data, I think it's interesting to see that they do have also expansion and responses with their CAR-T. So there is the ability to do this, and this is not extraordinary. What is important is to see on this cell per kg or in general, like the flat dose that you give and the type of response that you get with the amount of T-cell that are injected gives you a hint on the quality of the product at the end, why that? Because in the vial inject, there is a need to have the right cells there that will get you the expansion and the right type of expansion, CD4, CD8, gamma-delta, et cetera, all the – the secret sauce around like the number of like T-cell memory, like the central memory cells, et cetera, everything that is inside the vial should be fit and great in there. And that's why I think also not only the way you culture the cell, but the gene editing technology that don't share the DNA to pieces is important, but also the early proportion technology and the way you deplete the cells at the end, come – all to the secret sauce to give you a product that can expand very powerfully, even with super low doses.

Got it, that’s helpful. Maybe if I may ask the last question is, for the alemtuzumab optimization, it couldn't play the fixed dose but do you think – do you see a feasibility to maybe personalize the dose based on the patient conditions or the baseline immunity or tumor protein or any other potential predictive biomarkers?

Yes. I can speak to that. I think that's a really good point and it is something that we're going to be looking at it. I think the complication obviously is when we're doing the development and the way the regulators look at it, as they look at the lymphodepletion regimen, plus a dose as the treatment. So we would have to, it becomes a little bit more challenging to do what you're saying though. I do think there is a place for that not only for the alemtuzumab but really for the entire regimen because there will be patients who have much more banged up bone marrows and other things where they can't tolerate as high doses, let's say a cyclophosphamide or what have you versus patients that can. And that could be partially contributing to some of the differences we see from study-to-study as well and from patient-to-patient. So I do think that is something that needs to be looked into and explored, as we move forward. But again, the straightforward plan is to have it be a standard, some sort of standard dosing, because that's just the way the agency, and the regulators look at it as a treatment paradigm, as a regimen, not just as the dose of cells, but that is something that's needs to be moved, not just for us but for the whole field, in my opinion.

Got it. Thanks a lot.

The next question is from Raju Prasad of William Blair. Please proceed with your question.

Hey, thanks for taking the question. Just a couple of clarifying questions, one, it seemed that Allogene’s made – alluded to potentially, taking over the manufacturing of the CD19 Allo product. Can you just maybe, with regards to UCART22 versus UCART19, maybe just describe a little bit more color in some of the differences in manufacturing there? And then, it says that – in the press release puzzles, it says that there's a dose cohort level 2 with alemtuzumab that’s being enrolled right now. Can you describe the dose and how the dose level will change over time?

Hey, Raju, thank you so much for the question. And it's very important to clarify that. On the manufacturing part, so UCART19 or the CD19 CARs have been manufactured since 2016 by our partners. First, that was Servier and Pfizer and Pfizer handed it over to Allogene. And now, because Allogene is doing fantastic work here in the U.S., it seems like, I think, I don't know all the details about it, but it seems that Servier and Allogene are consolidating their manufacturing efforts. So that's really great to see. But what I was saying earlier on another question is that we don't talk often about manufacturing, but I think we can proudly say that we have one of the best manufacturing of CAR T-cells in the space. This is sometimes not public information, so we don't share this in detail, but we get some of the highest yields with the most potent cells per manufacturing ones. So again, what we said previously, we can technically treat well over 100 patients out of one manufacturing run. We have a very high cell yield, our electroporation systems are giving close to 100% fidelity of cells, our gene knockouts are over 95% to 99% efficient. And this is in GMP at scale. This is already in basically commercial scale manufacturing. This is not in your lab. So I think the manufacturing at Cellectis is top-notch and that's why we're so excited to really fully make our CAR-Ts in-house because that is starting next year with the completion of our manufacturing facility. And I think Allogene is somewhat on the same track of finishing the build out of their own manufacturing facility as well. But it's great that the partner targets are being manufactured by our partners. Our proprietary targets are manufactured by Cellectis, because that obviously gives us the freedom to fully focus on our proprietary programs. And then the second question, I think, is for Carrie. Sorry, Raj, maybe you can just repeat the second part of the question.

Can you repeat the question?

Yes, sorry. Firstly, because the Dose Level 2 plus alemtuzumab enrollment is ongoing. Can you disclose that dose and kind of the strategy around dose finding with the alemtuzumab dose moving forward?

Yes, absolutely. So we've disclosed before the dose level, so it was 100,000 cells per kg for Dose Level 1, Dose Level 2 was 1 million cells per kg. The way we designed the trial was that we were starting at Dose Level 1 without alemtuzumab, after we cleared Dose Level 2 without we would then split the trial into cohorts within – without that would enroll independently. So we now have able to dose escalate if we chose to, without alemtuzumab or repeat Dose Level 2 with alemtuzumab. And that's where we are now. And we're starting to move forward on that side of the trial.

And the dose with alemtuzumab that you are using?

Sure. I mean, we haven't disclosed what we're using, but we're starting at, somewhere in between where Allogene has been. So we're doing for this trial, 60 milligrams.

Got it. And would you anticipate given what you've seen with them, potentially moving up or what's in the protocol there?

Yes, I mean, I think we'd have to see, we came up with our dose based on scouring of the literature, not just their literature, but the transplant literature. And from my review and speaking with KOLs and others that do transplant and I've done the transplant myself. We know you need a dose probably higher than 30 milligrams, but you’ve gone at less than 100, typically you start to see significant infectious problems around 100 milligrams. So, we kind of wanted to start somewhere that seemed in the range of what you really need to get the depletion you need without overstepping with potential risk of infection. And obviously, we don't see what we want to see, we could always change. But I think from a prudent perspective, given the patient population, I think we're starting in the right place.

Got it. And is that 60 given all a split dosing or?

It split up over a couple of days.

Okay.

And we left that open because as you know, alemtuzumab comes in different formulations and things that we wanted to make it easy for the physicians to give it because it's not – and also some patients have issues with infusion related reactions and things. So some physicians like to titrate up and things like that. So to us, it's really the total dose that matters, not so much on how it's split up.

Great. That's really helpful. Thank you.

Sure. Thank you so much for the question.

The next question is from Madhu Kumar of Baird. Please proceed with your questions.

Hey, thanks. I apologize I might have missed some of these questions a little bit early. But just what are your thoughts on employing CD22 CAR-Ts in DLBCL, given what you've seen so far in B-ALL? And then given some of the kind of noise around latent virus reactivation, how did that impact your thinking about either screening protocols for patients or monitoring of latent virus reactivation in kind of the lymphodepletion CAR-T regimens you're employing now?

These are two great questions. Thank you so much, Madhu. I'll hand it directly over to Carrie.

I expected that. So really good question, so, yes. So, B-cell lymphoma, particularly DLBCL makes sense for CD22. It's something we will think about in our clinical development plans, as we move forward. I think, there's no reason, it's a highly expressed in B-cell NHL as well as in ALL. That said, and it's the same story as you would expect with, as we talked about earlier that it's a, target that there is not quite as much going on in as much competition right now. So it does give an opportunity for patients who have failed other things and could provide potential fast-track for approval. So it's a very good question. And it's something that we are thinking about. In terms of latent virus, absolutely, right, so almost everybody, at some point in their life has been exposed to and has living in them, all these viruses, particularly HHV6 and HHV7, which is an issue. And it's something that we're paying attention to. Unfortunately, unlike some of these other viruses where there are medications that you can get for prophylaxis, there really isn't anything for HHV6 and HHV7 and it is an area of current study in the field. There's really only one medication right now that really works well for it, which isn't something we'd want to give patients as prophylaxis because it has all of these issues with your kidney and other problems. So it is something we have to pay attention to, something we need to watch, and we have to make sure that patients as they are screened and monitored closely for reactivation of these viruses and that when something does happen, where you start to see some reactivation that is pounced on quickly. So it is something to pay attention to, absolutely. And we have incorporated into our trial monitoring and management of all these different latent virus infections, as well as other opportunistic infections that you can see in these patients with or without alemtuzumab quite frankly, to ensure that we're giving the best monitoring and management of these obvious potential problems. So it does not get in the way of developing our product.

Okay, great. And if anyone hasn't seen it, they called, Pennsylvania for Joe Biden. And so he's been called as President of the United States by decision desk.

What?

The next question is from Kelly Shi of Jefferies. Please proceed with your question.

Hi, thank you guys for taking my questions and congrats on the progress. And this is Kelly for Biren from Jefferies. I wonder if you have the information on CD22 expression level of treated patients. I know it's probably early. And also I'm curious if you see the response actually correlates with the CD22 expression level. And another question is, do you have any like, early sign of probably from the biology perspective, such as the CD22 expression level versus CD19 expression levels, I would suggest CD22 targeted strategy could it be better than say CD19 targeted strategy as a single agent therapy? Thank you.

Thanks, Kelly. Very, very important question, and I'll hand it over to Carrie, but obviously we picked CD22 for a reason because we think it's very, very well expressed. Carrie, go ahead.

Yes, I'm sorry. I'm still like reeling from the last comment.

Do you want to repeat? I can.

Yes, just do the first part again. And I heard the second part.

Okay. So the first question is, do you see any – do you see a correlation between CD22 expression level and the responses?

Yes, we haven't looked at that yet. I mean, we do have a requirement of a certain level or higher to get on the first part of the study because we want to make sure that we're not throwing the baby out with the bath water, so to speak. So we haven't done a correlation, because we are requiring a significant expression of CD22 at this point in the trial, but it is something we will be looking at, as we go into later stages of the program. And then as far as the second part of the question, I think as Simon said, CD22, we believe in it. We think it's an important target in ALL and in B-cell malignancies in general. I think that part of the reason, I think CD19 ended up kind of being the number one target for B-cell malignancies is just kind of, because it just was similar to how rituximab happened to just in CD20. And that's why CD20 became so important. But also back in many years ago, there was antibody, epratuzumab to CD22 that didn't really do very much. So I think CD22 fell out of favor a little bit, but we feel really strongly that it's an important target, it's ubiquitously expressed. And it really does provide a really exciting opportunity for patients who fail CD19, because as of right now, given the CD19s are way ahead in development, they will be something that is given first. And we know they relapse without a CD19 often, expression. So I think that we think it's a really important place to be and does provide multiple shots on goal for an approval.

Okay. Thank you. That's very helpful.

Thank you so much.

There are no additional questions at this time. I would now like to turn the call back over to Simon Harnest for closing remarks.

Yes. Thank you so much again, to everyone on the call. We really appreciate your interest in Cellectis. And we think we're really at a very unique moment for the company to start showing a lot of data on our proprietary programs. So we'll keep you posted and feel free to contact us if you have any further questions or would like a follow-up call. Thank you so much.

This concludes today's conference. You may now disconnect your lines. Thank you for your participation.