Cellectis S.A. (CLLS) Q2 2020 Earnings Report, Transcript and Summary

Greetings and welcome to the Cellectis Second Quarter Earnings Call. At this time, all participants are in a listen-only mode. A brief question-and-answer session will follow the formal presentation. [Operator Instructions] It is now my pleasure to introduce your host, Simon Harnest. Thank you. You may begin.

Thank you, and welcome everyone to Cellectis Second Quarter 2020 Corporate Update and Financial Results Conference Call. Joining me on the call today with prepared remarks are Dr. André Choulika, our Chairman and 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 June 30, 2020. The press release is available on our website at cellectis.com. As a quick 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 on file 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 SEC from time to time. I would now like to turn the call over to André. André Choulika: Thank you, Simon. Good morning and thank you everyone for joining us today. I will start with a quick introduction before handing the call over to our Chief Medical Officer, Carrie Brownstein for an update on our clinical programs and our Chief Financial Officer Eric Dutang for a review of the financials. The second quarter of 2020 has been very productive for Cellectis. We continue to be amazed by the commitment and the relentlessness of every nurse and doctor who gives outstanding care to cancer patients at the critical need in these exceptional times. I would like to highlight the outstanding progress of partners, Allogene and Servier have made in driving forward for the development of our lead license candidates UCART19 and UCARTBCMA which Allogene renamed into ALLO-501, ALLO-501A and ALLO-715 respectively. As a reminder, UCART19 or ALLO-501 is exclusively licensed to Servier and Servier exclusively sublicense its right in the U.S. to Allogene. UCARTBCMA or ALLO-715 is exclusively licensed to Allogene. ALLO-501 has made headlines at ASCO in June where our partners Allogene and Servier presented entering Phase I dose escalation data in patients with non-Hodgkin lymphoma with a complete response rate of 44% and an overall response rate of 75% in the subgroup of patients who were naive to CAR T-cell treatment. No GVHD an adequate safety profile this data update comes as a follow-up to the data presented at ASH 2018, where the Phase I dose escalation in relapsed/refractory ALL patients showed an 82% CR rate at an optimal lymphodepletion. UCARTBCMA or ALLO-715 is also progressing nicely into Phase I dose escalation trial in relapsed/refractory multiple myeloma patients. The advancement of our partner program significantly deal with the anticipated milestone and royalty revenue for Cellectis. Cellectis is entitled to receive up to $410 million in outstanding milestones payment, plus a low double-digit royalty on a worldwide sale from Servier and Allogene for the CD19-directed allogeneic CAR-T program, as well as up to $2.8 billion in milestone payment plus a high single-digit royalty on worldwide sales from Allogene DARPA for the 15 licensed allogenic CAR T-cell target including BCMA. On our side, we are pleased to see the progress in patient enrollment for our proprietary allogenic CAR T-cell program for UCART22 for a patient with relapsed/refractory BLL in the BALLI-01 trial, as well as new UCART123 for patients with relapsed/refractory AML in the AMELI-01 trial. Both programs are currently at dose level two in their respective Phase I dose escalation after dosing their first patient in December and January respectively. UCARTCS1 for patients with relapsed/refractory multiple myeloma in the MELANI-01 trial has been put on hold early July, following the death of a patient at DLT and we're currently working with the FDA to address the agency's request and hope to resume the trial. Our strategy is to give an early interim data update on one of our proprietary program in Q4 for this year, at around a relevant scientific meeting. This update will be the beginning of our proprietary clinical data readout, which we plan to give on a periodically at relevant scientific meeting in regular intervals. With that, I would like to hand the call over to Dr. Brownstein, our Chief Medical Officer to discuss the status of Cellectis sponsor trial. Carrie please go ahead.

Thank you, André. As previously mentioned BALLI-01 evaluating UCART22 in patients with relapsed/refractory T-cell acute lymphoblastic leukemia and AMELI-01 evaluating UCART123 in patients with relapsed/refractory acute myelogenous leukemia continue to progress through their respective dose levels in these Phase 1 dose escalation study. The primary objective of these Phase 1 studies is to evaluate the safety of the product candidates and determine an optimal UCART dose and corresponding lymphodepletion regimen. In addition to safety, correlative studies will evaluate T-cell expansion, window of persistence and antitumor activity at all dose levels. As a reminder BALLI-01 is planned to complete three consecutive dose cohorts and AMELI-01 is planned to complete four consecutive dose cohorts, followed by expansion cohorts at the optimal dose and lymphodepletion regimen. The optimal lymphodepletion regimen prior to the administration of allogeneic CAR T-cell product candidates remains an area of investigation in the field of CAR T-cell therapy. One of the fundamental goals of our Phase 1 dose escalation and expansion trials is to determine the optimal lymphodepletion regimen prior to treatment with the allogeneic CAR T-cell product. Cellectis is the patent holder and inventor of the CD52 knockout in allogeneic CAR T-cells that allows the use of a CD52 targeting antibody like alemtuzumab in the lymphodepletion strategy. This concept has demonstrated a prolonged selective host T-cell depletion, which correlated with Allo CAR-T expansion and is already incorporated in the current UCART19, UCART22 and UCART123 constructs. We recently filed protocol amendments with the FDA for both the BALLI-01 trial with UCART22 and AMELI-01 trial with UCART123 to include the evaluation of the addition of alemtuzumab to the cyclophosphamide plus fludarabine lymphodepletion regimen. Importantly this UCART22 program also allows the enrollment of patients who have previously failed prior anti-CD19 CAR T-cell therapies giving these patients with significant unmet medical need another CAR T-cell therapy option. UCART123 is currently in dose level two in patients with relapsed or refractory AML. To date the AMELI-01 study is advancing as planned and importantly we have not seen any adverse safety signals in the Phase 1 dose escalation. Moving on to UCARTCS1. On July 6, 2020 Cellectis announced that the MELANI-01 trial Phase 1 dose escalation and expansion study of UCARTCS1 in patients with relapsed and refractory multiple myeloma had been placed on clinical hold by the FDA. This hold, which impacts only this specific product candidate was initiated following the submission of a safety report regarding one patient enrolled in the study at dose level two. The patient who had been treated unsuccessfully with numerous lines of prior therapy including autologous CAR T-cells experienced a fatal treatment-emergent adverse event toward the end of the 28-day DLT observation period. Clinical evaluation of the case is ongoing and additional details as to the immediate and underlying causes of this event are being collected. Of note prior to the clinical hold being issued by the FDA, we had already decided to expand enrollment at dose level one, which may be an appropriate dose for further evaluation in the expansion portion of this trial and potentially the recommended Phase 2 dose based on assessment of the preliminary, clinical and translational data. We had already begun executing updates to the clinical protocol to reflect this and as well as to monitor and mitigate for potential risks given the novel mechanism of action of UCARTCS1 product candidate. We are working closely with the FDA to address the agency's request. Additional information and an amended protocol are expected to be submitted in due course as we are working diligently with the agency towards lifting the hold in order to advance this promising program in the clinic. With that I would like to hand over the call to our Chief Financial Officer, Eric Dutang for an overview of our first quarter 2020 financials. Eric?

Thank you, Carrie. Cellectis' first half 2020 was driven by strong financials. The cash, cash equivalents, current financial assets and restricted cash position of Cellectis stand alone without Calyxt as of June 30, 2020 was at $282 million compared to $304 million as of December 31, 2019. That reflects $28 million of proceeds received from Servier in connection with the March 2020 amendment to the license development and commonization agreement, which was offset by $48 million of net cash flows used in operating, investing and lease financing activities and $3 million of unfavorable ForEx impact. This cash position will be sufficient to fund Cellectis stand alone operations into 2022. The consolidated cash, cash equivalents, current financial assets and restricted cash position of Cellectis including Calyxt was $317 million as of June 30, 2020 compared to $364 million as of December 31, 2019. The change notably reflects $20 million and $26 million of net cash flows used in operating, capital expenditures and lease financing activities of Cellectis and Calyxt respectively. The Cellectis standalone net income, attributable to shareholders of Cellectis, was $3 million in the first half of 2020 compared to a net loss of $37 million in the first half of 2019. This $40 million increase in the net result, between 2020 and 2019, was primarily driven by a significant increase in revenues and other income of $26 million and a decrease in SG&A expenses of $1 million. That was partially offset by an increase in R&D expenses of $4 million and a decrease in financial gains of $4 million. The consolidated net loss attributable to shareholders of Cellectis, including Calyxt, was $12 million or $0.29 per share in the first half of 2020 compared to $49 million or $1.50 per share in the first half of 2019. The consolidated adjusted net loss, attributable to shareholders of Cellectis, excluding non-cash stock-based compensation expenses, was $4 million or $0.09 per share in the first half of 2020 compared to $39 million or $0.91 per share in the first half 2019. We are laser-focused to spend our cash at developing our deep pipeline of product candidates in the clinic and completing the construction of our state-of-the-art manufacturing facilities in Paris and in Raleigh in 2020. I will now turn the presentation back over to André for closing remarks. André? André Choulika: Thank you, Eric. We continue to invest our human capital and a big part of this is the growth of our in-house manufacturing platform. I'm excited to announce that Dr. Steve Doares recently joined Cellectis from Biogen as Senior Vice President of our U.S. manufacturing site and Head of our Raleigh manufacturing plant in North Carolina. At Biogen, Steve led all aspects of Global Manufacturing Sciences technology transfer and manufacturing process support. We're all looking forward to see his leadership and guidance advance our mission to develop life-changing allogenic cure CAR T-cell product for cancer patients. Dr. Leopold Bertea joined us in May 2020 in the role of Senior Vice President of Technical Operations, Europe. His mission is to ensure execution at the GMP Paris manufacturing facility with support to the development and production of Cellectis proprietary product candidate. Dr. Bertea, joined Cellectis from CELLforCURE, where he was General Manager and site head through the acquisition of CELLforCURE by Novartis. Dr. Bertea and Dr. Doares will be jointly leading Cellectis' technical operation replacing Bill Montes who is leaving the company on August 6, 2020 to pursue other opportunities. Both are joining the company executive committee. We're on track to complete our full manufacturing independence by mid of next year, which will be an important piece of further-established Cellectis as a leader in the allogeneic CAR T-cell field. I personally couldn't be more excited about Cellectis' position in the market today with a healthy lineup of clinical programs that will deliver data and create value for all patients and stakeholders one after the other. It was a long road with many challenges to get where we are today, but we always successfully overcame every challenge in our way. This speaks for the expertise and resilience of our team. We are well capitalized to achieve our next milestone and I'm excited for what is to come out for both our proprietary as well as licensed clinical programs together with our partners Allogene and Servier. With that, I would like to open the call to address any question you may have. Operator, please go ahead.

We will now be conducting question-and-answer session. [Operator Instructions] First question is from Jim Birchenough of Wells Fargo.

Hi, guys. Congratulations on all the progress during the quarter. A couple of questions. I guess first just in terms of the alemtuzumab preconditioning, what's the earliest that we might be able to get a sense on whether that's the optimal approach to preconditioning? And if it turns out that it does become part of the standard of care for allogeneic CAR-T therapy, how could you leverage your IP around CD52 knockout outside of Cellectis? And then I got a follow-up.

Jim, thank you so much. Good morning. Great question. This is Simon. I would like to direct this question to Carrie because she is obviously heading the clinical operations. Carrie?

Sure. Hi, Jim. Thanks for the question. So as we've previously said, we've submitted the amendment to FDA. We have to obviously get all that through at all the sites. We're hoping to have updates on our data as we've already disclosed, hopefully, by – for one of the programs by the end of the year. And it will really all depend on how long it takes to get through all the process that is required for getting changes to protocols updated throughout our sites and through FDA. But I'm hopeful that, we will have data in a reasonable short time frame to better understand that this is the appropriate way forward.

And second part of the question that's a good point on the IP on CD52. So just as a reminder for everyone, we are the inventor and the patent holder of the CD52 knockout in CAR T-cells, together with the concurrent administration of alemtuzumab, which is an antibody that is targeting CD52. So, this obviously is becoming a very interesting patent and concept that we pioneered in 2015 and now becomes to – it looks to become a real standard part of this prolonged persistence. And the question is like there are some programs that may need prolonged persistence of CAR T-cells. In some other cases, you don't want to have that prolonged persistence. But maybe André you can add some comments on our strategy around this. André Choulika: Jim, it's a very good question. And there's a very powerful tool for engrafting and expanding allogenic CAR-Ts in general, but there are flaxy exceptions in there. For example UCARTCSl1 that is definitely in hold today is depleting. Cartiva is supposed to have the same type of action similar to alemtuzumab. So for UCARTCS1 we don't precondition with alemtuzumab and we expect the CAR to have similar activity in there. So all in all, I think this could become one of the standards but there are other alternatives in there that could potentially also bring powerful approach into engrafting in the persistence of the CAR. And the IP of course like it's an important component. And I think Cellectis is being for now like eight years in a row building on this allogeneic approach and gene-edited CAR-T in general and I think that we have like a strong IP estate in there that we definitely are willing to leverage and find the industry. Our goal is not to block us is actively try to enable great options to would like and treat on the medical need in general.

UCARTCS1 and the adverse patient outcome here could you give us any more detail as to whether there were cytokine release syndrome associated with this patient? If this might have related to the self preconditioning of the product? Or if there are patient factors that could be easily excluded going forward?

Again, that's a good question for Carrie. And just upfront Jim, we haven't disclosed any of the details yet because we're still collecting the data and all the information for that patient. But just as we noted this patient death occurred very much towards the end of the DLT observation period which is 28 days long. So, Carrie, if you want to elaborate on that a little bit.

Yeah there's not that much additional to say. I think given they're still gathering information and we haven't disclosed the details at this time I don't want to further elaborate on it at this moment. But I think from what Simon just said, it was really towards the end of the DLT period. It's a complicated story and we will – once we're off hold and we're moving forward and have a plan we will be sharing this information.

Our next question is from Michael Schmidt of Guggenheim.

Hey, guys. Good morning. And thanks for taking my questions. Another question around the multi-myeloma program you did mention that you decided to expand already at dose level one prior to the safety event occurring. Maybe talk a little bit about what gives you confidence that this is the right dose already at this point. And how do you think about the need to potentially explore further doses in the future? Maybe just a few more color around that item.

Yes. So maybe I can start and hand it over to Carrie. So for UCARTCS1, just as a reminder, we started at one million cells per kilogram as a dose. This was with the consideration that UCARTCS1 is also targeting a portion of the patient T-cells expressing CS1, because the CAR-T itself has an edit to remove CS1 from the surface. So this kind of dual action of both targeting multiple myeloma cells and a portion of the patient's T cells led us to initiating the study at a slightly higher dose than for example UCART123 or UCART22. And now, Carrie maybe you can say a little bit of color on what we think the plan forward could be.

Yes. Sure. So thanks so much for that question. As Simon pointed out, so the dose at dose level one in this study was actually very close to some of the final doses for other CAR T-cells that are out there. So we're definitely starting at a higher dose. And as you know we're collecting safety activity translational data as we go along through the dose escalation. So once we open dose level 2, we were starting to get additional data from the first dose level and it just appeared that dose level 1 might. Now again, we didn't say for sure, because it's not -- it's early on in the development and there's still in the dose escalation phase, but it appeared that dose level one may have data that supports further expanding at that dose and potentially being the dose. It doesn't necessarily rule out expanding and exploring other dose levels. But I think the data that we were getting from dose level one seemed to support that it was at least worth further pursuit at that dose level.

Just on the incorporation of alemtuzumab-based lymphodepletion into the other two trial product CARs. I was just wondering if you could provide some additional thoughts on some of the protocol amendments. Are you planning for example to evaluate several different doses of alemtuzumab repeat dosing? Or is it just going to be one cohort in each study that were you evaluate a certain fixed dose? Maybe talk a little bit about how you think about the various parameters that need to be evaluated to optimize the lymphodepletion protocol there?

Yes. I can take that Simon.

Yes, Carrie go ahead.

Okay. So thank you so much for the question. And again, these -- since we're in Phase 1 and we're exploring all of the above so to speak, it's a work in progress. So I think that in my opinion the important piece with alemtuzumab isn't necessarily the schedule per se and how -- when it's given, how often it's given, but it's really more about the balancing the deep selective T-cell depletion that you get with alemtuzumab with the safety. Because as you're well aware we -- the alemtuzumab data has been presented for many years in the context of allogeneic matter what extent cell transplantation. There is definitely risks of viral infections, other opportunistic infections et cetera. So the real key here is to give enough to get the selective T-cell depletion we need without over immuno-compromising the patients such that they can be at significant risk of these types of hypertension infections, which then would defeat the purpose of what we're trying to do for their cancer. So that's the way I'm looking at it and we will be exploring the use of it and looking for the optimal way forward. And obviously that would include all of the above that you bring out. And I don't know if -- I don't think that you need to be trying multiple -- so many different ways of giving it. I mean you can, but I'm not sure if it's -- based on the data that already exists, if it makes that much of a difference. I think we have a good sense from not only the data from Allogene and Servier, but also from data previously with allogeneic cell transplantation of what an optimal dose is and how to give it safely since there are significant risks in terms of infusion-related reactions and other things with alemtuzumab. So I think all of that data together will really help us pinpoint how to do it. So we can move quickly as opposed to having to try one million different ways of giving it.

Question is from Gena Wang of Barclays.

Hi. Thank you for taking my questions. So regarding the UCARTCS1, just wondering I know since the last announcement has been one month, did you have additional communication with FDA? And can you share a little bit more of what FDA is looking for? And when do you think you can submit the package to the FDA? And then second question is later this year 4Q maybe hopefully at ASH, can you lay out the data we might see from all the programs the UCART22 123 and CS1?

Yes, Carrie, first question and maybe André can chime in on the second question.

All right. Perfect. So I'll start. So Gena, thank you so much for your question. And we know that you and others want to know exactly what FDA wants us to do and how quickly we'll move forward. And at this time, I don't think we want to disclose exactly what is being requested. I think what's important to know is that we were in discussions with FDA. They're supportive and we will be moving the program forward and ensuring with their help that we can do it in a smart appropriate way to ensure patient safety which is really the bottom line. So we will be working with them to come up with how we can best do that. That's really all, I can say at this point. But I understand that you'd love to know more.

No worries. And André maybe for the second part of the question how we're building our momentum for data presentation towards the end of the year. André Choulika: Well it's a great question Gena. The idea essentially like we have three trials. One I hope will resume as soon as necessary actually for the FDA and us to be sure that we're going not to repeat the same type of event hopefully. But we have three trials and interesting data to share, but we don't want to -- would like to keep the momentum in there. It's like out from the three trials we'd like to start potentially at the end of this year is releasing part of the data as we always said. And then on a regular basis scientific conferences or organized by us we will release regularly data from each trial and update you on the initial trials also as we think that the development of this is starting without alemtuzumab and adding alemtuzumab with the same doses and comparing the two and advancing is like did those escalation up to the time will arrive into the expansion phases. And I think this would be starting at the end of this year a very rich -- data-rich course for the company and hopefully potentially other things that would come up such as like the kickoff of the manufacturing the go-live of manufacturing site in Paris, the go-live of the manufacturing site in Raleigh that, I think are two very important events in transforming the company into a true biopharma and moving towards I hope for all the three trials for the pivotal trial and potentially registration and commercializing this product.

Which program do you think that we will see the data first? André Choulika: So kind of the trial which trial we're not saying that. Yes it's definitely something that we know it, but like to keep like the suspense up to the end. But as we said, it's going to be very early data on -- like we started the trials at the beginning of this year or end of last year. It will be early and it will be partial at this stage, but I think it's going to be interesting.

Next question is from Biren Amin of Jefferies.

Hi guys, thanks for taking my question. Maybe to start on CS1. For the first dose level, I believe investigators had activated the Rituxan switch. Can you just talk about the patients that receive Rituxan in that first dose level and what caused the investigators to administer on that? And then I guess on the CD22 CAR are you restricting patients that come in that have received prior CD19 CAR based on their prior response to CD19 CAR? And then I guess for both CD22 and the CD123 CARs what -- are you testing different doses of alemtuzumab in those studies?

Yes. I'll hand it over to Carrie to answer these questions. Thank you Biren. Carrie. I guess that you just mute. Potentially we don't hear you.

Oh sorry about that. Thank you. Yes thank you for the questions. At this time we haven't disclosed details about the patients in the CS1 -- the UCARTCS1 study. We're gathering all of our information. We are evaluating what happened with the patient as I said earlier with that patient. And we are -- will disclose and present this data when we have everything available so that we can be making smart decisions about moving forward, as well as giving a full picture as to what happened with the study. So at this point we're really not going to disclose the details about the individual patients and their course. So that's the first part of the question. And the second part I think was about the alemtuzumab, if I'm remembering correctly.

Whether...

Go ahead yes. Please.

The second question was regarding the CD22 and whether patients -- you're enrolling patients based on the prior response of CD19 CAR.

Yes. So patients who've had prior CD19 CAR are allowed -- are eligible for the trial and there have been patients enrolled, but it's not required for entering the study.

Next question is from Yigal Nochomovitz of Citi.

Hi. This is Samantha on for Yigal. Thanks very much for taking my question. Just a broad question just to start with, as you look over the recent ALLO-501 data and you think about correlation to your own program what are the big takeaways from read-through from that data that you think applies to your pipeline?

Hey Again, that's a good question for Carrie. Sorry Carrie, I don't know about you?

I don't know, that's a good -- it's a good question for anyone. So yeah thank you so much for the question. Again, we know that the UCART19 or ALLO-501 is the same construct which is obviously a different CAR, as our entire pipeline. And so I think, all of the data and the positive momentum in that program are reads through very nicely to our entire pipeline as well. And I think that it shows that and really validates our approach. It validates our gene editing. It evaluates -- it validates the constructs. And I think that we could read through significant important clinical as well as just programmatic data to move forward. I think that, it's really terrific. And I think we can take a lot of that in terms of the safety, in terms of the conditioning, in terms of all of the above. So I think it's a really positive important piece of our pipeline and our approach to CAR T-cells. I don't know, if Simon or André have anything additional to add to that. André Choulik: Things like for -- like it depends on the CAR-Ts for example 123 is totally different. And so it's like difficult to connect the two when the targets and the diseases are totally different, but when its B-cell malignancies like 19 over 22 and like it's the same architecture for both CAR-Ts, so totally similar. So it's the same type of structure of the CAR, it's the same type of like two types switch in there. And it was removed for DLBCL, the same type of stock-outs that were made with the same molecule. And it's the same type of diseases DLL and especially DLBCL. So there is potentially some conclusion that some connections that can be made and that's very fruitful to have already a CAR that is far more advanced and where we can tune out the way to do the things with that. So yes, I think the connections place when -- in the same indication for the same type of diseases. But when you go with the new targets, it's totally disconnected I think and then like, it's totally new story that has to be told.

Great. André Choulik: And CD8 for me is very interesting by the way.

Oh great. And that's very helpful and it sort of leads into my next question as well. For UCART22 you're focused on the B-ALL. But I'm curious if you of thought of expanding into non-Hodgkin lymphoma given CD22 also expressed in those tumours. And also Allogene's early data suggest that re-treatment of CD19 CAR-T might not be effective but potentially a CD22 CAR-T could have better results, just curious on your thoughts there, on that opportunity. André Choulik: Well I can take this question by the way. So thank you. So CD19 is an overcrowded target. You have everything against CD19, Bispec, CAR-Ts, Autologous, ReGeniC et cetera. So the pressure on the target a lot of patients is high. Therefore, you have a lot of patients that relapse after CD19 over pressure. That's where we believe, CD22 becomes an interesting product with a very high unmet medical need. Now it has to of course be efficient and provide benefit to the patient. But the over pressure around 19 like name and there's like. I don't know probably 80% of all the clinical trials that on CAR-Ts are targeting 19 over the world. And from Allogene Therapeutics to whatever other type of designs are all targeting the same thing because it did work at a time. So that's why we think we're in an interesting spot here, because it triggers also very high unmet medical need, same thing for BCMA by the way.

Our next question is from Raju Prasad of William Blair.

Hi. This is Sami on for Raju. And jumping off a previous question about learnings from Allogene, since they're developing a next generation their ALLO-501A without the rituximab safety switch, I was curious, if you guys had any plans to produce a similar product one of your either UCARTCS1 switch or UCART123 [Indiscernible]. But if that was an idea you guys had kind of thrown around at all or if you're waiting to see the data Allogene produces. Thank you.

Yes. Thank you for the great question. This is a very important part of our platform strategy because we have all these tools at our disposal. So it's a very interesting position that at Cellectis we find us in, because we were really the first ones to go into allogeneic CAR-T and think of all these parameters with an off switch with CD52 knockout for alemtuzumab, co-injection with different type of gene edits. So it's really kind of turning out to be a very enviable position that we're in because we have the ability to use all these tools at our disposals. So Allogene as you know triggered a larger upfront milestone payment to us with the demand of basically having an ALLO501A version without the rituximab off switch. And from their perspective this was to actually include patients in NHL that have been treated with rituximab in their course of therapy, so to not exclude these patients if that antibody is still present in their system. This is something we could do at any time. We haven't disclosed any program where we would do this ad, but just consider that all options are always on the table for us.

Thanks for taking my question.

The next question is from Wangzhi Li of Ladenburg Thalmann.

Hi. Thanks for taking my questions. Maybe start with a follow-up on the UCARTCS1 patient. I know you cannot share too much, but just curious do you know if the patient has pre-existing cardiovascular conditions or risks?

Thanks Wangzhi for the great question. And again I'm sure Carrie's answer will be the same that we haven't disclosed more information on these spaces. But Carrie if you want to add anything please go ahead.

Yeah. No. I really appreciate the question and I know everybody wants to know, but we really would like to wait and compile all of the data to present the story in a cogent consistent manner once everything is together as opposed to a little bit here and there. But thank you.

Okay. I can understand. So -- but any color if the autopsy what the status of autopsy analysis it's been done, or is it in the process, or just any sense on the time line?

Yeah. Again I don't want to comment on what information and additional data and clinical information we're going to receive and when. But again once we have everything together and we're able to present it all to FDA and have a plan forward, we will work on getting that information presented.

The next question is from the Salveen Richter of Goldman Sachs.

Good morning. Thanks for taking my question. So just kind of a follow-up here on the CD19 population for UCART22. But in the Allogene study when they looked at refractory autologous CAR-T patients, they didn't really have a response or they may have had resistance here. Just curious in your thoughts there as you look at this population if there's any way to kind of adapt from those learnings? And then a second question on Calyxt. Is there a strategy change here with a focus on kind of optimizing talent-based technology? Thank you.

Hey, Salveen, it's Simon. Thank you so much for all the good questions. I will maybe first address Calyxt and then talk about your first question on CAR-T naive versus pre-treated. So Calyxt is just evolving in their business as they have always pursued a strategy of monetizing the talent technology. The company is really a fantastic brain pool to address challenges through gene editing in the ag field that traditional companies just don't have the tool set for. So there's more and more demand for projects that other companies would like us to work on. And the company is also pursuing a very lean business model to have -- first of all the proof-of-concept with the soybean was made to show oh we can develop a product bring it into the market and commercialize it. It's a great product. There's demand for it, but there's a lot of work attached to kind of having this downstream integration but this was to show we can get into 100,000 acres and really build a huge business around this with railroad car access with crusher access for the soybeans et cetera. So that was fantastic work done by the team in record time, given they're the first company in the world that actually commercialize the gene additive agriculture food product. Now the transition is more into an asset light business model to not do it yourself so to speak with establishing that infrastructure, but working with partners to build products together for kind of like in the biotech industry for upfront and milestone fees. So for the question on CAR-T, so it's interesting because Allogene mentioned on their earnings call that they're exploring retreatment of patients. They have seen that patients that for example are partial responders in an initial shot are getting retreated or will potentially be retreated. So we're super excited for that part of the strategy to become more prominent because we think the allogeneic concept is positioned to be this way that you have an off-the-shelf drug that you can dose and where you can do repeat dosing. So that's very exciting. We saw the first data from that actually already a couple of years ago where a handful of patients were retreated successfully. So we're looking forward to what Allogene is working on and we'll be presenting in the future. We think about that type of strategy as well. But in terms of patients that have been treated with autologous CAR T as André said there's a lot of pressure on the CD19 antigen with a prior CAR T treatment whether it's autologous or allogeneic. And that's why we pursue this dual strategy of being first in the pack of an allogeneic CAR T-cell set of companies pursuing very prominent targets with CD19 and BCMA, for example, and these are our license programs. And then the proprietary program that Cellectis are with alternative targets that could address patients that have not responded or basically relapsed without the expression of any given antigen. And Carrie, if you want to elaborate on that further.

Yes. I mean, I think, the question regarding the fact that in the Allogene data that was presented that the patients who had prior CAR T did not seem to have the responses. The other ones, I think, we have to look at the targets as to point Simon. And so in that case it's the same target. So those are in NHL. The auto CAR Ts are also CD19. So it sort of, follows that even though they're going with an allogeneic product, it's still the same target. So it's not unexpected that they were less likely to respond to another T-cell therapy with the CD19. And I think our approach in our case is that it's a different target. So even if somebody had received whether it be an allogeneic product with CD19 that's already been -- that's in clinical trials like Allogene like our UCART19. Or if it's in auto 19 I don't believe that the fact that we're pursuing a different target I don't think it reads through to seeing there being an issue in terms of response.

The next question is from Hartaj Singh of Oppenheimer & Co.

Great. Thank you. Thanks for all the updates. I just had a question on manufacturing. I know that you've indicated on the prepared remarks that the manufacturing should be up and running by the middle part of next year both in Paris and Raleigh now. If you can just kind of walk us through where exactly are you with the three projects. Is this sort of clinical-grade material? And at some point as you move to larger clinical trials next year you will transition to commercial-grade material. I mean FDA has indicated that this is one of the really big rate-limiting steps for most cell therapies and it seems like you're close to potentially solving it. So could you just walk us through your -- how you see that transition happening for these three projects assuming they move on to larger pivotal trials with clinical to commercial manufacturing? And I just got a quick follow-up.

Yes. Thanks. That's a great question Hartaj. And this is kind of the basis of what we're doing is really differentiating ourselves with a rich pipeline of different programs and that are all going to be manufactured in-house. So this transition... André Choulika: I can...

Yes, André you can go ahead. André Choulika: Simon, maybe I can answer very simply the question to Hartaj because the answer is very simple. We are not starting by having the grading of the production at our manufacturing plants clinical supplies first and then upgrade it to commercial. We already start as if we're producing the pivotal and commercial CAR T and the grade will be commercial at start, but it will produce also our clinical supply. So it will be already totally fully GMP and inspection et cetera. So we're -- it's not done in two steps. It's a one full step for commercial and then it will be producing clinical supply there.

Great. André that's very helpful. And then so it seems like the as you go to larger trials and potentially pivotal trials any one of these three projects you should the CMC part of future application is sort of already kind of mostly locked into place? André Choulika: Actually, can you rephrase your question? I'm not sure I understood.

Yes. So I apologize. Yes. So assuming a future new drug application NDA for one of the three projects CMC is one of the three sections right preclinical clinical and CMC. So is it a good assumption on our part that moving forward your CMC portion of a potential future NDA is already sort of mostly as a company you have great visibility into that in terms of that section of a potential NDA following with the FDA. André Choulika: Well, yes, exactly. Like the goal is to start putting all the procedures internally to fulfill like CMC section for the FDA. That's the plan frankly. And we're preparing the company to -- because we don't know how these trials will go. But you always plan for success and that's what we're doing. If it's successful and the CAR-Ts are -- give promising results especially for example in AML or in ALL and there is like a very strong medical need in there and it can go pretty fast. So, it's better to be ready ahead of time and not to do it in like several steps. And so that's like the target is definitely in the DLA at the end. And that's what we have in view in there only.

Great. André that's very helpful. And I think that's very forward-looking. Another question is -- and you might have addressed this in your prepared remarks, so I apologize I just caught a little late. But you've managed to bring basically one product to the clinic over the last three years. You've got three in the clinic right now. And I know you've got a lot on your hands in all three. But what are your thoughts in terms of bringing more projects into the clinic? Are you still hoping to keep to that one project per year into the clinic goal? Or you think that the next one or two could take a maybe just a little bit longer? And thanks for all the questions. André Choulika: It's an excellent question because we needed to ramp up our clinical capacity and production capacity because the space is becoming overcrowded. So, like name it like gene therapy like retroviral vectors, gene editing, cell therapy, and immuno-oncology. You said all the buzzwords in the space and like everyone jumping in there. So, the goal we have, the strategy we have is like to positive terms of INDs up to the time we ramp up in terms of capacity for production will be fully fledged next year with the Raleigh side going live and Paris side going live this year will be producing like nucleic acids and vectors and also ramping up since the arrival of Carrie that's totally transforming all the clinical department in the company and ramping up also the department to large capacity. I give you rendezvous for I hope like in 2021 at an R&D Day, we will unveil all the thing that makes Cellectis so much distinctive and most of other companies are innovation department that is very, very productive. Like you can see through most of the publications but we decided to paying this down in terms of communication for now and we hope once there will be releasing the pressure over the clinical data and started releasing the data by the end of this year, we'll have maybe an appointment and like a nice R&D they will be able to show what is the power of this pipeline behind it and start releasing new INDs at this time. And I think that's going to be a very exciting time because very proud of our R&D department that I think is one of the most the of all the cell therapy and gene therapy space.

Our last question is from Madhu Kumar of Baird.

Hi, Rob on here for Madhu. I was just wondering how do you think you can use your candidates post-CAR-T? And if there are any specific safety concerns?

Carrie, would you like to start with that?

Sure. Just can you just clarify again what your -- the question? I'm sorry. It wasn't quite clear.

Sure. I was just wondering how do you think about the use of your candidates post auto CAR-T? And are there any specific safety concerns?

Sure. I don't see there being an issue using them post auto CAR-T at all. I think that obviously we're always in Phase 1 and in early studies looking at safety. Obviously, when someone's been previously treated with an auto CAR-T, they've received similar lymphodepletion prior to those products. So from that perspective, you may want to look a little bit closer at that. But from the perspective by the time they would be progressing from their prior therapy and getting to our study, there wouldn't be necessarily auto CAR-T around anymore. They wouldn't have been progressing. So I don't see there any being any real concern with those patients versus patients who hadn't received a prior auto CAR-T. But obviously, it's an area of -- a new area that needs to be focused on and pay attention to. But I don't foresee any specific issue that I would be concerned about.

All right. Thank you.

Sure.

That concludes our question-and-answer session. Thank you. I would like to hand the call back to Simon for closing comments.

Yes. Again thank you all very much for all these great questions and your patience in getting through the Q&A. We always love to hear.