Greeting and welcome to the Cellectis First Quarter 2022 Corporate Update and Earnings Call. At this time, all participants are in a listen-only mode. [Operator Instructions] As a reminder this conference is being recorded. I would now like to turn the conference over to your host Mr. Arthur Stril, Chief Business Officer for Cellectis. Please go ahead, sir.

Good morning and welcome, everyone, to Cellectis’ first quarter 2022 corporate update and financial results conference call. Joining me on the call today with prepared remarks are Dr. Andre Choulika, our Chief Executive Officer; Dr. Carrie Brownstein, our Chief Medical Officer; and Dr. Bing Wang, our Chief Financial Officer. Yesterday evening, Cellectis filed its interim reports and issued a press release reporting its financial results for the first quarter and three-months period ended March 31, 2022. The report and press release are available on our website at cellectis.com. As reminder, we will make statements regarding Cellectis' financial outlook in addition to its manufacturing, regulatory, and product development plan. These forward-looking statements which are based on our management's current expectations and assumptions and on information currently available to management, including information provided or otherwise publicly reported by our licensed partners, 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 reports, including the management report for the year ending on December 31, 2021 and subsequently filings Cellectis makes with the Securities and Exchange Commission from time-to-time. I would now like to turn the call over to Andre.

Thank you, Arthur. Good morning and thank you everyone for joining us today. Cellectis made progress with our pipeline this quarter. We took a notable step forward with the first pre-clinical data on UCART20x22, the allogeneic dual CAR T-cell product candidate being developed for patients with relapsed or refractory non-Hodgkin’s lymphoma or NHL. We were proud to see that the data demonstrated a robust pre-clinical proof-of-concept with strong activity against tumor cell lines expressing either a single antigen, CD20 or CD22, or both simultaneously. We remain on track to file an investigational new drug for UCART20x22 this year. UCART20x22 is expected to be Cellectis’ first product candidate with fully integrated in-house development. This showcases our transformation into an end-to-end cell and gene therapy company from discovery and pre-clinical development to product development and transfer into GMP manufacturing and to clinical development. We were proud to announce two back to back publication in major communication providing strong validation of UCART123 to treat acute myeloid leukemia or AML and blastic plasmacytoid denditric cell neoplasm or BPDCN. This is the first preclinical data published on UCART123 that supports our rationale for evaluating these allogeneic UCART123 in the clinic. While the few CD123 T-cell therapies evaluated to date rely on autologous approaches with complex clinical and logistical challenges, this set of preclinical data strongly supports the potential benefits of the allogeneic CAR T approach in AML and BPDCN. We are proud of these results that reinforced our commitment to cancer patients, specifically in very hard to treat diseases like AML and our mission to address unmet medical need. Our partnership provide to be an exciting highlight with Cellectis. In January, Allogene announced that the U.S. Food & Drug Administration removed the clinical hold on their clinical trials, which was announced on October 2021. Allogene…

Thank you for that overview Andre. UCART22, our CD22 directed TALEN gene edited allogeneic off the shelf CAR T-cell product candidates currently being evaluated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia continues to make progress in the clinic. At the annual meeting of the American Society of Hematology in December 2021, we released encouraging early data from the first set of patients who received UCART22 after lymphodepletion with fludarabine, cyclophosphamide and alemtuzumab in the BALLI-01 trial. These preliminary data shows that adding alemtuzumab to the fludarabine and cyclophosphamide lymphodepletion did not adversely affect the overall safety profile. Further, the addition of alemtuzumab sustained host lymphocyte suppression, and promoted expansion of UCART22. Signs of anti-leukemic activity of UCART-22 was observed. BALLI-01 is currently enrolling patients at dose level 3 and we plan to initiate the administration of UCART22 batches manufactured in-house from our Raleigh facility in the second half of this year. This month, we announced our first publication on UCART123 in nature communications providing strong preclinical validation of UCART123 to treat acute myeloid leukemia. Our AMELI-01 study evaluating UCART123 in patients with relapsed and refractory acute lymphoblastic leukemia continues to progress and enroll patients with Fludarabine, Cyclophosphamide and Alemtuzumab pre-conditioning regimen. We look forward to sharing clinical data from this program when it becomes available. I will now speak to UCARTCS1, our CS1 directed TALEN gene edited allogeneic CAR T-cell product candidate being evaluated in patients with relapsed or refractory multiple myeloma. Cellectis’ MELANI-01 evaluating UCARTCS1 is currently enrolling patients at dose level one who Fludarabine and Cyclophosphamide pre-conditioning. Lastly, I'm excited to announce that we anticipate filing an IND this year for UCART20x22, Cellectis first allogeneic dual CAR T-cell product candidate being developed for patients with relapsed or refractory non-Hodgkin’s lymphoma. UCART20x22 features TALEN mediated disruptions of both the attract gene to reduce the risk of graft versus host disease and the CD52 gene to permit use of CD52 directed monoclonal antibody in the pre-conditioning to enhance CAR T [indiscernible] expansion and persistence. Dual targeting of CD20 and CD22, both validated targets in B-cell malignancies is designed to enhance tumor cell killing and to prevent immune escape due to single antigen targeting. UCART20x22 has the potential to offer an alternative to CD19 directed therapies and CD19 negative relapses. This April Cellectis released preclinical data on UCART20x22 at the American Association for Cancer Research Annual meeting. These data established robust, preclinical proof of concept, and demonstrated with the potential to overcome common mechanisms of resistance to Car T cell therapy such as single antigen escape and tumor heterogeneity. As we previously stated, an investigation on new drug application for UCART20x22 is expected to be filed this year. With that, I would like to hand the call over to Dr. Bing Wang, Cellectis’ Chief Financial Officer for an overview of our financials. Bing, please go ahead.

Thank you, Carrie. I will provide a brief overview of our financials for the first quarter 2022. I would like to highlight that our financials, the cash, cash equivalents, current financial assets, and restricted cash position of Cellectis, exceeding Calyxt, as of March 31, 2022 was 142 million, compared to 177 million as of December 31, 2021. This difference mainly reflects 33 million net cash flows used in operating, investing, and lease financing activities, and 2 million in negative foreign exchange impact. Based on the current operating plan and financial projections, this cash position is expected to be sufficient to fund Cellectis standalone operation into early 2024. The consolidated cash, cash equivalents, current financial assets, and restricted cash position of Cellectis, including Calyxt, was 160 as of March 31, 2022, compared to 191 million as of December 31, 2021. The net cash flow used in operating capital expenditure and leases were 33 million at Cellectis, and 7 million Calyxt in the first three months of 2022, partially offset by a 10 million capital raise at Calyxt. The net attributable loss to shareholders of Cellectis, excluding Calyxt was 20 million in the first three months of 2022, compared to a loss of 6 million in the first three months of 2021. This 23 million increase in net loss between 2022 and 2021 was primarily driven by a decrease in revenues and other income of about 19 million and a decrease in net financial gain of $4 million. The consolidated net loss attributable to shareholders of Cellectis, including Calyxt was 32 million or $0.70 per share in the first three months of 2022, compared to a loss of 12 million or $0.28 per share in the first three months of 2021. The consolidated adjusted net loss attributable to shareholders of Cellectis, excluding non-cash, stock-based compensation expenses was 29 million or $0.64 per share in the first three months of 2022, compared to a loss of 11 million or $0.26 in the first three months of 2021. We are laser focused to spend our cash on developing our deep pipeline of wholly-owned product candidates in the clinic and operating our state-of-the-art manufacturing facilities in Paris or in Raleigh. On the other hand, our focus on maintaining an efficient corporate infrastructure should enable more limited growth in G&A expense.

Thank you, Bing. To close out this call, I would like to reiterate how excited we are about the continued progress of our clinical trials and the upcoming milestones for 2022 pioneering this field like this continually leverages gene editing and a series of breakthrough innovation into clinical development in order to transform lives of patients with cancer and rare genetic diseases. And we look forward to continuing this effort in the second quarter of 2022 and beyond. Cellectis’ proficiency and command of gene editing technology has enabled the successful development of the robust pipeline of novel preclinical product candidate, which are designed to overcome the challenges of cell based cancer treatment and gene therapy. At Cellectis, we strongly believe that our product candidate, our technology, and our in-house manufacturing capabilities will lead us to paradigm shift for patients with hard to treat cancer, positioning us at the forefront of this promising medical and scientific deal. With that, I would like to open the call for Q&A.

Thank you. [Operator Instructions] Our first question comes from the line of Gena Wang with Barclays. Please proceed with your question.

Thank you for taking my questions and congrats on the progress. So, maybe I would just start with a big picture question. I'm pretty sure you also saw, yesterday, the [indiscernible] release we first, saw the different approach try to improve the persistence or like a host versus graph regarding the allogenic CAR T using [indiscernible] knock out approach. Any thoughts there, do you think and you have a slightly different approach, do you think what could be a better approach or you think it's due too early at this point?

Hi, Gena. Thank you so much for the question. And I think this one is probably one for Andre.

Thank you, Gena Thank you for the question also it's appreciated. Of course, like this has been investigated series of different type of approaches to tackle the host versus graft as well as the graft versus host and we've been very much advancing series of different type of ways to do this. Of course, the first one that has been always used in the company since 2015 is the CD52 knockout plus TCRαβ knockout, TCRαβ for [GBHD] [ph] and CD52 to resist pre-treatment with Alemtuzumab, which has been today used as the platform in Cellectis, but also with our partner Allogene and [indiscernible]. Of course, one of the products does not get into this category, which is CS1 to treat multiple myeloma where we knock-out CS1 and CS1 is present a lot of different type of immune cells. Therefore, UCARTCS1 that has the knock-out of CS1 to prevent the [indiscernible] killing, has a self-lymphodepleting activity itself and self and graft. We've shown this last year at ASGCT and we see that the CAR does provoke self and graft in the patient and can pay for several weeks or/and month in the patient and can clear the tumor during this period. So, that's like a very interesting procedure of CS1 for the depleting and self and grafting CAR T such as CS1, but not all the targets have this property. And I think that it's going to be interesting for the next ASGCT there will be probably some approaches that Cellectis has been using and developing for many years that are going to be presented by one of our scientists at GCT, so we'll communicate very soon on this. So, there are series of things that can be – that approaches that we can do in this space. And of course, we are not bound to one way to do it, but several different ways. And of course, every very often copied.

Okay. Thank you very much.

Thank you. Our next question comes from the line of Yigal Nochomovitz with Citigroup. Please proceed with your question.

Hi, Andre, and Bing and team. Thanks taking the question. I just had two on 20x22. So first, with regard to the manufacturing capacity in Raleigh for 20x22, can you just expand on what is the current manufacturing capacity down there? And what do you expect to be the peak manufacturing capacity? And then secondly, obviously since you have two antigens in the one-cell product, does this mean that you're going to be able to get away with a lower dose or will you still be expecting to dose in the same range as with your other products? Thank you.

Hi, Yigal. Thank you so much for both questions. They are great. I will take the first one on manufacturing and then hand it over to Carrie for the clinical question. So, on manufacturing, I mean, we're extremely excited that both our Paris and Raleigh manufacturing are now up and running, which really allows us to manufacture the entirety of our product from A to Z. So, including buffers, plasmid DNA; mRNA, which is delivered with our proprietary electroporation devices, viral vectors all the way to the allogeneic CAR T candidate product in Raleigh. So that's truly a big milestone for the company and we definitely designed Raleigh to be supporting the entirety of our allogeneic CAR T clinical trials and then moving forward the ability to be geared up for commercial supply. So that's definitely the plan. And I will hand it over to Carrie for the clinical question on 20x22?

Hi, Yigal. Nice to hear from you. So, yes, that's a really good question about the dosing. I think the dual antigen targeting on 20x22 is really designed for a couple of things. One is, enhance the [indiscernible] between the tumor cell and the allogeneic dual CAR T to promote the expansion, as well as potentially help with antigen escape from relapse. So, I think there's different reasons for why the two antigens on our CAR for two antigens on ourselves would be helpful in the clinic. That said, it's hard to determine upfront how that's going to translate to dose and that's why like anything else we have go through our dose escalation trial and we'll see where we land.

Understood. Thanks.

Thank you. Our next question comes from the line of Kelly Shi with Jefferies. Please proceed with your question.

Thank you for taking my questions. My first question is on UCART20x22, could you share progress so far in the manufacturing in-house products and how far are you in tech transfer and the process validation? And the second question is, what are the anticipated milestone payments over the next 12 months to Cellectis? Thanks.

Yes, great. Thank you so much, Kelly. So, on the first question, so UCART20x22 has been manufactured at Raleigh, just by way of reminder, this year, we've announced that we will be replacing the current version of UCART20x22 manufactured at our CMO with UCART20x22 manufactured in-house. So, manufacturing has happened at Raleigh. We're finalizing the release and then we'll be filing the data with FDA in order to be using the product in the clinic by the end of the year at second half of this year. So, that's obviously going to be a great milestone and we'll definitely share that with you in the second half of this year. Now, regarding the milestone payments. I think the main significant milestone that we're expecting this year is the entry of pivotal trial of ALLO-501. So, the anti-CD19 allogeneic CAR T product candidate we licensed to all. So, Allogene has guided that they will enter pivotal trial with ALLO-501A in mid this year, which will trigger a milestone payment to Cellectis. And we'll definitely have other milestones… sorry, please go ahead.

Sorry. Go ahead.

I was going to say, we will also have other milestones that are coming from Allogene partnerships with Allogene, Iovance, and Cytovia.

Thank you very much.

Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question.

Hi, thanks. This is Matt on for Salveen. Just a quick question on 123. When do we likely assume to show Phase 1 data? I know you didn't guide anything specific on the CAR in the press release, but I was wondering when that could be likely? And then could you remind us of the registrational path, if those data are positive, when would you potentially move into a pivotal study? And then also for 123, are you thinking about the market opportunity with regard to fit versus unfit, is there anything we should consider there in AML? And then separately on the partnerships, are there any assets or indications you're most excited about? Thank you very much.

Great. So, I will hand over the 123 clinical questions to Carrie and then I will take the question on partnerships at the end.

Hi, thanks so much for that. So, we're still extremely excited about the UCART123 program. You know as you are well aware, even just based on your questions AML, particularly relapsed or refractory AML is an extremely challenging disease to treat. The patients are extremely fragile and it's difficult to move through given some of the difficulties of AML. That said, we remain extremely excited about the program and moving it forward. We haven't guided yet as to when we're going to share data, but what I can say is that we're, moving the program forward, we’ve extremely excited investigators. We're very engaged in the program and we're moving through to ensure that we have the right clinical development plan and the right path forward.

Yes. And so on the partnership, I mean, I think what's very interesting with the current pipeline is, we have several shots on goal. We will have four shorts goal as soon as you got 20x22 is in the clinic this year with – in very different hematological malignancies with very different risk profiles. So, I think all these assets are definitely interesting and I think having the ability to have these different products altogether in our pipeline is definitely a defining asset for Cellectis.

Thank you. Our next question comes from the line of Jack Allen with Baird. Please proceed with your question.

Hi team. Congrats on the progress and thank you so much for taking the questions. I just have one right now and it's with regard to the IP, we saw some interesting data from a competitor care view yesterday with their CD19 targeted allogenic CAR T. They use a unique gene-editing sequence, but I believe you have IP on the TCR knockout with a variety of gene editing modalities, I was hoping you could just touch on that a little bit more and how you plan to leverage your unique IP position as it relates to that aspect of creating allogenic cell therapies? Thanks so much.

Thanks, Jack. Excellent question. I'll hand it over to Andre for this one.

Well, of course in the cell and gene therapy, the IP space is always changing and what is interesting for Cellectis position is that we've been based in this space for a very long period of time and we've been in [indiscernible] series of different type of IP going from like gene-editing patents that are umbrella patterns covering also TALEN, [marketplaces] [ph], but also [Crisper] [ph]. And we've been using also a lot of our IP and covering all the innovation that the company has been doing from lymphodepletion regimen to the engrafting of the cells and going through, for example, like the questions we had before such as knocking out certain genes to enhance engraftments such as CD52, beta-2 microglobulin or replacement by HLA-E etcetera with a very nice package of IP around. Well, now – none of these drugs have been for now commercialized or therapies have been commercialized. And so, today the situation is that all the competition is still in clinical development and we hope that the first product to be to file BLA will be the one from our partner Allogene ALLO-501A, would be potentially the first one to file a BLA soon. And then once the other competition will start hitting the market that would totally change the position and I think then the IP will become an interesting asset for the company that holds a very large amount of IP. Now commenting all this more in detail, of course will be something that we're referring to do. I hope that answers the a question.

[Indiscernible] great contact. Thank you so much.

Thank you. Our next question comes from the line of Hartaj Singh with Oppenheimer. Please proceed with your question.

Great. Thank you for the two questions and all the really nice updates. The first question is on [20x22] [ph] the project you're going to file the IND on. I'm sure you're getting, close to getting the protocol finalized there for your Phase 1 dose escalation dose expansion. Can you just maybe give us some idea of what that could look like? Will it on with CD19 refractory patients, could it be sort all commerce in that area CD19, CD20, how do you envision the dose expansion, dose escalation happening and then going into dose expansion? That's number one. Number two is a financial question. So, if I just do kind of rough back of the envelope math, it looks like cash runway to 2024 means we have to, kind of make an assumption that you are going to get about $30 million to $60 million from potentially your partners coming in through milestone payments, and we're not looking for guidance there, but that's a pretty good chunk of change coming in. Can you just maybe give us some color around that over the next essentially 12 months to 24 months. That's sort of that runway. Thank you.

Hi, Hartaj, and thanks so much for the questions. The first one is definitely for Carey and I'll hand it over to Bing for the second one.

Hi, Hartaj. How are you? Good to hear from you. Yes. So, we're incredibly excited about the UCART20x22 program. As you are well aware, NHL remains high unmet medical need and what I think is great about our program has been also in a space where there is a tremendous proof of concept, not only for autologous CART cell therapy, but for allogenic as well. You know, we haven't disclosed what our Phase 1 design is going to look like. Suffice to say, it'll be on clinicaltrials.gov, when we open it, you will see it then, but it's, you know, it'll look like your – it'll be interesting and I think we are in a good place to move this through very quickly, given the proof of concept that's already there. Thank you for asking.

Great. Thanks Carrie.

Sure.

And Hart, on your cash question, we are comfortable with our cash position right now. And you're right, this is based on some assumptions on milestone payment. And we have already provided those guidance and that is all we can answer on that question for now.

Great. Alright. Thank you Bing.

Thank you. Our next question comes from the line of Raju Prasad with William Blair. Please proceed with your question.

Thanks for taking the question. Just curious to know, kind of as you're taking 20x22 into the clinic, you know expectations for, you know could we see this approach extend durability? I mean, I think Allo rejection has still been kind of the big question here and I was wondering, kind of is it antigen specificity that you think is the reason why we're seeing it in some of the 19 and 20 candidates that we've seen in the clinic thus far? And then I have a question after that.

Hi, Raju. Very interesting question. I think Carrie is probably the best place.

Sure. I think as I mentioned earlier, I think the dual antigen approach is more about having increased contact with the tumor cells or potential improved expansion, improved killing etcetera, as well as for patients who are [indiscernible] who may have had lots of antigen, you have the opportunity to kill both or actually cells that are only expressing 22, those that only express 20 and those that express both. So, it really provides a much broader killing mechanism than with a single antigen. In terms of persistence, again, I think that in the allogenic space, we are looking for a certain amount of persistence in order to have the appropriate engraftment and expansion and killing, but we're not necessarily looking for a long-term persistence. And I know in the auto space, mainly because there's not an easy ability to re-dose, as well as at least the data from AOL, which is really the only data that's shown is that long-term persistence that facilitate with the longer-term durability. We want durability of our responses. We don't necessarily need durability of ourselves more than enough to do the killing. So, I think again, we're going to continue with our approach that we think is a really terrific approach, which is the CD52 knockout, using Alemtuzumab it allows to kind of dial-in and dial-out the persistence as needed, because as you well know outside of the B Cell space, there's really not that many antigens out there that you would want to have persistence for a significant period of time. So, we really strongly believe in our current strategy. And we think that we're going be able do the persistence we need to see durable responses.

Great thanks. And then I just wanted to get some comments on some of the NK cell, AML data that was announced earlier this year. Just kind of curious on your thoughts on how that sets up, kind of the 123 readout when the NK cells cell approach is showing some MRD negativity in their CRs, is that something that you think that we should anticipate with a 123 T-cell approach? Thanks.

Yeah. Carrie, this one is for you as well.

Sure. I was extremely excited to see the [indiscernible] data. Again, I think that, and as I said earlier in the call, AML is such a horrible aggressive disease and as many shots on go to improve the lives and the outcome of patients with AML is an incredibly positive thing. So, we were really happy to see that data. And I think it actually bodes well for our programs as well and shows that allogeneic approach can work in the context of AML. So, we are looking forward to sharing data when we have it available and we're still, as I said, believe strongly in the program and have very engaged investigators. So, I think when we have the data share, we will share it.

Thanks Carrie.

Sure.

Thank you. Our next question comes from the line of Silvan Tuerkcan with JMP Securities. Please proceed with your question.

Thank you. Thanks for taking my question and congrats on that progress. I have two quick questions. The first one, about the [indiscernible] data that came out yesterday. The Caribou, they use a more enhanced lymphodepletion regimen. So, is that something that you may be looking at seeing that they kind of thread the needle and that may be responsible as well for the greater expansion and it's not only the PD1 KO here? And then my second question was around what are the learnings from your ongoing trials and also maybe from the Allogene trials that you can leverage directly to UCART20x22 to inform dosing lymphodepletion and kind of selection, patient selection? Thank you.

Hi Silvan. These are two great questions and I'll pass it over to Carrie.

Yes. Thanks. Thanks so much Silvan. So, yeah, I mean, I think their data is interesting. But I do think that the enhanced lymphodepletion, particularly higher doses of [flu] [ph], you have to be super careful, right? It's very dependent on the disease that you're treating and in addition to the doses. So for example, in the context of lymphoma, those patients are a little more sturdy. They're healthier. They're less fragile. Their marrow hasn't been completely desecrated by multiple rounds of chemotherapy. And so, higher doses of [indiscernible] maybe okay and those patients and not lead to higher issues from toxicity. I'm sure you saw for example the, it was I think it was the precision data in AOL and NHL where they gave much higher doses of [indiscernible] and they saw a significant toxicity actually and leading to [great side effects] [ph] from infection and among other things. So, it's a very fine needle to thread, which is why, again, our approach is also an enhancement to depletion, but not with giving more chemo, but with the flu, sorry with Alemtuzumab CD52 knockout, because it gives us selective lymphodepletion and selective T-cells, NK cells, and other lymphocytes as opposed to knocking out someone's marrow. And that approach, and you know we know the drug well. It has a profile that we understand well. We have very strong guidelines in terms of toxicity management for infections, which are – you know been published by [NTCN] [ph]. So this is something that's been around for a long time, and we're very comfortable with and allows us to have much more manageable and manageable and tweaking, so to speak of what that lymphodepletion may look like for specific patient populations. So, we're sold on what we're doing and we'll see how their data, how their data progresses as time goes on.

Thank you. Ladies and gentlemen, that concludes our question-and-answer session. I'll turn the floor back to Mr. Choulika for any final comments.

Thank you very much everyone for your time. I know we're in a very special period for cell and gene therapy. There is a lot of trials ongoing, a lot of different methods that are ongoing using different approaches for lymphodepletion, for CAR expansion, different type of [AAV’s] [ph], etcetera, but we see also that Cellectis has been very interestingly positioned us with our partners, Allogene, Servier, but also Cytovia and Iovance into a fantastic space where we're being leading into this space. Now, when we come up with another CD19 allogenic data that comes out like from a new conference, with a new approach, etcetera, it doesn't make the thing where we see that with us, with our partners are getting into new phases and probably the first products that are going to get two registration at the end will come up from labs that have been selected for a long period of time and we're being excited about what we're doing. And we are excited also by providing some data on our four asset, 22, which is differentiated; 123, which is differentiated; 20x22, which is differentiated in non-Hodgkin’s lymphoma, and finally CS1 in multiple myeloma. So, please watch a bit what's going to happen in the company and I think the next month is in this for whole cell and gene therapy space is going to be very interesting and Cellectis is here to contribute to this space. Thank you very much for your time, and have a good day.

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