Good morning, everyone and welcome to Cellectis Fourth Quarter and Full Year 2022 Earnings Conference Call. [Operator Instructions] Please be aware that today’s conference call is being recorded. I’d now like to introduce you the first speaker, Arthur Stril, Chief Business Officer. You may begin.

Good morning and welcome everyone to Cellectis fourth quarter and full year 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. Bing Wang, our Chief Financial Officer; and Dr. Mark Frattini, our Chief Medical Officer. Yesterday evening, Cellectis issued a press release reporting its financial results for the fourth quarter and full year 2022 ended December 31, 2022. The press release is available on our website at cellectis.com. We expect to file the annual reports in the coming days. As a reminder, we will make statements regarding Cellectis’ financial outlook in addition to its manufacturing, regulatory and product development status and plans and product development of its license partners. These forward 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 Securities and Exchange Commission, SEC and the financial reports, including the management report for the year ended on December 31, 2021 and subsequent filings Cellectis makes with the SEC 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. 2022 has been a milestone year for Cellectis. We have reached key milestones for our clinical trials that we are thrilled to share with you today. In December 2022, Cellectis presented positive preliminary clinical data from 5 additional patients from our BALLI-01 trial evaluating UCART22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia or ALL. In this Phase 1/2a study, the 5 additional patients received UCART22 at dose level 3 after lymphodepletion with fludarabine, cyclophosphamide and alemtuzumab, or FCA preconditioning regimen. These results showed evidence of UCART22 anti-tumor activity observed in 3 of the 5 or 60% of the patients. Overall, these preliminary data support the continued administration of UCART22 after FCA linked to depletion in patients with relapsed or refractory B-cell ALL. We are excited by these preliminary clinical responses for ALL patients who have limited, if any, treatment options, especially for those who have failed prior CD19 directed CAR-T cell therapy and allogeneic stem cell transplant. UCART22 is currently the most advanced allogeneic CAR-T cell product in development for B-cell ALL. We believe that our off-the-shelf treatment approach, coupled with our ability to manufacture our UCART22 product candidate completely in-house, give us a main advantage on market. It potentially maximizes the chances for eligible patients to be treated without delay. In December 2022, we also presented encouraging preliminary clinical data from our AMELI-01 study evaluating UCART123 in patients with relapsed or refractory acute myeloid leukemia, or AML. An oral session at the American Society of Hematology, the preliminary data showed that adding alemtuzumab to the fludarabine and cyclophosphamide lymphodepletion regimen was associated with sustained lymphodepletion and significantly higher UCART123 cell expansion, which correlated with improved anti-tumor activity. 25% of patients at dose level…

Thank you, Andre and good morning everyone. As Andre mentioned, 2022 has been a productive year for Cellectis with our proprietary clinical programs making progress and we were specifically excited to share additional preliminary clinical data from our BALLI-01 trial evaluating UCART22 in a live webcast last December. BALLI-01 is a Phase 1/2a open-label, dose escalation trial currently evaluating the safety and clinical activity of UCART22 given an escalating dose levels after lymphodepletion with fludarabine, cyclophosphamide and alemtuzumab or FCA regimen in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Alemtuzumab was added to the lymphodepletion regimen to sustain host T-cell and NK-cell depletion and to allow for UCART22 cell expansion and clinical activity. Compared to the last clinical update on BALI at ASH 2021, the webcast presented after the ASH meeting in December revealed data from 5 additional patients who received UCART22 at dose level 3, 5 million cells per kilogram after lymphodepletion with FCA. No dose-limiting toxicities, Grade 2 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome or adverse events of special interest were observed. Evidence of UCART22 anti-leukemia activity was observed in 60% or 3 of the 5 patients at dose level 3. One patient experienced a durable minimal residual disease negative complete response with incomplete count recovery that continued beyond 6 months as of December 2022. The second patient experienced a minimal residual disease negative complete response that continued beyond day 70 as of December 2022. And the third patient experienced a minimal residual disease-negative morphologic leukemia-free state that continued beyond day 84 as of December 2022. As Andre mentioned, these preliminary data support the continued administration of UCART22 after FCA lymphodepletion in patients with relapsed/refractory B-cell ALL and are very encouraging for patients who have limited, if any, treatment options, especially for…

Thank you, Mark. I will provide a brief overview of our financials for the fourth quarter of 2022. I would like to highlight that our financials, the cash, cash equivalent, current financial assets and restricted cash position of Cellectis, excluding Calyxt as of December 31, 2022, was $95 million compared to $177 million as of December 31, 2021. This difference mainly reflects $104 million of net cash flow used in operating, investing and lease financing activities, and $6 million of negative foreign exchange impact, partially offset by $6 million of cash received related to research tax credit prefinancing and $22 million received from milestones and licensees. On the current operating plan and financial projections, this cash position is expected to be sufficient to fund Cellectis’ stand-alone operations into the third quarter of 2024. On January 13, 2023, Calyxt, Cibus and certain other parties entered into a merger agreement, pursuant which Calyxt and Cibus will merge in an all-stock transaction. Following the closing of the proposed Calyxt merger, Cellectis SA is expected to own approximately 2.4% of the equity interest of the combined company. Accordingly, if the proposed Calyxt merger is consummated, it will result in a loss of control over Calyxt, and Calyxt should no longer be a consolidated subsidiary. The closing of the proposed Calyxt merger is expected in the second quarter of 2023. In this context, Calyxt is presented as a discontinued operation in the financial statements for the year ending December 31. The net loss, excluding Calyxt was $99 million in the 12 months of 2022 compared to a $97 million in the 12 months of 2021. This $2 million increase in net loss between 2022 and 2021 was primarily driven by an increase of net financial loss of $60 million due to Cytovia’s convertible note loss…

Thank you, Bing. To close out this call, I would like to reiterate how proud we are of what Cellectis has achieved thus far and especially in 2022, and how excited we are as we move forward into 2023. Cellectis will continue to reach key clinical milestones with our clinical stage pipeline of four allogenic CAR-T in hematological malignancies, this year. At Cellectis, we strongly believe that our product candidates, our technologies and our in-house manufacturing capabilities will lead us to a paradigm shift for patients with hard-to-treat cancers, positioning us at the forefront of this promising medical and scientific field. With that, I would like to open the call for Q&A.

Thank you. [Operator Instructions] Our first question comes from the line of Kelly Shi from Jefferies. Please go ahead.

Hello, can you hear me?

Yes, we can.

Hi, thank you for taking our question. This is Dev on for Kelly Shi at Jefferies. So a couple of questions. For UCART22, could you share more color on enrollment, including a number of active sites and pace of patients in recruitment? And just one general question on expenses, if you could guide for expenses in ‘23 and ‘24, should we expect lower R&D expenses since most of the manufacturing is in-house now? Thank you.

Hi, Dev. This is Arthur. Thanks for these two great questions. I think the first one would be best for Mark and the second one for Ben. So Mark?

Yes, thank you for the question. So for – ‘22 enrollment is proceeding very well. We have – we have sites open in the U.S. and in France that we’re currently enrolling in this study. And as we discussed, we’re using the completely in-house manufactured P2 product candidate for these patients.

And Bing maybe for the question?

Sure. Regarding R&D expenses in ‘23 and ‘24, a very good point, thank you for pointing that out. We transferred the manufacturing to in-house. So that actually reduces some of our R&D expenses, as you can see from our financials from 2021 to 2022. So going forward, we can expect to see the 2022 R&D expense on the runway at a very similar level in 2023. we have not provided – or we will not provide guidance for 2024 R&D expense because as you can imagine, some of the data that we’re working on right now turns out to be very good, potentially won’t have to expand that in the future years. So those expense could go up. At least for 2023, we expect R&D expense to be in the – roughly the same area as we are for 2022.

Thank you.

Thank you. Our next question comes from the line of Gena Wang from Barclays. Please go ahead.

Thank you for taking my questions. I have two questions. First one is regarding the BALLI-01 trial, the in-house manufacturing product at dose level 2. Wondering how many patients will we see at the initial data report? And will we see the data at ASH? What kind of clinical profile can warrant a quick transition to pivotal study? And then quickly, second question for Bing regarding the recent capital raise, and can you give a little bit more color on the rationale of the timing?

Thank you so much, Gena, for the two questions. Let’s start with Mark and then Bing.

Hi, Gena, thank you for the question. So – so yes, we are currently enrolling with the P2 product. And right now, we’re currently at dose level 2, as we discussed. We will – we are planning to have – a to discuss the results of the enrollment of the P2 product at a point later this year.

Thank you for the question, Gena. So regarding the timing of the recent financing, so I’d like to highlight, in December of 2022, there was two events from us that’s worthy of note. The first is, obviously, we had a webcast on the last day of ASH regarding some of the data that were announced on UCART123 and UCART22. But on December 28, we signed a credit facility agreement with the European Investment Bank as we mentioned on the call earlier. And there is three tranches in the European Investment Bank loan. The first is tranche A with €20 million. To the extent that we – when we issue the warrants, we can draw on this loan. But the second tranche of that loan, tranche B is €15 million, and it has two precedent conditions, one of which is we need to receive at least €15 million from any partnership or collaboration. And as we mentioned, we received that from Servier end of last year. The other precedent condition that we need to meet is to raise at least €20 million worth of capital, whether in the form of equity, convert or anything that’s junior to the European Investment Bank loan on the capital structure. So to satisfy the second precedent condition, we timed the raise so that we can trigger and draw on the – satisfy the condition for the tranche B of the European Investment Bank loan.

Thank you. Very helpful.

Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Please go ahead.

Hi, this is Andrea Tan on for Salveen. We had two questions on the AML program. First, what gives you confidence that there won’t be any new safety issues or allogeneic rejection following the two-dose regimen. And then second, to evaluate if the two-dose regimen is effective, what are the initial signals that you’re going to be looking at? And what would be the clinical bar for success here? Thank you.

Thank you for the focus on the 123, and I’ll hand both to Mark.

Hi, thank you for the question. So as we’ve disclosed earlier, the two-dose regimen is being done such that we’re giving the first dose on day zero as per usual, and we’re giving a second dose 10 to 14 days after that. To address your question about allo rejection, by doing – giving that second dose between 10 and 14 days later, we will – based on what we’ve seen, we will see a peak of activity before day 28. And as we’ve shown with multiple patients at the ASH presentation, the use of alemtuzumab in these patients has allowed us to have host immune suppression past day 28. So from the standpoint of having host recovery that rejects the cells, we think this is – we think this is going to be extremely minimized by the planning of when we’re giving the second dose. And to answer your next question about – clinical success will obviously be monitored by looking at disease activity with bone marrows during this process. They will have a bone marrow 28 days after the second dose that will evaluate the – that will evaluate the cumulative activity of the two doses against the disease, in addition to our translational studies, which we will look at flow cytometry of CAR-T cells in the peripheral blood as well as the vector copy number analysis.

Thank you. Our next question comes from the line of Jack Allen from Baird. Please go ahead.

Okay. Thank you so much for taking my question. The key question I had was I wanted to ask you about some of the recent data coming out of the CD22 CAR-T space and some of the auto programs at ASH. I was wondering if you could compare and contrast with some of those auto programs are seeing as compared to the UCART-22 data and just give an overview of how you are thinking about allogeneic and opportunity in this space?

Hi Jack. Thanks for the great question on 22, that would be for Mark.

Hey Jack. Thank you for the questions. So, as you are probably aware, there were two presentations at ASH on the autologous CD22 product, one from the Stanford Group and one from the group at UPenn. And specifically to your question, in terms of the response rates and – specifically more the duration of response that was shown at the meeting, the – again, small numbers in all three settings, both autologous and ours. But the trend is that the allogeneic 22 appears to have a longer duration, a significantly longer duration of response that’s been seen to-date at least in the data that was discussed at the ASH meeting with the autologous product. Again, I think we think a lot of this is also due to the fact that the allogeneic product is from normal healthy donor T-cells, and therefore, this product could potentially be more potent and result in a longer duration of response than the autologous product.

Great. Thank you.

Thank you. Our next question comes from the line of Hartaj Singh from Oppenheimer & Company. Please go ahead.

Great. Thank you and thanks for the question. Really nice update on the clinical programs. Can you just give an update on 20X22? What dose or the dosing levels you are going to go through I believe the product is in-house, if you can just update that? And then lastly, what line of patients in relapsed refractory NHL are you recruiting? Thanks for the question.

Hi Hartaj. Thanks for the great question on 20x22, that would be for Mark.

Hi Hartaj. Thank you. So, the – yes, the 20x22 product is completely in-house manufactured product. That is in the clinic. Currently, we are currently enrolling in this study. And this study is like most of the other NHL studies is done via flat dosing of the UCART-20x22. And so we are beginning with a dose level there. And I don’t know, was there another part to the 20x22, I am sorry, Hartaj.

No worries. Just what the line of patients are you recruiting in that relapsed refractory NHL, what are you sort of going after post various lines of therapy. Just any color there? Thanks.

Yes. So – thanks. So particularly, as you know, given the approvals for the autologous 19 directed products as well as the cell therapy products as well as the antibodies that it’s likely that patients are going to be receiving these therapies, if possible prior to receiving 20x22. So, I think in the setting of – if they can’t receive an autologous product for various reasons, either they can’t be [indiscernible] successfully, they don’t manufacture a successful product, or their disease is too hyperproliferative that it can’t be controlled during the waiting period for an autologous product, or if they have a CD19 escape via prior exposure to blinatumomab. For example, those patients would all be eligible for our study. But we fully expect that the majority of them will have had some 19-directed therapy prior to enrolling in the study.

Great. Thanks Mark. And sorry, one last question, are you going to be using alemtuzumab or an FCA preconditioning regimen here or not?

Yes. There we will be getting FCA, just like in the 22 study.

Great. Thanks for all the questions.

Thank you. Our next question comes from the line of David Dai from SMBC. Please go ahead.

Yes. Thanks for taking my questions and congrats on the progress here. I have a question on UCART-20. Just want to follow-up on Gena’s prior question. Could you maybe just talk about the efficacy bar for in UCART-22 in BALL – for the BALLI-01 trial. We have seen a dose level 3 [ph] trial showed about 52% CR rate. Would this be the bar, or should we be expecting some sort of haircut since the patient had received a prior CD19 therapy? Thank you.

Thank you, David for the question. And I will hand it over to Mark.

Thanks David. So yes, the short answer is that we – given the line of therapy that we would be in, we would expect the bar would be a little bit lower than that. But however, what we have seen in the dose level 3 data that we have disclosed with a 60% response rate two long-term one CR, one CRI and an MRD-negative MLFS. Those are significant responses. And I will just remind you that those patients, all three of them failed, both prior CD19 autologous CAR therapy as well as prior allogeneic stem cell transplant. So, these are super refractory patients that we are seeing these responses in. So, the investigators are super excited by this as well.

Alright. Thank you so much.

Thank you. Our next question comes from the line of Yanan Zhu from Wells Fargo Securities. Please go ahead.

Hi. Thanks for taking the questions. On BALLI-01 for UCART-22, is there any update on the duration of response for those the three patients who responded, as you just mentioned, at those level 3? And also for 20x22, are we still expecting data this year? And, at the time of data, do you expect to be at effective dose at the dose escalation? Thanks.

Thank you, Yanan. These are great questions and definitely for Mark.

Thank you. So, for the 22 patients, we have not yet discussed an update on the durations. But later this year during data presentation, we will update the DORs for these patients at dose level 3. In terms of your question for 20x22, we do expect data from the early first-in-human dose escalation later this year, by the end of this year. To answer the second part of your question, right now, we don’t know if it will be the – will be added in what we can say is an RP2D or not, we have to see where the data goes.

Great. Thanks for the color.

Thank you. Our next question comes from the line of Brooke Schuster from William Blair. Please go ahead.

Hi. Thank you, guys for taking my question. So, regarding UCART-CS1, where do you see UCART-CS1 fitting into the current CAR-T landscape in multiple myeloma? And I guess, what would you consider benchmarks for success in that future Phase 1 data?

Hi Brooke and thank you for the focus on the CS1, and I will pass it to Mark.

Hi. Thanks for the question. So yes, so CS1, obviously, there is – as you know, there is a great number of BCMA-directed both cellular therapy and antibody, antibody drug conjugate trials and the recent approval of [indiscernible]. So, we feel that CS1 is obviously going to be – going to fit in currently after a BCMA-directed therapy. And the question would be if it’s after one or two BCMA-directed therapies, but this is sort of in a patient-dependent, investigator-specific question, but we do see it fitting in after BCMA.

Okay. Thank you.

Thank you. Our next question comes from the line of Silvan Tuerkcan from JMP Securities. Please go ahead.

Hey. Good morning and thank you for the update, and thank you for taking my question. First, on UCART-22, now that you have dosed a patient with the new in-house manufactured product, could you really comment on the potency and where you have seen it trending? And then, secondly, could you just comment on the primary therapeutics collaboration. How does this come about? And how much expense and work does this collaboration mean for you, or is it primarily driven by Primera? Thank you very much.

Thank you so much, Silvan. I will let Mark start with the first question, and then I can take the question on Primera. Go ahead, Mark.

Great. Thank you for the question. So, what we have discussed previously is one of the reasons why we did a dose de-escalation with the P2, in-house manufactured product, is because our in vitro potency test showed that the Cellectis’ in-house product was far superior to the CDMO product that was used prior. And so that’s why we dropped down to 1 million cells per kilo, which is still a great dose. And we will disclose later this year on the effects in the patients as we begin the escalation there, whether that becomes the RP2D or whether we have to escalate further will be determined based on the responses.

Yes. And so on Primera, we are very excited to be partnering with Hibiscus BioVentures and the Mayo Clinic on the mitochondrial disorders. I think what’s very interesting is that this is a place where we can leverage our tailing gene and TALEN gene editing platform. And that this is indications of the mitochondria where other gene editing techniques like CRISPR have been extremely difficult to work. So, this is where having a platform like the TAL based platform, both doing nucleases and gene editors is an extremely powerful advantage. So, we are very excited to be working with them. This is obviously – there is a 19% equity ownership that Cellectis is having on Primera. And we are eligible for up to $750 million of development and sales milestones that could stem for the potential partnership products if Primera exercise the option for up to five product candidates. And we do not expect this will materially impact our expenses. A lot of the work is going to be driven by Primera, we will contribute to the activities, but this is not going to be materially impacting our expenses.

Thank you.

Thank you. Our next question comes from the line of Jack Allen from Baird. Please go ahead.

Thanks so much for taking the follow-up. I just wanted to ask a little bit about your rationale for deciding to utilize both the CD20 and CD22 CAR-T in this CD19 auto refractory patient population. Is there any external data that provides you confidence in the selection of those two kind of dual targets?

Thank you, Jack and welcome back. We are – I will hand it over to Mark for that question as well.

Yes. Jack, thank you for the follow-up. So yes, the reason for 20 and 22 in the NHL space is, they are both antigens that are present and clearly expressed very well on essentially most all subtypes of B-cell NHL. So, it does provide a very attractive alternative for those people that are obvious – patients that have obviously failed a 19-directed product. And the dual antigen effect, obviously, will – we think will be beneficial into giving us a better response rate without a potential antigen escape that was seen with the single ‘19 product.

Great. Thanks so much for taking the questions.

Thank you. Ladies and gentlemen, we have reached the end of the question-and-answer session. And I would like to turn the conference over to Andre Choulika, CEO, for closing comments.

Well, thank you very much. Thank you very much for joining the call. It’s really appreciated all the list of questions to the team. is something else because it give us confidence in the coming near future for like the development of the company and on the long-term to – there is a lot of excitement on our side and also the network of CIs and hospital centers that we have. And we look forward for the next update on the company, and there are plenty of things that should happen in the coming year. Thank you very much.

Thank you. The conference of Cellectis has now concluded. Thank you for your participation. You may now disconnect your lines.