Greetings. Welcome to the Cellectis Q3 2021 Earnings Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] Please note this conference is being recorded. I will now turn the conference over to your host Eric Dutang, Chief Financial Officer. Thank you.

You may now begin..

Thank you, and welcome, everyone to Cellectis third quarter 2021 corporate update and financial results conference call. Joining me on the call today with prepared remarks is Dr. Andre Choulika, our Chief Executive Officer; Dr. Carrie Brownstein, our Chief Medical Officer.

Yesterday evening, Cellectis filed its interim report and press release reporting our financial results for the third quarter and nine-months period, ending September 30, 2021. These reports and press releases are available on our website at cellectis.com.

As reminder, we will make Forward-Looking Statements regarding Cellectis financial outlook in addition to its manufacturing, regulatory and product development plans. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

A description of these risks can be found in our most recent Form 20-F filed with the SEC and the year ending on December 31, 2020, and subsequent filings Cellectis makes with the SEC from time-to-time. I would like now to hand the call over to Andre..

Thank you, Eric. Good morning, and thank you, everyone for joining us today. Over the course of the third quarter and the last nine-months of 2021 Cellectis has achieved a series of key milestones and we are incredibly grateful and proud of all the hard work achieved by our team, our partners and our stakeholders.

2021 has been a productive year thus far for Cellectis. We have made significant progress on all fronts that we are thrilled to share with you over the next half hour. Notably, yesterday, Cellectis announced that the release of two abstracts accepted for presentation at the 63rd American Society of Hematology Annual Meeting.

Cellectis will present additional preliminary clinical data from its BALLI-01 trial a UCART22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia and presentation of our first preclinical data of TALGlobin01 for the treatment of sickle cell disease.

Additionally, with regard to our preclinical UCART pipeline focusing on solid tumors, we have made notable progress with UCARTMESO, our allogeneic CAR T-cell product candidate targeting the document expressing solid tumors.

We are excited to share them the first preclinical data demonstrating in vitro and in vivo anti tumor activity will be presented at the Society for Immunotherapy of Cancer Annual Meeting later this month. In 2018, Cellectis made the transformative decision to internalize the manufacturing of its therapeutic products.

This decision revealed a crucial competitive advantage in today's world. This investment in our GMP manufacturing facility provides Cellectis with independence and control over gene and cell therapy processes, from buffers to DNA, messenger RNA vectors, and of course, our cell therapy such as our UCART's.

We create an own our processes, our developments and our production in the cell and gene therapy space. Whoever owns the process, owns the product.

Due to the success of completion of both of our GMP manufacturing facilities, we can move swiftly into an innovative ID at the R&D stage to clinical trials with potential to produce commercial levels supplies in the future.

We are proud to be one of the only companies of our size that are capable of moving into innovative new IDs from R&D to clinical trial, to manufacturing and delivery directly to the patient all in-house. We believe that bringing manufacturing in house could contribute to eliminating some of the barriers competitors are facing.

Our goal is to provide consistency and safety and our production and short lead time are met and adaptability. As each disease target by our advanced therapies may require cutting edge innovation at the level of our manufacturing capabilities, we need to fully master the process.

Importantly, having our manufacturing in-house means that we can rapidly version promising therapeutic candidates as we monitor clinical responses, leading to the best possible product at registrational filing. Our parents GMP manufacturing facility is now fully operational for the production t1hat starting material.

On the other side of the pond, our Raleigh GMP manufacturing facility qualification of the facility equipment and systems was completed successfully in Q3. Qualification of the second UCART production suite equipment remains on track to enable start of engineering grounds of the third UCART product in early 2022.

Now I would like to turn the call over to Dr. Carrie Brownstein, our Chief Medical Officer to give an update of our three sponsored clinical trials and preclinical product pipeline. Carrie, please go ahead..

Thank you, Andre. Cellectis continues to progress our Phase 1 clinical trials evaluating our three proprietary allogeneic CAR T-cell therapies in hematologic malignancies.

BALLI-01 evaluating UCART22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, AMELI-01 evaluating UCART123 in patients with relapsed or refractory acute myeloid leukemia and MELANI-01 evaluating UCART CS1 in patients with relapsed or refractory multiple myeloma.

As Andre mentioned, 2021 has been a busy and productive year for Cellectis with our proprietary clinical and preclinical programs making substantial progress, and we are excited to share additional preliminary clinical data from our BALLI-01 trial at the American Society of Hematology, 63rd Annual Meeting next month.

The abstract includes updated preliminary results from the Phase 1 open label dose escalation BALLI-01 study in patients with relapsed refractory B-ALL from the first cohort of patients who received UCART22 after fludarabine, cyclophosphamide and alemtuzumab lymphodepletion.

The addition of alemtuzumab is FC was well tolerated deepened host T-cell depletion and promoted CAR T-cell expansion and persistence. The data presented support the safety and activity of UCART22 after FCA lymphodepletion in patients with relapsed refractory B-ALL and the additional data will be presented at the Congress.

Enrollment in the study is ongoing. Additionally, preclinical data from the TALGlobin01 and autologous gene therapy product candidate designed to repair the mutated beta-globin gene and subsequently restore production of Hemoglobin A and patients with sickle cell disease was awarded a poster presentation at ASH.

The data that will be presented or the first demonstration that TALEN based engineering could be used to correct the mutation in the beta-globin gene of homozygous sickle cell anemia patient derived hematopoietic stem and progenitor cells.

The data showed high level of Hemoglobin A expression reversion of sickling phenotype, the capacity of TALGlobin01 edit itself to engraft in vivo, and a low level of off target cleavage.

Collectively the data demonstrate high efficiency and safety obtained treatment in HSPCs and positioned it as the best-in-class gene editing technology for gene therapy product development. We are also pleased to share that our partner Allogene will present data from our licensed allogeneic CAR That programs at ASH.

Data from both the Phase 1 ALPHA2 study evaluating ALLO-501A in patients with relapsed refractory non-Hodgkin lymphoma. And the Phase 1 universal study evaluating ALLO-715 in patients with relapsed refractory multiple myeloma will be shared in oral presentations.

Allogene will also present a poster on data from their Phase 1 Alpha study evaluating ALLO-501 in patients with relapsed refractory non-Hodgkin lymphoma.

During the second quarter of 2021, we presented preliminary translational data from the first group of patients enrolled in the MELANI-01 trial of UCARTCS1 at the virtual 24th Annual Meeting of the American Society of gene and cell therapy. The early preliminary data presented validates CS1 as a target for allogeneic CAR T-cells in multiple myeloma.

UCARTCS1 expansion and persistence was observed and correlated with changes in relevant serum cytokines and anti-myeloma activity. Cellectis is advancing one of the most robust allogeneic CAR T pipelines and we anticipate filing two additional new drug applications for two novel UCART product candidates in 2022. UCART20x22 and UCARTMESO.

UCART20x22 is the first allogeneic dual CAR T-cell product candidate which is being developed for patients with B-cell non-Hodgkin lymphoma.

UCARTMESO is an allogeneic CAR T-cell product candidate targeting mesothelin a tumor associated antigen that is highly inconsistently expressed in mesothelioma and pancreatic cancer, and it is also over expressed in a subset of other solid tumors.

In addition to expressing mesothelin directed CAR, UCARTMESO also leverages TALEN gene editing to overcome immune suppression mediated by TGF beta. UCARTMESO is being developed for patients with mesothelin expressing solid tumors.

Cellectis will present initial preclinical data that support anti tumor activity of UCARTMESO in a poster presentation at the Society for Immunotherapy of Cancers 36th Annual Meeting in Washington D.C. and virtually on November 10 to 14, 2021.

With that, I would like to hand the call back over to Eric Dutang, Cellectis' Chief Financial Officer for an overview of our financials for the quarter. Eric please go ahead..

Thank you, Carrie. I will provide a brief overview of our financials for the third quarter and first nine-months of 2021.

I would like to highlight that the cash, cash equivalents, current financial assets and restrict cash position of Cellectis excluding Calyxt as of September 30 2021, was $201 million compared to $244 million as of December 31, 2020.

This difference mainly reflects $92 million of net cash flows used in operating investing and lease financing activities which were partially offset by $45 million of net equity proceeds raised from the company’s ATM program in April 2021 and $10 million proceeds from the stock option exercise.

This cash position is expected to be sufficient to fund selectee standalone operations into early 2023. The consolidated cash, cash equivalents, current financial assets and a recent cash position of Cellectis including Calyxt was $216 million as of September 30, 2021, compared to $274 million as of December 31, 2020.

The net cash flows used in operating capital expenditures, and lease financing activities were $92 million at Cellectis and $15 million a Calyxt in the first nine-months of 2021. The net loss attributable to shareholders of Cellectis, excluding Calyxt was $75 million in the first nine-months of 2021, compared to $21 million in 2020.

This $54 million decrease in the net loss between 2021 and 2020 was primarily driven by a decrease in revenues, and other income of $30 million and an increase in R&D expenses of $32 million, which was partially offset by an increase in net financial gains by $8 million.

The consolidated net loss attributable to shareholders of Cellectis including Calyxt was $89 million or $2 per share in the first nine-months of 2021, compared to $42 million, or $0.98 per share in 2020.

The consolidated adjusted net loss attributable to shareholders of Cellectis excluding non-cash stock based compensation expenses was $80 million or $1.79 per share in the first nine-months of 2021, compared to $30 million of $0.72 per share in 2020.

We are laser focused to spend our cash on developing our deep pipeline of fully owned product candidates in the clinic and operating our state-of-the-art manufacturing facilities in Paris or in Raleigh. On the other end, our focus on maintaining and efficient corporate infrastructure should enable more limited growth in G&A expense.

With that, I would like to hand the call back over to Andre for concluding remarks. Andre, please go ahead..

Thank you Eric. Our TALEN UCART platform position us at the forefront of developing novel CAR T therapeutics that usher in the next generation of cancer therapies. We continue to leverage our expertise in gene editing and clinical development to transform the lives of patients with cancer and rare genetic diseases.

And we look forward to continuing this effort in Q4 2021 into 2022 and beyond. At Cellectis, we continue to leverage our groundbreaking gene editing platform to develop novel proprietary medicine to transform the lives of patient with serious diseases.

Our current proprietary clinical stage programs are focused on patient with advanced and mythological malignancies. And we continue to advance a robust pipeline into the clinic to tackle additional oncology settings, including solid tumors, and to address the unmet medical needs of patient with severe genetic disease.

With that, I would like to open the call for question-and-answers..

Thank you. At this time, we will be conducting a question-and-answer session. [Operator Instructions] Our first question comes from the line of Yigal Nochomovitz with Citigroup. Please proceed with your question..

Yes hi Andre and team, thank you very much for taking the question. I had a question on UCART22 and the ASH data.

Could you provide a bit more detail with respect to the types of data that we will see in the presentation and what is your internal bar that would qualify as an initially successful dataset?.

Well thank you so much for this question and I think the most appropriate person to answer the question is probably Carrie.

Carrie, do you like to take this question?.

Sure absolutely. Hi Yigal, nice to hear from you. So what we are planning on showing is the first handful of patients that were treated with the fludarabine and cyclophosphamide and alemtuzumab, lymphodepletion regimen. So in the abstract is the first group that we had ready to prepared for the abstract, but we will have additional data at the meeting.

And just know where as you know, we are still in the dose escalation phase of the study. So we are not quite where we need to be for what we consider a bar for an approval, so to speak. But as you know, we are in a very relapsed refractory group of patients, we will have patients who have previous CD19 directed therapy.

So for acute leukemia, I'm not expecting as we move through our clinical development plan for our first shot on goal so to speak with this product. I would not expect the bar to be tremendously high..

Got it. Okay, thanks. And then I just had a question on the UCARTMESO for the data to be presented at [SITC] (Ph).

To the extent that you can comment, could you give us any preview of that data set and what are the key features of that preclinical data set that are supporting the clinical development?.

Carrie, do you want to also describe MESO?.

Andre I think you are in a better position to do that. Yes..

Yes. So like MESO have been developed it I think it is like the first off the shelf CAR T without that like, all the complication that you have seen in other types of sourcing for allergenic CAR T targeting MESO.

And one of the features is extremely interesting that would be shown that ASH and this is like the knockout of the TGF beta receptor on the cell. TGF beta receptor is always is a potential down regulator for T-cells in the tumor microenvironment.

And one of the big challenges like this is tackling through all the CAR T, we are developing for solid tumors is trying to tackle the tumor and like microenvironment the TME, such as SAP, for example, that there is something that is supposed to blow the like an article, but definitely SAP the product that will poke holes into the solid tumor protection.

And MESO is essentially a CAR That is not going to be shut down by the negative feedback loop that you have with TGF beta-2, that is present in the macro environment.

And this is type of data that we have, we show also that this type of CAR will probably work in combo and that will probably give very interesting features not only for mesothelioma but potentially for a lot of different type of cancers, that we were selected also with all the attributes that this CAR has, which is like a CDC.

It is same platform as all the other CAR with developed which is a CD52 knockout, so it will work on alemtuzumab and TCR alpha, plus it is a triple knockout. I think it is the first of its kind triple knockout CAR T.

We are currently preparing this CAR to go into clinic and I think the data are compelling and definitely encourages us in vitro as well as in vivo frequent data gets like the compelling results for the tackling theories of solid tumors..

Thank you..

Thank you. Our next question comes from the line of Gena Wang with Barclays. Please proceed with your question..

Thank you for taking my question. I have a few regarding a model big picture questions. So the first one, maybe for Andre wondering your partner Allogene had the clinical hold. And I think that the earnings call the come and - they didn’t disclose too much, but it come and there is some concern about translocation.

So just wondering, how the read through to your programs and then also regarding your drug product, how much do you test regarding each step with the chromosome translocation events and how do you detect that? And then my second question is regarding the allogenic CAR T approach in general.

We did see several companies and also your partner Allogene would share some data on consolidation approach. And we did see improve the complete response letter, the complete response rate, and we don't know about the durability of any faults from this approach, like apply to your programs..

Well, thank you Gena, so much for the questions. First of all, I think I'm going to let the Allogene management commands on the critical hold because I think it is like we are definitely very supportive and very confident on the handling of the situation by the allogeneic team that is making fantastic work on their side.

We are extremely excited by the data they are showing on UCART19 or ALLO-501A actually. And I think this is definitely a transformative data on the allogeneic CAR special with the consolidation, but I will come back to this.

To speak about the impact on Cellectis, there is like, of course, we are monitoring the situation very closely, we are helping as much as we can do whatever we can, we will definitely help allogeneic to go through this period.

And we have like a strong confidence in the product and the outcome and we believe that this is like this trial is going to resume definitely. Nevertheless, chromosomal aberration are quite frequent in non-human population.

And would it be - certain chromosomes have more aberration, because they are subjected to DNA recombination due to the state where they are. So like a lot of our immune cells B and T-cells undergo DNA recombination at this stage at a certain stage, and sometimes these DNA recombination can lead to some normal changes in there.

However, few things that should be said, first, the product is not in danger I have. Like the inhibitors, like series of patients that have been - dealt with the same platform. So we are confident on selected global platform and not only gene editing, but also the global platform where we develop our allogeneic CART to be very stable.

The second thing is that T-cell, adult T-cells, you don't, there is no cell line of adult T-cells in general. And then finally, the cancer is like allergenic cells turn cancerous.

This is all the beauty about an allogeneic approach on gastric cancer, especially T-cell cancer, T-cell cancer from an allogeneic donor, this is not going to happen actually it has never happened in history and it is something that could be quite rare.

So we are quite confident with this and we believe that this platform, on the contrary will come stronger from this phase and also with a lot of confidence that what we have. So we have no concerns today on the potential risk on what Cellectis and our partners are doing. And we believe that this is like on an intermediate phase in there.

On the contrary, we are very focused and very positive on the outcome of the data that not only our partners are having, but also Cellectis troops producing. And these old are IDs and products and target that is like this has been incepting.

And I think for the size of the company, in driving so many life saving products, something that is definitely transformative and will remain with the same type of technologies that we have. Now on the consolidation study is something I have been always a very strong advocate.

But I think it could be interesting to have Carrie’s view, because I have been speaking about like the consolidation studies and fears and we have discussed this together, Gena and but Carrie have like a fresher eye than myself more medical doctor.

So Carrie, if you want to say a few words about this?.

Sure, hi Gena nice to hear from you as well. So I'm really excited about the presentation that includes all the consolidation treatment. I think that I have been saying this since I joined Cellectis now a year and a half ago.

And one of the main beauties and key points that I think is going to make the allogeneic CAR T-cell therapies successful is the fact that you can give additional doses. And that is one of the huge drawbacks of the oncologist setting.

We all know that these additional treatment, whether you are using chemotherapy, whether you are using antibody therapies, whether you are using small molecules, whatever it is, and the history of treating any of these diseases, has to do with being able to get the cancer cells to a state that not only you don't see them anymore, but that you can't measure them anymore.

And the deeper the remission that you can bring a patient to the longer their duration as well as their longer their survival and potential for cure. So giving additional treatment is always the right way to go when you can.

And therefore, it is really excited to finally being able to see larger datasets of patients who have received more than one therapy in the allogeneic setting and showing that it is able to really make a difference in treatment for these patients..

Thank you very much..

Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim. Please proceed with your question..

Hey this is Kelsey on for Michael. Thanks for taking our questions. I have two quick ones. First, could you just provide some color on where you are at with the other ongoing CAR T programs so UCART123n CS1.

And then with respect to the TALGlobin01 program, I guess, could you just remind us kind of the key areas of differentiation versus existing competitors in the field and how you kind of think about that? Thanks so much..

Carrie, do you want to give an update on 123 and CS1, I can give an update for TALGlobin01..

Yes, sure. That is perfect. Sorry, I was on mute for a second. Yeah. So for UCART123 for relapsed refractory AML and for the - I will start with that one first. So that study, as we said, has been moving through dose escalation.

I think as you know, AML is a tough space with patients who are quite sick and tend to be a little more fragile than you would see with acute lymphoblastic leukemia or with lymphoma. So it is taking a bit longer, but we are moving through dose escalation and we are hoping to have additional data at some point next year.

We will see to share with everyone. As far as the myeloma study for you UCARTCS1 that too, as you know, we had been on clinical hold. We reopened after changing the protocol adding some additional safety pieces for - guidance for treatment of adverse events, as well as some other rules that the FDA was requiring to ensure safety as we move forward.

So we have been moving through dose escalation. And that too, has been moving along nicely. There is lots of interest from all of our investigators. And again, this is another program that we hope to be able to show additional data later next year.

As you know, earlier this year, we did present the original translational data from that first dataset before the hold, which did show some interesting translational data that included the expansion of the cells, it shows all the cytokines that we expect to see. And we did see some response.

So we are super excited about this program continuing to move forward and are looking forward to share data when the time is right..

Thank you, Carrie. On the TALGlobin01 side, the big differentiation that we have, most of the current trials that you see for tackling beta-globin or beta thalassemia or sickle cell disease is based on the knockout of one repressor to reactivate a different type of hemoglobin which is sickled hemoglobin.

So you keep the sickled hemoglobin in the cells. You destroy an another gene, so there is one gene that is disrupted with a mutation and they are sickling the cells to destroy another gene that is a repressor.

And finally reactivate the gene that is not supposed to be expressed, that can restore kind of the phenotype, which works actually there is like results that have been produced so far.

What people imagine on what could be the gene editing, is if there is a point mutation that induces a sickling in the hemoglobin gene, people imagine figure out that editing the mutation would be fixing back the mutation which is not happening in most of these trials.

So the approach Cellectis to is taking is repairing the mutation in the Hemoglobin B gene, and fixing this mutation and restoring the adult hemoglobin in the cells without leaving any scars or new scars in the DNA. So you put back the gene to the sequence it was supposed to be. This is an approach.

We are not, of course, there are - there is competition in this field but we believe that Cellectis approach with the technologies we are developing such a talent and approach we have is our electrician technology which the gene engine and the Cytovia technology brings it to a very high level repaired adult hemoglobin select cells that are totally fixed with a very reduced side effects around and very high on target with very accurate repair of this hemoglobin at the end.

So that is what differentiate us for most of their approach that you see currently in the clinic and we believe that this is what patient wants their hemoglobin to be fixed..

Great. Okay. Thank you so much..

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

Hi this is Dave on for Kelly. Thank you for taking the question. Just quick question on Allo read through. Is it possible that other things like CD52 lymphodepletion regimen could be the reason for this unexpected outcome and another option is the for ASH data.

Can you provide some detail that directly include patient who had prior CD19 CAR T treatment? Thank you..

Well thank you very much for the question.

Like just to ask her precision like you mean that like the CD52 monoclonal antibody could induce an inversion or like a chromosomal aberration somewhere is that was a question?.

Yes..

So personally, I might not to have all the information about this, but it seems to me complex, especially for a non-internalizing antibody such as like alemtuzumab or by generic alemtuzumab to induce such type of chromosomal aberration that are quite classical in general.

It is not something that has not been observed and is observed quite often and a lot of not only patient, but potentially the global population. It is not a locus that is not susceptible to chromosomal changes in there. It is part of whole, but extremely unlikely on a mechanistic side.

Excuse me, like the second part of the question I just stepped out..

The second part of the question is, if you can provide any color on ASH update.

Do you any data on patient with prior CD19 CAR T treatment?.

I can answer that. To make long story short, the ASH abstract will include the next group of patients treated on the study all of their prior therapies, whether it was CD19, or otherwise will be included in their past medical history, past prior treatment dataset. So that data will be included.

But I'm not going to speak to today, what proportion of those patients. We do allow patients in the trial who have had prior CD19 directed therapy.

And I think we have already disclosed in terms of our study designs or the expansion, we are going to focus on those types of patients, but the dose escalation, we are not limiting to only those types of patients..

Thank you..

Sure..

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

Great, thank you and thanks for the update. I just got a couple of quick questions. One is the follow-up on the CD19 project. Some of those patients that that are in CD19 directed therapies also have an antigen loss. I don't know if that is all of the patients that relapse of CD19 directed therapies, that is a subset.

And if it is a subset, could that be a biomarker, for example, in dose expansion for an accelerated sort of like approval, assuming you see good responses. So that is number one. And then number two, in terms of your solid tumors with these affiliates, it is really interesting.

You are looking forward to this data among the first I believe in solid tumors with pre-clinically with allogeneic CAR T. But Andre, you have spoken this earlier, but can you talk specifically how a clinical development planning Phase 1 and Phase 2 could work.

I mean, in the PD-1 and PDL, the initial PD-1 were approved in three to four years as immunotherapy in various cancers. Solid tumor seemed to be, you can move faster. Any thoughts there seem to be, you can move faster.

Any thoughts there just in terms of, what a development program could look like, assuming you see success early on in the middle period? Thank you..

Thank you Hartaj for the great questions. And I'm going to split it in two like so the first part of the question your question maybe Carrie can answer this because she knows a lot. And part of the question to get also answered I guess she can answer to all the question..

Yes or maybe I won't answer, but I will some I did..

I can work for both, certainly I believe Carrie..

Yeah, sure. So the first part of the question about CD19. So I think that is a good point. But no, not everyone who relapses and or doesn't respond to a CD19 directed therapy has the antigen law. I think the numbers, if I'm not mistaken, is somewhere between 20% and 30%.

That said, I wouldn't necessarily call that a biomarker, but I will get to that in a second.

So there is not a tremendous amount of data in leukemia obviously after a CD19 directed therapy when we have the blinatumomab data and there is some of the UCART19 data from survey, but there is no, it is not as that of a data set as you would, as we have seen for lymphoma. So it is hard to compare what we know from one dataset to another.

But that said, in terms of a development plan, and we have been very open about this from the get go, my plan for this program is to try to get it into patients as quickly as possible and have a therapy that can go to BLA.

And as you know, that is exactly the group of patients that while it is a super small nation vacation, it is a place where the bar would be extremely low for the amount of data as well as the risk, the response rate to see something.

And so absolutely, that is a group of patients that we are focused on, it is in our clinical trial design for our expansion to focus on that group, because we know that group really needs therapy and needs to quickly and could help us bring a product to market quick.

That said, the reason it is such an interesting piece is that it gives depending on how good the data is. So even if it is works in patients who have failed, and maybe they have CD19 loss, it also may show dramatic activity, even in patients who haven't failed.

So it gives us an opportunity to kind of move into multiple spaces in the treatment paradigm for these patients. And I think is super, super important. So, yes, and it is yes and yes, but also know if that makes sense..

And just on the solid tumor question.

Just broadly, whether your thoughts and if you want to get into the clinic, any potential for accelerated approval in this new way of doing over expressing cancers?.

Yes, I mean, I think that the mesothelin program is a really interesting and exciting. I do think, however, it really will be the first program targeting mesothelin from an allogeneic setting. And while yes, can we have a chance for an accelerated approval, it is all going to depend on the data we see.

And until we get into the clinic and see what we see. It is going to be hard to make that calculation, but obviously, in my plans, and when I look into how do we do clinical development, I'm always looking for multiple different avenues to take.

So we can have staggered approaches and whether there is an accelerated approval path or a specific mesothelioma for example, highly specific cancer where there is clear, consistent over expression where you would likely see your proof of concept and where there isn't a ton of options, I would be looking for one option to go quickly and fast and that could be one.

I would also be looking for broader ways of getting larger indications and bigger market share and things like that. So all of that will be looked into and we would be putting together a comprehensive program. So we can find ways of doing that quickly and efficiently..

What is interesting is that, like the monoclonal antibody like PD-1 enters or PDL1 blockers enter into the solid tumors, so they can get into there. The problem is that immune cells are protected by the cancer associated fibroblasts and 70% of solid tumors, they do not respond because of the difficulty of the immune system to access.

The tumor itself that continue to grow protected by the cast.

So the concept of blowing up the cast with the SAP CAR can be transformative in these type of combos and approach to this is I think what Carrie is describing is a very wise type of approach that can definitely expand the potential that is today not really, we cannot really have a grasp on if it could be transformative..

Great. thank you Andre, thank you Dr. Brownstein..

Sure, thanks..

Thank you..

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

Hi thank you guys so much for taking the question. I just had one brief one. And I know we are going to avoid commenting on Allogene’s specific instances here.

But I was wondering if you could provide any update with regard to ongoing regulatory interactions you have with FDA and regulators had any requests for additional product specifications or anything of that nature as we move past this hold without Allogene? Thank you so much for taking the question..

Hi Jack thank you so much for the question. It is a hard question to answer fully, for the simple reason that a lot of these interaction we have on a regular basis with the FDA are confidential and under, I don't want to share particularly, because it is also a competitive advantage selected.

But so far, we haven't seen any significant change into this. I guess that things are going to - so there is some - these exchanges are very fluid today and doesn't change anything. So I think that it is important to monitor the situation on a daily basis, but Cellectis is so far on a very good track with our own trials.

Excuse me, but like it is difficult to share more than this..

Alright totally understand. Thank you so much..

Sure..

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. In the ASH abstract for BALLI. I said the three patients in the FCA do to discontinue, I was just wondering why. And as we think about the 20x22, next gen candidate committee put that into the context of UCART20 development? Thanks..

Sure. Andre I can take this one. So our abstract includes the first three patients, we will have the other patients, additional patients in the abstract presentation at the meeting. And all that data will be in there. So I don't want to get into reasons for discontinuation all that could sort of be in the dataset.

Now, I think, I can share that to the Embargo Rule since it is part of the dataset. But again, suffice it to say that we are still in dose escalation and we haven't reached our recommended Phase 2 dose yet, so there will be different reasons for why patients can study.

And as far as 20x22, I mean, I think the big differences and why this is important is you will know the UCART22, which was our first, one of our first programs has there, are - CD20 materials on it, so we would be potentially deactivated and killed with rituximab on board.

And as in lymphoma, we can't really use that as well since most patients will have rituximab on board. And rituximab has been shown to be floating around in patients bodies for up to six months or longer, and therefore it would potentially diminish the activity of our cells. So we wouldn't want to do that for lymphoma.

So we are positioning UCART22 for ALL for leukemia, because of that, and rituximab is rarely used in ALL, but 20x22, which not only is fantastic because it does the dual card really has an opportunity to really differentiate itself from what's out there, but therefore would not cause an issue with rituximab..

Thank you. Our next question comes from the line of [indiscernible] with SMBC. Please proceed with your question..

Thank you so much for taking my question. I have two questions. First, I just wanted to get some clarification on the UCART22 ASH abstract data. Were just said one patient had glass reduction consistent with CRI. Could you provide some additional color on this reduction is that a confirmed a CRI.

And then second question is that you will also present really encouraging preclinical data for TALGlobin01 at ASH, and your foot is very differentiating from competitors.

But could you comment on how do you see preclinical data compare to the competitive programs from CRISPR and blues and also is the IND still on track for next year?.

Yes. So I can start with the first part of the question about UCART22. Now I'm trying to remember exactly what the company was..

Sorry, so the question is just the reduction consistent with CRA not come from CRI or?.

Yes, well, the thing is with leukemia, it all depends on, it is not the same as there is no such thing as confirmed or not confirmed in terms of the response criteria.

So it is sort of, it depends on which response criteria are being used, whether you can count it as a actual CRI or not and you will see in the dataset, when we present the data, what the patient had and what their blast reduction was, it was quite impressive let's say.

And however depending on which response criteria you use, in leukemia, and there is a few. So the one is the NCCN, which is what we were using, there is also the modified [indiscernible], which was what was used for inotuzumab, and it just a, each one of them has different dependents on how long you can measure it for.

But unfortunately, unlike with other with like, resist, for example, we are not checking the Leukemia status in the bone marrow every day. So it is really hard to know exactly whether or not it meets certain criteria. So that is why we were kind of careful and cagey with our answer there. But I think it is extremely interesting.

And it is extremely encouraging data at a very lower dose level in our first group of patients treated with FDA, which is pretty amazing, in my opinion. And then I don't know Andre, if you want to speak to TALGlobin01..

Yes, the TALGlobin01 is currently being manufactured, but once we are finished manufacturing, we have to go through all the requirements with the GMP material to start preparing the IND package. This is something the work that will start probably next year once the product will be released. And this is all done internally.

So it is something that is quite exciting. And I'm not giving any guidance for the IND filing today, but it definitely a product that will go into clinic..

Thank you. Our next question comes from a line of Nick Abbott with Wells Fargo. Please proceed with your question..

Hi, thank you. First question, just going back to the ASH abstract in what data will be presented. So have you cleared 2.5 mg per kg dose if not, when do you think you will do that and there is the next step five million per ml and I expect per kilo and I have a follow on? Thanks..

Sure. I mean, again, I really given the Embargo Rules for ASH, I don't want to get into exactly what we are going to be presenting and which cohorts in which datasets unless it was already in the abstract that is been released. But the pointed out that the dose level two was the one million and the 2i is 2.5 and the next stage would be five, yes..

Thanks. And then just on the absolute account profile, there are no range bars on the data that is in the abstract, but it shows only a 50% reduction, nine-days after infusion of the CAR bottoms out at 11.

Is that the profile you wanted, I would have expected ALC to have bottomed out pretty before infusion or at the time of infusion?.

I have to pull up exactly what you are looking at because maybe it is not accurate, the way it is being interpreted. But what I can tell you is the patients all went to zero with the lymphodepleting and the alemtuzumab. So you may be looking at the other line, which is the UCART expansion..

NO.

I’m looking at the blue line which says that is lymphocyte counts?.

Oh, I have to pull it up and I know in one of the patient data was shown. Yes, I have to look at it. I don't have it open in front of me.

But what I do know is that we can get back to the email to explain it but what I can tell you is it depends on which where it was being measured from so in some cases we are measuring the actual UCART cells and the absolute lymphocyte counts, that actually what you are looking up, but I will look at it and can send with a clarification..

Maybe last one obviously is a very heavily pretreated population. As you said, I think median is five and the abstract versus three at ASH last year. As you think about expansion, is this the kind of population five medium priors with CAR T failure and if so, is that a population.

Do you think you can successfully complete a trial, I mean, we already have a patient here who there is apparently no benefit from the CAR T, but it is still has no lymphocytes, because they had the alemtuzumab and since the depletion. It is that patients, obviously in a very challenging place..

Yes, it is a really good question. I think the answer, though, is yes. I mean and if you go to clinicaltrials.gov, it has the information on our expansion cohort, I believe. But I think that this goes to what I said before, it is really important to have a comprehensive, multiple shot on goal plan for development of any product.

And I think particularly given our size, and wanting to be able to bring a product to [VLA] (Ph) and approval, this is definitely something that we can do. And I think that while in leukemia, even with you have had multiple, multiple therapies. It is a disease that typically is of younger, healthier people.

So it is not like acute myeloid leukemia, where most people, the vast majority of patients are over 65, or even over 75, for that matter, and are super frail, and multiple therapies, their organs don't work well. Generally speaking, leukemia patients are younger, it is most common cancer in children, it is the most common cancer for young adults.

And we are going to be as one of our arms, so to speak of development for this program is to really focus on these patients who are otherwise in super good shape.

Well maybe they have had multiple therapies, but they're in super good shape and can keep taking more, and bring them to hopefully to a cure somewhere where they can continue to have a long life and I think that is, it is super important.

So I think in ALL in particular, it is a little bit of a different story than when you are talking about myeloid leukemia, or some of these other diseases that you see in older people. So I think in our expansion, and where we would want to potentially have a faster market strategy would be in these younger, CD19 directed failures.

So it is still need a therapy and are still otherwise, with the exception of their leukemia really well and need to be treated and need something that can they can move forward and potentially have a life.

So that said, though, it is a small nation vacation and therefore, other strategies and other development plans are in place for us in terms of where else we can go and how we would go about doing that. So we can bring it to a larger group.

And to your point, potentially, not necessarily people who failed by therapies and have also failed CAR T already..

Okay. Thank you very much..

Yes, thank you..

Our final question comes from the line of Ingrid Gafanhão with Kempen. Please proceed with your question..

Hi team thank you for taking my questions. I will keep it a bit brief then. Just checking, do you want to check with you once again, what are your plans of scaling and your shareholder ship. I think you mentioned you are planning to maintain it.

But will you be keen to monetize this any let's say in the short to mid-term?.

Hi Ingrid. I missed the beginning of your question actually was not super clear.

It is about what?.

I was meant to check with you, what is your current thinking on Calyxt and your shareholder ship?.

Actually, currently, we think, Calyxt just announced the leadership change with the arrival of Michael Carr, and also changing strategy that has been induced not only by the new leadership, but also by the Board of Director under a chairmanship of Yves Ribeill, and we believe that this change is about to transform the company in a very meaningful manner.

And Cellectis has a significant stake into Calyxt. I think that we are positive on the fact that this is going to bring a lot of value and you see that since then, it has been quite well received by the market. As I said, like Cellectis is definitely has a vested interest in the success of Calyxt and waiting up to this.

And it is something that we believe is going to be very valuable in the future for us as shareholders of Calyxt. So we have to wait up to the time this changing strategy is implemented.

And we believe that the current company has all the pieces to be extremely successful in the implementation of this new strategy very rapidly and very swiftly, which should lead to our advantage..

Thank you, that is clear.

And if I may have just one more question for Eric, just looking ahead into next year, considering that you are planning to move some programs INDs forward are you providing any guidance on your cash burn?.

We don't provide any guidance on our cash burn. What we say, the cash run way is early 2023 on Cellectis. And we don't disclose management payments. We have partnership with [UCLA] (Ph), where we can get up to $410 million from 2019 programs and also the partnership with Allogene where we can get up to $3 billion on 15 targets..

And also is IO vast, and it was titled A series of milestones to be paid, but translating the cash flow into 2023 is unchanged..

Alright. Thank you very much..

Thank you..

Thank you..

Thank you..

Ladies and gentlemen, we have reached the end of the question-and-answer session. I will now turn the call over to Andre Choulika for closing remarks..

Well, thank you very much everyone for this Q&A. We are extremely excited to have all these questions and excited of our trials and our partners trials. There is a lot of things ongoing at Cellectis, I think that Cellectis at seriously leaping point, a turning point for the company with internalizing older manufacturing.

And what comes next in the coming months and years is a transformative Cellectis that it is becoming a true like bona fide biopharmaceutical company, making things from A to Z and like one-stop shop with gene editing CAR T and oncology gene therapy, and of course, with a powerful strategy in the clinic as we have been sharing with Carrie, and I think that this is going to change so please watch closely and come to our meetings and posters at ASH, we are waiting for you.

Thank you very much..

This concludes today's conference and you may disconnect your lines at this time. Thank you for your participation and have a wonderful day..