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. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the conference over to your host, Arthur Stril, Chief Financial Officer. Thank you. You may begin.
Thank you, and welcome everyone to Cellectis Q3 2021 corporate update and financial results conference call. Joining me on the call today with prepared remarks is Dr. André Choulika, our Chief Executive Officer, and Dr. Carrie Brownstein, our Chief Medical Officer. Yesterday evening, Cellectis filed its interim report and press release reporting our financial results for the Q3 and nine-month period ending September 30, 2021. This report and press release are available on our website at cellectis.com. As a reminder, we make forward-looking statements regarding Cellectis financial outlook in addition to its manufacturing, regulatory, and product development. 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 for 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 over the call to André Choulika.
Thank you, Eric. Good morning, and thank you everyone for joining us today. Over the course of the Q3 and the last nine months of 2021, Cellectis has achieved 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're 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 of UCART22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and presentation of our first preclinical data of TALGlobin-01 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 Mesothelin-expressing solid tumors. We are excited to share that the first preclinical data demonstrating in vitro and in vivo antitumor 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 therapies such as our UCARTs. We create and own our processes, our development, 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 IND at the R&D stage to clinical trials with potential to produce commercial level supplies in the future. We're proud to be one of the only companies of our size that are capable of moving into innovating new INDs from R&D to clinical trials 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 in our production, ensure lead time are met, and adaptability. As each disease targeted by our advanced therapy may require cutting-edge innovation at the level of our manufacturing capability, 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 products at registration and filings. Our Paris GMP manufacturing facility is now fully operational for the production of 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 runs 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, André. Cellectis continues to progress our phase I clinical trials evaluating our three proprietary allogeneic CAR T-cell therapies in hematologic malignancies. BALLI-01, evaluating UCART22 in patients with relapsed refractory B-cell acute lymphoblastic leukemia. AMELI-01, evaluating UCART123 in patients with relapsed or refractory acute myeloid leukemia. MELANI-01 evaluating UCARTCS1 in patients with relapsed or refractory multiple myeloma. As André mentioned, 2021 has been a busy and productive year for Cellectis, with our proprietary clinical and pre-clinical programs making substantial progress. 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 I 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 to FC was well tolerated, deepened post-T-cell depletion, and promoted CAR T-cell expansion and persistence. The data presented supports 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, an autologous gene therapy product candidate designed to repair the mutated beta globin gene and subsequently restore production of hemoglobin A in patients with sickle cell disease, was awarded a poster presentation at ASH.
The data that will be presented are 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 edited cells to engraft in vivo, and a low level of off-target cleavage. Collectively, the data demonstrate high efficiency and safety of TALEN treatment in HSPCs and positions 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 T programs at ASH.
Data from both the phase I ALPHA2 study evaluating ALLO-501A in patients with relapsed/refractory non-Hodgkin lymphoma and the phase I 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 I 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 & 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 and consistently expressed in Mesothelioma and pancreatic cancer and is also overexpressed 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 pre-clinical data that support antitumor activity of UCARTMESO in a poster presentation at the Society for Immunotherapy of Cancer's 36th annual meeting in Washington, D.C. and virtually on November 10th to 14th, 2021. With that, I'd 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 Q3 and first nine months of 2021. I would like to highlight that the cash equivalents, current financial assets, and restricted 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 Cellectis's standard operations into early 2023. The consolidated cash equivalents, current financial assets, and restricted cash position of Cellectis, including Calyxt, was $216 million as of September 30th, 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 at 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 gain 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, or $0.72 per share in 2020. We are laser-focused to spend our cash on developing our deep pipeline of early-stage product candidates in the clinic and operating our state-of-the-art manufacturing facilities in Paris and in Raleigh. Our focus on maintaining an efficient corporate infrastructure should enable more limited growth in G&A spend.
With that, I would like to hand the call back over to André for concluding remarks. André, please go ahead.
Thank you, Eric. Merci. Our allogeneic CAR T platform positions 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. We look forward to continuing this effort into 2021, into 2022, and beyond. At Cellectis, we continue to leverage our groundbreaking gene editing platform to develop novel proprietary medicines to transform the lives of patients with serious diseases. Our current proprietary clinical-stage programs are focused on patients with advanced hematological malignancies. We continue to advance our robust pipeline into the clinic to tackle additional oncology settings, including solid tumors, and to address the unmet medical needs of patients with severe genetic diseases. With that, I would like to open the call for questions and answers.
Thank you. At this time, we will be conducting a question and answer session. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from the line of Yigal Nochomovitz with Citigroup. Please proceed with your question.
Yeah. Hi, André and team. Thank you very much for taking the question. I had a question on UCART22 on the ASH data. Could you provide a bit more detail with respect to the types of data that we'll see at the presentation? And what is your internal bar that would qualify as an initially successful data set?
Well, thank you so much for this question. I think the most appropriate person to answer the question is probably Carrie. Carrie, would you like to take this question?
Sure. Absolutely. Hi, Yigal. Nice to hear from you. What we're planning on showing is the first handful of patients that were treated with the fludarabine, cyclophosphamide, and alemtuzumab lymphodepletion regimen. In the abstract is the first group that we had ready to prepare for the abstract, but we will have additional data at the meeting. Just know we're—as you know, we're still in the dose escalation phase of the study, so we're not quite where we need to be for what we consider a bar for an approval, so to speak. As you know, we are in a very relapsed or refractory group of patients. We will have patients who had previous CD19 directed therapy.
For acute leukemia, I'm not expecting as we move through our clinical development plan, you know, 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. I just had a question on the UCARTMESO for the data that you presented at SITC. 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 UCARTMESO? Well, as you want. Okay. I think
André, I think you're in a better position to do that. Yeah. Thanks.
Yeah. Like MESO has been developed. I think it's like the first off-the-shelf CAR T without like all the complication that you see in other type of sourcing for allogeneic CAR T targeting MESO. One of the features is extremely interesting that would be showed at ASH, and this is like the knockout of the TGF-beta receptor on the cell. TGF-beta receptor is always a potential down regulator for T-cells in the tumor microenvironment.
One of the big challenges Cellectis is tackling through all the CAR T we're developing for solid tumors is trying to tackle the tumor microenvironment, the TME, such as CAF, for example, that is something that's supposed to blow the, like, you know, I've seen like an article that the depth of the CAF is the product that will poke holes into the solid tumor protection. MESO is essentially a CAR that's not going to be shut down by the negative feedback loop that you have with TGF-β that is present in the microenvironment. 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 a very interesting feature not only for Mesothelioma, but potentially for a lot of different type of cancer. The SCID was selected also with all the attribute that this CAR has, which is like a CDC. It's same platform as all the other CAR we developed, which is a CD52 knockout, so it will work on our nivolumab and TCR alpha, plus it's a triple knockout. I think it's the first of its kind triple knockout CAR T. We're 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 gives like very compelling results for the tackling series 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 questions. I have a few regarding on the big picture questions. So the first one, maybe for André wondering, you know, the your partner Allogene had the clinical hold, and I think that the earnings call, they comment. They did not disclose too much, but they've come, and there's some concern about translocation. So just wondering, you know, how does it read through to your programs? And then, you know, also regarding your drug product, how much do you test regarding each step, you know, with the chromosome translocation events, and how do you detect that? And then my second question is regarding the allogeneic CAR T approach in general. We did see several companies and also your partner, Allogene, will share some data on consolidation approach.
We did see improved complete response rate. We don't know about the durability yet, but any thoughts, you know, from this approach, like, you know, 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 team comment on the clinical hold because I think it's like we're definitely very supportive and very confident on the handling of the situation by the Allogene team that's making fantastic work on their side. We're extremely excited by the data they're showing on UCART19, or ALLO-501A, actually. I think this is definitely a transformative data on the allogeneic CAR, especially the consolidation. I'll come back to this. To speak about the impact on Cellectis, there is like of course, we're monitoring the situation very closely. We're helping as much as we can. Do whatever we can.
We'll definitely help Allogene to go for this period, and we have like a strong confidence in the product and the outcome, and we believe that this trial is going to resume definitely. Nevertheless, chromosomal aberrations are quite frequent in the human population. Would it be certain chromosomes have more aberrations because they're subject to genetic recombination due to the state where they are. So like a lot of our immune cells, B and T cells undergo genetic recombination at a certain stage. Sometimes these genetic recombination can lead to some chromosomal changes in there. However, few things that should be said. First, the product is not in danger.
Like the team that there's like series of patients that have been dosed with the same platform. We're confident in Cellectis' global platform and are not only gene editing, but also the global platform where we develop our allogeneic CAR T to be very stable. The second thing is that T cell adult T cells, there is no cell line of adult T cells in general. Then finally, the cancer is like it's an allogeneic cell turned cancer. This is all the beauty about an allogeneic approach. You don't catch a cancer, especially T cell cancer, adult T cell cancer from like an allogeneic donor. This is not going to happen. Actually, it never happened in history, and it's something that could be quite rare.
We're quite confident with this and we believe that the platform on the contrary will come stronger from this phase and also with a lot of confidence that's what we have. We have no concerns today on the potential risk on what Cellectis and our partners are doing. We believe that this is like only an intermediate phase in there. On the contrary, we're very focused and very positive on the outcome of the data that not only our partners are having but also Cellectis is producing. These all are INDs and products and targets that Cellectis has been investing, and I think for the size of the company in driving so many life-saving products, something that's definitely transformative and will remain with the same type of technology that we have.
Now, on the consolidation study, it is something that I've been always a very strong advocate. I think it could be interesting to have Carrie's view because I've been speaking about like a consolidation study since years, and we've discussed this together, Gena. But Carrie has like a fresher eye than myself and more medical doctor eye. Carrie, if you want to say a few words about this.
Sure. Hi, Gena. Nice to hear from you as well. I'm really excited about the presentation that includes all the consolidation treatment. I think that I've been saying this since I joined Cellectis just now a year and a half ago. I mean, it's one of the main beauties and key points that I think is going to make allogeneic CAR T-cell therapies successful is the fact that you can give additional doses, and that's one of the huge drawbacks of the autologous setting.
We all know that these additional treatment, whether we're using chemotherapy, whether you're using antibody therapies, whether you're using small molecules, whatever it is in 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. The deeper the remission that you can bring a patient to, the longer their duration, as well as their longer survival and potential for cure. Giving additional treatment is always the right way to go when you can.
Therefore, it's really exciting to finally being able to see larger data sets of patients who've received more than one therapy in the allogeneic setting and showing that it's 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 question. I got two quick ones. First, could you just provide some color on where you're at with the other ongoing CAR-T program, so UCART123 and CS1? And then with respect to the TALGlobin 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.
Yeah, sure. That's perfect. Sorry, I was on mute for a second. Yeah. For UCART123 for relapsed/refractory AML, and for the. I'll start with that one first. 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, you know, quite sick and tend to be, you know, a little more fragile than you would see with acute lymphoblastic leukemia or with lymphoma. It is taking a bit longer, but we're moving through dose escalation and we're hoping to have additional data at some point next year, we'll see to share with everyone. As far as the myeloma study for UCARTCS1, that too, as you know, we had been on clinical hold.
We reopened after changing some of 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. We've been moving through dose escalation, and that too has been moving along nicely. There's lots of interest from all of our investigators. 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 expansion of the cells. It showed all the cytokines that we expect to see, and we did see some response.
We're, you know, super excited about this program continuing to move forward and are looking forward to share data when the time's right.
Thank you, Carrie. On the TALGlobin side, the big differentiation that we have, most of the current trials that you see for tackling the 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 fetal hemoglobin. You keep the sickle hemoglobin in the cells. You destroy another gene. There is one gene that is disrupted with a mutation in there, sickling the cells. You destroy another gene that is a repressor, and finally reactivate the gene that is not supposed to be expressed, that can restore the phenotype, which works actually, which are the 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 the 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. The approach Cellectis is taking is repairing the mutation in the beta globin gene and fixing this mutation and restoring the adult hemoglobin in the cells without leaving any scars or new scars in the DNA. You put back the gene to the sequence it was supposed to be.
Of course, there is competition in this field, but we believe that selected approach with the technologies we're developing, such as TALEN and the approach we have with our exortion technology, which is gene editing and the cytopath technology, brings it to a very high level of repaired adult hemoglobin. Like cells that are totally fixed with a very reduced side effects around and a very high on target with very accurate repair of this hemoglobin at the end. That's what differentiate us from most of the approaches 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 Jefferies. Please proceed with your question.
Hi, this is Devon 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? Another question is for ASH data, can you provide some details whether it includes patients who had prior CD19 CAR T treatment? Thank you.
Well, thank you very much for the question. Well, like, just to ask a precision. Like, you mean that, like the CD52 monoclonal antibody could induce an inversion or like a chromosomal aberration somewhere?
Yeah.
That was the question.
Right.
Well, personally, I might not have all the information about this, but it seems to me complex, especially for a non-internalizing antibody such as like alemtuzumab, too, or like a bispecific as alemtuzumab to induce such type of chromosomal aberrations that are quite classical in general. It's not something that has not been observed and is observed quite often and in a lot of not only patients, but potentially the global population. It's not a locus that is not susceptible to chromosomal changes in there. It's extreme. It's possible, but extremely unlikely on the mechanistic side. Excuse me, like the second part of the question I just blacked out.
The second part of the question is, if you can provide any color on ASH update. Do you have any data on patients with prior CD19 CAR T treatment?
I can answer that. Sure. I mean, to make a 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, prior treatment data set. That data will be included, but I'm not going to speak to today on what proportion of those patients. We do allow patients in the trial who have had prior CD19-directed therapy. I think, you know, we have already disclosed in terms of our study design. The expansion, we're going to focus on those group of patients, but for the dose escalation, we're not limiting to only those types of patients.
Okay. That helps. 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 a follow-up on the CD19 project. You know, some of those patients that are on CD19-directed therapies also have an antigen loss. I don't know if that is all of the patients that relapse off of CD19 directed therapies or that's a subset. And if it is a subset, you know, could that be a biomarker, for example, in dose expansion for an accelerated sort of like approval, assuming, you know, you see good response rates. That's number one.
Number two, you know, in terms of solid tumors with Mesothelin, it's really interesting, you know, looking forward to this data among the first, I believe, in solid tumors with preclinically with allogeneic CAR T. André, you'd spoken this earlier, but can you talk specifically, you know, how a clinical development plan, phase I and phase II could work? I mean, you know, the PD-1s and PD-L1, the initial PD-1s were approved in two to four years, as immunotherapy in various cancers. You know, solid tumors seem to be you can move faster. Any thoughts there just in terms of, you know, what a development program could look like, assuming you see success, you know, early on with the Mesothelin cell type? Thank you.
Thanks, Hartaj, for the great questions. I'm going to split it in two. Like, the first part of the question, your question, maybe Carrie can answer this because she knows a lot. The second part of the question, she can also answer it. I guess she can answer.
Yeah.
Both questions. I'm like
Maybe I won't answer it.
She wants it like we can do either both, but I can work. Go ahead please, then.
Yeah, sure. The first part of the question about CD19. I think that's a good point, but no, not everyone who relapses and/or doesn't respond to a CD19 directed therapy has the antigen loss. I think the numbers, if I'm not mistaken, is somewhere between 20%-30%. That said, I wouldn't necessarily call that a biomarker, but I'll get to that in a second. There's not a tremendous amount of data in leukemia, obviously, after a CD19-directed therapy. I mean, we have the blinatumomab data, and there's some of the UCART19 data from Servier. But there's no, it's not as vast of a data set as you would, as we've seen for lymphoma. It's hard to compare what we know from one data set to another.
That said, in terms of a development plan, and we've been very open about this from the get-go. You know, 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 a BLA. As you know, that is exactly the group of patients that while it's a super small niche indication, it is a place where the bar would be extremely low for the amount of data as well as the response rate to see something. Absolutely that is a group of patients that we're focused on.
It's in our clinical trial design for our expansion to focus on that group 'cause we know that group really needs therapy and needs it quickly and could help us bring a product to market quick. That said, the reason it's such an interesting piece is that it gives, depending on how good the data is. Even if it's, you know, 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. It gives us an opportunity to kind of move into multiple spaces in the treatment paradigms of these patients, and I think it's super important. Yes, and it's yes and yes, but also no if that makes sense.
Yeah. Thanks. That's clear. Just on the solid tumor question, just, you know, broadly, what are your thoughts there? You know, once you get into the clinic, you know, any potential for accelerated approval in those Mesothelin overexpression cancers?
Yeah. I mean, I think that the Mesothelin program is really interesting and exciting. I do think, however, it really will be the first program targeting Mesothelin from an allogeneic setting. While, yes, can we have a chance for an accelerated approval, it's all going to depend on the data we see. Until we get into the clinic and see what we see, it's going to be hard to make that calculation. 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's an accelerated approval path for a specific, high.
Like Mesothelioma, for example, highly specific cancer where there's clear, consistent overexpression, 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. 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.
Great. As I said, what is interesting is that, you know, like the monoclonal antibody, like PD-1 enters our PD-L1 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. In 70% of solid tumors, they do not respond because of the difficulty of the immune system to access the tumor itself that continues to grow protected by the CAF. The concept of blowing up the CAF with a CHOP CAR can be transformative in these type of combos and approaches. 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 it. It could be transformative.
Yeah. Great. Thank you, André. Thank you, Dr. Brownstein .
Yeah.
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 questions. I just have one brief one, and I know we're going to avoid commenting on Allogene's specific instances here. I was wondering if you could provide any update with regard to ongoing regulatory interactions you have with the FDA and have regulators had any requests for additional product specifications or anything of that nature as we move past this hold with Allogene. Thank you so much for taking the question.
Hi, Jack. Thank you so much for the question. It's a hard question to answer fully for the simple reason that a lot of the interaction we have on a regular basis with the FDA are confidential and under. I don't want to share particularly because it's also a competitive advantage Cellectis has on its side. So far, we haven't seen any significant change into this. These exchanges are very fluid today and doesn't change anything. So I think that it's important to monitor the situation on a daily basis. Cellectis is so far on a very good track with their, well, with our own trials. Excuse me, but like it's difficult to share more than this.
I 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. Taking the question. In the ASH abstract for BALLI, it said that the three patients in the FCA DL2 discontinued. I'm just wondering why. As you think about the 20x22 next-gen candidate, can you put that into the context of UCART22 development? Thanks.
Sure. André and [inaudible], I can take this one. Our abstract includes the first three patients. We will have the other patients, additional patients in the abstract presentation at the meeting. All of that data will be in there. I don't want to get into, you know, reasons for discontinuation and all that because it'll be in the dataset, and I don't think I can share that due to embargo rules since it's part of the dataset. Again, suffice it to say that we're still in dose escalation, and we haven't reached our recommended phase II dose yet. There'll be different reasons for why patients came off the study.
As far as 20x22, I mean, I think the big difference is and why this is important is, as you well know, the UCART22, which was our first, you know, one of our first programs, has the RQR8, CD20 mimotope on it. So it would be potentially deactivated and killed with rituximab on board. As you know, in lymphoma, we can't really use that as well since most patients will have rituximab on board. 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. We're positioning UCART22 for ALL, for leukemia because of that. You know, rituximab is rarely used in ALL.
UCART20x22, which not only is fantastic because it has the dual CAR and 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 David Dai with SMBC. Please proceed with your question.
Hey, thank you so much for taking my questions. I have two questions. First, I just wanted to get some clarification on the UCART22 ASH abstract data, where you said one patient had blast reduction consistent with CRI. Could you provide some additional color on this reduction? Is that a confirmed CRI? Second question is that you also presented really encouraging preclinical data for TALGlobin at ASH.
Your approach is very differentiating from competitors. Could you comment on how you see the preclinical data compare to the competitor programs from CRISPR and bluebird bio? Also, is the IND still on track for next year?
I can start with the first part of the question about UCART22. Now I'm trying to remember exactly what the question was because there's so many questions.
Sorry. The question is just, the reduction consistent with CRI.
Yeah.
Confirmed CRI, or?
Yeah. Well, the thing is with leukemia, it all depends on. It's not the same as. There's no such thing as confirmed or not confirmed in terms of the response criteria. It's sort of, you know, it depends on which response criteria being used, whether you can count it as an actual CRI or not. And you'll see in the data set when we present the data, what the patient had and what their blast reduction was. It was quite impressive, let's say. However, depending on which response criteria you use in leukemia, and there's a few. The one is the NCCN, which is what we were using.
There's also the modified Cheson, which was what was used for inotuzumab, and it just depends, each one of them has different dependence on how long you can measure it for. Unfortunately, unlike with other, like the CIS, for example, we're not checking the leukemia status in the bone marrow every day, so it's really hard to know exactly whether or not it meets certain criteria. That's why we were kind of careful and cagey with our answer there. I think it's extremely interesting, and it's extremely encouraging data at a very, you know, lower dose level in our first group of patients treated with SGI, which is pretty amazing in my opinion. Then, I don't know, André, do you want to speak to TALGlobin?
Yes. The TALGlobin is currently being manufactured, but once we finish the manufacturing, we have to go through all the requirement with the GMP material to start preparing the IND package. This is something the work will start probably next year once the product will be released. This is all done internally, so it's something that's quite exciting. I'm not giving any guidance for the IND filing today, but it's definitely a product that will go in the clinic.
Thank you. Our next question comes from the line of Nick Abbott with Wells Fargo. Please proceed with your question.
Hello. Thank you. First question, just going back to the ASH abstract and what data will be presented. Have you cleared the 2.5 mg per kg dose? If not, when do you think you'll do that? Is the next step 5 mg per kg? 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're going to be presenting and which cohorts and which datasets, unless it was already in the abstract that's been released. As you pointed out, the dose level two is the 1 million, and the DL2 is the 2.5, and the next stage would be five. Yeah.
Just on the absolute lymphocyte count profile, you know, there are no range bars on the data that's 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 want? 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're looking at because maybe it's not accurate the way it's being interpreted. What I can tell you is the patients all, you know, went to zero with the lymphodepletion and the alemtuzumab. You may be looking at the other line, which is the UCART expansion.
Oh. I'm looking at the blue line which says absolute lymphocyte counts.
Oh, I have to pull it up then. I know in one of the patients.
That's just what the.
The data was shown. Yeah, I have to look at it. I don't have it open in front of me. What I do know is that we can get back to you in an email to explain it. What I can tell you is it depends on where it was being measured from. In some cases, we're measuring the actual UCART cell in the absolute lymphocyte count, so that could be what you're looking at. I'll look at it and can send you an email with the clarification.
Okay. Thanks, a nd maybe last one, and obviously it's a very heavily pretreated population, as you've said. I think.
Yeah.
Median is five in the abstract versus three at ASH last year.
Mm-hmm.
As you think about expansion, you know, is this the kind of population, five median priors with CAR T failure? And if so, you know, is that a population you think you can successfully complete a trial? I mean, we already have a patient here who has apparently no benefit from the CAR T, but it still had no lymphocytes, because they had the alemtuzumab and lymphodepletion.
Mm-hmm.
It's that patient is obviously in a very challenging place.
Yeah. Yeah, that's a really good question. I think the answer there is yes. I mean, I think it's in our, if you go to clinicaltrials.gov, it has the information on our expansion cohort, I believe. I think that this goes to what I said before. It's really important to have a comprehensive multiple shot on goal plan for development of any product. I think particularly given our size, and wanting to be able to bring a product to BLA and approval, this is definitely something that we can do. I think that while in leukemia, even once you've had multiple therapies, you know, it is a disease that typically is of younger, healthier people.
It's not like acute myeloid leukemia, where those people, the vast majority of patients are over 65, even over 75 for that matter, and are super frail, had multiple therapies, their organs don't work well. Generally speaking, leukemia patients are younger. It's the most common cancer in children. It is the most common cancer for young adults. You know, we're 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, who maybe they've 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. I think that's super important.
I think in ALL in particular, it's a little bit of a different story than when you're talking about myeloid leukemia or some of these other diseases that you see in older people. 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 who 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 they can move forward and potentially have a life.
That said, though, there are. It’s a small niche indication 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. To your point, potentially not necessarily people who failed five therapies and have also failed CAR T already. That will all be obviously. Yep. Thanks.
Yeah, thank you very much.
Yeah, thank you.
Our final question comes from the line of Ingrid Gafanhao with Kempen. Please proceed with your question.
Hi. Hi, team. Thank you for taking my questions. I'll keep it a bit brief then. Just checking. I just want to check with you once again, what are your plans with Calyxt and your shareholdership? I think you mentioned you're planning to maintain it, but would you be keen to monetize this any, let's say, in the short to mid term?
Hi, Ingrid. Excuse me. I missed the beginning of your question. Actually, it was not super clear. It's about what?
Yeah, sure. I just want to check with you what is your current thinking on Calyxt and your shareholdership.
Oh, yeah. Actually, currently, we think Calyxt just announced, you know, leadership change with the arrival of Michael Carr and also change in strategy that has been induced not only by the new leadership but also by the board of directors under the chairmanship of Yves Ribeill. We believe that this change is about to transform the company in a very meaningful manner. As Cellectis has a significant stake in Calyxt, I think that we're positive on the fact that this is going to bring a lot of value. Indeed, since then, it has been quite well received by the market. As I said, like, Cellectis definitely has a vested interest in the success of Calyxt and looking forward to this.
It's something that we believe is going to be very valuable in the future for us as shareholders of Calyxt. We have to wait up to the time this change in strategy is implemented. We believe that the current company has all the pieces to be extremely successful in the implementation of the new strategy very rapidly and very swiftly, which we should be to our advantage.
Right. Understood. That's clear. If I may, I have just one more question for Eric. Just looking ahead into next year, considering that you're planning to move some programs, IND forward, are you providing any guidance on your cash burn?
We don't provide any guidance, you know, on our cash burn. What we'd say, you know, the cash runway is early 2023 on Cellectis. We don't disclose, you know, milestone payments. We have, you know, partnership with, you know, Servier, where we can get up to $410 million on 19 programs. Also the partnership with [inaudible] , where we can get up to $3 billion on the 15 targets.
Also with Iovance and with Cytovia, a series of milestones to be paid. Currently, the cash burn was into 2023 if unchanged.
All right. Thank you very much.
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 André Choulika for closing remarks.
Well, thank you very much, everyone, for this Q&A. We're extremely excited to have all these questions and excited about our trials and our partners' trials. There's a lot of things ongoing at Cellectis. I think that Cellectis has hit seriously a leaping point, a turning point for the company with internalizing all the manufacturing. What comes next in the coming months and years is the transformative Cellectis that is becoming a true, like, bona fide biopharmaceutical company, making things from A to Z in a, like, one-stop shop with gene editing, CAR-T, in oncology, gene therapy, and of course, with a powerful strategy in the clinic, as we've been sharing with Carrie. I think that this is going to change. Please watch closely and come to our meetings and posters at ASH. We're waiting for you.
Thank 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.