Good morning, everyone, and welcome to the Cellectis second quarter 2022 earnings call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. Please be aware that today's conference call is being recorded. I'd now like to introduce the first speaker, Arthur Stril, Chief Business Officer. You may begin.
Good morning, and welcome everyone to Cellectis second quarter 2022 corporate update and financial results conference call. Joining me on the call today with prepared remarks are Dr. André Choulika, our Chief Executive Officer, and Dr. Bing Wang, our Chief Financial Officer. Dr. Brownstein is absent for today's call, so I will be speaking about our CAR T program updates. Yesterday evening, Cellectis filed its interim report and issued a press release reporting its financial results for the second quarter and six-month period ended June 30th, 2022. The report and press release are available on our website at cellectis.com. As a reminder, we will make statements regarding Cellectis' financial outlook in addition to its manufacturing, regulatory, and product development plans.
These forward statements, which are based on our management's current expectations and assumptions and on information currently available to management, including information provided or otherwise publicly reported by our licensed partners, are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent Form 20-F filed with the SEC and the financial report, including the management report for the year ending on December 31st, 2021, and subsequent filings Cellectis makes with the Securities and Exchange Commission from time to time. I would now like to turn the call over to André.
Thank you, Arthur. Good morning, and thank you everyone for joining us today. Cellectis continues to make progress enrolling patients in our three sponsored phase I dose escalation trials and take notable steps forward with our preclinical data and programs. This week, we're proud to announce the FDA clearance of our investigational new drug application for UCART20x22, our product candidate being developed for patients with relapsed or refractory non-Hodgkin lymphoma. The UCART20x22 program is very exciting and will be Cellectis' first dual targeting allogeneic CAR T-cell product candidate to enter clinical trial. Targeting CD20 and CD22, both validated targets in B-cell malignancies, has the potential to enhance tumor cell killing and increases the breadth of antigen targeting. These advantages may increase the addressable patient population and provide a potential therapeutic alternative to CD19-directed therapy.
UCART20x22 will also be our first product candidate with fully integrated in-house development, showcasing our transformation into an end-to-end cell and gene therapy company from discovery and product development and transfer into GMP manufacturing and clinical development. This quarter, we're also pleased to publish research data on our novel immune-evasive universal CAR T- cell in Nature Communications following our oral presentation at the American Society of Gene & Cell Therapy. These novel immune-evasive universal CAR T-cells are very promising, and they may address the main challenges of allogeneic CAR T-cell. The first of which is depletion by the host immune system via the host versus graft reaction, followed by enabling the proliferation of cells without attacking host tissue via the graft versus host reaction.
While the prevention of graft-versus-host disease can be readily addressed by an inactivation of T-cell receptor TCR alpha expression in CAR T-cells, our engineering approach could enable the universal CAR T-cell to become transiently invisible to natural killer cells and allogeneic T-cells, allowing them to eradicate tumor cells before being rejected by the patient's immune system. This could enable the broad use of universal CAR T-cell in allogeneic settings for the benefit of a wider population of patients. This quarter, we also continued to expand our incredible leadership team. Cellectis announced that during our annual shareholders meeting that Axel-Sven Malkomes and Dr. Donald Bergstrom have been appointed as directors for the company's board of directors. We are very pleased to continue our work with Dr. Bergstrom and to welcome Mr. Malkomes to the Cellectis board.
They are both seasoned leaders with the healthcare industry who brings decades of experience in both the healthcare and financial services sector to Cellectis. We're confident that they will provide meaningful and valued perspectives as we continue to progress toward becoming one of the few end-to-end cell and gene therapy companies. Now, I would like to turn the call over to Arthur Stril, our Chief Business Officer, who will give an overview of the three sponsored clinical trials and preclinical product pipeline. Arthur, please go ahead.
Thank you, André. Our clinical-stage allogeneic CAR T- cell product candidates continue to make progress in the clinic. The BALLI-01 study evaluating UCART22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia is currently enrolling patients at dose level three, 5 million cells per kg, with fludarabine, cyclophosphamide, and alemtuzumab preconditioning regimen. We plan to initiate the administration of UCART22 batches manufactured fully in-house from our Raleigh facility in the second half of this year. The MELANI-01 study evaluating UCARTCS1 in patients with relapsed or refractory multiple myeloma is currently enrolling patients at dose level one, 1 million cells per kg, with fludarabine and cyclophosphamide preconditioning regimen. We look forward to sharing clinical data from at least one of these three programs by the end of the year when we will have a robust and meaningful data set to present.
Lastly, as André mentioned, we are pleased to announce the FDA IND clearance for our product candidate UCART20x22, the first allogeneic dual CAR T- cell product candidate being developed for patients with relapsed or refractory non-Hodgkin lymphoma. UCART20x22 features TALEN-mediated disruptions of both the TRAC gene that has been shown to reduce the risk of graft-versus-host disease and the CD52 gene to permit use of a CD52 directed monoclonal antibody in preconditioning to enhance CAR T engraftment, expansion, and persistence. We are extremely excited to start the NATHALI-01 study evaluating UCART20x22 in patients with relapsed or refractory non-Hodgkin lymphoma in the second half of this year. This quarter, our partnerships also proved to be an exciting highlight for Cellectis.
In June, Allogene announced that the FDA granted Regenerative Medicine Advanced Therapy designation to ALLO-501A in relapsed refractory large B-cell lymphoma. The RMAT designation was based on the potential of ALLO-501A to address the unmet need for patients who have failed other therapies and follows positive data from the phase I ALPHA2 trial in heavily pretreated patients with relapsed refractory large B-cell lymphoma. Allogene previously announced that enrollment in the phase I portion of the ALLO-501A ALPHA2 trial in relapsed refractory large B-cell lymphoma reopened with the goal of offering ALLO-501A to patients while Allogene prepares to launch the pivotal phase II ALPHA2 trial. They also previously said that the single-arm pivotal ALPHA2 trial of ALLO-501A in relapsed refractory large B-cell lymphoma is on track to begin mid-year 2022, with FDA discussions directed at finalizing clinical trial design and chemistry manufacturing and controls requirements.
In May, Allogene also announced that the FDA granted Orphan Drug Designation for ALLO-605 for the treatment of relapsed refractory multiple myeloma. Allogene previously announced that enrollment had resumed in trials targeting BCMA for the treatment of patients with relapsed refractory multiple myeloma and targeting CD70 for patients with advanced or metastatic clear cell renal cell carcinoma. Enrollment also resumed in the universal trial with ALLO-715 and the IGNITE trial with the TurboCAR candidate, ALLO-605. I will now move on to our research collaboration with Iovance and Cytovia. This quarter, Iovance began site activation and patient recruitment for the IOV-GM1-201 first in human study of IOV-4001. IOV-4001 is a PD-1 inactivated TIL therapy that incorporates the TALEN gene editing technology.
IOV-4001 may leverage a combination of TIL and interruption of PD-1 signaling within a single therapy. In a murine model of melanoma, the antitumor activity of IOV-4001 was superior to non-edited TIL product, whether alone or in combination with an anti-PD-1 antibody. The IOV-GM1-201 study includes two patient cohorts. Advanced melanoma patients who were previously treated with anti-PD-1 therapy and metastatic non-small cell lung cancer patients whose disease has progressed after up to three lines of prior therapy. Iovance announced it looks forward to dosing the first patients in the study in the second half of this year. Finally, Iovance has a robust research pipeline advancing toward the clinic.
Following the success of IOV-4001, several targets for genetic modifications are in preclinical studies using the gene editing TALEN technology, including double genetic knockout program. Our research and development collaboration with Cytovia to develop TALEN-edited induced pluripotent stem cell NK and CAR NK cells is progressing. Cellectis has developed custom TALEN, which Cytovia is using to edit iPSCs in a safe and effective manner. Additionally, Cytovia has generated promising preclinical data of TALEN-edited iPSC-derived NK cells that it expects to present at upcoming scientific conferences later this year. These announcements reiterate once more that TALEN is a technology of choice for gene editing, which continues to provide the company with expanded business opportunities. With that, I would like to hand the call over to Dr. Bing Wang, Cellectis Chief Financial Officer, for an overview of our financials for the second quarter of 2022.
Thank you, Arthur. I will provide a brief overview of our financials for the second quarter of 2022. I would like to highlight that our financials, the cash equivalent, current financial asset, and restricted cash position of Cellectis excluding Calyxt as of June 30th, 2022 was EUR 123 million compared to EUR 177 million as of December 31st, 2021. This difference mainly reflects EUR 56 million of net cash flow used in operating, investing, and lease financing activities and EUR 4 million of negative foreign exchange impact, partially offset by EUR 5 million of cash received related to research tax credit pre-financing. Based on the current operating plan and financial projections, this cash position is expected to be sufficient to fund Cellectis standalone operations into early 2024.
The consolidated cash equivalent and current financial assets and restricted cash position of Cellectis, including Calyxt, was EUR 135 million as of June 30, 2022, compared to EUR 191 million as of December 31st, 2021. The net cash flow used in operating capital expenditure and leases were EUR 56 million at Cellectis and EUR 30 million at Calyxt in the first six months of 2022, partially offset by a EUR 10 million capital raise at Calyxt and EUR 5 million of cash received related to research tax credit pre-financing at Cellectis. The net loss attributable to shareholders of Cellectis, excluding Calyxt, was EUR 47 million in the first six months of 2022, compared to a loss of EUR 43 million in the first six months of 2021.
This EUR 4 million increase in net loss between 2022 and 2021 was primarily driven by a decrease in revenue and other income of EUR 18 million, partially offset by an increase in net financial gain of EUR 8 million and a decrease of R&D expense of EUR 4 million. The consolidated net loss attributable to shareholders of Cellectis, including Calyxt, was EUR 51 million or $1.12 per share in the first six months of 2022, compared to a loss of EUR 52 million, or $1.17 per share in 2021. The consolidated adjusted net loss attributable to shareholders of Cellectis, excluding Calyxt, excluding non-cash stock-based compensation expenses, was EUR 43 million or $0.95 per share in the first six months of 2022, compared to a loss of EUR 38 million or $0.86 per share in 2021.
Based on current plans, we anticipate our cash runway will take us into early 2024. We are focused on spending our cash, developing our deep pipeline of wholly owned product candidates in the clinic, and operating our state-of-the-art manufacturing facilities in Paris and in Raleigh. Our focus remains on maintaining an efficient corporate infrastructure that will enable us more limited growth in G&A spend. Thank you very much, and back to André.
Thank you, Bing. To close out this call, I would like to reiterate how excited we are about the continued progress of our clinical trial and our upcoming milestones for the remainder of 2022. To date, close to 200 patients have been treated with allogeneic CAR T-cell utilizing technology developed by Cellectis, both in Cellectis sponsored clinical studies and those of our licensed partner, Allogene and Servier. We continue to make progress with our pipeline with our three ongoing clinical trials in hematological malignancy this quarter as we make steps closer to becoming a true end-to-end cell and gene therapy company. These updates clearly show our potential and ability to advance the field of allogeneic CAR T-cell therapy.
At Cellectis, we strongly believe that our product candidates, our technologies, and our in-house manufacturing capabilities will lead us to a paradigm shift for patients with hard-to-treat cancer, positioning us at the forefront of this promising medical and scientific field. With that, I would like to open the call for Q&A.
Thank you. At this time, we will be conducting a question-and-answer session. If you would 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 would 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. One moment please while we pull for questions. Our first question comes from the line of Gena Wang with Barclays. Please proceed with your question.
Thank you for taking my questions. Congrats on the IND clearance. Announcing, you know, your UCART20x22 can start clinical trial second half this year. Would you be able to share a little bit more color regarding the clinical trial design, including like initial thoughts on initial dose and also the patient population that specifically related to, you know, which line or whether they will have a prior CD19 CAR T therapy? And then my second question is regarding the your Nature Communications publication. It is very impressive data. So wondering, do you have a what kind of IP you have for your new approach? You know, HLA-E knockout and beta-2-M knockout.
Thank you so much, Gena, for these two great questions to start this call. This is Arthur, and I think I will hand over the questions to André. I don't think we can hear André for now, so I will take the first question. On the UCART20x22, we're indeed extremely excited to have the IND cleared. This is the first allogeneic CAR T, developed, designed, and manufactured end-to-end at Cellectis, so it's a fantastic milestone for the company, and we definitely look forward to administering this product to patients. We haven't disclosed the full clinical trial design yet. We have said that this will be in relapsed refractory non-Hodgkin lymphoma patients.
We will be disclosing the full clinical trial design later this year as the trial is getting started. We do believe that this will be a very strong differentiated allo CAR-T in the NHL space, in particular because of the dual targeting approach and the fact that it's strongly differentiated versus the CD19 targets. So on your other question around IP, I mean, definitely we strive to protect all the innovation that we're doing at Cellectis. We have a strong protection on the CD52 knockout approach for heme malignancies, CAR-T, and we definitely have protection as well around the B2M HLA approach that we recently disclosed in the Nature Communications.
We think this is indeed exciting to have a very strong arsenal of persistence enhancing technologies that allow us to adjust and adapt depending on the indication that we target, be it in the heme space or in the solid tumor space.
Thank you.
Our next question comes from the line of Yigal Nachomovitz with Citi. Please proceed with your question.
Hi, team. This is Ashik Mubarak on for your call. Thanks for taking my questions. For UCART20x 22, just as you're thinking about starting the study, I'm just curious how you're thinking about dose escalation generally. I think we've seen kind of a wide range of starting doses from some of the other cell therapies. I'm just kind of curious if you can comment at all where you think you'll start, maybe relative to those other cell therapies out there. Just more generally, how dual allogeneic targeting might make your dose escalation different, if at all.
Yeah. Thanks a lot for this question. André has disconnected, so I will take it. This is Arthur. I think it's a great question, and we've put a lot of careful thought into the clinical trial design, both in terms of the starting dose as well as the lymph depletion regimen, indeed due to the dual targeting nature of the shield of the CAR-T. At this stage, again, we are not disclosing the exact dose. I think what we can say safely is this will be a standard dose escalation, dose expansion design.
Since this is a very competitive field right now, in particular for dual targeting, we are not yet disclosing the trial design, and we'll do so in due course, when the trial is starting.
Okay. Makes sense. Maybe if I can ask one more about UCART 22. I think you've indicated that you're switching to your fully in-house manufactured version. I think you've previously alluded to this version being more potent compared with the product you've used before. Just wondering as you switch over, if you'll need to make any adjustments to the dose escalation or maybe even dose de-escalate a bit. Is this version the commercially ready version, or will there be additional iterations down the road? Will you have to do, maybe do some comparability work for those versions if there are any further ones? Thanks.
Thank you, these are excellent questions on UCART22. I think André reconnected. André, do you wanna take this? Apparently not. I will again take the question on UCART22. Basically on UCART22, you're absolutely right. The product from what we've seen is more potent than what we had manufactured at our CMO in the past. This is definitely a big milestone and testimony to our Raleigh internal manufacturing capabilities. We definitely have had an intense discussion with the FDA on comparability and what will happen with the dose escalation. There is a possibility that the FDA asks us to de-escalate.
If that's the case, this will be to acknowledge that the product is more potent, and therefore a smaller dose could lead to the same effect with obviously the added benefit of a reduced cost of goods. If that happens, this will not delay the trial, and we will still be able to rely on the data from the previous version of UCART22 that was manufactured at our CMO.
Okay, great. Thanks for all the color.
Sure.
Our next question comes from the line of Kelly Shi with Jefferies. Please proceed with your question.
Hi, this is Dave on for Kelly Shi. Thank you for taking our question. Just a quick question on overall plan for the next 12 months. You said you'll be disclosing at least one set of data. Apart from that, what investor should look forward in next 12 months? Additionally, can you add color on milestone from Allogene on pivotal trials of ALLO- 501 and ALLO- 715 data update? Thank you.
Great. Thank you so much. We will try, André another time. André, are you on the line?
Thank you so much for this. Actually, do you hear me?
Yep.
Yes.
Well, we know that Allogene is starting their clinical trial, their pivotal phase very soon. Of course, there are milestones, stages that are preclinical milestones, like a clinical milestone up to the BLA and post-commercialization milestones. These total approximately EUR 410 million in total. But the details have not been disclosed on the part of the confidentiality we have between us and them. The other thing is also we expect potentially next year to have also the BCMA trial from Allogene to start pivotal trial and also to receive milestones. These are like EUR 185 million in total up to the BLA and post-commercial milestones.
The details also are not disclosed and are part of the confidentiality the company has with Allogene. We're very excited by the data that they have obtained with both CAR-T. We think that ALLO-501A is not only a first-in-class, allogeneic CAR-T, but is also part of the first-in-class autologous and allogeneic all, of the CD19 CAR-T. We think that this product is going to totally wipe out the competition in this space. We're very excited by the start of the pivotal trial, seeing the data. On the BCMA part, we are also very excited by the data that has been obtained by Allogene. We definitely believe that this data definitely matches, if not better than Abecma. Of course, there are like, other type of, BCMA CAR-T autologous products.
Given all the difficulty and the logistics, we believe that also the performance, the commercial performance and the potential for physicians of these two CAR-T being on the shelf will definitely change, will be a game changer in this space.
Thank you.
Our next question comes from the line of Hartaj Singh with Oppenheimer. Please proceed with your question.
Great. Thank you for the question. André, I might suggest, I know you're helping get some of that product out the door there down in Paris, but you might want to move away from those steel tanks, reception-wise. Just a quick question, André and team, on, you know, the data at the end of the year from one, you know, one of the projects and then maybe looking to next year. You know, the trials for UCART123, UCARTCS1 and UCART22 have been designed with like a dose expansion with if you'd seen a really good signal in some tumor type to maybe go to a pivotal trial. Are you still thinking of those two projects in that regard?
You know, how could we see that play out, you know, assuming you have some good-
Thank you so much, Hartaj, for the question. Always great as usual. Do you want to take this, André?
Well, Arthur Stril, if you want to get started, I can continue. No problem.
Okay. I can get started. Hartaj, you're spot on, and I think this will be not only very indication-specific and very data-specific, but definitely we've designed the phase I/II trials in two blocks, a dose escalation and a dose expansion, that could have, depending on data and the indication, the potential of being registrational. We think, for example, that for UCART22, because there is a high unmet need and a scarcity of options beyond CD19 autologous, there is definitely room for the dose expansion phase of the trial once we found the recommended phase II dose with our Raleigh internal manufactured product, for the dose expansion to be potentially registrational.
That's why we decided to switch the product to our Raleigh facility so that when we get closer to BLA, we don't have to switch from a CMO and we completely control the production and we can file our own facility in the BLA. I don't know, André, if you want to add any additional color to that.
Yes, I would like to add, like, one thing. First of all, it's a great question. The thing is that, you know, we've been developing a series of CAR T's, allogeneic CAR-T's for a number of years now, like, you know, UCART19 that has been renamed ALLO-501. We started dosing the first patients six years ago, like in 2015, like seven years ago, by the way, more than seven years ago. Then since then, there was like the BCMA CAR-T. So UCART19 was licensed to Servier, BCMA to Pfizer, then became Allogene, and Allogene is very brilliantly developing these two CAR-T. We went for UCART123, then UCARTCS1, then UCART22. We think it's a lot of things on our plate, and now, like, we're moving to UCART20x22.
There are, like, certain targets that are, let's say, de-risk targets like such as CD19 and BCMA, but there's plenty of them. Some are de-risked targets such as CD22 or CD20, and this is why we think these two UCART20x22 and UCART22 are fairly straightforward. The ones that, like, we see as potential jokers in the game, which are UCART123 for AML and UCARTCS1 for multiple myeloma. Of course, there are two. AML is a hard to treat indication, and the target is a complex target that has been challenged several times. We expect eventually to see some data in the future in this space effectively.
Great. Thanks, André. Thanks, everyone, for the answers and the color.
Thanks, Hartaj.
Our next question comes from the line of Jack Allen with Baird. Please proceed with your question.
Hi. Thank you so much for taking the questions, and congratulations on progress. I just have two quick questions. On the UCARTCS1 program, I was hoping you could add some more color as to how enrollment is going. It sounds like you are at dose level one. I just love to hear about how many patients maybe have been given dose level one and what you're looking for to advance to additional doses potentially in that study. On UCART20x22 , I know study design is going to be disclosed as you enter the clinic, but I'd love to hear any thoughts you have as far as how quickly we could reach proof of concept with that asset as well. Thank you so much for taking the questions.
Thank you so much, Jack, and I can start and André can definitely chime in. For UCART CS1, again, we're not disclosing individual patient numbers. I think the thing that we can say is that DL 1, as mentioned in the call, is 1 million cells per kg. It's already quite high compared to the other dose levels of the other CAR T. We started that trial at a dose level that was higher. That's definitely one indication we can give towards the overall trial by itself.
For UCART20x22, I think, again, without going into specifics of clinical trial design, what we can safely say is, there is a very large patient population and unmet need at this stage because, once patients are refractory to the CD 19 options that have actually moved to second line, there is very limited options and a very limited target opportunities. We've taken the two most de-risked targets that are not CD 19, CD 20 and CD 22, to offer a meaningful alternative not only to patients that will relapse from CD19 but also to patients that could potentially not receive a CD19 in particular in the autologous field.
We believe there is a large patient population, a large opportunity, and this could be conducive to a swift enrollment. André, any thoughts to add?
Yes. Like for UCARTCS1, yes, we're at DL 1. Like the enrollment is not very fast, but there is a lot of trials in the space in the U.S. There is a scarcity with available patients, and it's not the fastest trial we are having currently for numerous reasons. The enrollment in the United States, when we talk to a lot of physicians, is something that is difficult. Like maybe the plan also is to expand to other countries.
Great. Thanks so much for the color.
Our next question comes from the line of David Day with SMBC. Please proceed with your question.
Hey, great. Thanks for taking my questions. I also want to add my congratulations to the current progress. So, two quick questions from me, André. The first question just around the UCART22. Could you just remind us how many patients have been enrolled in those level three with the FCA preconditioning regimen so far? Then, second question is just around the data expectations in the second half this year. I know you're gonna be providing some, you know, some updates from all the programs. So just, you know, can you just maybe position us in terms of what kind of data to expect? Thank you.
André, you want to take this?
Is it like pictures on like UCART22? Actually, I missed a little piece of it. On FCA-
Yeah.
I guess that's. Okay, on FCA, there is three patients per level, DL 1, DL 2, DL 3. We completed DL 3. Like the plan is to try to bridge with few patients with the product that has been made at in-house, so at our Raleigh facility. Globally all the FC part and FCA part has been completed with the full cohort on both sides. That's the whole thing that has been done. Now we're expecting to then to start dosing patients with the Raleigh manufactured, and then move to the expansion. We hope, of course, we believe this is the product that's going forward also. If that answers the question. I think you can do the math.
Our next question comes from the line of Silvan Türkcan with JMP Securities. Please proceed with your question.
Yeah, hello. Congrats on the quarter, and thanks for taking my questions. Maybe one question, your UCART22. Could you just remind us of the exact mechanics of what still needs to be done to get the ALLO material into the clinic? So what are the mechanics of interactions with the regulators here? And I think last time we were talking about the potency assays or the assays required for comparability, are they now all in place? It would be great if you could provide some more color there. Then my second question is around recently there was a deal with Roche and obviously Poseida.
As part of that rather large deal and interesting that Roche is getting into the allo CAR T space now, there was a CD19, CD20 CAR T. Could you just tell us a little bit about the differences? Obviously, you know, CD19 retargeting with CD19, why would you do that and why is CD20x22 perhaps a better idea? Thank you.
Yeah. Thank you so much, Silvan. Great questions, and I can start on the Raleigh one. Definitely as mentioned before, we had interactions with regulators to understand exactly what they would be looking for in a seamless transition from our CMO manufactured product to the Raleigh manufactured product. We have a good understanding, and basically the steps are filing an IND amendment with the FDA in order to approve the Raleigh manufactured product. This then has to go through the clinical centers and their IRBs so that we can then safely administer the product. All of this is undergoing.
We have all the assays in place to make that happen, and we're confident that we'll be able to dose the first patients with the Raleigh product in the second half of this year. I think on the...
Uh-
Yeah. Yeah, André, please go ahead.
Yeah, on the size of the potency assays, it's like quite straightforward. I'm not gonna get into the details of this for numerous reasons. First of all, I think that I'm not sure that's really interesting for anyone. Plus, I don't want to disclose everything we're doing to do these type of comparabilities. Globally, it's essentially killing potency. The number, like the potency of release of perforin and granzymes and the number of recycling that it could do, the time of the recycling between two releases, the expansion potential of the cell, the number of like cell division they can do, the interferon gamma assays, et cetera. All of this gives you quite a broad idea of the performance of these type of products.
Well, I think it's good, but the performance that we obtain is totally not that bad, and we're very excited to see that they're very performing products. Definitely the comparability doesn't stand. It's not totally comparable. That's why there is a potential necessity of potentially quite like few doses below and re-expand after you do them, do a full cohort, but that's what you get. There was a technical question. Like, the beginning of the question was about what? Like, Silvan, excuse me.
Oh, there was a question around the Roche partnership and their CAR dual targeting CAR T, which also retargets basically CD19. Just what is the rationale here?
Yeah.
Why?
Well, I don't see the rationale behind the fact that most of the patient receives a CD19 CAR T at start, and they will arrive, they will probably deliver in a space of a full span of CD19 CAR T allogeneic and autologous. Of course, the allogeneic CAR T will be approved by then. Of course, you have Yescarta, Kymriah, et cetera. Then you come with yet another CD19 CAR T, where you see the performance are already quite good. Either you show superiority compared to the other CD19 CAR T and added a CD20, or I think it's way more interesting to have a CD20 x 22 whereas all the relapses of CD19 are not gonna give them another CD19 CAR T.
It's better to give them a CAR T that we believe the performance really high but don't have CD19. I'm super surprised of the reaction of this type of approach.
Great. Thank you. Thanks for taking my questions.
Thank you, Silvan.
Our next question comes from the line of Nicholas Abbate with Wells Fargo. Please proceed with your question.
Oh, good morning. Thanks for taking the questions. The first one just on UCART22. Have you filed the IND amendment? If not, when do you intend to do that?
Andre?
It broke up a bit at the time, actually. Like, just repeat the question. Excuse me.
Yeah, André, I'm asking whether you have filed for UCART22.
Hi, Nick.
Yeah. Good morning. If you filed the IND amendment, and if not, when you think you'll do that?
Oh, for UCART22?
Yes.
Well, you should expect to see patient dosing, I hope, sooner than later.
Okay, fair enough.
We haven't disclosed it, but we are not delayed.
Okay.
We're on time.
I may have missed it. I didn't hear. I think it was in Arthur's prepared comments on UCART123, but I seem to recall that you had completed dose level two. The next dose was gonna be an intermediate, so dose level two point five before jumping to dose level three. Can you just provide us an update on precisely where you are with UCART123?
Well, yeah, actually, you know, we've been very cautious with this type of CAR because we had a series of CRS in the past, and we think that dose level two could be an interesting dose. So far, we are concerned by dose level three, that being a too high dose. We're trying an intermediate dose. Potentially, I think that maybe there is like an intermediate between the two, like giving a repeat dose on two or something like this because it's quite a reactive target, and it's not an easy disease. I'm not gonna go through all the detail with this, but I think we're in waters that are interesting for the dose level DL 2 or that maybe it can be, you know, high waters on DL 3.
So-
It's not a simple CAR T to be dosed.
Right. Understood. Have you filed, like, an amendment to IND? Do you need to file an amendment to IND dose level tow point five or repeat dosing?
DL 2I, you just like how you can do this. To do a repeat, you need to file an amendment, and we're not delayed on this. It's still a challenging approach and we've been very cautious with that.
Okay.
But, uh-
Great. Thanks, André.
This is something we're not considering, but we're just doing.
Okay. Thank you.
Our next question comes from the line of Brooke Schuster with William Blair. Please proceed with your question.
Hi, this is Brooke Schuster on for Raju Prasad. I had a question regarding the manufacturing of UCART20x22. I was wondering if you could provide more color on how the manufacturing process for dual differs from the single target products and any details on the run yields between the two.
Thank you, Brooke. This is a great question, and I can definitely start. The UCART20x22 uses the same allogeneic CAR T manufacturing platform that we developed at Cellectis. The same manufacturing process as UCART123, UCART22, UCARTCS1, with all the improvements that come from manufacturing it in-house from our Raleigh facility. There is definitely some specificities in the viral vector construct due to the dual targeting. We use a bicistronic construct to carry both CARs, and we found that this was the most optimal construct for the allogeneic approach.
We have found that this does not modify at all the value proposition of allogeneic, which is getting significant yields in order to get a true off-the-shelf therapy that can be distributed at an industrialized scale. There was definitely a lot of process improvements to cater for this dual targeting approach. We have found that we could get to similar yields and to the hundreds of doses per manufacturing campaign that we're getting for the other CAR Ts.
If you take a technician that is making UCART22 or UCART20x22, if you don't write exactly on the tube, for example, containing the lentiviral vector for CD20x22 versus CD22, he will not realize. It's exactly the same process. The only thing that differs is in the QC at the end to be sure that both CARs as expressed are like the killing on 20 and on 22, notwithstanding the fact that the other target's not present, etc. There is a QC process that's slightly more complex for UCART20x22 to be sure that you have the dual. But during the manufacturing process itself, if you don't know what's contained in the lenti, then you don't know. It's exactly the same.
Okay, awesome. Thank you.
Our last question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question.
Hey, good morning. This is Matt on for Salveen. Could you elaborate on the rates of patient enrollment across the portfolio? Are there any headwinds we should be aware of? On CD20x22, given the CD52 gene disruption, are you able to use a less toxic preconditioning regimen? Thank you.
Thank you, Matt. Great questions. André?
Patient enrollment so far has been slow for numerous reasons across the three trials. UCART22 in acute lymphoblastic leukemia is a rare disease compared to Non-Hodgkin lymphoma. There are like 120,000 patients in the U.S. every year versus like 6,000. 120,000 versus 6,000, so it's quite huge. The enrollment has been slow on the UCARTCS1, as I said before, also there are a lot of products in this space. The trials are recruiting patients that fit the criteria, and they are tight criteria for numerous reasons also. It's quite slow. Our DL 1 was completed, DL 3 for P1 for UCART22, but we're still at DL 1 for UCARTCS1 following the hold.
UCART123 is a difficult disease to treat, so also like the patient selection and is something that slows down the enrollment. We are like completed DL 2 and moving to DL 2I. Have difficulty to jump to DL 3, as I described before. That takes also a lot of time. Now, one of the things we're doing, we're expanding to other countries because like in the U.S. there is a lot of trials that are ongoing and we are opening other countries and we believe that other countries have less these complex cell and gene therapy trials, so there is more potential in recruiting patients. That's what we believe so. UCART20x22, which is Non-Hodgkin lymphoma, is opening in multiple countries.
Not altogether because the U.S. is faster, but potentially we'll see the trial expanding to other countries. That should accelerate also the trials.
I think, Matt, on the CD52 knockout, I think what's super interesting with this approach compared to others is that you can definitely tune the lymphodepletion, because you can dial up or down the level of administration of this anti-CD52, which is true for the single dose, but which could also be true in a redosing regimen. So we really have a dial as opposed to an on/off like B2M. We really have a dial that will definitely allow us to fine-tune the lymphodepletion in a single and potentially a repeat dose setting exactly to the right safety benefits ratio. So you're spot on, and I think this is what we love about the CD52 approach, is it's inherent tunability.
Great. Thank you very much.
We have reached the end of the question and answer session. I'll now turn the call back over to André Choulika for closing remarks.
Thank you very much for all of you for supporting the company and asking questions, and I think they're all like very great questions. Of course, we're super excited by the start of UCART20x22. I think the company is heading at a very interesting moment in the near future. UCART22 is moving to P 2 in-house manufactured. UCART20x22 in-house manufactured product also. We are also progressing on UCARTCS1 and UCART123. The thing is like, we'll definitely keep you updated on these trials in the near future. With that, I would like to thank all of you and wish you a very great day.
This concludes today's conference, and you may disconnect your lines at this time. Thank you for your participation.