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spk06: Good morning, everyone, and welcome to the selected 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, Artis Drill, Chief Business Officer. You may begin.
spk15: Good morning. and welcome everyone to SELECTIS' 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, Selectis filed its interim reports 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 selectis.com. As a reminder, we will make statements regarding Selectis Financial Outlook in addition to its manufacturing, regulatory, and product development plan. 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 reports, including the management reports, for the year ending on December 31st, 2021, and subsequent filings selected makes with the Securities Exchange Commission from time to time. I would now like to turn the call over to Andre.
spk03: Thank you, Arthur. Good morning, and thank you, everyone, for joining us today. Rectis continues to make progress in enrolling patients in our three sponsored phase one 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 UCAR20x22, our product candidate, being developed for patients with relapsed or refractory nub Hodgkin's lymphoma. The UCAR20x22 program is very exciting. and will be selected as first dual targeting allogenic 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. UCAR-T 20x22 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 communication following our oral presentation at the American Society of Cell and Gene Therapy. These novel immune-evasive universal CAR T-cells are very promising, and they may address the main challenges of allogenic CAR T-cells. 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 reaction can be readily addressed by an inactivation of T cell receptor, T alpha expression in CAR T cells, our engineering approach could enable the universal CAR T cell to become transiently invisible to natural careless cells and allogenic T cells, allowing them to eradicate tumor cells before being rejected by the patient immune system. This could enable the broad use of universal CAR T cell in allogenic settings for the benefit of a wider population of patients. This quarter, We also continue to expand our incredible leadership team. Selectives announced that during our annual shareholders meeting that Axel Sven Malkimus and Dr. Donald Bergstrom have been appointed as director for the company's board of director. We are very pleased to continue our work with Dr. Bergstrom and to welcome Mr. Malkimus to the Selectives Board. There are both seasoned leaders with the healthcare industry who brings decades of experience in both the healthcare and financial services sector to select us. 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 Strill, our Chief Business Officer who will give an overview of the three sponsored clinical trials and three clinical product pipelines. Arthur, please go ahead.
spk15: Thank you, André. Our clinical stage allogeneic CAR T-cell product candidates continue to make progress in the clinic. The BALI-01 study, evaluating UCAR22 in patients with relapsorefractory B-cell acute lymphoblasting leukemia, is currently enrolling patients at dose level 3, 5 million cells per kg, with fludarabine, cyclophosphamide, and alemtuzumab preconditioning regimen. We plan to initiate the administration of UCARTS 22 batches manufactured fully in-house from our Raleigh facility in the second half of this year. The MELANIE-01 study, evaluating UCARTS CS1 in patients with relapsore refractory multiple myeloma, is currently enrolling patients at dose level 1, 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 UCARTS 20x22, the first allogeneic dual CAR T-cell product candidate being developed for patients with relapsorefractory non-Hodgkin lymphoma. UCAR20x22 features talon-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 NATALI-01 study, evaluating UCAR20x22 in patients with relapsor refractory non-Hodgkin lymphoma. in the second half of this year. This quarter, our partnerships also proved to be an exciting highlight for Selective. In June, Allogene announced that the FDA granted regenerative medicine advanced therapy designation to Allo501A in relapsed refractory large B-cell lymphoma. The RMAT designation was based on the potential of Allo501A to address the unmet needs for patients who have failed other therapies and follows positive data from the Phase I Alpha-2 trial in heavily pretreated patients with relapsed refractory large B-cell lymphoma. Allogene previously announced that enrollment in the Phase I portion of the Allo501A Alpha-2 trial in relapsed refractory large B-cell lymphoma reopened with the goal of offering Allo501A to patients while Allogene prepares to launch the pivotal Phase II Alpha-2 trials. They also previously said that the single-arm pivotal alpha-2 trial of allo501A 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 allo605 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 Allo715 and the IGNITE trial with the Turbocar candidate, Allo605. I will now move on to our research collaboration with Iovance and Phytovia. This quarter, IOVENT began site activation and patient recruitment for the IOF-GM1-201 first in human study of IOF-4001. IOF-4001 is a PD-1 inactivated TIL therapy that incorporates the TALEN gene editing technology. IOF-4001 may leverage a combination of TIL and interruption of PD-1 signaling within a single therapy. In a murine model of melanoma, the anti-tumor activity of IOF-4001 was superior to non-edited cell products, whether alone or in combination with an anti-PD-1 antibody. The IOF-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. IOVANTS announced it looks forward to dosing the first patients in this study in the second half of this year. Finally, IOVANTS has a robust research pipeline advancing toward the clinic. Following the success of IO4001, several targets for genetic modifications are in preclinical studies using the gene editing tail end technology, including double genetic knockout programs. Our research and development collaboration with Cytovia to develop TALEN-edited induced pluripotent stem cell NK and CAR-NK cells is progressing. Selectis 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 is expected to present at upcoming scientific conferences later this year. These announcements reiterate once more that Talon 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, Selective Chief Financial Officer, for an overview of our financials for the second quarter of 2022. Thank you, Arthur.
spk11: 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, CASH RECLUVANT CURRENT FINANCIAL ASSET AND RESTRICTED CASH POSITION OF SELECTIVES EXCLUDING CALEX AS OF JUNE 30, 2022 WAS 123 MILLION COMPARED TO 177 MILLION AS OF DECEMBER 31, 2021. This difference mainly reflects 56 million of net cash flow used in operating, investing, and lease financing activities, and 4 million of negative foreign exchange impact, partially offset by 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 selective standalone operations into early 2024. The consolidated cash, cash equivalent, and current financial assets and restricted cash position of Selectus, including Calix, was $135 million as of June 30, 2022, compared to $191 million as of December 31, 2021. The net cash flow used in operating capital expenditure and leases were $56 million at Selectus and $13 million at Calix in the first six months of 2022. partially offset by a $10 million capital raise of CALEX and $5 million of cash received related to research tax credit pre-financing at Selectus. The net loss attributable to shareholders of Selectus excluding CALEX was $47 million in the first six months of 2022 compared to a loss of $43 million in the first six months of 2021. This $4 million increase in net loss between 2022 and 2021 was primarily driven by a decrease in revenue and other income of 18 million partially offset by an increase in net financial gain of 8 million and a decrease of R&D expense of 4 million. The consolidated net loss attributable to shareholders of Selectus including Calix was 51 million or $1.12 per share in the first six months of 2022 compared to a loss of $52 million or $1.17 per share in 2021. The consolidated adjusted net loss attributable to shareholders of selectives excluding CALEX, excluding non-cash stock-based compensation expenses was $43 million or $0.95 per share in the first six months of 2022 compared to a loss of $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 Andre.
spk03: Thank you, Bing. To close out this call, I'd 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 allogenic CAR T-cell utilizing technology developed by Selectives. Both in Selectives sponsored clinical studies and those of our licensed partner, Allogene and Servi. 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 allogenic CAR T-cell therapy, At Selectus, we strongly believe that our products, candidates, our technology, 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.
spk05: With that, I would like to open the call for Q&A.
spk06: Thank you. And at this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 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 forward questions. Our first question comes from the line of Gina Nguyen with Barclays. please proceed with your question.
spk10: Thank you for taking my questions. Congrats on the R&D clearance. Now since your UCAR 20 by 22 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 thoughts on initial dose and also the patient population that specifically related to which line or whether they will have a prior CD19 CAR T therapy. And then my second question is regarding your NatureCom publication. It is very impressive data. So wondering, do you have a, what kind of IT you have for your due approach, you know, HLE knocking and beta 2M knockout?
spk15: Thank you so much, Gina, for these two great questions to start this call. This is Arthur, and I think I will hand over the questions to André. So I don't think we can hear André for now, so I will take the first question. So on the UCAR 20 by 22, 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 Selectis. 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. And we will be disclosing the full clinical trial design later this year as the trial is getting started. But we do believe that this will be a very strong differentiated Allocard T in the NHS space, in particular because of the dual targeting approach and the fact that it is 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 Selectis. We have a strong protection on the CD52 knockout approach for heme malignancies CAR-T, and we definitely have protection as well around the BDETUM HLA approach that we recently disclosed in the NatroComms. And 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.
spk05: Thank you.
spk06: Our next question comes from the line of Igor Nokomovic with Citi. Please proceed with your question.
spk13: Hi, team. This is Ashok Mubarak on FreeCall. Thanks for taking my questions. For 20 by 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. So 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, and just more generally how dual antigen targeting might make your dose escalation different, if at all.
spk15: Yeah, thanks a lot for this question. So Andre has disconnected, so I will take it this is Arthur. So, 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 lymphodepletion regimen, indeed due to the dual targeting nature of the field, of the CAR T. So, 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. But since this is a very competitive field right now, in particular for dual targeting, we are not yet disclosing the trial design and will do so in due course when the trial is starting.
spk13: Okay, makes sense. And then maybe if I can ask one more about UCAR 22. I think you've indicated that you're switching to your fully in-house manufactured version. And I think you've previously alluded to this version being more potent compared with the product you've used before. So I was 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. And is this version the commercial-ready version? And will there be additional iterations down the road? And will you have to maybe do some comparability work for those versions if there are any further ones?
spk07: Thanks.
spk15: Thank you. And these are excellent questions on UCAR22.
spk05: I think André reconnected. So André, do you want to take this? Apparently not.
spk15: So I will again take the question on UCAR22. So basically on UCAR22, 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. So this is definitely a big milestone and testimony to our Raleigh internal manufacturing capabilities. We definitely, we have had an intense discussion with the FDA on comparability and what will happen with the dose escalation. And there is a possibility that the FDA asks us to de-escalate. But 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. So 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 UCAR22 that was manufactured at our CFO.
spk05: Okay, good. Thanks for all the color. Sure.
spk06: Our next question comes from the line of Kelly C. with Jefferies. Please proceed with your question.
spk09: Hi, this is Devon for Kailishi. Thank you for taking our question. So just a quick question on overall plan for the next 12 months. You said you'll be disclosing at least one set of data. So apart from that, what investors should look forward in next 12 months? Additionally, can you add color on milestones from Allogene on pivotal trials of LO501 and LO715 data update? Thank you.
spk15: Great, thank you so much. We will try André another time. André, are you on the line?
spk07: And thank you so much for doing this.
spk03: Actually, do you hear me? Yes. Yes, okay. Okay, so the... Well, we know that allogene is starting their clinical trial, their pivotal phase very soon. And of course, there are milestones, there are stages that are preclinical milestones, like a clinical milestone up to the DLA and post-commercialization milestones. And these total approximately 410 million in total. but the details have not been disclosed and 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 Allergy to start pivotal trial and also to receive milestones. These are like 185 million in total. up to the BLA and post-commercial milestones, and about the detail also are not disclosed and are part of the confidentiality company has with Allergy. But 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 product, Allergenic CAR T, but is also part of the first in class pathologist and allergenic all of the CD19 CAR T. And we think that this product is going to totally wipe out the competition in this case. And we're very excited by the start of the DEVOLU trial seeing the data. On the BCMA part, we are also very excited by the data that has been obtained by Allergy We definitely believe that this data definitely matches. It's not better than a BICMA. Of course, there are like other type of BCMA CAR T autologous therapy. But 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 off the shelf will definitely be a danger in this case.
spk05: Thank you. Our next question comes from the line of Haritav Singh with Oppenheimer.
spk06: Please proceed with your question.
spk04: Great. Thank you. Thank you for the question. And, Andre, I might suggest, I know you're helping get some of that product out on the door there down in Paris, but you might want to move away from those steel tanks reception-wise. But just a quick question, Andre, team, on, you know, the – the data at the end of the year from one of the projects and then maybe looking to next year. You know, the trials for 123, CS1, and UCAR22 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 regards? And then, you know, how can we see that play out you know, assuming you have some good data readouts, you know, essentially over the next 12 months. Thank you for the question.
spk15: Thank you so much, Hartaj, for the question. Always great as usual. Do you want to take this, André?
spk03: Well, as long as you want to get started, I can continue in the problem.
spk15: Okay. I can get started. So, Hartaj, you're spot on, and I think this will be not only very indication and very data-specific, But definitely, we've designed the phase 1, 2 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 UCOT 22, 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 2 dose with our Rally internal manufactured product for the dose expansion to be potentially registrational. And that's why we decided to switch the product to our Rally 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.
spk03: Yes, I would like to add one thing. First of all, it's a great question. But the thing is that, you know, we've been developing series of CARs and allogenic CARs in numbers of years from now, like, you know, UCAR T19 that has been renamed ILO 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. And then since then, there was like the BCMA CAR-T. So 19 was licensed to survey, BCMA to Pfizer, then became Allogene. And Allogene is very brilliantly developing these two CAR-T. Then we went for 123, then CS1, then 22. And we think it's a lot of things on our plate. And now like we're moving to 20 by 22. There are like certain targets that are, let's say de-risk targets like such as 19 and bcma but there's plenty of them some are de-risk targets such as cd22 or cd20 and this is why we think these two cartes 20 by 22 and 20 22 plane like rt22 uh fairly straightforward the ones that like you should see as potential jokers in the game which are one two three four ml and cs1 for multiple myeloma of course there are two AML is a hard-to-treat indication, and the target is a complex target that is being challenged several times, and we expect potentially to see some data in the future in this space, definitely.
spk04: Great. Thanks, Andre. Thanks, everyone, for the answers and the call.
spk03: Thanks, Artaj.
spk05: Our next question comes from the line of Jack Allen with Baird.
spk06: Please proceed with your question.
spk16: Hi, thank you so much for taking the questions. Congratulations on progress. I just have two quick questions. On the CS1 program, I was hoping you brought some more color as to how enrollment is going. It sounds like you were at dose level one. And I just wanted 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. And then on 20 by 22, 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.
spk07: Thank you so much for taking the question.
spk15: Thank you so much, Jack, and I can start, and Andre can definitely chime in. So, for UCARTS CS1, again, we're not disclosing individual patient numbers. I think the thing that we can say is that DL1, as mentioned in the call, is one million cells per kg. So it's already quite high compared to the other dose levels of the other CAR T. So we started that trial at the dose level that was higher. So that's definitely one indication we can give towards the overall trial by itself. And then for UCAR 20 by 22, 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 CD19 options that have actually moved to second line, there is very limited options and very limited target opportunities. And so we've taken the two most dearest targets that are not CD19, CD20, and CD22 and to offer a meaningful alternative not only to patients that will relapse from 19, but also to patients that could potentially not receive a 19 in particular in the autologous field. So we believe there is a large patient population, a large opportunity, and this could be conducive to a swift enrollment. Andre, any thoughts to add?
spk03: Yes, like for CS1, yes, we're at DL1. like the enrollment is not very fast, but there is a lot of trials in the States, in the US. So we have, there is a scarcity of available patients, and it's not the fastest trial we are having currently for numerous regions. Their enrollment in the United States, and we talk a lot of physicians, is something that is difficult so like maybe the plan also is to expand to other countries great thanks so much our next question comes from the line of david day with smbc please proceed with your question
spk12: Hey, Greg. Thanks for taking my questions, and I also want to add my congratulations to the current progress. So two quick questions for me, Andre. So the first question is just around UCAR-D22. Could you just remind us how many patients have been enrolled in Bill Level 3 with the FCA preconditioning regimen so far? And then the second question is just around the data expectations in the second half of this year. I know you are going to be providing some updates from all the programs, so just you know, can you just position this in terms of what kind of data to expect?
spk05: Thank you. Andre, you want to take this? Is it, is it like QCAR T22?
spk03: Actually, I missed a little piece of it. Okay. So, on FCA. Yeah, so. Okay, so on FCA, you, there is three patients per level. DL1, DL2, DL3, we completed DL3. So like the plan, we tried to bridge with a few patients with the product that has been made in-house, so at our Rally facility. But globally, all the FCA part has been completed with the full cohort. on both sides. So that's the whole thing that has been done, but now we're expecting potentially to start those invitations and rally and then move to the expansion and we hope, of course, we believe this is probably going to evolve also.
spk05: If that answers your question, I think we can do the math.
spk06: And our next question comes from the line of Sylvain Turcan with JMP Securities. Please proceed with your question.
spk14: Yeah, hello. Congrats on the quarter, and thanks for taking my question. Maybe one question, UCAR22. Could you just remind us of the exact mechanics of what still needs to be done to get the relay 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 we could provide some more color there. And then my second question is around, recently there was a deal with Roche and obviously Poseida. And as part of that rather large deal, and interesting that Roche is getting into the Alucard key space now, There was a CD19, CD20 CAR-T. Could you just tell us a little bit about the differences? Obviously, you know, 19, retiring with 19, why would you do that?
spk07: And why is 20 by 22 perhaps a better idea? Thank you.
spk15: Yeah, thank you so much, Sylvain. Great questions. And I can start on the Rallye one. So definitely, as mentioned before, we've had interactions with regulators to understand exactly what they would be looking for in the seamlessly transitioning from our CMO manufactured product to the Rally manufactured product. This, we have a good understanding, and basically the steps are filing an I&D amendment with the FDA in order to approve the Rally manufactured product. This then has to go through the clinical centers, their IRBs, so that we can then safely administer the product. So 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 Rally product in the second half of this year. And I think on the... Yeah, André, please go ahead.
spk03: Yeah, on the size of the potency assays, it's quite straightforward. I'm not going to get into the details of this for numerous reasons. First of all, I think that there's – I'm not sure that's really interesting for anyone. And plus, I don't want to disclose everything we're doing to do these type of comparabilities. But globally, it's essentially killing potency. So the number – like the potency of release of – of perforins and granzymes and the number of recycling that it could do, the time of the recycling between two releases, the expansion potential of the cells, the number of cell division they can do, the interferon gamma assays, et cetera. And all of this gives you quite a broad idea of the performance of these type of products. And 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 a very performing product, but definitely the comparability doesn't stand. It's not totally comparable, so that's why there is a potential necessity of potentially doing quite a few doses below and re-expand after. You don't 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, Sylvain, excuse me.
spk14: Oh, there was a question around the Roche partnership and their dual-targeting CAR-T, which also retargets basically CD19. Just what are the rationale here and why?
spk03: Well, I don't see the rationale behind the fact that most of the patient receives a 19-card at start, and they will arrive, they will probably deliver in a space of a full span of CD19 CAR-T allogenic and autologous. Of course, the allogene CAR-T will be approved by then, of course. You have, yes, Carta, Camry, et cetera, et cetera, et cetera. And then you come with yet another CD19 Cartier where you see the performance are already quite good. So either you show superiority compared to the other CD19 Cartier and added the CD20, or I think it's way more interesting to have a CD20x22 where there are all the relaxers of 19. You're not going to give them another CD19 Cartier. So it's better to give them a CAR T that we believe the performance really high, but don't have CD19. So I'm super surprised of the reaction of this type of approach.
spk05: Great. Thank you. Thanks for taking my questions. Thank you. Our next question comes from the line of Nicholas Abbott with Wells Fargo.
spk06: Please proceed with your question.
spk02: Oh, good morning. Thanks for taking the questions. The first one just... on UCR 22. So have you filed the IND amendments? And if not, when do you intend to do that?
spk05: Andre? It broke up a bit at the time, actually.
spk03: Just repeat the question. Excuse me.
spk02: Yeah, Andre, I'm asking whether you have filed for UCAR 22 if you filed the IND. Yeah, good morning. If you filed the IND amendments and if not, when you think you'll do that?
spk03: Oh, for 22?
spk05: Yes.
spk03: So, well, you should expect to see patient dosing, I hope, sooner than later.
spk07: Okay, fair enough.
spk03: Revenue disclosed it, but we are not delayed.
spk02: Okay.
spk03: We're on time.
spk02: And then I may have missed that. I didn't hear in, I think it was Arthur's prepared comments on 1, 2, 3, but I seem to recall that you had completed dose level 2. The next dose was going to be an intermediate, so dose level 2.5 before jumping to dose level 3. Can you just provide us an update on precisely where you are with 1, 2, 3?
spk03: Well, yeah, actually, you know, we've been very cautious with this type of card because we had a series of CRS in the past, and we think that dose level 2 could be an interesting dose so far, and we are concerned about those level three that being a too high dose so we're trying an intermediate dose and potentially i think that maybe uh there is like an intermediate between the two like giving a repeat dose on on two or something like this because it's quite a reactive uh reactive target and it's not an easy disease so i'm not going to go through all the details with this but i think we're in waters that are interesting for the dose level, GL2, and that maybe it can be high waters on GL3. It's not a simple CAR-T to be dosed.
spk02: Right. Understood. So then have you filed an amendment to try? Do you need to file an amendment to try dose level 2.5 or repeat dosing?
spk03: Uh... DL2I you just like you can do this but to do a repeat you need to file an amendment and we're not delayed about this but it's still it remains a challenging approach and we've been very cautious with that but this is something we're not considering but we're just doing okay thank you
spk05: Our next question comes from the line of Brooks Schuster with William Blair.
spk06: Please proceed with your question.
spk01: Hi, this is Brooks Schuster. I'm for Raj Prasad. I have a question regarding the manufacturing of UCART 20 by 22. I was wondering if you could provide more color on how the manufacturing process for JUUL differs from the single target products and any details on the run yields between the two?
spk15: Thank you, Brooke. This is a great question, and I can definitely start. So, the UCAR 20x22 uses the same halogen ACAR key manufacturing platform that we've developed at Selectis. So, the same manufacturing process as 123, 22, CS1, with all the improvements that come from manufacturing it in-house from our Rally facility. There is definitely some specificities in the viral vector construct due to the dual targeting. So we use a bisectronic construct to carry both CARs, and we found that this was the most optimal construct for the allogeneic approach. And we have found that this does not modify at all the value proposition of allogeneic, which is getting significant yields in order to get the true off-the-shelf therapy that can be distributed at an industrialized scale. So there was definitely a lot of process improvements to cater for this dual-targeting approach, but 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-T.
spk03: If you... If you take a technician that is making UCAR T22 or dual-CAR 20x22, if you don't write exactly on the tube, for example, containing the lentiviral vector for CD20x22 versus 22, he will not realize. So it's exactly the same process. The only thing that differs is in the QC at the end, To be sure that those cars as expressed are like the killing on 20 and on 22, notwithstanding the fact that the other targets not present, et cetera. So there is a QC process is slightly more complex for your party 20 by 22, to be sure that you have to do well, 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.
spk05: Okay. Awesome. Thank you.
spk06: And our last question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question.
spk08: 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? And then on CD20 by 22, given the CD52 gene disruption, are you able to use a less toxic preconditioning regimen? Thank you.
spk05: Thank you, Matt. Great questions. Andre?
spk03: Well, the patient enrollment so far has been slow for numerous reasons across the three trials. So 22 in acute lymphoblastic leukemia is a rare disease compared to not Hodgkin's lymphoma. There's like 120,000 patients in the U.S. patients every year in the U.S. versus like 6,000. 120,000 versus 6,000, so it's quite huge. So it's been, the enrollment has been slow. On the TS1, as I said before, also there are a lot of products in this space, so the trials are like a recruiting patient that fits the criteria, and there are like tight criteria for numerous reasons also. It's quite slow. We're at DL1. We've completed DL3 for P1 for 22, but we're still at DL1 for CS1 following the hold. And 1, 2, 3 is a difficult disease to treat. So also like the patient selection and is something that slows down their enrollment. And we are like completed DL2 and moving to DL2I. have difficulty to jump to DL3, as I described before, and 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 experience these complex cell and gene therapy trials, so there is more potential in recruiting patients. That's what we believe so. And UCRT 20 by 22, which is not Hutchins lymphoma, is opening in multiple countries, not all together because the U.S. is faster, but potentially we'll see a trial expanding to other countries that should accelerate also the trials.
spk15: And 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 beta-2M. We really have a dial here. that will definitely allow us to fine-tune the lymphodepletion in a single and potentially repeat dose setting exactly to the right safety benefit ratio. So you're spot on, and I think this is what we love about the CD52 approach is its inherent tunability.
spk05: Great. Thank you very much.
spk06: And we have reached the end of the question and answer session. I'll now turn the call back over to Andre Jolico for closing remarks.
spk03: Thank you very much for all of you for supporting the company and asking questions. And I think they're all like very great question. Of course, we're super excited by the start of your car T 20 by 22. I think the company is heading at a very interesting moment. in the near future. EUCAR T22 is moving to P2 in-house manufactured. EUCAR T20 by 22 in-house manufactured product also. We are also progressing on CS1 and 1, 2, 3. And the thing is, like, we'll definitely keep you updated on these trials in the near future. And with that, I would like to thank all of you and wish you a very great day.
spk06: This concludes today's conference and you may disconnect your lines at this time. Thank you for your participation.
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