Cellectis SA Sponsored ADR Aktie

Hello, and welcome, everyone, to today's Cellectis' Full Year 2025 Earnings Conference Call. [Operator Instructions] Please note this call is being recorded [Operator Instructions]. It is now my pleasure to turn the meeting over to Arthur Stril, Chief Financial Officer and Chief Business Officer. Please go ahead.

Good morning, and welcome, everyone, to Cellectis Fourth Quarter and Full Year 2025 Business Update and Financial Results Conference Call. Joining me on the call today are Dr. Andre Choulika, our Chief Executive Officer; and Dr. Adrian Kilcoyne, our Chief Medical Officer. Yesterday evening, Cellectis issued a 20-F and press release reporting our financial statements for the 12-month period ended December 31, 2025, and a business update. The report and press release are available on our website at cellectis.com.

As a reminder, we will make statements regarding Cellectis' financial outlook, including the sufficiency of cash to fund operations in addition to its manufacturing, regulatory and product development status as well as product development status of its license partners. These forward statements, which are based on our management's current expectations and assumptions and on information currently available to management, including information provided or otherwise publicly reported by our licensed partners are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent Form 20-F filed with the Securities and Exchange Commission, SEC, and the financial report, including the management report for the year ended on December 31, 2025, and subsequent filings Cellectis makes with the SEC from time to time. I would now like to turn the call over to Andre.

Thank you, Arthur. Good morning, and thank you, everyone, for joining us today. Cellectis was founded with the conviction that gene editing could fundamentally transform how we treat patients in the 21st century. That foundation and ID, we pioneered the allogeneic CAR T approach ready on day 1, built for all patients regardless of their condition. Today, I'm proud to say that Cellectis is the one of the only company running a pivotal Phase II allogeneic CAR T trial, specifically in B-cell acute lymphoblastic leukemia. The past several years have been among the most challenging in recent memory of biotechnology companies. Many programs were shelved and many companies were forced to retreat. While others were stepped back, Cellectis stepped forward. We held the line. We manage our cash with rigor.

We invested where it matters, and we kept our team focused entirely on one thing, delivering clinical results for patients who are running out of time with no therapeutic solution. In 2025, that discipline paid off. In October, at our R&D Day, we presented the full Phase I data set for lasme-cel, our allogeneic CAR T candidate targeting CD22 in relapsed or refractory B-cell acute lymphoblastic leukemia. lasme-cel achieved 100% overall response rate in the target Phase II population. Critically, lasme-cel converted all patients in the target population to transplant eligible candidates. These results were achieved in patients in third line and beyond. Most of them have already failed CD19 CAR T, blinatumomab and inotuzumab. Their options were exhausted.

This is clinical proof that allogeneic CAR T can deliver deep, durable responses in one of the most difficult cancer to treat. Let me take a moment to explain why our bridge to transplant strategy is medically powerful. For patients with relapsed or refractory BLL, only known path to long-term cure is a bone marrow stem cell transplant. But to be eligible for transplant in a patient, a patient must first achieve deep remission, ideally minimal residual disease negative or MRD negative. The challenge is that heavily pretreated patients often too burdened with disease or too time constrained to wait for an autologous therapy to be manufactured. Window is narrow.

This is precisely where our allogeneic CAR T product, lasme-cel becomes a game changer, off the shelf, immediately available. Lasme-cel has the potential to reach a patient in days, not weeks, rapidly eliminate residual disease and open the door to transplant. For the patients, it is the difference between a chance to cure and no chance at all. Without our pivotal Phase II trial now initiated, we will continue site openings in North America and Europe and enroll expansion in 2026. The first interim analysis of the pivotal Phase II trial is expected Q4 2026.

Turning to our second product candidate, eti-cel for patients with relapsed or refractory non-Hodgkin lymphoma. Eti-cel is a best-in-class allogeneic dual CAR T targeting CD20 and CD22 simultaneously, 2 differentiated antigens validated in oncology. This dual targeting is a deliberate answer to one of the most stubborn clinical problem in lymphoma, antigen escape. When cancer cells lose on surface marker to evade a single target therapy, they cannot hide from both. Eti-cel was built for that challenge. At the ASH 2025 Annual Meeting in December 2025, Cellectis presented Phase I interim results, which demonstrated an encouraging overall response rate of 88% and a complete response of 63% in heavily pretreated patients.

These preliminary data underscore the potential of this innovative approach to transform outcomes for relapsed or refractory non-Hodgkin lymphoma patients. Trial is now investigating any potential impact of low-dose interleukin-2 support to significantly enhance expansion and the persistence of CAR T cells to boost CAR T efficacy without exacerbating toxicity. Cellectis expects to present the full Phase I data set of eti-cel this year. Now a few words on our partners. Cellectis is not operating in isolation. Our gene editing platform has become technological backbone of a broader allogeneic CAR T ecosystem.

Two of our key partners are approaching pivotal moment. Servier through Allogene's cema-cel program is currently in a pivotal Phase II study, evaluating it as a consolidation therapy in first-line large B-cell lymphoma patients. Allogene anticipates that an interim futility analysis is on track for Q2 2026. Our partnership with Iovance is another powerful signal to reach any versatility of our platform. Iovance is advancing IOV-4001 in PD-1 inactivated tumor infiltrating lymphocytes or TIL cell therapy. In previously treated advanced melanoma patients, leveraging our gene editing capacity, clinical results of IOV-4001 in melanoma are anticipated this year.

R&D activities continue to advance under our research and collaboration agreement with AstraZeneca, which leverages Cellectis' gene editing expertise and manufacturing capabilities to develop up to 10 novel cell and gene therapy products for areas of high unmet medical need, including oncology, immunology and rare genetic disorders. Partnership is a further testament to the industrial credibility of our gene editing platform and our manufacturing capabilities. 2026 will be a year of data of milestones and of momentum for Cellectis. We are grateful for your continued trust and support. We look forward to updating you through the year as we execute against each of these milestones. With that, I would like to turn the call over to Dr. Adrian Kilcoyne, our Chief Medical Officer, who will provide further details on our clinical programs. Adrian, please go ahead.

Thank you, Andre. I will provide a focused clinical perspective on our lasme-cel and eti-cel programs. The Phase I BALLI-01 study of lasme-cel in third line and beyond acute lymphoblastic leukemia enrolled 40 patients with confirmed at least 70% CD22 expression. These patients were heavily pretreated with a median of 4 prior lines of therapy. The median number of prior lines of therapy at the recommended Phase II dose was higher at 5. These heavily pretreated patients have already relapsed following multiple targeted therapies. Most patients have been previously treated with blinatumomab and relapsed.

Approximately 50% have also relapsed following CD19 CAR T and alemtuzumab, a CD22 directed antibody drug conjugate.

Therefore, there remains very few, if any, therapeutic options for these patients. At the recommended Phase II dose, lasme-cel achieved an overall response rate of 83% and a CR/CRi rate of 42%. In the target Phase II population with an upper age cutoff of 50 years old, response rates were even higher with 100% overall response and a CR/CRi rate of 56%. Importantly, of those subjects who achieved a CR/CRi, 80% achieved MRD-negative status. Additionally, of the 9 patients in the target Phase II population, all became transplant eligible with 7 of 9 receiving stem cell transplant at the time of data cutoff.

This is a very positive outcome for these patients. In patients who achieved MRD-negative , median overall survival was 14.8 months, a meaningful survival benefit in this heavily pretreated population. The safety profile of lasme-cel was favorable and similar or lower than observed with other autologous CAR T therapies. Greater than or equal to Grade 3 cytokine release syndrome occurred in 2.5% of patients and greater than or equal to Grade 3 ICANS occurred in 5% of patients at the recommended Phase II dose. The full Phase I data has been submitted for presentation at the 2026 European Hematology Association Congress to be held in Stockholm in June.

The Phase I program also addressed 2 important additional questions. The first is whether our internally manufactured product could result in similar or indeed improved efficacy compared to product manufactured by an external CDMO. The second is whether alemtuzumab as part of the preconditioning lymphodepletion regimen results in superior lasme-cel expansion and therefore, efficacy compared to the standard lymphodepletion regimen. Validating our decision to internalize our manufacturing capabilities, Cellectis' manufactured product demonstrated meaningfully higher response rates than external CDMO manufactured product with overall response rates of 68% and 28%, respectively. Secondly, the data demonstrated that increased alemtuzumab exposure correlates with improved response. These data were outlined at the American Society of Hematology Annual Conference in December 2025.

Additional data have also been submitted for presentation at the 2026 European Hematology Association Congress. We are now enrolling in the pivotal Phase II program focused on the target Phase II population of patients aged between 12 and 50 years of age. We are accelerating site opening and are on track to reach our goal of approximately 75 recruiting centers across Europe and North America. As Andre highlighted, we expect to complete the first interim analysis of 40 patients in Q4 2026. These data will be shared publicly in a forum to be determined. I will remind you that as previously disclosed, the anticipated BLA submission is planned for the second half of 2028.

Our second ongoing program investigating our dual CAR asset, eti-cel, targets CD20 and CD22 expressing tumors in third line and beyond non-Hodgkin's lymphoma. This highly differentiated product offering important and much needed alternative targets of CD19 continues in Phase I. The preliminary Phase I data presented at ASH 2025 showed an 88% overall response rate and a 63% complete response rate at the current dose level in the 8 evaluable patients. Cellectis believes we can further enhance these already high response rates through the addition of low-dose IL-2 support. The addition of low-dose IL-2 offers the potential to further enhance CAR T expansion, tumor killing and persistence without negatively impacting toxicities.

We expect to present the Phase I data set, including the IL-2 cohort results later this year. We plan to progress this program to pivotal Phase II in 2027 and anticipate a BLA submission in H2 2029. As you can see, 2026 promises to be an exciting year for Cellectis with a number of critical milestones and catalysts as we transform into a late-stage development organization. I look forward to sharing our progress later this year. With that, I would like to hand the call over to Arthur Stril, Cellectis' Chief Financial Officer and Chief Business Officer, for an overview of our financials for the fourth quarter and full year 2025. Arthur, over to you.

Thank you, Adrian. Let me now walk you through our financial position. As Andre mentioned, we have managed our cash with discipline over the past year, focusing our spend on what matters most. The development of lasme-cel and eti-cel and the operation of our end-to-end manufacturing facilities in Paris and Raleigh. We believe our current cash position gives us the financial runway to execute on our pivotal Phase II program for lasme-cel and our Phase I for eti-cel and delivered 2 key readouts in Q4 2026. The first interim analysis with 40 patients for lasme-cel and the full Phase I data set for eti-cel . We are well positioned financially to execute on these 2 trials as our cash, cash equivalents and fixed term deposits as of December 31, 2025, remain sufficient to fund our operations into H2 2027.

We are also looking forward to the upcoming data readouts for our partner programs, in particular, Servier and Allogene cema-cel in April 2026 and Iovance's IOV-4001 this year as well. Finally, we are excited that activities are progressing under our strategic collaboration with AstraZeneca, which has positively impacted our 2025 revenue. As of December 31, 2025, our cash, cash equivalents, restricted cash and fixed term deposits classified as current financial assets amount to $211 million compared to $264 million as of December 31, 2024.

This $53 million decrease is mainly due to $36.9 million cash in from revenue, $8.4 million of interest received from our financial and cash equivalent investments, partially offset by cash payments from Cellectis to suppliers of $50.5 million. Cellectis wages, bonuses and social expenses paid of $40 million, the payments of lease debts of $11 million and the repayment of the PGE loan of $5.4 million. You are invited to refer to our press release for figures related to consolidated net loss attributable to shareholders of Cellectis for the 12 months ended December 31, 2025. We very much look forward to a rich 2026, especially with Servier and Allogene's readout for cema-cel next month and our 2 readouts for lasme-cel and eti-cel later this year. We'll now turn the call over to the operator for questions.

[Operator Instructions] Our first question will come from Amin Makarem with Jefferies.

Two from us. First, on the lasme-cel and the BALLI-01 enrollment. How is recruitment tracking in the pivotal study? And when do you expect to complete enrollment for the dose selection portion? And I have a follow-up.

Yes. Thanks, Amin. I can take that. Currently, we're doing very well. We're engaging many sites. Site opening is on track. We're certainly on track to complete our data analysis by the end of the year. So that's just for the other people on the call, that's the first 40 patients interim analysis, and that's part of the dose optimization phase of the study, looking at 2 alternative doses of alemtuzumab, which is required by CDER. So yes, it's going well, and we're on track for Q4 data sharing.

And for this dose optimization portion, as you evaluate the 2 alemtuzumab dose levels, what are the expectations? What differences should we expect between the 2 arms in terms of efficacy signal? Or are you expecting a meaningful difference in the safety? Or do you think the 2 arms are going to be generally in the same ballpark?

We don't -- it's very difficult to say, and almost require a crystal ball to decide will there be a big difference in terms of both. We anticipate, however, that we have designed a very strong analysis plan to allow us to differentiate between the 2 components. That will be based on efficacy, safety, but also significantly important translational markers in terms of our CAR T expansion, host T-cell reconstitution, et cetera. So we do believe that we will be able to define an optimized dose by the end of the year. We don't think that will be a significant challenge. However, we know that both of these doses of alemtuzumab, very importantly, they work. It's all about dose optimization now. It's not about finding an effective dose.

Our next question will come from Salveen Richter with Goldman Sachs.

Two questions from us. One is, could you provide more details on the Servier arbitration given the ruling that you have to engage in discussions with Allo regarding the direct licensing of 501? And help us understand how this impacts your eligibility for the $340 million in milestones into this interim data? And then secondly, could you talk about your decision to include CD52 preconditioning in both the studies in the context of safety as we see some of the competitors moving away from CD52.

Salveen, this is Arthur. Thanks for the question. I'll take the question on the arbitration and then hand it over to Adrian for the clinical question. So just as a reminder, so the arbitral decision of December 2025 ruled on the partial termination of the license agreement. with respect to one product, which is UCART19 V1, also named ALLO-501 by Allogene. So this product has been brought back to Cellectis, and we are free to develop it or moving forward.

The tribunal did not affect ALLO-501A or cema-cel. So we remain fully eligible for up to $340 million in development and sales milestones. That is obviously under the Servier agreement, which has been then sublicensed to Allogene. So this does not impact any eligibility to upcoming development and sales milestone as well as royalties down the line on cema-cel, but it gave us back UCART19 or ALLO-501 and we're free to do whatever we would like to do with it. And I will hand it over to Adrian for the clinical question.

One thing I'd like to add, like during our thinking is that once you -- like the pivotal trial is effective, then the milestone should be triggered. So we're definitely expecting to have this $20 million milestone paid one day.

Okay. I'll answer the alemtuzumab question. It's a great question. There's a few things -- just a few observations from our studies. One is that alemtuzumab is really important to optimize lymphodepletion. And as I said earlier, the more optimal lymphodepletion, the better the outcomes in terms of responses. You get a much deeper response. As part of our Phase I program, we did test a lymphodepletion regimen without alemtuzumab, and we failed to get any MRD-negative responses. So we know that alemtuzumab is very effective.

The second part is you're saying some people are moving away from it. Now we believe, as I've said already, alemtuzumab is important, but we also believe that it's critically important that you get the right dose. It's like everything too much is always too much. So we have -- compared to other companies that are using alemtuzumab or alemtuzumab similars, we're using a much lower dose. We spent a lot of time already optimizing our doses. So we believe we've got the right balance between optimal efficacy, mitigating the risks that may be associated with that more enhanced lymphodepletion regimen. But also, let's not forget that alemtuzumab has been widely used in other clinical context. So it's got a very well-characterized safety profile, and we've been able to build into all our protocols very extensive risk mitigation. So we believe we've got the right strategy with our alemtuzumab. I cannot answer why others may have transitioned away from it.

Our next question will come from Jack Allen with Baird.

Congrats to the team on all the progress. I guess the first one I wanted to ask was on eti-cel and how we should think about the update in the fourth quarter of this year. Any additional color you're willing to provide as it relates to the breadth of the update and number of patients and the durability of follow-up there would be great. And then I have a quick follow-up as well.

I can give you a top line update on top of the data we already have. As we've shared already at our current dose level, we're seeing a 63% complete remission rates, 88% overall response rates. By the end of the year, you will see data in cohorts with and without IL-2. Now we would acknowledge that 63% complete remission rate is actually a very strong result. And theoretically, we do not need to enhance that further, but we want to. We believe we can with the addition of low-dose IL-2. So by the end of the year, you will see -- we're currently expanded at our recruiting sites rather significantly we've doubled them. So we anticipate we will be able to get a reasonable -- and I cannot give you a number because I don't know what the recruitment rates are going to be. But we will be towards the latter part of the year also not in the staggering phase.

So we would anticipate a significant increase in recruitment. You will see some durability data is what you asked about. But of course, for the patients in the later phase, there will hopefully be good durability signals. We have in our mind the durability levels we want to achieve, and it's around the 6-month mark. But hopefully, by the end of the year, you'll be able to see a very clear picture. I think the efficacy question has already been answered. The question is, can we enhance it even further into the 70s rather than in the mid-60s. But also, it will give us a very good signal is to -- is IL-2 really a potential game changer for allogeneic therapy. We obviously based on our preclinical data, which is going to be presented at AACR and again, some at EHA that we believe it could offer a really, really a fundamental improvement for allogeneic cell therapies.

Great. And then we might be getting ahead of ourselves a little bit here. But on lasme-cel and the commercial opportunity there, I was wondering if you've been looking at Aucatzyl from Autolus. And if you have any thoughts around the initial commercial launch of that CD19 allo therapy in ALL.

I can give it from a medical perspective, and Arthur, maybe you want to talk a bit more broadly on the commercial opportunity. Let's not forget, our patients are generally post-CD19 failures. So we don't -- we are not seeing this as a competition. We have a very differentiated target CD22. We believe the market is pretty saturated with CD19. It's not to Aucatzyl isn't a very good product. It is. Their data is very strong. But these patients are very difficult to treat.

Many of them will relapse and they need to have an alternative target. So we believe that this is not a competing product, but actually a very differentiated one. In terms of market size, you may be aware, we're starting to look at earlier lines of therapy. We will have data starting to be generated next year on that frontline consolidation, very much aligned with what Allogene has done, which we think is a fantastic idea in the non-Hodgkin's lymphoma place. We will be looking at that in the ALL space. So we believe that's a really important part for those incredibly difficult to treat patients frontline.

I can add, I think from a commercial launch perspective, you absolutely cannot compare an autologous launch to an allogeneic launch. And I think the 2 primary differences is, one, you need to have leukapheresis access for the patients, and this is slow. This is very competitive, and this is controlled by hospitals, not by the pharma companies, whereas obviously, with off-the-shelf, we will have manufactured a huge number of doses in advance so that at the time of launch, we can address all our clinical centers immediately without having to set up these cumbersome logistics aspect.

And the second thing, obviously, is because of our off-the-shelf nature, we have very significant economies of scale, and we see it even at the pivotal stage, which will allow us to get extremely competitive gross margins and gross margin, which was much more the types of what pharma is now used to with small molecules and antibodies, whereas pricing of autologous has been difficult because of the significant cost of goods that make a very important impact on the margin. So I think the fact that we're off-the-shelf will allow us for a much smoother launch in terms of pure access due to the off-the-shelf nature and also in a much more economically competitive aspect due to the economies of scale and the very favorable gross margins. So I don't think Aucatzyl will be a very good comparator there.

One thing I'd like to add, Jack, one thing that was interesting. I was like recently visiting a clinical center we're working with for acute lymphoblastic leukemia with Adrian. And there was one ALL patient that was sitting in the backlog waiting for an available apheresis spot since long time, [indiscernible] with non-Hodgkin lymphoma, DLBCL patient, multiple myeloma patient, autoimmune patient, et cetera. And this patient -- like ALL is a very aggressive disease. And still this stage, I'm not going to say which type of product it was about to be given to him because I don't know. But the fact is that this patient was like in real distress waiting for this like apheresis spot, and this is what you would consider as autologous launch of yet another CD19 autologous CAR T.

Our next question will come from Silvan Tuerkcan with Citizens.

I just wanted to ask if you could just give us a brief recap of what you're expecting at EHA from these 2 programs that you have ongoing? Is it mainly longer follow-up?

So you will be aware that we shared our data at our R&D Day back in October. We, after that, actually added some more patients in because we wanted to do some level of dose optimization in advance of our Phase II program. We wanted to ensure that, that lower dose is an acceptable dose to give to patients. So there are going to be an updated data set, the whole data set, including those additional patients. So it is -- I would consider it a level of progression from the original Phase I package that we presented.

The data are not remarkably different, let me tell you, but it's an important addition to the data. The second thing that you -- we hope -- we're assuming that it will be accepted is really to try and understand what makes a product successful. And again, to build on the question from our Goldman Sachs colleagues, whether we're talking about alemtuzumab is the importance of that preconditioning and that day 0, not only from a level of lymphodepletion, but actually the environment in which you infuse your cells is critically important and in many ways, predicts the outcome. And the fact that we have now identified a really clear picture of optimal lymphodepletion, optimal environment in which you infuse your cells, we are now able to predict very early on our patient is going to respond. So all these data will be shared. So I think we're excited by it so far.

Our next question will come from Sebastiaan van der Schoot with VLK.

So I wanted to ask you how you're looking at the possibility of applying your lymphodepletion procedure in the outpatient setting as well as the allogeneic CAR T. And then maybe can you provide some insight on how the partnership with AstraZeneca is going? Can we expect any updates in the next 24 months?

I can take the first part of that, Arthur, in terms of outpatient setting. Right now, the regulatory authorities require inpatient delivery of products. And I think that's consistent with most autologous therapies as well in the CAR T space. And once there becomes some clinical confidence in how to use, will that transition into the outpatient setting? I think that may be a natural transition. But for that, you need a body of evidence. So hopefully, that will be provided not only by the Phase II program, but also by clinical usage from that.

But again, I think it's a very different offering in that to Arthur's point, we do not leave that leukapheresis, et cetera. So I do think it will take some time for this to be in the outpatient setting. But assuming that we continue to have a fairly reassuring safety profile, there's no real reason why that this cannot in time, transition to the outpatient setting.

And I will take the question on AstraZeneca. So first of all, we're extremely pleased to count AstraZeneca as a strategic partner. As you have seen, they have continued to invest very heavily in the cell and gene therapy space, and they're one of the few companies that are betting very hard not only on cell and gene therapy, but also on off-the-shelf treatments. And I think we're very fortunate to have them as a key shareholder, but also a strategic R&D partner.

The activities are going very well under the collaboration. There's a number of activities ongoing across a range of therapeutic area. Do not expect updates in the short term. This is at the request of AstraZeneca. They are essentially asking us for now to stay reasonably quiet, especially given the competitive nature of certain aspects that we are working on. But definitely, as we continue the dialogue with them around disclosure and as and when the time is right, we will be providing update. And I think you will be interested in seeing what has been brewing with them.

[Operator Instructions] Our next question will come from Yanan Zhu with Wells Fargo.

So first, regarding the lasme-cel pivotal study. I was wondering for the 4Q readout, is the focus there, the 3-month CRi from the 2 arms in that first 40-patient cohort? And then how do you manage the transition from completing that cohort to the start of the enrollment of the 80-patient portion for the optimal alemtuzumab dose, i.e., the final pivotal cohort. Will you be able to start enrolling before you have the data for the comparison of the 2 alemtuzumab cohorts? Yes. And then I have a follow-up.

Great. This has some great questions there. First and foremost, no, the decision for dose optimization is not based on the 3-month CR/CRi. It's actually based on an earlier time cutoff of 8 weeks. And that's important. We will still be looking at efficacy, safety, but all the important translational markers predictive of not only short-term but long-term outcomes, we have those answers by that first 8 weeks. So it's a composite of many of those that we will be presenting. In terms of that transition from that to the longer phase of the study, we have built a lot of flexibility into the protocol to allow us to continue recruiting. So importantly, this does not mean our study has to stop while we're engaging with the regulatory authorities. The recruitment will continue for the remaining [indiscernible] patients.

Great. Very helpful color. And the follow-up is mainly on the competitive landscape in terms of additional modalities in vivo CAR T specifically. Can you talk about the advantages or limitations for that modality or whether you have any interest in moving in that direction at early stage efforts?

I can have an initial thoughts on this. And I think I know that Andre and Arthur also have views on the positioning of in vivo CAR. We're looking at incredibly sick patients with incredibly aggressive disease that need a lot of therapy. We don't believe these very difficult-to-treat tumors will be the definition for in vivo CAR. We think in vivo CAR certainly have a place. But will it be the right therapy for incredibly difficult to treat tumors and incredibly difficult to manage patients? We don't believe so.

So yes, there will be in vivo CAR in some, maybe autoimmune may be a better destination. But any therapy that requires extensive gene editing and extensive patient management will probably -- maybe it will be a bridge too far for in vivo CAR. And I know, Andre, you have a view on this as well.

Think the process like in vivo CAR is similar to autologous CAR T. The only thing it allows is essentially try to leapfrog apheresis, which is a great thing. It's like it's a huge market access option that is given here. Nevertheless, it will still be totally linked to the fitness of the cells of the patient or their presence. So if it doesn't respond to blina, if you can't do an autologous, then you go for in vivo, well, if the cells are not really very well functional, it's not going to work anymore because you need the T cells to be fit. That's one point.

The second point is it will also be very much related to the current malignancies that are treated, which is essentially liquid tumors, B-cell malignancies or multiple myeloma. But the spread of this into solid tumor is going to be different. And finally, like there's a lot of papers that are coming out, like a lot of cells are transduced by these vectors that are not T cells. So like you need to restrict at the time. I think these technologies are going to come in the coming future, to try to restrict the cells to what needs to be transduced by the in vivo CAR T and not to go and deliver.

For example, I've seen a paper recently that shows more vector inside, for example, hepatic cells expressing CAR and then in T cells. So if you do this worldwide like really broadband, then the questions at a time. And also like the genome is only 6.4 billion base pairs, like 23, 2x chromosomes. If you inject trillions and trillions of vectors in hundreds of patients or thousands of patients, it's like I hope that this will be safely integrated. If you go, for example, with autologous CAR T, you can master exactly when the cells are transduced. If you go for an allogeneic CAR, you have all the QC that lasts a long period of time to show that everything is totally square. If you make the product in vivo, which is the case here, then you have to master how the product is made and not to have a lot of byproducts all around the place. So that's like the initial concern. But I'm sure that this will be solved in coming decades.

And at this time, there are no further questions in the queue. So I'll turn the meeting back over to our speakers for any additional or closing remarks.

Thank you very much, everyone. I really appreciate all the questions here. As you can see, this will be a very exciting year 2026 with a number of updates from our partners and from ourselves. And I think we are poised for a new dawn of allogeneic CAR T cell therapy. So stay tuned for more updates and looking forward to further discussions as our progress unfolds this year. Thank you very much.

Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.

Good morning, everyone, and thank you for joining us today. So my name is Andre Choulika. I'm 1 of the founders and the CEO of Cellectis. And I'm extremely pleased to have you all here for this first R&D day for lasme-cel. And so Cellectis is mission is essentially to try to bring allogeneic CAR-T therapies for safer, more scalable, more accessible type of therapies to all patients. Allogeneic therapies have essentially been providing the same chance to every patient. And when I'm saying the same chances for example, chemotherapy for now remains 1 of the main first-line treatment for acute lymphoblastic leukemia and chemotherapies works really well. However, also, there is a high relapse in -- especially in adults, and it tilts very much immune system. And as much as camera therapy remain 1 of the main first-line type of treatment for acute lymphoblastic leukemia, it will hurt also the immune system. And when you come for later lines of products, sometimes chemotherapy, but also sometimes other type of therapy sites such as immunotherapies that would rely on the immune system of the patient, then the immune system of the patient could be also hurt. So when we come up to a series of lines of therapies and the immune system of the patient has been better, then every patient don't have the same chance. For example, autologous therapies depend upon the T cells quality of the patient. Same thing, for example, T cell engagers or the same thing for in vivo therapies. This is why we think that this allogeneic therapy is becoming a game changer in the acute lymphoblastic leukemia. So where is my -- so we're very excited today because today is the moment where Cellectis will reveal the first for the first time the data of the full Phase I of our BALLI-01 trial trying a lasme-cel in acute and refractory relapse for acute lymphoblastic leukemia. And the first data that are going to be presented to you today are interesting because it's a car that targets not CD19. It's not yet another CD19 CAR. CD19 is an overcharged target. And it's very much used and it works really well, but there is a need for an alternate target. And we believe also that CD22, especially for refractory relapse patient is a game changer. So here is like today in just a few minutes, Adrian Kilcoyne and -- Dr. Adrian Kilcoyne, and Professor Nitin Jain from MD Anderson Cancer Center, it's like the head Professor of the Department of the MD Anderson Cancer Center. We'll walk you through all the data of our Phase I for lasme-cel, but we'll also walk you through the design of the Phase II that we hope will translate into pivotal trial and will be accepted. This will be followed by a presentation of Arthur panel discussion of world experts in the field that will share with you their experience and the clinical data that has been generated. Then this will be followed after this by presentation by our Chief Financial Officer, Arthur Stril, who will tell you the lasme-cel and where we creating value with lasme-cel. And finally, we have the pleasure and also the honor to have AstraZeneca, our strategic partner, represented by Mark Cobell who's the Head of the oncology cell therapy. AstraZeneca will share with you also the insights on how AstraZeneca is becoming 1 of the game changers in the field of cell and gene therapy in general and especially in oncology and the use of this because they have like a very strong positioning in on this side and also parts of the collaboration we're having with them. And 1 of the things I would like to say also is like the event will end up at 10:30 sharp.

With that, I will like to -- I lost my blue. So BALL is definitely on unmet medical need. First of all, there's roughly 10,000 patients worldwide. Not worldwide, but in the U.S. EU and the U.K. on a yearly basis. And most of the time, these patients are treated by chemotherapy as a first line. And as we just said before, we have a heavy relapse rate for adults essentially. ADCs have definitely an effect, but it's limited effect as there is a lot of relapses especially using certain type of ADCs targeting CD50, CD22, CD19 directed therapies have 50% relapse also rate afterwards. And all these therapies based on patient T cells, as said before, where the T cells can be unfit or scarce, have no solution. This is where it's important to come with healthy donor T cells to try to treat these patients, and this is what we're going to share today.

So why allogenic T cell? First of all, the quality of the T cell can be very, very stable on this site. And healthier, less exhausted T-cells coming from healthy donors and preselected patients can give the same chance to every patient. The patient don't have T cells work the same. Patient has plenty of T cells. It also works this thing. The speed of therapy as an off-the-shelf therapy in BLL, every day count, we're not talking about like months sometimes. We're talking about weeks, sometimes days, so it's very important. It's also 1 thing that is really important in this field is to standardize the product. repeatable quality of the product is 1 of the selected mission in the way we design this product. And finally, CV22 complements also pre-end, for example, for CD19 naive or post CD19 cells or even engaging CD22 could potentially rescue CD19 failures. You will see also that some people that are treated for a product targeting CD22, we can still pick them up with an allogeneic CAR-T targeting CD22.

So 1 of the prides of Cellectis is our manufacturing. People tend to forget about this. I've been talking about the importance of manufacturing for allogeneic T cells and usually for all cell therapies, most of the time, in cell therapies, the product is the most important thing because this is the thing that is going to make a change in the patient. And also at the time of the approval of the BLA, the quality of the production and the way to master the production is often not most important. This is why we decided in 2018 to integrate inside selective, all manufacturing. I would say, from A to Z because we do the buffers, we do the exploration machines, we do the messenger RNA, the plasmid DNA, lentivivectors up to the final product and also what we have is that our rally manufacturing plant that makes the final product, where we have integrated all the supply chain and the logistics. So storage, we have 1 in Europe and 1 in the United States, ready to go commercial today with the quality of the product we have, and we master all the details of the vouching. I think Adrian will walk you through P1 and P2. P1 is the process on that has been made at the CMO sell-for-cure at this time. Since then, it has been acquired by Novartis and things change. You cannot -- if you're a cell therapy company, give manufacturing to someone else because they're not going to treat it the same way you will treat it yourself. And you will see the difference between P1 and P2 is essentially the fact that Cellectis is just manufacture a process that we invented, and we make products that have no comparison there. And at the end, you have like an allogeneic T cells, it can be scalable. We do hundreds of doses per batch. This can also be scaled up more than this.

And then finally, we have controlled COGS, and this is in the presentation of Arthur is really important because if you want to have a product that is a pharmaceutical valuable product means not with negative gross margin, then you need to control the COGs to make a very valuable product, and we believe that we have this type of product today.

So lasme-cel we're developing this first indication as a bridge of transplant is going to be represented. HSCT, so hematopoietic stem cell transplant is currently the gold standard in acute lymphoblastic leukemia. This is what is going to give the best long-term chance to every patient, long curative disease and the patient don't come back to the hospital, it's over a patient who is considered as cured. It secures -- so like lasme-cel, will secure a window, you will see how we secure this makes patients eligible for NH ICT, you need to be MRD negative for this, not only like as a CR. And this gives a clear path for HSCT and long-term remission. And also, I will show you that's a very manageable safety profile, and this is something that is so much important.

With that, I would like to hand the presentation to Adrian Kilcoyne and Professor Nitin Jain, that will walk you through all the data of BALLI-01 and the way lasme-cel cell works. Adrian?

Thank you, Andre. Thank you all for being here today. And a special thank you to our 3 investigators who've been so supportive of this trial for being here to talk us through the data, but also discuss it during our panel. Why I'm opening this session up is really to create an element of context. This is an incredibly important meeting for us. This is us transitioning to Phase II, which is why we're focusing this day on UCART22, lasme-cel.

Now just so that people are aware, this shouldn't in any way be interpreted that we're not fully committed to our other program. We absolutely are, but given the importance of this event, we wanted to focus on lasme-cel. But I will give you a little bit of a snippet of -- sorry, wrong way, where we are with UCART22, which is now at cell. These are where we are at the current dose level. Now there will be more data shared at ASH this coming year in terms of the update on the program. we can talk about it more then, but I just wanted to reassure those of you who are in the audience and online, we remain committed to this. Dr. Ramakrishnan is an investigator on the study. He is here today himself, but what we're seeing right now is response rates that are very encouraging at 57% complete response rate, partial response rate at 86% based on the 7 patients at the current dose level.

Now I know you have lots of questions about this. But please, if we could hold that to we get ASH in our rearview mirror, that would be very good. But again, we just wanted to reassure you that we remain fully committed to this program.

Right. I also want to contextualize the data you're about to see because what we have seen over the coming -- the last few years is there's been advances in ALL. But what we've seen is increased access to targeted therapies. So if we look at front line, second line, third line, fourth line and beyond, hope becomes very clear is some of these targeted therapies are moving earlier line. Blincyto, for instance, is up at frontline consolidation. Second line, there's a lot more response auto CAR-T. By the time we get to third line, things have changed because most of these patients have already been exposed to at least 1 targeted therapy, and as you go down multiple lines, many of them have been exposed to all of them. So all of these salvage therapies also have an impact on your response rates. And the mere exposure to many of these targeted therapies also changes your response rates to following targeted therapies.

So when we look at our trial and Professor Jain will go through this in a lot more detail. We know that the patients that we've recruited in this trial are very late stage. And we know that many of them have been heavily pre-exposed not only to chemotherapy, but multiple targeted therapies. So for most of our patients, the real next line for them is yet again salvage chemotherapy. And the only real chance they have of getting a long-term remission based on what's currently available is to achieve a transplant. But what we can see from these data here is that getting to deep responses with MRD negative is very challenging with what's currently available. But we also acknowledge that our Phase I program is very complex. And I wanted to make sure just to give you a quick overview of how this program was run so that you can understand it. As you're seeing the data, it will allow you to interpret it a little bit more care for me. But as Andre already said, we needed to answer a few questions. One, can we make better products than an external CDMO. We needed to answer that question. What is very topical at the moment is an anti-CD52 antibody necessary to optimize response. We have looked at this. Of course, we want to know what the RP duty is, and Professor Jane will share that with you. And of course, touching on what Andre has said, in the context of these very heavily pretreated patients, what is the best outcome measure? What is the best endpoint to reflect clinical value for patients. And we will share with you after we see the data, all of the clinical trial design and time lines, so you'll be very clear of what our path forward is.

So this is the trial design. Now there's a number of questions to be asked. Now forgive the simplicity, but all the dosing schedules is in the box in the top left-hand corner. Dose Level 3 is the relevant dose here, 55 million cells per kilo. But as you can see, we started off with process 1. And as Andre said, that is our external manufacturer. And we did do dose escalation right up to dose level 3. But then we internalized our manufacturing for a number of reasons. And to Andre's point, nobody knows better how to make these living cells than we do. So we fundamentally believe that cell therapies like allogeneic cell therapies should be brought in-house. But what you will notice, as we transition from P1 to P2, we dose-escalated. Why did we do that? Because it was very clear from our in vivo data that our product appeared to be more efficacious. So in the spirit of and maintaining safety, we deescalated and reescalated back up to dose level 3. That's the first part. So throughout the data, you will see a cut of P1 and a cut of B2.

Also, you see on the bottom, we have Fc versus FCA. Now this is very topical. Fc is flus standard conditioning lymphodepletion. FCA is Flucelusalemtuzumab, and we will -- okay. Sorry. I'm going to I need to keep the microphone to in my mouth. So when we look at Fc versus FCA, we have looked at both to see what the responses were and what the depth of the responses were and you will see that we very quickly transitioned away from FC alone. We understand that alemtuzumab is important, and we will share that data with you. And beyond that, all of the usual stuff, efficacy rates at the dose optimization and including what our target Phase II population is. So hopefully, you will find today informative. But this data is not for me to present. It's actually for Professor Jain, who's been really key contributors to this trial, not only from delivering patients, but also the strategy behind it. I can give you a sneak peak of the response rates between P1 and P2 in advance of what Professor Jain will show hopefully, it's very clear to you that there is a significant difference between P1 and P2, reinforcing the importance of us internalizing our manufacturing process.

So without further ado, I'd like to welcome Professor Jain, who is the Chief Investigator on this study from [indiscernible].

All right. Thank you. And I guess I don't need it. Good morning, everyone. I hope this mic is working here. So let me take the data here. Let's see. All right. you use the microphone, sorry. Okay. I didn't -- because I had this thing, I thought maybe we'll cover for got it. All right. So good morning, everyone. So we just discussed this slide. So as is kind of shown here, we started the study with the Fc process, then those 1 dose level 2, then we added alemtuzumab, went to dose level 3 then the process change to P2, as we just discussed. And then we had 3 dose levels, L2DL2I and DL 3. And you can see the actual doses of the cell ranging from 1 tent 5 right now our deal 3, which is our current dose is 5 million cells per kilogram. So that's why overall, the study design had been over the course of last several years.

So in terms of the key inclusion criteria for this trial, patient age 15 to 70 years, so we have some pediatric population to say, 15 to 18 years of age, good performance status. And obviously, this is a CD22 CAR. So CD22 expression more than 70%, at least more than 2 prior lines of therapy. And obviously, these patients were transparent ineligible getting into the study because they had kind of active disease with eventual goal that many of these patients hopefully can go to transplant entromission. The key secondary key outcomes included, obviously, the safety of the product, investigator-assessed clinical response, recommended Phase II dose and also [indiscernible]. And then we had several exploratory objectives looking at the CAR T expansion, persistence and also immune for constitution. So this shows the overall demographic of the patients. So if you look at the rightmost column, there were 40 patients. Overall, the study, we have treated 40 patients over the course of last several years. You can see the median age for the all 40 patients was 27 years. But I would also like to highlight, if you look at the median number of prior therapies was 4. So these are heavily pretreated patients. And you can -- again, if you look at the entire group of 40 patients, you can see 45% had prior allo transplant, 55% had prior inotuzumab, 80% [indiscernible] and actually half of the patients had failed a prior -- had a prior stent in cardio cell therapy, which they had failed and then also I want to highlight the bone marrow blast count, which you can see is upwards of 60%, which is a high amount of disease these patients had.

Now what we have done is in the first -- you specifically -- we're looking at DL3 P2. So this is the dose level 3 at the process 2, where we have treated 12 patients overall. And also, we want to specifically highlight the 9 patients who were less than 50 years of age, which is kind of the focus of the trial, and we'll talk about that in fuselage down the line. So in that group of patients, you can also see still high amount of 5 prior lines of therapy for this group of patients. And again, you can see the bone marrow blast count to offer for 60%. So I think that point remains that these are very heavily pretreated patients who had failed most of these kind of therapies, which are available and then looking forward to next line of therapy. The same thing is kind of exemplified here in this kind of figure here. Again, heavily treated patient population, 4 to 5 prior lines of therapy, 80% had prior blinatumomab, 55% had prior anetumab and then half of the patients had seen an CAR-T cell therapy, either Atsal or Braxisol.

So what were the responses seen? So this kind of again goes through and you saw a snapshot briefly. So P1 is listed first, then the entire P2. So this makes the 40-patient cohort, the total patients we treated and as Adrian has showed you, I think we're already -- you can see that the P2 process appears better. And then we are also separated the response rates for the 12 patients in DL3 and then in patients who are less than 50 years of age, which is the target population for the Phase II study. The response rate here is this teas overall response rate, which includes CR/CRI as well as what is called MLfS.

So I should -- the bullet point, you see there that requited Phase II dose for this product is dose level 3, which is the 5 million cells per kilogram and the target Phase II patient population is at dose level 3, less than 50 years of age. Now the patients who achieve CR/CRI. So this is among those group of patients who achieved their emission, especially the CR/CRI. We are looking at MRD negativity within that group of patients. So the dark part of the curve here shows within the CR/CRI population, how many patients were MRD negative versus MRD positive, as you can see that majority of the patients who achieved a remission were also MRD negative Again, it kind of shows the kind of the same data kind of in a similar way. Again, we are split by P1 P2 specifically targeting those Level 3, 12 patients and then the 9 patients who are at the target Phase II kind of patient population. And again, among the CR/CRI or overall cohort, high rates of MRD-negative remission in these patients.

So next, we wanted to really specifically look at the 9 patients. We talked about the 9 patients who are at the target Phase II population. So again, to remind everyone, these are process 2 dose level 3 less than 50 years of age. So we happen to have 9 patients in the study who we have treated doing this. And this shows the kind of the summer plot going through these patients in more kind of detail. What you see here is the red triangle is the patients who achieved an MRD-negative response. Anyone which is a patient who had then a transplant. And then the arrows, which are for the 3 patients who are still live and they are censored at that time. So as you can see that I mean in this cohort, all actually 9 patients had a response. Again, response means either CR/CRI or MLFS. And many of these patients, as you can see, have gone to transplant and then there are a couple of patients who are still in the process of being evaluated for that. So this kind of shows you kind of the spectrum of the patients you have done, the patient #1 or like the patient -- the top patient who has the longest follow-up had a transplant and then doing well now close to 19, 20 months kind of down the line. So now this shows the overall survival. This is not a sense for transplant. So because that's our goal is to get the patients to transplant. You can see the summary at the bottom here. that the median survival for patients who achieved the MRD-negative remission was 14.8 months. And again, if you look specifically at the kind of the graph on the right side there, Overall, for P2, the median survival was 9.4 months. But if you look at, again, at the dose level 3 patients or the less than 5-year age group patients the median survival. Again, this is a group of patients who had 4 or 5 prior lines of therapy, the median survival was about 14 months.

Now 1 of the important aspect here was to get the patients to transplant. So this -- because we know that for these patients who are molecular lapse refractory at the end point for them is to get to a transplant and hopefully, they can achieve a long-term remission post transplant. And to get to a transplant, you really need to be in remission for patients with BALL. So the goal here and what we are kind of mentioned here is that the Phase II target population, which is those 9 patients we talk about all of them either have received or are eligible to get a sensor transplant for this patient population. And then again, it's kind of shown here kind of graphically that if you look at the last bar here, which is the 9 patients, 80% had proceeded with the transplant and the remaining 20% are still in kind of works, the more recent data for these patients. So I think majority of the patients are able to get to transplant, which is the kind of the goal for the study. And the transplant does seem to improve the outcome. Certainly, patients were able to get to transplant. They are doing better than versus patients who are not kind of make sense because then they're able to drive long-term benefit from the transplant. So you can see the curve, the top curve here is patients who -- this is the patients who received dose level 3 process 2. So these are the 12 patients and then patients were able to go to transplant versus not.

Now as we're thinking about designing kind of the Phase II part, 1 of the things we also wanted to look at is the number of prior lines of therapy. Certainly, when we split the number of patients by 4 or less lines of therapy, there doesn't seem to be a bit of a difference in terms of the survival seems to be the same with less than 4 or -- less than 4 versus 4 or more prior lines of therapy in this patient population.

Now as was mentioned before, right? I mean, these days, everyone at least moving forward, getting blinatumomab in the first-line setting because of approval at plenum in the first-line setting. Obviously, anituzumab is approved in the lapsed refractory setting. So most patients who come to the trial have -- generally have received blinatumomab have received anituzumab and many times, they may have received CCAR T cell therapy as well, because anituzumab is also a CD22 targeting drug. And obviously, UCART22 is also target 22, when we wanted to specifically look at the outcomes of patients who had prior [indiscernible] and again, as you can see, doesn't -- it appears to work in patients who had prior anituzumab as well. Obviously, all these patients before study entry were required to have at least 70% CD22 expression. This again shows the CRC right for the same -- so this is the CR/CRI rate and among the CR/CRI, how many were M&A negative. And again, as you can see, high rates among the patients who had prior anetumab.

Now you also wanted to look at the group of patients who really had all target therapies. So obviously, these patients had chemotherapy because that's pretty much default for everyone who gets ALL these days. patients who are anituzumab, patient blinatumomab and also patients who had a prior CD19 CAR-T cell therapy. So the number of patients become relatively small here. But if you just focus on the P2 dose level 3, 5 and then the target population for patients Again, these are the patients who have received all 3 kind of approved target agents in the context of B-cell ALL, the appear to be responding to this therapy. And this shows, again, the same kind of a patient population. Again, the numbers are small, but these are all patients who have received inoblina and signed CAR-T cell therapy. And again, this shows the CR/CRi rate. These patients are responding and their MRD negative. So like, for example, for patients at a target dose 3 out of 4 responded with CR/CRI and they had -- they were MRD negative.

How should be talking about the efficacy part. The next part is the toxicity part, how this CD product is doing. And this shows the CRS and icons first for the overall population, all 40 patients we have been treated. And that's specifically for the 18 patients at dose level 3, which have been treated. So as you can see, the -- in general, I mean, most of the CRS events were Grade 1 and Grade 2. Similarly, same thing for the icons, Grade 1 and Grade 2. You can see the grade 3, 2.5% overall population for CRS and then 5% for icons and the overall population for Grade 3. And then the right part shows specifically for the 18 patients at DL3 and overall low rates of Grade 3 or higher toxicity.

Now 1 of the other things which have been talked about is the IEC HS, which is -- has been associated with some other CAR-T kind of CD22 targeting agents. But -- and this, we had 1 patient who had IEC HS, which was -- which resolved with anakinra and exametasone. And so we haven't seen a higher incidence except this 1 patient who had the ICH. This shows -- these are the -- specifically the related Seres adverse events, which was reported for CRS and icons and others, which are kind of listed here. Again, overall, if you look at the 40 patient these are, again, that's only the serious adverse, we already talked about the overall CRS and icon incidents only 2 patients were reported as serious SAEs for CRS as well as for icons.

In terms of other adverse events of special interest, you can see here, 1 thing to highlight graft-versus-host disease, there's only just 1 patient, which was at the process on who had a grade 2 graphics disease of the skin, but we haven't seen that in GVHD in the process 2.

Now obviously, this is -- the product uses a CD52 antibody, so which can increase the risk of infections. And this shows all grade 3 or higher infections, which were related to CD52 exposure. So this kind of shows the process 1 or the dose level they were noted. And in the next slide, we'll talk more about the CMV reactivation, which is something common we see with the CD52 exposure. This shows specifically the CMV reactivation, which is -- you can see there were 6 patients who had CMV reactivation again at the dose level and the process they had and the investigator assessed in relation to alemtuzumab cyclophosphamide fludarabine.

Now as we mentioned in the -- how the study started very early on, initially, we were only using Fc without alemtuzumab. This is when the trial started, with process on then we move process 1 with FCA and then process 2 with FCA. 5 patients were treated, the first 5 patients in the study were with Fc alone. And at that time, we really didn't see any response in these 5 patients, making a point that at least for this product, I think eletuzumab is imported.

I think that is my part of the study. So I'll hand it back to Adrian. Thank you.

Thank you, Professor Jain. So I'm now going to talk you through the next steps as we're transitioning to our pivotal Phase II program. I'll give you an overview of what we've done thus far. So for those of you who have been following us, you'll be aware that we have already completed or in the Phase I and scientific advice meetings with both the EMA and the FDA. And these were very encouraging meetings. They all -- they both agreed that this was an area of a specific unmet need, and they also agreed that transplant represents a very positive clinical outcome for these patients. And this is an important step for us based on the data we've seen, where all patients were able to get to transplant and are chosen dose. This is, again, gives patients the opportunity of some durable remission and in some cases, hopefully cure. Equally importantly, we got agreement on our end points of our trial. And I will take you through the design of the program so that you're aware of what that is. And given that there is very little other option for these patients. The regulatory authorities have also agreed that this will be a single arm trial. And that's important for us in terms of patient numbers. But we will have an external control on supporting it, which we are designing, but nonetheless, what is clear from all our regulatory interactions is we have a registration path for this program, understanding the importance of achieving a transplant for this, particularly difficult-to-treat patient population.

So let me talk you through the single-arm study design. Now for those of you who are used to interacting with the regulatory authorities, they will always want us to have a traditional endpoint. And indeed, we have a traditional endpoint, which is CR/CRI rates in that 3 months between day 28 and day 84. You will notice from Professor Jain presentation's that our Phase I program covered patients 15 to 70. Based on our observed responses, we lowered the upper age limit. So our Move Forward Phase II pivotal program will be looking at patients aged 12 to 50 and this does 2 things. One, it gets us a registrational data, but it also satisfies a significant portion of our pediatric investigation plan, which we're also working on right now, and we'll talk about that in a couple of slides.

Now we also -- this is a CD22 targeted therapy. And within our Phase I, we had a cutoff of 70% of CD22 expression. Now we think that's important. But given the mode of action of a CAR-T, do we need higher levels of expression, like we've seen in the INNOVATE trial, et cetera, where there seems to be a cutoff of 70% below which efficacy starts to reduce. But nonetheless, we think it's important to answer this question. So there will be another cohort. Yes, the pivotal cohort will be with CD22 greater than 70%, which is the overwhelming majority of the patients, probably 85% and above. If you're CD22 positive, you're very highly positive. In the INNOVATE trial, for instance, I think the median CD22 positivity was in the region of 98%. So we know that we'll -- there will be some patient attrition from this, but we will still capture them in Cohort B, where we're going to specifically look at patients with a lower level of expression. So we will be capturing all comers within this trial.

An important part of this program is also the first part, which is the dose optimization of alemtuzumab. This is a requirement and we will be looking at 2 doses, the dose we already have investigated and 1 other dose, and it will be a randomized in terms of the exposure to alemtuzumab. And at the end of 20 patients in each arm, 40 patients overall, we will do our first interim analysis. And that will allow us to decide what is the optimal dose of alemtuzumab to take forward into the remainder of the trial? Now just to be clear, this is an inferentially seamless design. So the patients in the dose optimization at the chosen dose will also form part of the pivotal patient population. So it reduces the burden of recruitment on us the remainder of this study.

With that, we will have another interim analysis at 50% of the pivotal cohort recruitment and for the primary analysis for BLA will be based on CRC RI at 3 months following full recruitment. You will note that we have a follow-up analysis for overall survival which will be up to 2 years because as you've seen from Professor Jain's presentation, we believe that 1 of the challenges we've had in our recruiting our Phase I program, it's not fruiting it, but actually analyzing it is interpreting response in the context of durability of response. What we found is once patients got to MRD negativity with a deep response, they were immediately going to transplant. And therefore, by 3 months, most patients have already had a transplant. And because we were sensoring for transplant, it's very difficult to show durability of response.

Moving forward, because we won't be censoring for transplant, we will be able to show much more clarity around duration of response for these patients. So based on our Phase II plan, as I already said, we are currently working our pediatric investigation plan. The current Phase II program will capture patients from 12 to 50, but we will also have almost parallel pediatric plan, looking at patients from 0 to 12. So we are capturing the majority of patients from 0 to 50 years of age. That's not to say we're abandoning the patients above 50. We will look at those but not just yet. We believe our first indication will be in patients up to 50 years of age. And again, once we have an update on how we're going to address the remainder of the patients, we will share that with you. We now have our -- the protocol has been submitted to the regulatory authorities. We are now setting up our study to -- and because we want to accelerate this, we have increased the number of sites we are opening. So we're going to globally open site 75 centers across North America and Europe. The numbers for each of those countries are there. Apologies to the Italians. I forgot to shade in that one, but we will be going to Italy as well. But 75 centers will give us what we consider reasonably brisk recruitment to give us these time lines. These are the time lines we are working towards. We are, of course, hoping that we can beat those time lines, but we anticipate towards the end of this year, we will have our first patient recruited. Based on our recruitment projections, we will have our first inter-analysis at Q4 2026.

Now because we will continue to recruit, we will not be pausing recruitment at any point in time. And at that time, we will have all centers active in recruiting. The second interim analysis comes fairly quickly after in second quarter of 2027. And that will be at 50% of the pivotal cohort. By Q3 2017, we anticipate we will have completed enrollment and then we know that we have our 3-month follow-up for CR/CRI. We will -- should have our primary analysis complete, allowing for that in first quarter of 2028.

Now assuming all of that, we should be submitting for the second half of 2028, our BLA.

Now I just want to reiterate 1 thing that I haven't probably made clear enough. When we're submitting this BLA, we're actually submitting 2 BLAs because throughout this, we have 2 investigational products. We have lasme-cel, but we also have alemtuzumab. So by second half of 2028, we will be submitting not 1 but 2 BLAs.

Now that's all I'm going to cover, hopefully, the time lines and our plans are clear. But I'd like now to invite our 3 investigators I'm delighted to have them here. We've been introduced to Professor Jain already, who's the Chief Investigator of our study is and a huge supporter. I would also like to invite Professor Basel to join us from the hospital San Luis in Paris. And again, he's the head of Young Adults and Adolescents, and your insight is going to be really important. And very important also is Dr. Ramakrishnan from San Antonio Sarakin. Austin, sorry but he's particularly important today because he is the only investigator who's running both our studies. So he is doing 22 and 2022. So his insights are really helpful to us. So what we wanted to really do now is just you've seen the data and it would be great if we could really start thinking about the -- as we look at the data, just for the audience and for those online, what is the level of unmet needs that we are addressing. Maybe we can start with you to get a European perspective, Professor Bosel. Talk about the unmet need of these particular patients.

So let's start with your burn point of view. So we're not so far from what our colleagues here in the U.S. are doing for ALL patients and children in adults. We are, of course, now exposing our patient to blend a tumult frontline. So all the patients, including in first or second relapse we have been exposed to blinatumomab, CD22 targeted inotuzumab and also CAR T cells. So may be surprised to speak about first-line ALR because it's not something that we -- that has been usual in prior study, but that's the reality now. So we have a lot of drugs to propose to our patients and mostly CD19 targeted. What is probably also changing now in Europe is because of the use of blinatumomab front line, we will postpone allogenic stem cell transplant to sell. So we were traditionally more transplanting patients frontline that our colleagues here in U.S., but I think we will come closer to -- in terms of practice because of the use of targeted or immunotherapy frontline. And so obviously, the patient will have to deal with in terms of relapse or refractory status will be exposed to CD19 targeted therapy with 2 different profiles. Those are who will lose the target, so will be CD19 negative. And those were not completely identifying so far as those who are of immune system that is unfit to either to respond to blinatumomab or to provide efficient CAR-T even it's something that is still unclear. So there is with a question about the fitness of the T-cell of the patient exposed frontline or at relapse. So I think that -- yes, the first surprised about the results. It's how the patients were exposed -- the high rate of prior exposure to immunotherapy. I think none of the study or pivotal study we have done for ALN in relapsed refractory setting showed this kind of profile of prior exposure. So it's clear that fourth line and of blinatumomab. I don't remember exactly 55% or 60% inotuzumab and the high rate of transplant is something we have never seen before. And so clearly, these patients will require to have, yes, such innovating strategy as presented before.

So of course, I think that the agency has required to move to relapse factory setting, but you are addressing the question of unmet needs at different stages, including frontline patients, we are trying -- we are now identifying patients that are also refractory to CD19-targeted therapy. So it's still not well described because the intent study that led to the approval of pinotumumab frontline was for MRD-negative patients. So there were many negative good responders to Kamal and then bridge blinatumomab. So they are good responders but we know also from European studies, then if you consider the overall population of patients, we will identify very rapidly patients that are -- so not refractory, but a positive of the chemo and that do not convert to emerge negativity and especially with the high sensitive MRD tool that we are using now. So -- and this patient will know that they have a quite high risk of progression. And that in this situation, it's not a good option to bridge them to allogenic stem set transplant with this MRD-positive status. So it is clear that also this kind of population early phase or early line patients will benefit from strategy like [indiscernible].

Great. Thank you. And Dr. Ramakrishnan, you've put a number of patients on the trial recently. Well, probably the most recent recruiter of the trial, so thank you for that. What's your general -- you've seen the days on now and with your experience, what's your general view of the products micelle card? And how is you see its role in therapy?

Well, I think my perspective always comes from a transplant perspective because that's my background. So any tool that helps me bridge my patient to transplant, which can cure them, especially if we get them into an MRD-negative state, the advances in transplant regimens and toxicity management, we have very good outcomes. So getting them into an MRD-negative state is quite critical. Regarding that, the patients we're seeing now are also exposed to all these targeted therapies. So it's much harder to get them to that point. I mean I think when I see the data and look at numbers this high for MRT negativity and actually activity, it's very, very encouraging. I think the other thing I've worked with some allogeneic CAR-T therapies for some years now. And I want to highlight what Andre said, the manufacturing, I think, is very critical because I'm looking at do we get reproducible CAR T expansion and response. And I think that's also been very reassuring with this product. And I think a distinguisher -- oh, what's my boss on work. Oh well. So I mean, the critical thing we often see is patients coming in, they have refractory disease. With the standard CAR T, how are you going to collect T cells on someone while maintaining their disease at a state controlling them, getting them to transplant, this product provides a lot of advantages. It's ready to go. We know it works very well. We have a very good target, and we have high rates of MRD negativity. So we're typically planning a transplant while they're going through this process. So it's been very encouraging.

Nothing, I will just send the same point. I think 1 of the things which I -- so I treat ALL, but -- so I think 1 of the challenges with the autologous CAR-T cell therapy, which have been great that we run into issues with these patients who are cytopenic from the disease. So their white count is like 0.5, 0.3 and there is no -- you cannot collect. There's nothing to collect. I mean there are no circulating T cells. So I think -- and that's a challenge specifically for BLL, maybe not so much for NHL, I mean, maybe, but because BLL is a mono disease. So I think that's also a point that I think for pico an allogeneic CAR T cell therapy would have a point because you don't need to worry about blood can so the cells are already premade. So I think that's another important point, we sort of clearly run into issues in our department trying to let's do a CAR T cell therapy, but oh, the white con is 0.2, okay? We were talking about automatic stand of care and oh, we kind of do that because there are no cells to collect. So I think that is a potential challenge for BLL as well.

What was really interesting, I met with you a few weeks ago, and all 3 of you asked me the same question, which was, tell us what's happening with prior CD22 exposure. And it would be great to get your view on the data you've seen because I was a little surprised when I saw the response rates, if I'm being honest. So maybe we'll start back with you, Professor Bosel.

Yes, the question was, I think, obvious because you have the experience about the repeated CD19 targeted therapy, so blinatumomab and then CAR T cell, then we have now nice data, also emerging from real-life experience here in the U.S. where we know that prior blunt exposure may have an impact on the early response, but also on the risk of progression after response to a CD19-targeted CAR-T, but the mechanisms are a little bit different in terms of CD22 expression modulation between CD19 and CD22. But we know that and also from daily experience and then exposure to CD22 with inotuzumab may modulate sometimes transiently the expression of CD20. So we start to have some data, but I think it was very important to have this analysis done. And so yes, I was indeed surprised by the result you show me yesterday because it doesn't since a number quite small, but yes, we have to confirm that, but there is no clear evidence that prior exposure to inotuzumab as modulate the response lasme-cel. So it's -- yes, it's something that is encouraging, clearly.

Yes. Dr. Ramakrishnan would you [indiscernible]?

Yes. So I would concur. I think with a lot of blend usage, what you see is down regulation of '19, and those patients are no longer eligible for CD19 CAR-T because we can't detect the target. So I was a little surprised with prior inotuzumab and the majority of patients are getting it, perhaps the mechanism of resistance is a little bit different in the targets is still -- I mean, it is a different type of approach. It's an ADC versus a T cell redirecting agent. So -- but it's very encouraging that I can tell you, I had a patient with heavy high in exposure that went into an MRD-negative remission. So they're very encouraging.

Yes, continuing the same thoughts. I think for -- as was mentioned, I think for CD19, it's more of an issue because of the not lost with Lena and obviously after signing CAR-T cell therapy. I think for CD22 with inotuzumab, yes, there could be some loss, but it's not very as frequent as has been described in CD19. So I think in that sense, I think it's a very good because you're preserving your target even after prior exposure to anetumab but also the fact that -- which is encouraging is that, yes, you had product explosion inotuzumab, but all these patients are still sensitive to another CD22 targeting kind of agent. So -- and I think moving forward, I think it's quite likely that I think, at least in the U.S., certainly, I think a lot of patients will have prior anetumab for sure. And I think a lot of these patients, as we saw in the study will have prior anituzumab exposure before they go into the CAR-T cell therapy here.

So I think we also have to address the alemtuzumab issue. Now we have seen that alemtuzumab appears to be very important in achieving a response. So it would be great to get your insights on the management of your patients with alemtuzumab. We've seen the toxicity profile, which I think is reasonably reassuring. But -- just to get your view on using this. Maybe we can mix it up. We'll start you first.

So when I first took on the study again, alemtuzumab, I heard that -- and I was like really, but that being said, now we're actually using it, I think the advances in infectious prophylaxis have made it more safe particularly with CMV, we've had a big advance with letermovir for prophylaxis. And that's pretty much gotten rid of that issue for the most part. We also have other drugs. So I think the key aspect there is having goes anti-infectious prophylaxis and being on top of that, so you manage that with your patient, good antifungal prophylaxis with posaconazole and other drugs. And I think it can be safely delivered. And clearly, it seems to be very important in the expansion of the T cells and activity of the product.

Yes. So I think my previous , we use alemtuzumab for on a different disease T cell PLL at a much higher doses for much longer, and they are certainly think CMV reactivation and all this is a issue is a challenge. But here, as you kind of discussed, we're using much shorter duration, overall dose is much lower than what we use for deep PLL. And again, I think with the infectious prophylaxis, margin divisions closely, I think, thankfully, the infectious issues have not been a major issue with elements and it appears as we just discussed at least for this product, use of lintuzumab appears to be quite important in a sell expansion.

Yes, I have a few things to add. We are also using imitatoransparent or I think we used to manage this infectious AEs that there are not that impressive in terms of viral events in the first patients year. Of course, domination of the Phase II will be important to explore this 2 dose levels. And I think it was -- yes, it was required by the agencies, but it seems wise on to happy to go forward with this kind of questions.

Good I suppose I have maybe 1 more question. I'm mindful of time. When we look, I know the numbers are really small and we have to contextual-have to interpret a base on the small numbers. We have those really heavily pre-exposed to targeted therapies, getting those level of MRD-negative responses, which we think are very encouraging. But it will be great to get your insight into based on your practice, what really would be the likely response rates for those patients with what's available to them, be the next available salvage therapy, if at all. So maybe we'll start with the IFRS press.

So I think if you're talking about patients who are 3 or 4 prior lines of therapy and who have failed, obviously, chemotherapy, blina in and maybe a CD19 CAR-T cell therapy I think that we are really -- there's no approved available agents. I mean chemotherapy at that time will have a less than 20% chance of response and additional chemotherapy, I mean to say. And really, I think you're relying on some kind of a clinical trial on new drugs. And I think we're talking about, again, response rates of, I don't know, hopefully, 20%, 30% response rate where we hope and then they're MRD negative and then they continue to transplant. So I think if you go -- I think -- and that's an important wide I think also, I think in the I think if you go 4 or 5 prior lines of therapy, these are really -- I mean, I think -- I don't think there's anything standard here, and we're talking about really very dismal outcomes, unfortunately.

I would concur. I think I typically -- when I see these patients, I do not recommend chemotherapy because the rates of response are going to be so low. We're always looking for a clinical trial. For these patients, usually, if we don't have anything, I call Nitin and send the patient to him to try to get them on some sort of clinical trial. And that's I can't emphasize how refractory this population is. And often, they're very young individuals also. So it's heartbreaking stories. For example, 23-year-old girl with a 2-year-old kid. And just imagine, sitting in front of that person and telling them, yes, we got nothing else. And to be able to take that type of individual and give them a product that gets them MRD negative, get them to transplant and changes their life, she's now going to be able to raise her child. That's sort of, I think, why we all here do what we do. It's to make sure we give patients that type of outcome.

Yes, it's a difficult question. But -- and I'm not surprised because other study have shown that when you treat 1 million 4 line, and you compare less than 4 line and more than 4 lines, you don't see any difference. So it's important for this drug, of course, to move forward and particularly and come back to the MRD-positive population of patients first or also second line because we have to deal also with these kind of patients in second line. And we'd be very happy to see the results of this kind of strategy. I think there are built also for this kind of patient and of course, not only to be used in a third or fourth line. So advanced phase of disease.

Well, thank you all for your insights. I'm going to ask 1 cheeky question of you, Dr. Ramakrishnan, because I know we didn't want to focus at all on 2022. But maybe for the audience, at least just give your own view of how your patients are doing with it, what's your experience thus far.

Again, the experience has been very positive so far. I think we are seeing more targeted therapies in lymphoma as well where CD19 CAR is coming earlier in the line of treatments. And -- but there is an unmet need there for patients who relapse. And again, I think 1 of the things about T cell fitness, you kind of wonder in those patients, whether how good were the T cells that we started off with for the CD19 CAR and lymphoma is also, I think, a little bit different than ALL, where maybe we don't need the same duration of T cell persistence maybe a couple of months, and we get a good response. We get rid of lymphoma and can get durable remissions. So again, I think the product so far, we've been very happy with cell expansion and responses. Everyone I've treated has responded, which is very encouraging. Again, durability is, I guess, what we need to wait to see. It's early days, but also encouraging so far.

Great. Well, thank you so much in the spirit of time, I would say thank you to our investigators. Thank you for your ongoing support. And I'd like to hand over to Arthur Stril, our Chief Financial Officer and Chief Business Officer.

Thank you, Adrian. So good morning, everyone. Thank you so much for being here, none of what you've seen today, and we'll see in the coming months would be possible without your support. So thank you so much for being here. I think as we have our BLA in line of sight, as Adrian has explained, it was a good time to discuss the commercial opportunity for lasme-cel. What are we talking about in terms of sales and commercial opportunity? Now if you have to take 2 takeaways from my presentation, the first 1 would be that this is a meaningful opportunity from a peak sales perspective, as you will see, but the second thing is that not all peak cells are created equal. There is peak cells from autologous therapies with razor-thin margins and individualized complicated therapies to scale and there is peak cells coming from allogeneic therapies, which are true pharmaceutical off-the-shelf products that benefit from all the economies of scale that you've been used to in the antibody or small molecule world. And this is this kind of peak cells that Cellectis is bringing forward today.

So you've heard a lot about lasme-cel. I'm not going to repeat too much, but the differentiation of the CD22 approach, the fact that this is an allogeneic off-the-shelf therapy. The fact that we have fully internalized manufacturing, which will be highly beneficial for a fast uptake upon BLA potential BLA approval and of course, the highly attractive margins linked to the off-the-shelf allogeneic approach are key differentiators of this product. Now we've talked a lot about the competitive landscape. Today, as you know, if you accept chemotherapies, the vast majority of therapies are targeting CD19. And there is a desperate need. We've heard it many times from our panelists for another target. The only other product targeting CD22 is the best on site, an ADC. So it doesn't fully benefit from the T cell mechanism of action that you can see with CAR T and T cell engagers. And of course, the other therapies are leveraging the patient's own T cells, which can be really problematic, whereas last muscle would be the only product to leverage off-the-shelf donor-derived T cells.

So thinking a little bit when we start building the peak sales opportunity about the landscape, again, we heard it today from our panelists. Today, the majority of frontline patients are treated with chemotherapies There's, of course, the arrival of Benito. We heard about its importance in the frontline consolidation, especially following the 2024 label expansion. In the second line, there's often multiple classes. We've heard about Blincyto. We've heard about, again, rounds of chemo. We've heard about Baspana and Auto 19, and physicians would generally alternate between these therapies. Starting from the third line, it starts breaking down and efficacy is going lower and lower. And of course, if you're going fourth line and beyond, as we've heard, especially from Professor Ramakrishnan, everything is becoming clinical trial. So really, the focus today, when you think about the first opportunity for last pace is going to be this third line and fourth line and below patient population.

Now how many patients are we talking about? So here, we're looking only about U.S., EU4 and U.K. And so we start with the incidence first-line treated population, and this is projected to 2035, which is our year of expected peak sales. So we have about 9,200 patients, of which 5,100 in the U.S. and 4,100 in the EU4 plus U.K. Now from these patients, we estimate that about 45% will go into the second line, mostly adolescents and adults given the good outcome of treatments in children in the first line. So that brings it to about 3,900 patients treated in the second line setting.

Moving from that second line setting, we expect that about 2/3 of patients will require further therapeutic intervention, which will bring you to about 2,700 patients in the third-line setting. This is, of course, annually. And then finally, we apply a last cutoff for CAR-T eligibility, which would be about 70% based on the outcome we've seen with auto CAR-T and this is mostly to take into account the patient fitness and comorbidities to account for eligibility for CAR-T. So our core target population in the U.S., EU4 and U.K. for the year of peak cells would be about 1,900 patients. Now of course, this is the addressable market. And to get into peak cells, you have to have an estimate of what is going to be the preference for lasme-cel.

So as you have heard during the panel from Adrian and our physician experts, we think that lasme-cel will be a very promising opportunity for the third line and above markets. last muscle as an alternative target to CD19. It benefits from the convenience of a one-off dosing. It's obviously an off-the-shelf availability, so no need to extract T cells no need to bring them to manufacturing, no need to have patients to go through bridging chemotherapy. It can be immediately available from the hospital pharmacy. And of course, as you have heard, we benefit from the deep MRD negative responses in this setting. So we estimate based on oncology precedent, but also interviews from physicians, preference market share of about 65% for this line of treatment. We think that the other therapies be it because they target CD19, they're leveraging the patient's own T cells or they have very limited efficacy and a high toxicity profile, which is the case of chemotherapy, as we have just heard, would not be the prominent therapies once lasme-cel is approved.

Second, we think that lasme-cel has high pricing potential due to the unmet medical need it is going to solve. In Europe, we're being a bit conservative. So we're using the -- an anchor price in 2025 of the average price of the approved therapies, Tecartus and Kimi and we project a flat pricing until a year of peak sales, so 2035. So we have an anchor 2035 expected list price of about $365,000 for the EU. In the U.S., we have looked at what has happened with the price of Kymriah, Ocado and Tecartus the 3 autologous CAR-Ts that were approved. The current anchor price for 2025 has been about USD 515,000. And we think we can apply a modest growth of 5% across all the way to peak sales in 2035. And which is what has been seen in terms of pricing dynamics for the auto CAR-T since their approval. So we come to a 2035 expected anchor list price of about USD 840,000, now we are going to bring this all together, looking at the target patient population, the expected price and the expected preference share.

So if you look at the initial addressable patients, you come back to about 10 patients, which is the number that was -- that came from the previous slides, about 1,100 in the U.S. and 840 in EU4-plus U.K. This is, of course, annual numbers. You apply the preference share of about 65% in this line. We still put a cut of 90% for market access of CAR-T therapies, which is standard for CAR-T therapies, which brings you to about 620 patients annually at year of peak sales for U.S. and 480 patients in EU4 plus U.K.

Then finally, you apply gross pricing, which brings you to a 2035 expected potential peak gross sales of up to $700 million for the U.S. EU4 and U.K. And of course, this is excluding Rest of the world. We think this therapy will have also tremendous potential in other geographies like the Asia Pacific region, especially due to its off-the-shelf nature, but we've been conservative and this up to EUR 700 million is the figures for U.S. EU4 and U.K.

Now of course, the core indication that Adrian has mentioned for our initial label will be third line plus, but we think if the results hold in this first trial, we will have the potential to expand lasme-cel in other areas. We think that lasme-cel has the potential to have a place in the second line and we think that lasme-cel has the potential to have in first-line MRD positive consolidation in place, pretty much like Blincyto, especially as you're going in earlier lines of treatments where patients are more fit. So if you factor in an additional opportunity for these label expansions in the future, we believe that peak sales could increase to up to EUR 1.3 billion with this additional label expansion.

So to put it all together, we think that lasme-cel again, has a very strong commercial opportunity. This has the potential to be the first-in-class immunotherapy beyond CD19. And we think that what will especially drive adoption, as we have heard today, is the deep responses with high CR rates and the impressive MRD negativity that you've seen. We believe that there is a robust peak sale potential of up to $700 million in the first indication that we have. And again, very importantly, with the allogeneic approach. This is not just about peak cells, but this will be about EBITDA. And this is true pharmaceutical EBITDA, not autologous EBITDA. And we think that the industrialized off-the-shelf approach with the internalized manufacturing is going to be critical for launch and commercial success as we go into peak sales territory.

So thank you very much for your attention. And I will hand it back to Andre for the next steps.

Thank you very much, Arthur, and hold your horses because you're definitely going to see things you thought with science fiction, but we're making it real. As we said, we might have like an update soon, and that's going to be really interesting.

So I'm going to make a quick conclusion on the presentation that we saw this morning. And then we're going to open Arthur, myself and Adrian question for like Q&A session and answer your questions. So Adrian presented this slide, a few takes away that I think are extremely important on your side, we're deep believers in the fact that allogenic CAR-T therapies fits definitely needs in various spaces in oncology and potentially beyond oncology, as Mark has just showed it in autoimmune disease and maybe beyond this. And it's interesting for the simple reason that you get a really standardized product. And this is all the difficulty is to make it super stable and standard and reproducible. And this is something Cellectis know how to do. We've been doing this for more than 10 years with CMOs some difficulties. Remember, the first patient we ever dosed was UCART19 10 years ago with an allogeneic CAR-T. So we made the CAR before 2015. So that was 10 years ago. And like UCART19 like is now like ALLO501 not ALLO501-able, and this is something that we're extremely proud of. And since then, we've been working and working and working and improved the process to something that is extremely stabilized, and we believe we know how to make a pharmaceutical commercializable product that would give the same chances to every patient. Same chances to every patient. Remember, you have T cells, you have no T cells, it works. Why, for example, a DC works differently than a CAR-T. So you know the hierarchy. It's like a monocle antibody will kill a cell if there is more than 100,000 tumor acetated antigen on the surface of a T cell -- of the target cell. For an ADC, it's 10,000. Below 10,000 is not going to work. This is why, for example, some failures of ADCs gives the same chance for a car because it will be few hundreds. We don't know exactly the number of tumor assisted antigen that needs to be expressed under surface can still take them down. And this is what makes the difference between being able to bring a patient to MRD negativity versus not. And that's where CAR-T cells are a real game changer and coming with something even if you don't have T cells, the patient have like few blood cell counts still works.

So we're excited about this. And also, we're excited by the strategy that has been developed and also endorsed by regulatory bodies in terms of making this first product the best chances for a patient go for bridge transplant. This is something that is totally innovative and a game changer. So first patient would be recruited this year by the end of the year, we'll have next year an interim analysis for patients and then it will continue up to general enrollment and then we'll have the BLA in 2020. So lot of things to do in the meantime, of course, like opening 75 sites, et cetera, but we have a clear road to success for this. Well, the strategic road map, something that you need to keep in mind for Cellectis, we're not all about last missile. We're super excited. We believe lasts a game changer. We believe it's a product that definitely fits the size of Cellectis and the ability to develop a product like this with a very valuable product. and something that have given asymmetric value creation for a company our size, and at the place where we are today. So I really consider this.

The second thing that you have to keep in mind that after lasme-cel, you have T-cell talked a bit about ethical. There is like a bit of a peek on where it goes, but it's 20 by '22, still not in '19 still a very high unmet medical need with a product that has a double targeting and like a very nice strategy because you can grab even 2 targets instead of only 120 -- CD20 and CD22, and you will have also a bit of information by the end of this year at ASH. So keep an eye on ASH. But that will be end of Phase I in refractory labs, not Hodgkin lymphoma in 2026. And also some data on trials that we are doing that will be probably very exciting, I'm very excited about it, and we're definitely looking forward to present this. And finally, a bit of a peak of the preclinical proof of concept in 2026 of in vivo gene therapy. Gene therapy has been always very complex, have to take the cells out, it's complicated, et cetera. But if you take a pair of mRNA, package it. It's something that can bring this to the right cells inside the body and can do this as an injection IV who had RNA in vector that was injected in the blood in the room here. I'm not asking the question to raise your hand, but it's something that has been acceptable since many years now, like probably 4 -- 3 or 4 years, and so it's something that is going to be the game changer in vivo gene therapy, and we believe that our technology, and I should say, our technologies because we go beyond nucleases, base editors, modifiers, epigenic modified, et cetera, is something that is going to go in vivo and is going to be a shot with something that can be -- also have very powerful and decent COGS and that we give probably also something that would play more on the EBITDA at the end of a company and allow us to develop. So that's going to be a revolution in medicine. And we're here to bring revolution in medicine. This is our mission and our task, and we're doing this.

With that, I would like to thank you again for your attendance, and I'd like to open the questions for the audience. Adrian and Arthur, please.

So we'll start by Gina. Do we give a mic to...

Maybe I can give you a mic, I don't know it's working or not.

Is it working?

I don't know. Never like giving that? Yes, yes, that's working. Yes, go ahead. That's working.

First, I wanted to say congratulations. It's a great update. You really covered a lot of the questions and that's very impressive data. So I have -- I'll try to limit myself. I know a lot of questions will be asked. I will limit myself to 2 to 3 questions. One is about lasme-cel pivotal study. I just want to confirm the trial design is confirmed, agreed by the FDA and EMA. And 1 question is for the 2 doses. I assume, one, including dose level 3 and the other dose is a higher or lower dose. And then what is the definition of success given the primary endpoint strengthening CR? So that's 1 of the questions, sorry.

And then the other question is about manufacturing and also AstraZeneca. So the manufacturing, I think you share the square footage. So what is the capacity here, current capacity and future peak capacity. And I assume, will be also part of helping AstraZeneca providing certain products, right? And then related question is when will we see the pipeline of the collaboration from AstraZeneca? And will we see the data from Cellectis collaboration?

So I may take first question. There's probably really 5 questions. That's a great question. So yes, we're completely aligned with the mega authorities. The biggest issue is really finding the right end point, and I think we've got there and get agreed with that really, this is a single-arm trial.

So yes, there is with that. There's a bit of clarification from my end and sorry if I didn't make a care. There's no dose optimization for lasme-cel. It's dose level 3. That's our recommended Phase II dose. The dose optimization is actually for alemtuzumab, where they want us to make sure we've got a dose and there was to try a lower dose as well within the dose optimization, and that will be that first card patients. So we will not be testing any alternative doses of the lasme-cel. There was another question that was there.

I think that's it. And what is the definition of success for primary endpoint? Because you only say CR is like 3 months, right? So what is defined as you have 2 arms. Is that comparison of the 2 arms or FDA set a threshold, you have to reach a certain CR rate in order to define as a success.

So for a single-arm trial, there's always the same wording for the regulators. It has to be compelling. So right now, there's an assumption in the background. These patients have, I think, generously a CR/CRI rate maybe of 20%, although what we've seen when you -- that, that is probably a threshold of many patients would meet. We have exceeded that quite significantly as our market success, and that's been generally agreed as appropriate. So we believe this threshold is probably the data we have here, if we hit this, we will start to surpass that [indiscernible].

Yes. I'm going just like back now fine. So for the manufacturing question, yes, we share the square footage. Well, that's -- of course, something that is not relevant for the manufacturing capacity that we have. First of all, you're all invited to visit our site in Raleigh. It's like the nice picture of this building that you see is the entrance of our building in rally. Some of you have visited, I see some friendly faces that have visited the site, but definitely, it's something that will show you how powerful and efficient and well organized it is, and it is set for commercial production. We have currently 1 suite that is active and allows us potentially to produce up to 4,000 doses a year, which covers way more than what is needed in terms of completing, for example, as selling ECL, et cetera. We're -- as we're opening our collaboration with AstraZeneca, we decided to enable a second suite that will have the same capacity, and we have spots for 2 other suites, so 4 in total on 1 side of the building, but the second side of the building can be cloned on the other side that would allow 2 other suites. So we will have 2 suites that will be ready to go within -- by the end of next year and -- or early '27, but it's something, but it's supposed to be by the end of next year. So it will increase the capacity. Not only this, but the numbers that I'm giving you can be augmented pretty meaningfully because today, we don't have the need to have like that many vials. But once we believe that we can supply the whole world in terms of the 2 products that we have, and potentially also some of the product that we will be producing for AstraZeneca, and there is no limit for this. So the rally site can fill with multiple products, the global needs for even larger indications also.

And then the last -- Yes. So Mark said it 2026, maybe a first peak on the things that we're going to do, right? But I speak under the control of Extra. I like 26, they say, "Oh, no, we don't want you to share this [indiscernible] so great, then we'll not share because they're our partners, and we do what our partners are willing to do.

I'm from Wells Fargo, and thanks for the invitation to the R&D Day. I was wondering if I can ask a question to the doctors. If any of them would like to comment, I was wondering in terms of using lasme-cel, would the doctors use it exclusively after Blincyto and autologous CAR T? Or is there scenarios where they can use it because this is to be followed by transplant, right? And essentially, will they use lasme-cel followed by transplant as an alternative to either cycle?

Perhaps, Nitin, you can take?

Sure. Yes. I think right now, as you know, BLINCYTO is approved in the first-line setting. So practically, every patient in the U.S. is getting Glenside or blinatumomab in the first-line ALL setting. So practically all patients will have exposed to blinto coming onto the label. In terms of the -- whether they need to be a CD19 refractory, in the trial, you saw 50% of the patients had a prior set CAR-T cell therapy. But as I said during the discussion, there are patients who cannot get an autologous T Cell collection done because the accounts are too low, there are no T cells to collect. Or there may be situations where you want a quick CAR T -- there's no time for bridging and like cell collection leukophrases, all those things are taking too much time and where you want to go quickly to your cell product where the having an allergenic product is helpful. So I don't think it's a requirement per se that you must fail in CD19 CAR-T to go into this. But I think -- and there will be some situations where suddenly this may be kind of preferred just because of the logistics issue and how quickly you want to go to the CAR-T.

And also to a company, I think you talked about regulatory bodies agree with the importance of transplant, but in the label or in the trial design. How is that reflected? Will the label because CR/CRI, that's transplant, right? Would that reflect or would that will be officially recognized in the label?

Yes, that's the great question. So yes, we agreed with them. They wanted to see efficacy first, which is CR/CRI. That's what they want is the primary endpoint. However, within the design with including key secondary end points, we will be capturing the proportion of patients who become transplant eligible. And that will allow us then to capture those patients following up. We will not be mandating a transplant, but all patients entering the trial would be considered to be -- to benefit from transplant, and that is the goal of the treatment. So I think the design has allowed us to capture I would consider a more traditional endpoint with, however, the aspirational endpoint of showing that getting these patients to transplant with the follow-up and improvement in overall survival would that actually give us the label that we are seeking.

Jack?

Congrats on all the obvious very impressive data. I guess maybe the first 1 is for the physicians. I'd love to get some more context around how many transplant eligible patients have access to a transplant. Is the match rate very high in T cells ALL? And how do you think about that when you're looking at potential treatments that can be bridged to transplant?

It's probably worthwhile getting a U.S. and a European view on this. So maybe Professor Bosel, do you want to...

It's not different to Europe.

It's not different. Okay. It's not different. So you -- Dr. Ramakrishnan, you're in the community setting. So perhaps there's a [indiscernible]?

As far as getting a donor for transplant, the era where we need to match is going away. In fact, we're doing clinical trials right now where we're doing mismanastron-related donor transplants and having similar success rates. So 6 out of 8, 7 out of 8 or even a trial with season marrow registry source that we can use for transplant. So pretty much in this era, almost every patient has a donor. It's very rare that we have to send someone -- we don't do cord blood transplants in our center. Very few centers are doing it. If we do, in the rare occasion, have to do that, we send a J. Shale and the Anderson and that pretty much covers everybody. I think you can pretty much guarantee 100% if you needed a transplant, there's a donor out there for you.

Great. That's great context and incredible to see the innovation in that space. And then maybe to Adrian on the design of the Phase III study. I guess you mentioned that maybe the comparator is on the 20% to 25% response rate also, I think earlier you talked about still looking at the literature. I'm not sure if that pinned down that external control. And if there is any changes in the assumptions around that external control, would that dictate the size of the study as well. Is that ENVISION study locked in? Or did you go lower if you had a lower response rate based on the literature.

So that's a great question. The size of our trial is not really driven by our assumed efficacy. It's actually driven by the size of the safety database required for BLA. If we were to power our trial based on efficacy, it would be much smaller. So that is the first point. So even if there's any change in numbers, we have so much room. We're very confident regardless of what we see in our control arm. We're very much overpowered to demonstrate the efficacy required. In terms of the synthetic control arm, and we've been talking to our investigators here about it, I don't want to dismiss this as being easy. It's not. This is a very specific group of patients that will require both an element of retrospective and prospective data collection. We have pretty much designed most of our propensity score matching and how we're going to capture them. There is really what is required for us now, and we have a little bit of time is where we're going to get these patients from? Is it a mixture of databases versus academic institutions, there's going to have to be an element of capture, both in Europe and in the U.S. It's complex, but I think we have a very good plan.

Got it. Great. And maybe just 1 last 1 on the study design. You mentioned that alemtuzumab doses that are going to be tested in the pivotal study are going to be dosed down. I just want to hear any context you can provide around contribution to components in those discussions with FDA and their reassurances of the ability to show that with your current plan.

Yes, we've had a lot. As you may expect, we've had a lot of conversation with the regulatory bodies in terms of how are we going to differentiate between 2 doses of alemtuzumab in the context of patients who are incredibly on well from a disease perspective itself, they get a lot of toxicities. But we believe that the doses we've chosen are differentiated enough. But however, we will be monitoring it. This is still open label. We want to make sure that patients are not underexposed to alemtuzumab. What we've done over the last year is we've done a tremendous amount of modeling as to what is the right dose. What is underexposure and over exposure look like because what we've tried to get, and I think it's 1 of the learnings you can have, having had so many patients treated with alemtuzumab in this context, we can start to see a picture of what is the right level what dose levels are too low, so you get early host T cell reconstitution and you don't get your expansion. So we're coming into our Phase II really better informed. So I think our 2 doses, we will be able to differentiate between the two. And as always, if we can get away with a lower dose of alemtuzumab maintaining efficacy and minimizing toxicity, that is a good outcome for patients.

So congratulations on progress and presentations. So just to follow up on the question, Jack asked about the external control arm. So what are the key design considerations for this external control arm, whether you're going to discuss with environment or agency or on the key design elements.

And then maybe also want to ask the KOLs here that how do you think about the comfort level from community-based doctors to handle the addition of alemtuzumab given the data you show today. the importance of the FCA regimen here and the company's vision.

Yes. I'll take the first one. But Dr. Ramakrishnan, since you are kind of a community-based practice, he can answer the second question for you.

So in terms of 1 of the key considerations for the external control arm, which I think was your question, it is not easy to develop this control arm. We acknowledge that because there's not a lot of standard of care for these patients. These patients have had so heavily pretreated, there's not enough clarity on what the comparator arm looks like. So it will require a significant amount of propensity score matching. Now as we're looking at our databases, we decide, well, how many patients do we need in the database to qualify 1 patient in our external controller. And that is actually far more reassuring than I thought it was going to be. I thought it was going to be a pretty big number, but it's actually fairly small. So I think, based on our initial analysis, we have enough patients in existing databases, both clinical trial databases, registries and academic institutions that I believe we'll be able to fulfill the requirements. And Dr. Ramakrishnan?

So the question was...

[indiscernible] the sometimes toxicities.

I think the -- more than that, I think cell therapy right now, I mean we're in the community, but we're a specialized center. I don't see anyone doing cell therapy in the community at this point. But if you think about access, most of the care is delivered to the community, I think we have to figure out ways how to expand that. As far as alemtuzumab, I think that itself, I'm not too concerned about toxicity-wise, has been around for a long time. People have used it. We have patients in the community with T-PLL who are getting alemtuzumab. They're not getting it at academic centers and community physicians are treating them and are knowledgeable if they're educated on toxicity management, infection prophylaxis.

Thank you. Well, the event have reached 10:33. We've been extremely generous with your time. I would like to thank you. This doesn't mean that we can't continue the discussion after with further meetings, et cetera. It's like this would be extremely happy to take more questions in the future. But I think that for here like the -- we need to clear the room Again, thank you very much for your time. It's been a great pleasure and a great moment for Cellectis because it's the first time we're showing this kind of data. And keep it by the end of the year. Plenty of things are going to happen. In the meantime, there's a lot of data points that you'll have to see and '26 will be extremely rich. We are going to present and continue to flow you with information and innovation for the next years. So stay put on Cellectis. Thank you very much.

Good day, everyone, and welcome to today's Cellectis' Second Quarter 2025 Earnings Call. [Operator Instructions] Please note this call may be recorded. And I will be standing by, if you should need any assistance.

It is now my pleasure to turn the conference over to Arthur Stril, Interim Chief Financial Officer. Please go ahead.

Good morning. and welcome, everyone, to Cellectis' Second Quarter 2025 Business Update and Financial Results Conference Call. Joining me on the call today are Dr. Andre Choulika, our Chief Executive Officer; and Dr. Adrian Kilcoyne, our Chief Medical Officer.

Yesterday evening, Cellectis issued a 6-K and press release reporting our financial statements for the 6 months period ended June 30, 2025, and a business update. The report and press release are available on our website at cellectis.com.

As a reminder, we will make statements regarding Cellectis' financial outlook, including the presentation of our BALLI-01 and NatHaLi-01 clinical trials, the timing and ability to progress our clinical trial into a later phase, the progress of our R&D activities under the AstraZeneca partnership, the timing and outcome of our arbitration with Servier and sufficiency of cash to fund operations.

These forward statements, which are based on our management's current expectations and assumptions and on information currently available to management, including information provided or otherwise publicly reported by our licensed partners, are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

A description of these risks can be found in our most recent Form 20-F filed with the Securities and Exchange Commission, SEC, and the financial report, including the management report for the year ended on December 31, 2024, and subsequent filings Cellectis makes with the SEC from time to time.

I would now like to turn the call over to Andre.

Thank you, Arthur. Good morning, and thank you, everyone, for joining us today. I would like to begin this call with an important announcement.

On October 16, 2025, Cellectis will be hosting an Investors R&D Day in New York City. Our leadership team, along with key opinion leaders will present the Phase I data set and late-stage development strategy for lasme-cel, UCART22, in relapsed or refractory acute lymphoblastic leukemia, and will share insights on the Company's vision and differentiated capabilities.

Cellectis' Investors R&D Day is scheduled as an in-person only event. However the recording of the event will be made available in the following days after the event. Despite the challenges of the biotech market, our teams have remained focused on advancing research and developing solutions for patients with unmet medical needs. In July 2025, Cellectis completed end of Phase I discussion with both the United States Food and Drug Administration and European Medicines Agency.

We are excited to prepare for the initiation of the pivotal Phase II trial for lasme-cel, UCART22, in relapsed or refractory acute lymphoblastic leukemia in the second half of this year.

Regarding the NatHaLi-01 study, which is assessing eti-cel program, UCART20x22, in relapsed or refractory non-Hodgkin lymphoma. Cellectis anticipates presenting data from Phase I and outlining its late-stage development strategy late 2025.

On the partnership front, Research and development activities are ongoing under the three cell and gene therapy programs under our Joint Research and Collaboration Agreement with AstraZeneca: one allogeneic CAR-T for hematological malignancies, one allogeneic CAR-T for solid tumors, and one in vivo gene therapy for a genetic disorder.

Regarding our licensing agreement involving Servier and sublicensee, Allogene, and following Servier's decision in September 2022 to seize the development of the licensed CD19 Products. We've initiated an arbitration before the Paris Mediation and Arbitration Center to protect our interests.

We're asking the tribunal to terminate the agreement with Servier and to award fair compensation for the losses incurred due to the lack of development of the licensed products and the payment of the milestone which we consider due under the agreement. The arbitral decision is expected to be rendered on December 15, 2025 or before.

Earlier this quarter, Cellectis announced that during its Annual Shareholders Meeting, Mr. André Muller has been appointed as a member of the company's Board of Directors. I'm pleased to welcome André at Cellectis Board. His extensive experience will be an invaluable asset to the company.

We would also like to express our gratitude to Mr. Pierre Bastid and Mr. Axel-Sven Malkomes, who have terminated the directorship for their esteem commitment to Cellectis. It has been a huge honor and a pleasure for us all to work with them during their term. Their contribution over the past years has been exceptional and their precious support has greatly contributed to the advancement of the company's strategy.

With that, I would like to turn the call over to Dr. Adrian Kilcoyne, our Chief Medical Officer, who will give an overview of our clinical trials.

Adrian, please go ahead.

Thank you, Andre. As Andre mentioned, Cellectis continues to focus its development efforts on the BALLI-01 and NatHaLi-01 studies. Recruitment to the dose escalation component of the Phase I BALLI-01 study which is evaluating UCART22 in relapsed or refractory B-cell acute lymphoblastic leukemia has been completed. This study addresses an important unmet need for patients who have relapsed following multiple prior lines of therapy, including a CD19 bispecific or autologous CAR-T and a few, if any, other treatment options.

The Phase I data set has been shared with both FDA and EMA as part of the end of Phase I and scientific advice meetings. Following productive interactions with both agencies, we now have a clear path to commence our pivotal Phase II study later this year. We have set up additional trial sites in order to accelerate accrual into the Phase II study, and we'll continue to focus on expanding sites in the United States and Europe, including the United Kingdom.

We anticipate having sites open for recruitment into our Phase II study by the end of the year. We are also planning to publicly share the full Phase I dose escalation data set during our R&D Day, as highlighted by Andre earlier.

Additional data from the Phase I study has also been submitted for consideration of presentation at the ASH Annual Conference in the fourth quarter. We also continue to enroll in the NatHaLi-01 study of our dual CAR-T asset, UCART20x22 in relapsed or refractory non-Hodgkin's lymphoma. This study is addressing an important unmet needs for patients who have relapsed following previous lines of therapy, including when available, an autologous CD19 CAR-T.

Data from this program has also been submitted for presentation at the ASH Annual Conference in the fourth quarter. We are expanding our clinical trial sites to accelerate recruitment and we hope to transition to Phase II preparation in 2026.

With that, I would like to hand the call over to Arthur Stril, Cellectis' Chief Financial Officer and Chief Business Officer, for an overview of our financials for the second quarter 2025.

Arthur, please go ahead.

Thank you, Adrian. We are pleased about the progress of our wholly owned product candidates, lasme-cel and eti-cel, as well as over the three cell and gene therapy programs in partnership with AstraZeneca.

In this context, we are excited to be hosting an R&D Day on October 16 to focus on the Phase I data set and late-stage development strategy of lasme-cel as we prepare to launch a pivotal Phase II in H2 2025. We also expect to provide an update on eti-cel by the end of the year.

Finally, the arbitral decision in our arbitration with Servier is expected to be rendered on or before December 15, 2025.

Importantly, we are well positioned financially to execute on our pipeline as our cash, cash equivalents and fixed-term deposits as of June 30, 2025, remain sufficient to fund our operations into H2 2027.

Our cash. Cash equivalents, restricted cash and fixed-term deposits classified as current and non-current financial assets as of June 30, 2025, amounts to $230 million compared to $264 million as of December 31, 2024. This $33.2 million decrease is mainly due to $13.4 million of cash in from our revenue and $5.1 million of interest income, offset by cash payments from Cellectis to suppliers of $23.2 million. Cellectis' wages, bonuses and social expenses paid of $23.6 million. The payments of lease debt of $5.4 million and the repayment of the PGE loan of $2.6 million.

You are invited to refer to our press release for figures related to consolidated net loss attributable to shareholders of Cellectis for the 6 months ended June 30, 2025.

We're very much looking forward to welcoming you at our Investor R&D Day as well as to providing further updates later this year.

And now I would like to turn the call over to Andre for closing remarks.

Thank you, Arthur. To close out this call, I would like to reiterate how excited we are to have one of our first product moving into Phase II pivotal trial powered registration. I'm confident about the continued progress of our ongoing clinical trials in hematological malignancies as well as how excited we are about our strategic collaboration with AstraZeneca.

At Cellectis, we strongly believe that our product candidates, our technologies and our in-house manufacturing capabilities will lead us and our partners to a paradigm shift for patients with hard-to-treat cancer and genetic disorders, positioning us the forefront of this promising medical and scientific field.

With that, I would like to open the call for Q&A.

[Operator Instructions] Our first question will come from Gena Wang with Barclays.

Congrats on the progress. So I have two questions. One is regarding the Servier arbitration decision by December 15. Could you contextualize the different scenarios and your likely actions?

The second question is regarding the lasme-cel. You already met with both FDA and EMA regarding the pivotal Phase II trial design. Could you share a bit high-level thoughts with us? What could be the path forward there?

Gena, this is Andre speaking. I'd like to answer the first question. It's complicated to answer your question for the simple reason that, I guess that probably there is still thinking on the way the things are going to go. And I don't want to draw here any kind of scenario, knowing that any kind of scenario can happen from one side or another.

And I personally hope that we're going to prevail in this arbitration, it means that we're going to get back our CD19 products and that we're going to have the compensation for like the loss incurred by the non-development by Servier. However, it's very difficult to forecast exactly what could be the decision at the end in these type of arbitration.

So I'd like to keep the door open as much as possible for any kind of scenarios. But we believe that we're totally right in our position knowing that there is nothing has been happening so far.

A question mark on, -- if I start like putting some scenario, it means, I already thought about the fact that we can have some back position, but we don't have any back position. And for the question for, like the interaction with the FDA and the EMA, I'd like to defer this to Adrian. Adrian?

Yes. Thanks, Andre. Great question. Yes, we've interacted with both EMA and FDA. And just in the spirit of transparency, the EMA, it was a written feedback. They felt the, our submission was clear, and therefore, they could give us very clear guidance on that and a very productive feedback that was.

The FDA was a face-to-face meeting. And while I can't go into the details, but certainly at the R&D Day on October 16, we will share a lot more detail around the study design, et cetera. But a few top-level take homes is, we got clear agreement on end points. We had -- there was no concerns raised around our statistical plan. There was no issues raised about the size of the database we would have as we go to BLA with -- based on what we had submitted. So overall, in our view, there is a very clear path forward for our Phase II program.

So again, I'd reiterate very productive meetings with both regulatory authorities, who are generally aligned in their feedback, which is always a bonus, I feel.

Our next question comes from Kelly Shi with Jefferies.

This is Anqi Yu on behalf of Kelly Shi from Jefferies. I have two questions. For the R&D Day, what data points should we expect? And supposing we don't have the trial design at this point, you will disclose on the R&D Day. Then how do you consider the dynamic in the FDA that could potentially have any impacts on the pivotal trials?

This is Arthur. I will start on the R&D Day and then let Adrian add any points and also on the FDA question.

So the purpose of the R&D Day is really twofold. We want to be presenting the full Phase I data set for lasme-cel that will include all patients that have been dosed so far and a particular focus on the patients at the recommended Phase II dose, and that will be safety, efficacy and durability data set.

And the second point is, we want to present what we call the late-stage development strategy, which indeed will include the Phase II design, the patient population and then provide some color on the path to BLA. So it will be both a look into the path that all the Phase I set, but also look into the future as to the plans for the product all the way to commercialization.

And then, I'll hand it over to Adrian, if you want to add any color and address the FDA question.

I mean, I think, if I can answer with a question. Are there any barriers that became evident in our interactions with either regulatory authorities to progressing to Phase II and pivotal? Absolutely not. I think the regulatory authorities, both of them acknowledged the high unmet need that is -- that exists within the space, we're going -- positioning that product. But also, I think it was very clear from the tone of these meetings that they're broadly supportive of what we're doing.

So again, to get alignment on endpoints, to get alignment broadly on the study design as we had presented it to them and patient numbers, overall, we don't see any significant roadblocks. So again, alignment between ourselves and the regulatory authorities, we -- and again, as Arthur said, we will be presenting the study design in detail, discussing through those endpoints.

But I think, again, I would restate that the registration path for this product seems relatively clear. And of course, everything is dependent on ultimately Phase II data.

Our next question will come from Jack Allen with Baird.

Great. Congratulations on the progress. I guess maybe I'll start with one on UCART22 and the upcoming R&D Day. I wanted to ask what -- how the team is thinking about the bar for success in relapsed or refractory. I know, there's some data about best response out there and also some autologous CD19 CAR-Ts. But as you move toward the pivotal study, what are you looking at as the bar for success?

And what kind of expectations do you have for durability of response from UCART22? And how much follow-up should we expect on Phase I patients when we get that data update in the back half of this year and then, I guess, in mid-October? And then I have a quick follow-up as well.

Thanks, Jack, for the great questions. Adrian, do you want to take this?

Sure. So there's many questions in there. Suffice to say, again, more detail on the endpoints, the timing of those endpoints will be shared in detail during the October 16, R&D Day. But durability of response in the allogeneic setting is really important. And on sharing the data with both regulatory authorities, they are very clear on the approach we're taking will give you the adequate data in order to support a registration, assuming the data is positive based on our -- what we're showing.

Of course, this is also, there will be a longer-term follow-up in all these. You know we're committed to a 15-year follow-up with these patients. But also within the trial, we have -- we will have a longer survival. It's a long overall survival follow-up for a number of years. So -- but that is not part of the primary analysis. So the primary analysis, as we will share is a much more short-term surrogate endpoint, which, again, has been agreed with the regulatory authorities.

Got it. That's very helpful. And then maybe for Adrian, again, with ALLO, correct it, as he sees fit. I'd love to hear any high-level thoughts you have on the recent decision by Allogene to move away from the CD52 lymphodepletion. How are you thinking about that as it relates to your programs moving forward? And would you anticipate including alemtuzumab in a potential pivotal study of UCART22?

Well, I can start on that, Arthur and Andre. Yes, we've been following the Allogene story very closely. We believe that alemtuzumab is really important as part of the lymphodepletion regimen. And we want to be really cautious in how we interpret our approach in the context of Allogene's approach.

I want to stress that these are very different positionings of the products. We're talking very late-stage ALL, and we're talking very late stage NHL compared to the Allogene approach is much earlier.

While we -- and we also don't know very much around the pharmacokinetics of the ALLO product. But it appears to be at a much higher dose than we gave within our clinical trials.

And of course, the third thing, which is really, really important is that everything we do is based on risk benefits. So the risk-benefit assessment within the Allogene program is very different to the risk-benefit assessment we see in our programs. So all in all, very difficult. I think it would be unfair to draw any comparisons between these programs. We are fairly confident about our risk-benefit assessment across our programs with alemtuzumab. And we believe that adds a critical improvement in responses, which we're fairly confident in our approach moving forward.

Yes. And if I can add something, I think, Adrian, you're spot on, obviously, on the dose, but it's also important to -- remember that these are different products. And I think our strategy has always been from the get-go to secure direct access to alemtuzumab, which is something that we've done with Sanofi a few years back. So we know we have access to actual alemtuzumab. ALLO-647 is a different product. And honestly, we're not exactly aware as to how it compares, what are the glycosylation patterns, what are the -- what is the structure of the antibody. And so it's very difficult to compare apples to oranges. And we're very pleased to be moving forward with actual alemtuzumab.

Great. I guess just maybe one last one on the topic. Any high-level thoughts on ways you could mitigate potential infection risk in your study? I know the CD52 lymphodepletion can lead to a longer depletion of T cells. Have you given any further thought on the protocols you can put in place to mitigate infection risk?

Yes. I mean, it's part of all our trials. We have a mandatory prophylaxis. So that's already built in. We have significant risk mitigation strategies already built into our trials. So yes, I think we've already addressed much of that. But of course, we remain vigilant.

Our next question comes from Yanan Zhu with Wells Fargo Securities.

Great. Just maybe a follow-up on the FDA discussion for the BALL program. Wondering -- I know you will provide more details at the R&D Day. Wondering if the population for the pivotal trial, is that specific population like post CD19 CAR-T? Or is that a more broader population? And also in terms of the patient number, could we look to the most recent CD19 autologous CAR-T programs for BALL for the rough range? Or could the trial be smaller than that?

Yes. Good questions. So as you're probably aware, we're looking at a very late stage treatment. So -- but we're going for a fairly broad patient population in terms of age cutoff. And again, we'll share the details with that, we would anticipate there will be a significant number of lines of therapy for most patients in our clinical trial. And that will include, obviously, CD19, CARs, et cetera. So you'll see detailed breakdown of this at the R&D Day. So I would encourage you to come along.

In terms of the number of patients, I think the number of patients in our trial is driven by two things. One is the powering of our trials. And the two is the requirement of the safety database, which often takes precedence. So I think, your suggestion that, looking at other autologous CD19, CARs in this space will give you, while not entirely accurate, it will give you a ballpark as to what kind of numbers we need to have in these kind of trials. And it's driven by the size of the safety database rather than the assumed statistical powering.

Great. That's super helpful. And then as a follow-up for the Servier program arbitration discussion. I was just wondering, could you give us a sense of the size of the milestone payments that potentially could be awarded at that point?

Yes. Thanks, Yanan. Unfortunately, as this is an ongoing legal matter, we're not going to be able to give more details on this. Sorry.

No problem. Congrats on the progress.

Our next question will come from Sebastiaan van der Schoot with Kempen.

Just two from my side. The first one is a follow-up on Allogene decision to not move forward with the anti-CD2 or CD52 antibody. Can you maybe give some insight whether there's been any feedback from the regulators from inclusion of the anti-CD52 in your treatment regimen? And do you expect that there might be another conversation with the FDA after these filings from Allogene? And then, I have a follow-up.

Thanks, Sebastiaan. Adrian, do you want to take this one?

Sebastiaan, I just want to make sure I've understood the question. Could you just repeat it?

Sure. So it comes down to whether you expect that this decision from Allogene that came after your conversation with the regulator, but that can still influence the design of the pivotal study with the use of the anti-CD52 antibody.

No. We -- honestly, we don't believe so. Again, we have an established safety profile and an established risk-benefit assessment. As Arthur already stated, this is -- the Allogene product is different. And if we assume they may be even similar, our dosing levels are significantly lower than we see with the Allogene product. And again, the regulatory authorities have reviewed our full in the Phase I package including detailed look at the safety profile. So I don't see that there will be -- we don't foresee any changes, based on what we've seen with Allogene.

Got it. Very clear. And then, maybe regarding the cash runway and cash position. Could you indicate whether that incorporates the entire completion of the pivotal study for lasme-cel?

Yes. Great question. So the cash runway into H2 2027 does include pivotal studies. Actually, we've made assumptions both for lasme-cel and for eti-cel. So all the costs are fully loaded in that front. We've also been very prudent, as we've always done on cash in from milestones and non-dilutive funding. So this one have been probabilized, so there is potential for upside there if they do materialize. And we will provide the full detailed time lines of the Phase II at the R&D Day. But to answer your question, yes, the runway does include the pivotal studies.

Great. And then maybe a last one, it's on the data set for eti-cel by year-end. Can you just give some color on the size of that data set? Will it be similar in patient size? I understand that there will not be enough follow-up, but in terms of patient size, will be similar to the lasme-cel disclosure back in October.

Yes, I'll take that, Arthur. So obviously, lasme-cel is a much more -- it's early candidate with much more patients within the Phase I program than eti-cel. So you will be anticipating smaller patient numbers. And again, we will -- you'll see based on our submissions to ASH, you'll see much more of that data then.

Our next question will come from Salveen Richter with Goldman Sachs.

This is Mark on for Salveen. I have, I guess, a follow-up on eti-cel. There's been a lot of news from autologous dual-targeting CAR-Ts recently. And -- what are your thoughts? How do you view that data? Is there any read-through to eti-cel? And sort of beyond the allogeneic autologous, sort of, difference? How do you think eti-cel is differentiated in the dual targeting space?

Yes, it's a great question. We believe we've got a very well differentiated product with eti-cel. We believe our positioning is very clear. It's a later line diffuse large B-cell lymphoma, most likely, certainly within the non-Hodgkin lymphoma space. We think our -- and again, when you see what's presented at ASH, it will be assuming it's accepted. You'll see a clear strategy, which I think differentiates the product significantly from the current batch of autologous products. So I can't really say much more until we -- you see what we will be hopefully presenting at ASH.

If I can add -- and thanks, Mark, for the great question. I think the -- I'm sorry, I'm going to state the obvious, but the big important piece about eti-cel is, it does not target 19. A lot of the dual targeting data we've seen is like 19, 20, 19, 22. So I think it's great, but it's yet again hitting 19. So the primary competitors to 19, 20 or 19, 22 are going to be the approved autologous 19 and potentially some of the ALLO-19.

I think where eti-cel is pretty unique to our knowledge at this stage is that it is a 20 and 22. And so it will be particularly relevant to physicians who have hit 19 once and will then want to -- or twice. And we want to alternate the targets.

I think, the other important thing to remember is, right now, 19 is firmly entrenched in the second line. This is primarily YESCARTA and BREYANZI. If Allogene is successful with this first-line consolidation approach, to which, by the way, we have a vested interest in. There is a potential for 19 to come already up to the first-line consolidation. And then there will be a very, very strong need to hit orthogonal targets.

So coming at it with an off-the-shelf alternative that does not require an additional round of leukapheresis, harvesting of the patient, slots, et cetera. So pure off-the-shelf alternative that does not target 19, I think in our universe of NHL and LBCL is pretty differentiated and unique.

It appears we have no further questions at this time. I would now like to turn the program back over to our presenters for any additional or closing remarks.

Well, we would like to thank you all. And we definitely -- there is a very rich second half this year for Cellectis. So please stay tuned and we hope that you will be all at our R&D Day event on October 16 and probably wait to what's going to happen for Cellectis by the end of the year. So a lot of like rich event things that will come up. Thank you very much for your attention, and have a good day.

Thank you, ladies and gentlemen. This concludes today's event. You may now disconnect.