Good day, everyone, and welcome to today's Cellectis Full Year 2024 Earnings Conference Call. At this time, all participants are in a listen-only mode. [Operator Instructions] Please note, today's conference is being recorded. [Operator Instructions] It is now my pleasure to turn the conference over to Arthur Stril. Please go ahead..

Good morning, and welcome, everyone, to Cellectis fourth quarter and full year 2024 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 12-months period ended December 31, 2024, and a business updates. 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 our manufacturing, regulatory and product development status as well as product development status of our 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 license 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. Thank you, Arthur. Good morning, and thank you, everyone, for joining us today. 2024 has been an important year for Cellectis. On the business development front, we were excited to announce the start of research and development activities for three programs developed under our collaboration and research agreement with AstraZeneca.

So far, we announced the start of one program of an allogeneic CAR T for hematological malignancies, one program of an allogeneic CAR T for solid tumors, and the first of an in vivo gene therapy for a genetic disorder.

We're thrilled to grow the strategic collaboration with AstraZeneca, a top leader of the pharmaceutical industry aimed at shaping the future of our next generation of cell and gene therapies. We're very excited about the huge opportunities this partnership will bring in the months ahead.

Additionally, this year AstraZeneca completed the additional equity investment of $140 million in Cellectis. As part of the additional investment, AstraZeneca subscribed for 10 million Class A convertible preferred shares and 18 million Class B convertible preferred shares in each case at a price of $5 per convertible preferred share.

Giving effect to the conversion of Class A and Class B preferred shares and immediately after the closing of the subsequent investment, AstraZeneca would own approximately 44% of the share capital of Cellectis and approximately 30% of the voting rights.

We also drew down the two last tranches of the finance agreement signed in December 2022 with the European Investment Bank for up to €40 million credit facility. We're now confident that our cash runway allows us to fund operations into mid-2027. On the clinical side, we're thrilled to have Dr.

Adrian Kilcoyne join us as Cellectis Chief Medical Officer. Adrian is a huge leader and a strategic forward thinking drug developer who's passionate about delivering life-saving therapies to patients. He joined us at a pivotal time as we're progressing in our core clinical programs.

2024 was an exciting year with a grant by the FDA to our product candidate UCART22 of an Orphan Drug Designation and Rare Pediatric Disease, as well as an Orphan Drug Designation granted by the European Commission for the treatment of relapse or refractory acute lymphoblastic leukemia.

These designations represent a step toward developing widely available allogeneic product for patients in need. Cellectis expect to present the Phase 1 data set and late stage development strategy for UCART22 in the third quarter of this year.

In the NATHALI-01 study evaluating UCART20x22 in relapsed or refractory non-Hodgkin lymphoma, Cellectis continues to focus under enrollment of patients and expect to present Phase 1 data set and late state development strategy in late 2025.

In 2024, Cellectis innovation team showcased promising CAR T strategies utilizing TALEN gene editing technology to target solid tumors and overcome their immunosuppressive tumor microenvironment.

Preclinical data were presented at both AACR Immunology and SITC Annual Meetings, and two scientific articles were published in Molecular Therapy and Science Advances.

We're proud to collaborate with leading scientists in the gene editing field who continuously pushes the boundary of innovation and are committed to cancer patients with unmet medical needs.

This year, Cellectis will continue to focus its efforts and expenses on advancing its core clinical trial, BALLI-01 and NATHALI-01 while building the next generation of genomic medicines to address areas of high unmet medical needs within our partnership with AstraZeneca and within our preparatory preclinical pipeline.

With that, I would like to turn the call over to Dr. Adrian Kilcoyne, our Chief Medical Officer, who will give you 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 in BALLI-01, a study evaluating UCART22 and relapsed or refractory B-cell acute lymphoblastic leukemia has progressed well.

The study is addressing an important unmet need for patients who have relapsed following previous lines of therapy, including a CD19 bispecific or autologous CAR T. We plan to share the full Phase 1 dose escalation data set in the third quarter of 2025 with additional data presentation planned at the ASH Annual Conference in the fourth quarter.

Regulatory interactions are planned with both FDA and DMA to align on our Phase 2 registration strategy. We are currently planning additional study sites in both the United States and Europe, including the United Kingdom, in anticipation of an agreed registration path for a pivotal Phase 2 study.

We expect the Phase 2 study to be open for recruitment in the fourth quarter of 2025. We also continue to enroll in the NATHALI-01 study of our dual Car T asset UCART22in relapsed or refractory non-Hodgkin's lymphoma.

This study is addressing an important unmet need for patients who have relapsed following previous lines of therapy, including when available, an autologous CD19 Car T. As Andre mentioned previously, we will endeavor to share data for the Phase 1 program in late 2025 at the ASH Annual Conference.

Pending data assessment, we plan to transition to Phase 2 preparation in 2026. With that, I would like to hand the call over to Arthur Stril, Cellectis's Chief Financial Officer and Chief Business Officer for an overview of our financials for the fourth quarter and full year 2024. Arthur, please go ahead..

Thank you, Adrian. We are excited about our partnership and financing activity which have been positively impacting our financial position. First, we completed the additional equity investment of $140 million of AstraZeneca in Cellectis.

Giving effect to the conversion of all their preferred shares, AstraZeneca would own approximately 44% of our ordinary shares and may exercise voting power with respect to approximately 30% of the voting rights outstanding with respect to our share capital. We are proud of counting AstraZeneca as a strategic shareholder.

Second, thanks to the progress of our collaboration with AstraZeneca. Up to year-end 2024, $47 million have been paid to Cellectis under the joint research and collaboration agreement of which $25 million upfront and $22 million reached development milestones in addition to reimbursement of research costs incurred.

Third, last year we drew down the second tranche of €15 million and the third and final tranche of €5 million under the credit facility agreement entered with the European Investment Bank, EIB in 2022.

Following such activities our cash, cash equivalents, restricted cash and fixed term deposits classified as current financial assets as of December 31, 2024, amount to $264 million compared to $156 million as of December 31, 2023.

This $108 million increase is mainly due to $140 million cash received from AstraZeneca as part of the second tranche of its equity investment in Cellectis, $20 million cash received from the EIB pursuant to the disbursement of the second and third tranches under the finance contract with EIB, $43 million of cash in from our revenue, partially offset by cash payments from Cellectis to suppliers of $47 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 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, 2024. We believe that our cash, cash equivalents and fixed term deposits as of December 31, 2024 will be sufficient to fund our operations into mid-2027.

In 2024 we were able to extend our cash runway through financing activities, the progress of our partnerships, as well as prudent cash management for R&D pipeline and controlled SG&A expenses.

We're focusing our, spend on developing UCART22 and UCART20x22 potential new product candidates, and operating our end-to-end cell and gene therapy manufacturing facilities in Paris and Raleigh. While research costs under the AstraZeneca collaboration are funded by AstraZeneca.

We're very much looking forward to providing Phase 1 data sets for our wholly-owned clinical product candidates in acute lymphoblastic leukemia and non-Hodgkin lymphoma 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 that we are 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 at the forefront of this promising medical and scientific field.

As previously said, Cellectis will hold calls only when there is significant information to discuss, or if there is a key update on a business activity. We invite you to refer to our press releases for quarterly earnings, and remain available to address any question you may have. With that I would like to open the call for Q&A..

Thank you. [Operator Instructions] We'll take our first question from Gena Wang with Barclays. Please go ahead..

Thank you. Maybe this will be the last earnings call. With that I wanted to ask the upcoming data for the UCART22, you said that you will have a data in 3Q.

Maybe could you give us a little bit more color in terms of amount of data including patient number, the type of data point you will be sharing with us in 3Q, and in what kind of forum you will share with us?.

Hi Gena, thank you so much for the great question. I'll hand it over to Adrian..

Thank you, Gena. Yes, so as we have said over the last few minutes, we would plan to have the full Phase 1 dose escalation data set available in the third quarter. So again a full data set, how we're planning on - sharing that Arthur can update you on. That's not to say, we also won't have additional data being shared at ASH.

And as you're aware, the cut-off for ASH is in August, so we'll be submitting data for ASH, but we will have a full Phase 1 dose escalation data set available in Q3. Arthur, you probably want to add some..

Yes. As for the specific event, I think we're likely that we'll give you a bit more update as the quarter moves on. But we're definitely targeting something that would be an ad hoc event [technical difficulty] follow-up at medical conferences including ASH this year. But the data released is likely going to be at an ad hoc event. So stay tuned.

We'll give more details very shortly..

Thank you..

And our next question comes from Jack Allen with Baird. Please go ahead..

Great. Thanks so much for taking the questions, and congratulations on the progress. I guess maybe dovetailing on the question about UCART22. I'd love to hear any thoughts the team has, as it relates to how they're shaping up the internal bar for success, as we move towards that third quarter readout.

Yes, maybe I'll start there, and then I do have a few follow-ups, if I could?.

Yes, it's a great question, Jack. Thanks for it. We're confident in the data we have seen thus far. We have to put this in the context, of what patient groups we're looking at here.

And we're looking at very heavily pretreated patients, many of whom have been exposed, as we said in the earning call earlier, exposed to CD19 therapy, including an autologous CAR T. With that in mind though, we're very encouraged by the data we're seeing thus far.

So the broad question, while we can't share any data for this yet, do we have concerns over the quality of the data, that it would be able to surpass a regulatory requirements? We believe so, but we are. We will have ongoing interactions with FDA and EMA in the coming months, and then once you see the data we'll be able to.

You'll obviously - see much more granularity to that..

Great, great. And then just two quick follow-ups more on the collaboration side of things. It sounds like the AstraZeneca programs are moving forward quite quickly. Any additional context around near term milestones you might expect there, or when those programs can enter the clinic.

And then, how to think about these programs, as it relates to the novelness of the targets, or these probably novels programs. Are they potentially me too kind of auto programs where auto has already shown proof-of-concept.

I know that's a multi-part question, but one other one that I just wanted to throw in there too, was if there are any updates around the Servier discussions that you're having with your partner there, or I guess I should say maybe formal partner there as well?.

Thanks, Jack. I'll take the question. So I mean, we're obviously we share the excitement around the progress of the 0neca partnership.

I think what's interesting, is that there's been a lot of very, very active discussion and work stream between the R&D teams of both companies, over the last few months and we've really cast a pretty wide net, in terms of therapeutic areas and indication.

As you can see, we're not only in heme, which was our initial playground, but we're in solid tumors as well as in vivo gene therapy. So there's really a breadth and the targets and the selection of the targets have been the follow-up of numerous discussions with AstraZeneca.

So we believe that each target under these programs has been very carefully selected, and will be pretty exciting. We're keeping this under wraps for now. Progress is very good, but we want to be in a position where we present a comprehensive data set, both from in vitro, in vivo, proof-of-concept, line of sight to IND.

And this is something that we could potentially disclose this year, so stay tuned. But we're very happy about the progress. And on the Servier arbitration story, as it is still an ongoing matter, I'm not going to be in a position to comment..

Great. Thank you so much for taking all the questions. Maybe I'll hop back in the queue, but congratulations again on the progress..

Thanks, Jack..

Thank you. We'll next go to Salveen Richter with Goldman Sachs. Please go ahead..

Hi, this is [Lydia] on for Salveen. Thanks so much for taking our question, and congrats on the progress. Just another on UCART22. Could you just discuss the different potential late stage development strategies, and how the data might inform this decision? Thanks so much..

So again, we are currently planning our interactions with both FDA and EMA. And of course, we cannot prejudge exactly how these conversations will go. So without us publicly sharing our data, I think it's very difficult for me to come further. However, we do believe as we see our data, we believe there's a registration path.

We believe that's a clear registration path. We're just, over the next few months, will endeavor to get alignment with the regulatory authorities regarding that. So, you will see again in Q3, when we share the data. I think again that added granularity will be helpful to you..

Thank you. And next we'll go to Sebastiaan van der Schoot with Kempen. Please go ahead..

Hi, team, good morning and thank you for taking my questions.

Wondering regarding the late safety program, can you maybe comment a little bit on where you expect these registration trials will be similar to what we've seen from autologous CD19 CAR T, and could you also remind us for the partnership details with the allogeneic on the cema-cel? Thank you..

Sorry, your line cut a little bit.

Can you repeat the first part of the question?.

The first part is regarding whether a potential registrational trial in Phase 2 will be similar to what we have seen from autologous CAR T in adult ALL for UCART20x22..

I think as an allogeneic therapy, we've always said we - our trials reflect the unique nature of allogeneic cell therapy. So I think - but also we need to look at the previous autologous CAR Ts in this space, we're much earlier line therapy. So there is some subtle differences.

But nonetheless, as these are what would be ALL cell therapies, we would expect a similar approach in terms, from a regulatory perspective. But again, harnessing the unique characteristics of allogeneic cell therapy. So again, as I've said, to previous questions.

Once you see the data in Q3, and I would encourage you to come on to our event, I think that will become very clear..

And I can take the question on Allogene. So I mean we're very pleased about the progress of allogeneic and the assets that we've licensed. So cema-cel which is licensed to Servier and sublicense to Allogene, and then ALLO-316 the CD70 renal cell carcinoma.

I think Allogene has laid out a very, very interesting strategy in terms of leapfrogging autologous CD19 CAR T in the second line, by going straight into first line consolidation.

They have a clear line of sight with selected lymphodepletion mid this year, having an interim analysis in the first half of 2016 and a potential BLA submission in '27 per their guidance. And I think this will be very interesting if the trial is successful.

That will be, A, a very interesting read through into our platform and then B, obviously, we're eligible to up to $410 million milestones and low double-digit royalties, on this particular asset. And I think - the progress of 316 also in renal cell carcinoma is very interesting.

This is really the first ALLO CAR T that is making strides in solid tumors and in particular, in renal cell. So we're also very excited for Allogene to be sharing update on this outlage..

Great. Thank you, guys..

We'll next go to Silvan Tuerkcan with Citizens. Please go ahead..

Yes, good morning and congrats on the update and thanks for taking my question. Maybe just coming back on the allo collaboration you just outlined here.

Do any of these near-term maybe the mid-2025 readout trigger any milestone payments? Or is that expected rather to the - towards the end when we get the interim EFS analysis? And then I have a follow-up?.

Yes. Thanks, Silvan. So we're not disclosing the specifics of the individual milestone payment I think the only guidance I can give at this stage - I can give us two guidances.

The first guidance I can give is the overall $410 million milestones for cema-cel are pretty well spread out across the development, registration sales life cycle of the products. I think that, that would be the first guidance.

And the second guidance, which I think is important for everyone is - when we say that our cash runway is mid-2027, we've pretty severely discounted any cash in we may receive from our partners, including Servier and Allogene. So this is - we've been very conservative in the way we've accounted for cash in, with the mid-2027 runway..

Great. That's very helpful. Thanks. And maybe if you could just breakdown your R&D spend and remind us of the terms with your AstraZeneca collaboration. As for AstraZeneca reimburse you for all of the expenses you incur with those three programs or just a portion of it? And how much is set of your total R&D spend? Thank you..

Yes, it's a great question, Silvan. So basically, the way the AstraZeneca collaboration is structured is the research activities we're doing with AstraZeneca, or fully reimbursed by AstraZeneca.

And so, when I gave the breakdown of the cash coming from our revenue, this is a mixture of, obviously, milestones we've received, but also reimbursement of R&D cost. And that has allowed us to partially offset our cash burn back in 2024. So in total, we had a cash burn, excluding cash in from partnership of a little bit over $100 million.

But the net cash burn has been $60 million. So I would say it was roughly a 40-60 split. Obviously, this is what happened for 2024. It is not necessarily your guidance, for the later years. But I've mentioned again, we've been very conservative in cash in - when we think about the mid-2027 runway.

And we've included expenses for potentially registrational trials for both 22 and 20x22. I hope it helps..

Yes, great. Thank you. Looking forward to the update in the third quarter. Thanks..

Thanks, Silvan..

And next, we'll go back to Jack Allen with Baird..

Great. Thank you again for taking all the questions. Just a few more, if I may. I know you mentioned that you're not going to comment on the Servier litigation.

But I guess to what extent, are you willing to kind of comment on the potential outcomes here? What are you seeing from the arbitration? And how could that play out if you are able to acquire a positive outcome from your perspective?.

Yes, Jack, it's obviously great question. But I mean, given this is an ongoing legal activity, we're not going to be commenting right now. Sorry about that..

Yes. No worries. I have a backup question. So I wanted to ask about the recent discontinuation of CARGO's CD22 targeted asset in post-CAR T NHL, that's an autologous program.

But I was wondering what, if any, read-throughs you see as it relates to UCART20x22 program, which is an allogeneic product?.

Thanks, Jack. I'll give you just some thoughts on the competitive landscape, and then I'll leave Adrian to discuss a bit more about the actual medical implications for this. I think from the competitive landscape, what was interesting in the CARGO story and obviously, it's an unfortunate setback for the field.

But what has been interesting is that CARGO really proved that there is a clear unmet need, and market for non-CD19 CAR T in that space. I mean, obviously, CD19 has made strides - they're now firmly entrenched in the second line. Allogene is trying to get them to the first line in the allogeneic version.

But patients do relapse, or can be refractory to CD19, and there's a clear unmet need and desire from physicians, to hitting other targets like 20 or 22. So I think what CARGO proved, is that this is a clear market and a fantastic opportunity.

Now again, from a pure competitive perspective, the fact that the trial doesn't go through, is really opening up an avenue for a non-19 CAR T assets, which we really want to be occupying with 20x22. And then, I'll leave it to Adrian to give a bit more color on the medical front..

Yes, it's a great question, Jack. So when we look at this decision, again, it is unfortunate for CARGO. We do believe that CD22 is an important target in this space. But if we look at the rationale why, one is they had reasonably good CR rates, and this is based on their data. So my interpretation of it.

Good response rates early by three months, I think it was at an 18% CR rate. So they were struggling with durability. But equally importantly, when you look at the tolerability profile with the IAC HS that was at about 18% greater than Grade 3. So clearly, they had - that risk benefit wasn't adding up. And we look at everything in terms of risk benefit.

So it was great that we saw that they had efficacy from the target. Yes, the durability wasn't what they probably expected. But also, they had a toxicity profile. Now we do not believe that this toxicity, is uniquely related to CD22 target. And that's certainly something that, we haven't been seeing those kind of rates of IHS in our programs.

So overall yes, it's disappointing for Cardinal. But I do think it is making us double down really, because the commercial opportunity is now greater for us. And I do believe with our strategy, we want to improve on that level of durability certainly. So I think, yes hopefully, that answered your question, Jack..

That's great context. Thank you so much for that. Now I'll just throw one more out there, as you do mention the potential to improve on durability with an allogeneic CAR T product. I know it's been a key question is for the field, how allo compares to auto and durability.

With that context in mind, I was just hoping if you can provide any comments you're willing to make, on the recent data update from the ALLO-501A Cema-Cel program from Allogene. It seems like it had some really strong durable responses out to four years plus..

Yes, absolutely, Jack. I think this is very encouraging. And thanks for flagging it. I mean, in addition to the progress and the roadmap they've laid out for ALPHA3 in the pivotal trial and the potential registrational indication.

I think the data set that was published by Allogene back in February on the ALPHA, ALPHA2 trial are very interesting for two reasons. I think the first interesting takeaway is indeed the long-term durability.

And I think as you all know, there was - this was the final question that allogeneic CAR T had to address is can you get durability levels that are on par with autologous.

And I think long-term data set is from Allogene, which, again, is coming from our own platform is really giving a very interesting showcase that this is real, and that you can get to these very durable responses with an allogeneic CAR T.

I think the other interesting analysis that came from Allogene, is really the fact that this is - they've looked at patients with a lower burden of disease, which are likely patients that will come into the ALPHA3 trial, because this is a first-line consolidation story for MRD-positive patients.

And they've seen a very interesting outcome for the subset of patients. So I think all in all, it's definitely removing an overhang around durability of the assets, which I think is super interesting. But it's also paving the way for increased confidence into the outcome of the ALPHA3 trial.

So thanks for flagging, and I think it was a really, really interesting and promising data sets..

Awesome. Great. Well, I always appreciate you guys transparency, and taking all the questions. Thanks so much..

Thanks, Jack..

We'll next go to Kelly Shi with Jefferies. Please go ahead..

Hi, thanks for taking my question. This is Hangfei Fu for Kelly. Just a quick follow-up on your enrollment on the two program, your UCART22 and UCART20x22, what is the enrollment progress there? And will we expect any recommended Phase 2 dose at your update? And how many patients we're looking to? Thanks..

Yes. Thanks for the question. Well, as you have probably understood by this at this time that we are at for 22, because we're planning our end of Phase 1 meeting. Clearly, this is at the end of Phase 1. We had planned up to 40 patients within that cohort, and we have hit what we needed to in relation to that.

So hopefully, that will give you an idea in terms of the number of patients, you're likely to see at our Q3 update. In terms of the patient numbers for the clinical trials, I don't want to be to explain too much, because those numbers are completely dependent, on an agreed registration path with the regulatory authorities.

However, we do believe we have a plan for what I would consider to be a realistic number of patients, given that this is a smaller indication, we do believe that we can execute a Phase 2 program reasonably quick time with the numbers we anticipate we will need..

Thank you..

Thank you. And I'd like to now turn the call back over to Adrian Kilcoyne for any additional or closing remarks..

I think, we're going to hand that over to Andre Choulika..

Well, thank you very much, Adrian, for handing this back to me. And thank you very much for everyone for participating to this conference. We're extremely excited by the 2025, outcome and further for the company. And we definitely look forward for the next update of the company, and give you some guidance for third quarter this year.

With that, I would like to wish you all a great day..

Thank you. And ladies and gentlemen, that does conclude today's conference. We appreciate your participation. You may disconnect at any time..