Cellectis - Earnings Call - Q4 2024

Transcript

Operator (participant)

Good day, everyone, and welcome to today's Cellectis FY 2024 earnings conference call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question-and-answer session. You may register to ask a question anytime by pressing the star, then the 1 key on your telephone keypad. You may withdraw yourself from the queue by pressing the star 2 key. Please note, today's conference is being recorded. I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Arthur Stril. Please go ahead.

Arthur Stril (CFO and Chief Business Officer)

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. André 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-month period ended December 31, 2024, 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 our manufacturing, regulatory, and product development status, as well as product development status of our licensed 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, 2024, and subsequent filings Cellectis makes with the SEC from time to time. I would now like to turn the call over to André.

André Choulika (CEO)

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 our 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 allogeneic CAR-T for hematological malignancies, one program of allogeneic CAR-T for solid tumors, and the first of an in vivo gene therapy for a genetic disorder.

We are 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 are 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 EUR 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 in rare pediatric disease, as well as an orphan drug designation granted by the European Commission for the treatment of relapsed or refractory acute lymphoblastic leukemia. These designations represent a step toward developing widely available allogeneic products for patients in need. Cellectis expects to present the phase I dataset 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 on the enrollment of patients and expects to present phase I dataset and late-stage 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 Immuno-Oncology 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 push 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 proprietary 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.

Adrian Kilcoyne (CMO)

Thank you, André. As André mentioned, Cellectis continues to focus its development efforts on the BALLI-01 and NATHALI-01 studies. Recruitment in BALLI-01, a study evaluating UCART22 in relapsed 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 autologous CAR-T. We plan to share the full phase I dose escalation dataset 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 EMA to align on our phase II 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 our pivotal phase II study.

We expect the phase II 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, UCART20x22, in relapsed refractory non-Hodgkin 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 André mentioned previously, we will endeavor to share data for the phase I program in late 2025 at the ASH Annual Conference. Pending data assessment, we plan 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 fourth quarter and full year of 2024. Arthur, please go ahead.

Arthur Stril (CFO and Chief Business Officer)

Thank you, Adrian. We are excited about our partnership and financing activities, 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 such 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 EUR 15 million and the third and final tranche of EUR 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 European Investment Bank pursuant to the disbursement of the second and third tranches under the finance contract with the European Investment Bank, $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 payment 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 our 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 I datasets for our wholly owned clinical product candidates in acute lymphoblastic leukemia and non-Hodgkin lymphoma later this year. I would like to turn the call over to André for closing remarks.

André Choulika (CEO)

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 questions you may have. With that, I would like to open the call for Q&A.

Operator (participant)

Thank you. As a reminder, ladies and gentlemen, if you would like to ask a question, please press the star one on your telephone keypads. You may withdraw yourself from the queue by pressing star two. Once again, that is star one for a question. We'll take our first question from Gena Wang with Barclays. Please go ahead.

Gena Wang (Managing Director and Senior Research Analyst)

Thank you. Maybe this will be the last earnings call. With that, I wanted to ask the upcoming data for the UCART22. You said you will have data in 3Q. Maybe could you give us a little bit more color in terms of the amount of data, including patient numbers, the type of data point you'll be sharing with us in 3Q, and in what kind of form you will share with us?

Arthur Stril (CFO and Chief Business Officer)

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

Adrian Kilcoyne (CMO)

Oh, thank you, Gena. Yes. As we have said over the last few minutes, we would plan to have the full phase I dose escalation dataset available in the third quarter. Again, a full dataset. How we are planning on sharing that, Arthur can update you on. That is not to say we also will not have additional data being shared at ASH. As you are aware, the cutoff for ASH is in August. We will be submitting data for ASH, but we will have a full phase I dose escalation dataset available in Q3. Arthur, you probably want to add some.

Arthur Stril (CFO and Chief Business Officer)

Yeah. As for the specific event, I think we're likely that we'll give you a bit more update as the quarter moves on. We're definitely targeting something that would be an ad hoc event and follow-up at medical conferences, including ASH this year. The data release is likely going to be at an ad hoc event. Stay tuned. We'll give more details very shortly.

Gena Wang (Managing Director and Senior Research Analyst)

Thank you.

Operator (participant)

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

Jack Allen (Analyst)

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. Yeah, maybe I'll start there. And then I do have a few follow-ups if I could.

Adrian Kilcoyne (CMO)

Yeah, 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. We're looking at very heavily pretreated patients, many of whom have been exposed, as we said in the earnings call earlier, exposed to CD19 therapy, including an autologous CAR-T. With that in mind, we're very encouraged by the data we're seeing thus far. The broad question, while we can't share any data with you, do we have concerns over the quality of the data that it would be able to surpass regulatory requirements? We believe so. We will have ongoing interactions with FDA and EMA in the coming months. Once you see the data, you'll obviously see much more granularity to that.

Jack Allen (Analyst)

Great. Great. 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 get into the clinic, and how to think about these programs as it relates to the novelness of the targets? Are these completely novel programs, or 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, is there any updates around the Servier discussions that you're having with your partner there, or I guess I should say maybe former partner there as well?

Arthur Stril (CFO and Chief Business Officer)

Thanks, Jack. I'll take the question. I mean, obviously, we share the excitement around the progress of the AstraZeneca partnership. I think what's interesting is that there's been a lot of very, very active discussion and workstream between the R&D teams of both companies over the last few months. 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 in vivo gene therapy. There's really a breadth. The targets and the selection of the targets have been the follow-up of numerous discussions with AstraZeneca. 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.

We want to be in a position where we present a comprehensive dataset both from in vitro, in vivo proof of concept, line of sight to IND. This is something that we could potentially disclose this year. Stay tuned. We are very happy about the progress. On the Servier arbitration story, as it is still an ongoing matter, I am not going to be in a position to comment.

Jack Allen (Analyst)

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

Adrian Kilcoyne (CMO)

Thanks, Jack.

Operator (participant)

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.

Adrian Kilcoyne (CMO)

We are currently planning our interactions with both FDA and EMA. Of course, we cannot prejudge exactly how these conversations will go. 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. Over the next few months, we'll endeavor to get alignment with the regulatory authorities regarding that. You will see again in Q3 when we share the data. I think, again, that added granularity will be helpful to you.

Operator (participant)

Thank you. Next, we'll go to Sebastiaan van der Schoot with JMP. Please go ahead.

Hi, team. Good morning. Thanks for taking my questions. Wondering regarding the late-stage development. Can you maybe comment a little bit on whether you expect that these registration trials will be similar to what we've seen for autologous CAR-T? Could you also remind us for the partnership details with the Allogene on the same cell? Thank you.

Adrian Kilcoyne (CMO)

Sorry, your line cut a little bit. Can you repeat the first part of the question?

The first part is regarding whether a potential registration trial in phase II would be similar to what we have seen from autologous CAR-T in adult ALL for UCART22?

I think as an allogeneic therapy, we've always said our trials reflect the unique nature of allogeneic cell therapy. I think we also need to look at the previous autologous CAR-Ts in this space. We're much earlier line therapy, so there are some subtle differences. Nonetheless, as these are what would be all-cell therapies, we would expect a similar approach in terms from a regulatory perspective. Again, harnessing the unique characteristics of allogeneic cell therapy. As I've said to previous questions, once you see the data in Q3, and I would encourage you to come along to our event, I think that will become very clear.

I can take the question on Allogene. I mean, we're very pleased about the progress of Allogene and the assets that we've licensed. Cema-cel, which is licensed to Servier and sublicensed 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 selecting lymphodepletion mid this year, having an interim analysis in the first half of 2026, and a potential BLA submission in 2027 per their guidance. 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.

I think the progress of 316 also in renal cell carcinoma is very interesting. This is really the first allogeneic CAR-T that is making strides in solid tumors, and in particular in renal cell. We are also very excited for Allogene to be sharing updates on this hopefully.

Okay. Great. Thank you, guys.

Operator (participant)

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

Yeah, good morning. Congrats on the update. Thanks for taking my question. Maybe just coming back on the Allogene 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 towards the end when we get the interim EFS analysis then have a follow-up?

Adrian Kilcoyne (CMO)

Yes. Thanks, Sylvain. 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 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, and sales lifecycle of the products. I think that would be the first guidance. 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. 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. Maybe if you could just break down your R&D spend and remind us of the terms with your AstraZeneca collaboration. Does AstraZeneca reimburse you for all of the expenses you incur with those three programs, or just a portion of it, and how much is that of your total R&D spend? Thank you.

Yeah, it's a great question, Sylvain. Basically, the way the AstraZeneca collaboration is structured is the research activities we're doing with AstraZeneca are fully reimbursed by AstraZeneca. 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 costs. That has allowed us to partially offset our cash burn back in 2024. In total, we had cash burn excluding cash in from partnership of a little bit over $100 million. The net cash burn has been $60 million. I would say it was roughly a 40/60 split. Obviously, this is what happened for 2024. It is not necessarily a guidance for the later years. As mentioned, again, we've been very conservative in cash in when we think about the mid-2027 runway.

We have included expenses for potentially registrational trials for both '22 and '20x22. I hope it helps.

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

Thanks, Sylvain.

Operator (participant)

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

Jack Allen (Analyst)

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. I guess to what I've sent, are you willing to kind of comment on the potential outcomes here? What are you seeking from this arbitration, and how could that play out if you are able to acquire a positive outcome from your perspective?

Adrian Kilcoyne (CMO)

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

Jack Allen (Analyst)

Yeah. No worries. I have a backup question. I wanted to ask about the recent discontinuation of Cargo's CD22 targeted asset in post-CAR-T NHL. That is an autologous program. I was wondering what, if any, read-throughs you see as it relates to your UCART20x22 program, which is an allogeneic product.

Arthur Stril (CFO and Chief Business Officer)

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. What has been interesting is that Cargo really proved that there's a clear unmet need and market for a 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. Patients do relapse or can be refractory to CD19. There's a clear unmet need and desire from physicians to be hitting other targets like 20 or 22.

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 does not go through is really opening up an avenue for a non-19 CAR-T asset, which we really want to be occupying with 20x22. I will leave it to Adrian to give a bit more color on the medical front.

Adrian Kilcoyne (CMO)

Yeah, it's a great question, Jack. When we look at this decision, again, it is unfortunate for Cargo. We do believe that CD22 is an important target in this space. If we look at the rationale why, one is they had reasonably good CR rates. This is based on their data. This is my interpretation of it. Good response rates early by three months, I think it was an 18% CR rate. They were struggling with durability. Equally importantly, when you look at the tolerability profile with the ICANS, that was at about 18% greater than grade 3. Clearly, that risk-benefit was not adding up. We look at everything in terms of risk-benefit. It was great that we saw that they had efficacy from the target. Yes, the durability was not what they probably expected. Also, they had a toxicity profile.

Now, we do not believe that this toxicity is uniquely related to the CD22 target. That is certainly something that we have not been seeing, those kind of rates of ICANS, in our programs. Overall, yes, it is disappointing for Cargo. I do think it is making us double down, really, because the commercial opportunity is now greater for us. I do believe with our strategy, we want to improve on that level of durability, certainly. I think, yeah, hopefully, I have answered your question, Jack.

Jack Allen (Analyst)

Yeah, 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 that's been a key question for the field, how allo compares to auto on durability. With that context in mind, I was just hoping you could provide any comments you're willing to make on the recent data updates from the ALLO-501A cema-cel program from Allogene. It seems like they had some really strong durability responses out to four years plus.

Arthur Stril (CFO and Chief Business Officer)

Yeah, absolutely, Jack. I think this is very encouraging. Thanks for flagging it. I mean, in addition to the progress and the roadmap they've laid out for ALPHA3 and the pivotal trial and the potential registrational indication, I think the dataset that was published by Allogene back in February on the ALPHA2 trial are very interesting for two reasons. I think the first interesting takeaway is indeed the long-term durability. I think, as you all know, this was the final question that allogeneic CAR-T had to address is, can you get durability levels that are on par with autologous? I think the long-term dataset 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 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. They've seen a very interesting outcome for these subset of patients. I think all in all, it's definitely removing an overhang around durability of the assets, which I think is super interesting. It's also paving the way for increased confidence into the outcome of the ALPHA3 trial. Thanks for flagging. I think it was a really, really interesting and promising dataset.

Jack Allen (Analyst)

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

Adrian Kilcoyne (CMO)

Thanks, Jack.

Operator (participant)

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

Hi. Thanks for taking my question. This is Hanfei Fu for Kelly. Just a quick follow-up on your enrollment on the two programs, UCART22 and UCART20x22. What is the enrollment progress there? Will we expect any recommended phase two dose at your update? How many patients will we look into? Thanks.

Arthur Stril (CFO and Chief Business Officer)

Yeah, thanks for the question. As you have probably understood by this time, we are for '22, because we're planning our end-of-phase one meeting, clearly, this is at the end of phase one. We had planned up to 40 patients within that cohort. We have hit what we needed to in relation to that. 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 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 II program in reasonably quick time with the numbers we anticipate we will need.

Thank you.

Operator (participant)

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

Adrian Kilcoyne (CMO)

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

André Choulika (CEO)

Thank you very much, Adrian, for handing this back to me. Thank you very much for everyone for participating in this conference. We're extremely excited by the 2025 outcome and further for the company. We definitely look forward to the next update of the company and give you some guidance for the third quarter this year. With that, I'd like to wish you all a great day.

Operator (participant)

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