Cellectis S.A. (ALCLS) Earnings Call Transcript & Summary

Thank you, everyone, for attending Barclays' first Gene Editing & Gene Therapy Summit. My name is Gena Wang. I'm SMID cap biotech analyst at Barclays. Before I start, I wanted to thank our health care corporate access team and event team to make this event possible. I also want to thank my wonderful team members, Sheldon Fan, [ Tong Liu ] and [ Hashida Apolocheti ] who burned the midnight oil to make this summit happen. Gene therapy and gene editing are still -- is the emerging field among all the therapeutics. And we have seen -- overseeing evolving dynamics from initial skepticism to enthusiasm and now more mature process from the regulator following the initial learning phase. We will discuss some of the topics in our panel discussion today. In 2021, we saw some progress regarding clinical data and a regulatory update. We finalized our clinical hold removal for spinal muscular atrophy of Zolgensma intrathecal program. We also saw initial impressive data from in vivo genetic approach. We continue to believe significant advances in clinical development, and the body of data could lead to numerous potential approvals of novel therapies in the next decade that would be disruptive to the current treatment paradigm. We continue to see substantial opportunities for investment in this space and a strategic selection of the key players could provide long-term value appreciation. With that, it is my great pleasure to introduce today's first presenting company, Cellectis. With us, we have Chairman and CEO, Andre Choulika. We have our CFO, Eric Dutang. We also have David Sourdive with us today. With that, I hand over to you, Andre.

Thank you very much, Gena, for this very nice introduction. I would like also to join my praise to all the Barclays team for organizing this conference and inviting us. We're extremely excited to be in the cell and gene therapy space. Since inception of the company, Cellectis has been always a gene-editing company forever. And the concept of the company has always been to bring what people expect as being the best in the way to play with tool that can improve the stage of people and modify cells and genes in order to have like a meaningful change in people. Cellectis has been making a tremendous amount of progress and being at the origin of the clinical trials for allogeneic therapies for CAR T-cells. And our first product, our UCART19 and ALLO-501 or UCARTBCMA or ALLO-715 are CAR T that are making it quite quickly and the data that have been presented by our partner, Servier and Allogene, makes definitely the difference. Notwithstanding the fact that Cellectis has a very important pipeline of product led by UCART22, which we're going among -- which we're going to present some data at this. We're going to present some...

Sorry. Andre, I don't know if you have a slide to share, you can share your screen with the investors so they can see the slide, if you have a slide to share.

Additionally, I thought it was a fireside chat so they have not prepared a slide show. But our slide show is available.

Yes. I can share the slide show.

Eric can share the slide show. So like again, very quickly speak about our product pipeline. Maybe if you can put the product pipeline slide online.

Yes. Yes, I'll do.

So currently, you see the UCART22 BALLI-01 is in dose escalation. We're going to share some data on the -- at next ASH conference. But it's followed also by 2 very interesting allogenic CAR T, which is like UCART123, AMELI-01, and UCARTCS1 and MELANI-01. The 3 trials are progressing well currently in the clinic, and we're enrolling patients on a regular basis. We're very excited by the outcome of these 3 CAR-Ts. And we believe strongly, they're going to change the space of acute lymphoblastic leukemia, acute myeloid leukemia and multiple myeloma. We're also going to share some data of our mesothelin CAR-T in the ISCT conference, but there are a series of other solid tumor CAR-T. Mesothelin is going to be the first solid tumor CAR-T to go for mesothelioma and other type of solid tumors. [indiscernible] is a broad spectrum of solid tumors that we're pushing forward in clinic, and also UCARTMUC1 in triple-negative breast cancer. Last but not least to speak about because it's the next CAR-T to file an IND will be UCART20x22 in B-cell malignancy, the Hodgkin's lymphoma, which we believe is a very exciting CAR-T following UCART22. Building on the success of UCART22, we'd like to develop this CAR in a lot of different type of B-cell malignancies. We believe that having a dual CAR-T, having multiple contact points on the cell make these CAR-T way more powerful than any type of CAR-T. Maybe I would like to jump, Eric, if you can, on the manufacturing slide, if it's possible. And then maybe we can go for the Q&A with Gena. So here, the manufacturing -- so Cellectis is extremely proud. And when we're talking about the excitement around the gene therapy and -- cell and gene therapy space, it's essentially about the manufacturing. Why is it essential about manufacturing? Because the determination of the product, the way you can qualify a product is qualified among the process that has been developed and also the way you're going to manufacture the CAR-T. Our understanding of this space and playing with -- since 2012, with a series of different type of CMOs, it's utmost importance for cell and gene therapy company to master the manufacturing. And Cellectis has been investing since 2018, tremendous amount of energy and intelligence in building 2 GMP plant to manufacture our own CAR-T but also our cell and gene therapy space. 14,000 square feet -- square foot facility based in Paris, manufacturing buffers, messenger RNA, plasmids, vectors, all with QC labs, warehouses and cryogenic storage. These raw materials, but also products to make also our gene therapy platform here are shifted to our Raleigh facility, where we have 82,000 square foot facility for cell therapy manufacturing suite with QC lab, warehouse, cryogenic storage that is ready, not only for clinical, but also for commercial stage. We believe that UCART22, UCART20x22, mesothelin and all the CAR-T are going to be built there will be embedded in the company to be able to start launching the expansion into both trial and be able to launch with our own internalized manufacturing. And that's what makes the difference at the end in this space. And we strongly believe that this is a move that is becoming very crucial for any type of company in this space. With that, I would like to hand it to the Q&A, if like David or Eric, you'd like to share something. David?

Yes. Maybe just to...

David, by the way, is Co-Founder of Cellectis.

Yes. Hello, everyone, nice to be here and kudos to you Barclays for opening this meeting. Just to let you understand that the capabilities that we've built allow us to go very quickly from the design of a particular set of modifications we want to make into a cell into its clinical implementation. So from the concept to the bed, it can go very fast, making the appropriate gene editing tools, implementing them and making the cells. We don't rely on CMOs where we have a lot of waiting time. The lead time for a slot today in manufacturing a vector can be, 18, 24 months, can be very long. So what we have built is really a smart cell platform that is, we believe the way to go after solid tumors, because we can go very quickly, do versioning, and do the sophisticated modifications, that's the future of cell and gene therapy, it's smart cells, and that's what we're building right now.

Thank you very much, David, Andre and Eric. So yes, so I think since you mentioned the manufacturing, maybe I wanted to start with manufacturing questions. I know you did spend quite some time optimized, I think, with the FDA, the manufacturing process before. I think in the last year they spent quite some time on the manufacturing part regarding the product, the product release and the CMC part, wondering any learning or from the other people in the space that can learn from this process. And we know that your partner, Allogene, actually had a clinical hold. We don't know if -- how -- exact reason that could be, probably could be the chromosome of normality. And what caused that, and why it was not detected early on? Would that be an addressable issue that goes back to the manufacturing process? I'm just wondering if you can share with something specific the protocol, how would you do the quality control release? And what kind of testing you will conduct for the drug product? So maybe I will start with that regarding the manufacturing process.

David, do you want to take this one?

Yes. I'll take this one. Well, thank you for asking. So it's a general question about the process itself and the way we control our products as well as the starting material [ cells ] that we start from the allogeneic [ door ] cells. So we've been developing this process, and we're very confident in the way we've gradually implemented it. We're very careful in the way we process it. It's a constant dialogue we have with regulators, and we continue to be in close relationship with the regulators. Our trials are still accruing, they're ongoing. And we've gradually define all the metrics that are necessary to ensure that the product is what it's supposed to be that the genomic properties that it has are appropriate and so forth. So we're very positive on this thing. Now you're addressing a particular finding that was made by our partner Allogene. Of course, for more details, you should talk to Allogene, that goes without saying. What we see in our own trials, in our own technology -- and the way we deploy it is that, first, we are using allogeneic cells. And we must say that we're quite a bit surprised that we could have a clinical hold on something that is going to be rejected anyway by the patient. So we don't think it's an issue that relates to safety or any kind of [indiscernible] because we continue to accrue our own trials anyway. So we think it is more a CMC question, how do you control, and this is what you were asking, how do you control for these things? It still happens that chromosome 14 is a chromosome that is naturally cut in the normal course of life of T cells because that's where they recombine. So they deliberately cut the genome there, and they do recombine quite often. So the finding that is there is actually quite naturally occurring quite often. It's a well-known inversion, and you can literally find it in people, in healthy people actually. So we don't know for sure that it has anything to do with the process at this stage. We can't really say so, and there's no sign of it. So we're very confident in the process itself. We're also extremely confident in the spectacular risk-benefit ratio that it provides. I mean to this date, our technology has been infused in more than 140 patients. And the very patient you're referring to is doing very well actually. And the superb results that our partner Allogene has presented, as disclosed so far on the ALPHA trial in non-Hodgkin's lymphoma speak for themselves. So we don't think this is of any kind of issue on the safety side. We think that it's more pushing us further into understanding the natural situation and the intricacy in the genome and the way things are modified and rearranged in the normal course of cells. So that being said, we think we can always do a more -- further push on the QC, both on the end product and on the starting material. But we're very confident this is going to be resolved soon. And we would like to echo the optimism of our partner with respect to that.

So from your end, I don't know if you could share like do you have any chromosome abnormality of the translocation rate? And then has FDA request or do you plan to implement any additional safety monitoring for that particular?

So I can take that question as well. So it's a question we've discussed with the regulators. So there are DNA -- double-stranded DNA breaks that occurred when we cut with TALEN, so we expect some elements, some modifications. And those are the ones that we measure. We've never measured anything that was off target or side or anything of the kind. So -- and this has been done systematically in all our batches. It's actually part of the release criteria of our GMP UCART batches. That being said, we continue to study this. We also have functional tests that ensure that there is no competitive advantage given to a particular clone in the population of cells. So there's nothing that will outgrow the rest. There's nothing that has a privileged growth property in the mix. So we ensure the functional safety of the cell preparation that also was put on, very early on, in the first design of the products. And on top of that, we have also additional tests that we didn't disclose yet. But yes, we do have a lot of controls there that go with the normal -- well, activities when you do gene editing, you have to do that. And it's something that we're pioneer as well. We have to set the metrics because there was no precedent. So this is something we had to develop from 2015 or '14.

And the chromosomal abnormalities is something that could be, for example, a preleukemic mutation or something like this, would be definitely something to monitor in an autologous transplant because definitely a pre-cancer cell can turn cancerous at a certain moment. And it's like the patient's own cancer that can develop. As you've seen, for example, in old gene therapy trial for -- if you're combining the deficiencies 20 years ago, where certain -- some of these patients had leukemia that was induced by the integration of the retrovirus close to oncogenes that led to leukemia. But these aren't their own cells, and you can develop your own cancer, but you cannot develop the cancer of an allogeneic donor, or it would be really something that will be newly described in medicine where an allogeneic donor can provide a cancer to a receiver, which seems kind of an insanity because normally the cells should be rejected by the immune system per se at the end. And this is why it's difficult to understand how the life-saving therapies such as our allogeneic CAR-T license or cells owned can generate such type of reaction when the rest seems to be extremely moderate.

Bear in mind that the donors are completely unmatched. We never match the donors to their -- so they're truly unmatched. So that's why the cells are always rejected.

Yes. So we will see how the regulatory -- former regulatory expert will say like why FDA makes such a drastic action on this case, and then we will have a panel discussion this afternoon. So let's see how the FDA regulator will say.

Yes.

Okay. So well, thank you very much. So maybe we're diving to specifics. We have a few more minutes. I want to dive in your particular programs. You will have data presenting at the ASH, UCART22. So from the abstract, we saw that [ ex the ] regimen did help CAR-T expansion. However, the efficacy did not appear to improve significantly. Any thoughts there?

Well, we -- this is like really preliminary data from the first half of this year where we're comparing like cohorts with or without alemtuzumab. So FC with alemtuzumab or FC without alemtuzumab, and I think this is the first of its kind. Nevertheless, we believe that the -- there will be more data that will be presented in the future, showing the expansion and [ wrapping ] of potential of this product candidate. And I'm not like [ airing ] all the data. I'm not saying that it's going to be [ growth ] revolution. But the fact is that, yes, we believe like UCART22 is a product that have like strong chances of going into an expansion in pool trial, and will have a clean option to go for BLA at the end. It's only of its kind. There is no competition for allogeneic CAR-T outside the CD19 space that it's overcrowded. And UCART22 can have like a very strong impact, a lot of different lives, knowing that the CD19 target is very overcharged, and UCART22 can make a difference for all the potential relapse of [ 19 ], which represent quite a significant cohort between 1/4 and 1/3 of all the patient target like with from [ 19 ] blinatumomab to all the CD19 engager to all the CAR-T autologous as well as allogenic.

Okay. I forgot, I think that my team told me I should remind everyone who's listening, there is -- upper right corner, there is ask a question box and feel free to type in any questions you have there, and then we will try to address your questions. Andre, so the -- what additional color -- I mean the additional data should we expect at the meeting for the full presentation?

Well, we'll see what the physicians -- Gena, I'm not going to air everything that's going to happen. And like there is no secret. It's going to be only kind of more progress on this trial that's like -- giving peak at -- upstream is like breaking the surprise. Plus, I personally don't know exactly...

So it's more like a -- what kind of like should we see more patient data, longer follow-up data? Like more of the big picture, not like the actual data, more like what kind of data package.

Gena, so between the abstract and the presentation, more patients will be approved, that's essentially the case. You'll see more data on the alemtuzumab cohort and the comparison with the previous data on the non-alemtuzumab cohort. We are still in dose escalation. So those will be -- still the -- these very first steps that we're through. And we'll see interesting, I think, elements that we are not at liberty to disclose today, but that speaks to this alemtuzumab addition, which we think is quite positive to what we're doing across all our approaches right now.

Okay. Okay, good. And also last question regarding the redosing. So I think you see also the interest in redosing. And we did see like a few other programs that include Allogene or CRISPRs program, they're all thinking about redosing the, call it, consolidation regimen, and some with repeated conditioning regimens, some without within like say, 28 days. So any thoughts there? Do you think that -- is that actually a sign of a failure? We haven't achieved that with a single dose, therefore, we have to do 2 doses. Or do you think the 2 doses, that consolidation regimen could truly provide the long-lasting clinical benefit?

Well, thank you very much for this question. When you look at the history of our communication [ towards ] allogenic CAR-T therapies in general, for the past 6 years or 7 years, we've been developing them. We've always been strong advocates of repeat dosing and consolidation studies in there. So yes, maybe it's a big discovery for all our competitors in this space, and say, we have -- we can do suddenly redosing. We have constantly, at Cellectis, been big advocates of the fact that the single-shot magic bullet would not work these type of therapies. Yes, these type of therapies, as an off-the-shelf with very competitive cost of goods at the end, allow us to develop a consolidation study with an attack dose, consolidation doses. And a way to administer this over the time would give the best chances to have a very long durability and stability and the best chances to the patient. It has been and it will always be Cellectis strategy. I'm glad to see we've been a leader in this space. And all the force are coming and as they were discovering how [indiscernible] include this. But this is what the strategy at the beginning of Cellectis. And we've done like -- the repeat dosing comes like the first patient that had been redosed was from 4 years ago. It's not new.

Yes, at least 4 years.

Okay. That's great to know. So unfortunately, we are running out of time, it's really short. Andre, I will see you again at the panel discussion, and we can go a little bit more detail on the CAR-T part. Certainly, you are the leader in the space, and we will have more discussion there. Thank you, Andre, David, Eric for joining us today. Thank you, everyone. Bye-bye.

Thank you.

Thank you.

Thank you very much. Thanks. Bye.