Good afternoon and welcome to the Citizens JMP Virtual Hematology and Oncology Summit. My name is Silvan Tuerkcan, and I'm a senior analyst covering precision medicine. If you have any questions during today's Q&A, please email me at silvan.tuerkcan@jmpsecurities.com. Now it's my pleasure to host Cellectis. Here with me today are Arthur Stril, Chief Financial Officer and Chief Business Officer, and Adrian Kilcoyne, the new CMO of Cellectis. Thank you so much for joining us today.
Thank you, Silvan. Great to see you.
Thank you, Silvan.
Great. So before we dive into your programs in detail here, I would like you to perhaps describe your deal and relationship with AstraZeneca around gene editing technologies and also manufacturing.
Yeah, thank you, Silvan. So we're very excited about this partnership. We signed the end of last year with AstraZeneca. So AstraZeneca has a very important ambition in cell and gene therapy. The CEO, Pascal Soriot, recently announced that it will be a core component of them reaching $80 billion in revenue in 2030. And we're happy to be part of an ecosystem that AstraZeneca is building around cell and gene therapy. So basically, the transaction was part of two components. There was an equity investment in Cellectis from AstraZeneca. They invested $220 million at $5 per share and got a 44% ownership of Cellectis as a result. And the second piece is we are developing novel cell and gene therapy products with them across a wide range of therapeutic areas, including oncology, immune disorders, as well as genetic disorders.
Recently, we announced that the first three programs have been selected, and work is on the way on these three programs. There is one CAR-T in hematological malignancies, one CAR-T in solid tumors, and then one gene therapy for genetic disorders. So we are in full execution mode with them and looking forward to presenting some data soon.
Great. And then maybe if you would tease out, obviously, AstraZeneca has a lot of capabilities. So what were the specific capabilities that they were interested in? And then what will the investment allow you to do in terms of your capabilities and your labs? Obviously, you're going to be investing in those joint programs, but what is the read across to your work?
Absolutely, so what was interesting from the AstraZeneca perspective is, first, the strength of the innovation engine of Cellectis. We were the inventors of allogeneic CAR-T, and we've put forward a number of innovations in the field of gene editing, in the armoring and engineering of CAR-T cells, and more recently in gene therapy. The second piece that was of high interest is our manufacturing capabilities. Recall, Cellectis decided to fully internalize allogeneic CAR-T production, ranging from starting materials, viral vectors, mRNA for the editors, buffers, bands, plasmids, et c., all the way to the final cells. And we have been investing an enormous amount of time also in process and analytical development to be doing absolutely high-quality allogeneic CAR-T cells. We recently celebrated our 10,000th batch, so we've been doing batches after batches after batches to really get the perfect recipe for potent and efficient allogeneic CAR-T.
So I think both our innovation, the strength of our R&D, as well as our manufacturing capabilities in the field of allo were of high importance for AZ. And I think they recognize, as we do, that to start tackling some of the higher prevalence indications, like solid tumors or autoimmune disorders, allogeneic is going to be the way forward because of the intrinsic limitations of autologous, both from a cost of goods perspective and from a capacity perspective.
Great. And I mean, you already mentioned the outlined three programs that you've already announced here. What are some of the first opt-in decisions to do, and what are some of the next steps from this collaboration that will become public?
Yeah, great point. So we are definitely moving forward. I mean, recall, these are novel products, and we started when the deal was inked late last year. So we're really in full execution mode right now. I think next year, we potentially want to be unveiling the curtain and show some preclinical proof of concept around at least one of these programs. And then we also want to be discussing additional programs with AstraZeneca. And to also answer your question around our own programs, I think it's important to recall that our wholly owned clinical stage program, UCART22 and UCART20x22, are not part of the AstraZeneca collaboration. So we are using the funding from both the AZ equity investment as well as the milestones that we're receiving from AZ to fully progress our clinical stage pipeline. So 22 in acute lymphoblastic leukemia and 20x22 in non-Hodgkin lymphoma.
So this is also allowing us to get a good cash runway, which is now pushed to 2027, to be executing on our clinical stage assets.
Great. That makes sense, and just a last question on the topic. What's the ownership level now after everything is said and done of AstraZeneca and Cellectis?
Yeah, so at the time of closing of the agreement back in May, they were at 44% of the share capital.
Great. Maybe before we dive into the program also, obviously, you've mentioned that Cellectis has been doing this for a very long time, and you've been at the foundation of CAR-T therapies here. How do you position yourself as a company now within the allo-CAR-T space? Lately, a lot of companies jumping into I&I bandwagon, maybe deprioritizing oncology. You're forging ahead with two oncology programs. Just maybe outline a big picture, like what makes you confident here, especially in oncology and in the assets?
Yeah, so we really didn't want to be part of the freight that would deprioritize oncology over I&I. And Adrian will speak to that when we talk about our own programs, A, because we think our programs have tremendous potential, but B, because we think there is still some tremendous unmet need in the hematological malignancies that we're addressing. Our strategy is, as you know, we've licensed our first asset, the CD19, to Servier and Allogene. And our strategy here is to go with differentiated non-19 targets to address the unmet need with patients that are either relapsing or refractory after a 19 treatment. And this is true both in ALL and NHL. So yes, we're still very much moving forward in oncology, very excited to be presenting results next year. And we're definitely looking very hard at the I&I field, but we want to be very careful.
We do not want to be jumping into the fray with yet another CD19 in lupus. We want to be thinking carefully about this before making a move.
Great. Thanks. Yeah, talking about the asset, you recently guided to data from UCART22 from the BALLI-01 trial in ALL in 2025. Could you just please walk us through some of the data that you have most recently announced from your internal manufactured product?
Yeah, I'll take that, Arthur. So for those who aren't aware, we started this trial, the BALLI-01 trial, with an externally sourced product. And we decided for, I think, which was a good move to internalize this, what we see is our own internally manufactured product has better expansion and certainly better efficacy data. So our data package is split between P1 and P2, our P2 being our product. During the last end of quarter, we guided to the fact that we were really on track to recruit up to 40 patients, which is the total patient selection for the Phase I study. And at that time, we also guided to the fact that, as we do with many of these products, we retain slots for identified patients. And we had identified all patients in those slots.
In relation to the data that's already been shared, we've shared data from early on in our dose escalation. We have now progressed to that. We will have up to 40 patients. That whole data package will be available to us during 2025.
That's very helpful, and maybe while we talk about enrollment, so the data that you chose, since then and since you've taken over, I guess, the clinical management here, how would you characterize enrollment speed and kind of like the drive towards a recommended Phase II dose? Are we closing in? Will 2025 be the year where we get that?
Absolutely. That is certainly within our plan. We believe that's a reasonable assumption. Now, again, at the end of the quarter, we did guide to the fact that we were continuing to recruit in the non-staggering portion of the trial. Now, that probably should give people who are working in this area would be very clear. You get to a point when you do no longer have to stagger the patients. That is certainly a marker to suggest we are believing we're close to finding the recommended Phase II dose. Hopefully, that answers your question.
Yeah. No, that's helpful. And so maybe talking about the results we have to date, obviously, there was not expansion, but dose escalation. Can you please put these results in context with respect to the patient population that you enrolled and also the alternative treatment options that are currently out there? And then obviously also recent results in the ALL space.
Yeah, that's a great question. First, I want to say this is because this is a Phase I study, we are recruiting what I would be considered very late line patients. Many of these patients, almost all of them, in fact, in our trial have had a previous CD19 CAR, and certainly all patients would have had blinatumomab, inotuzumab ozogamicin, et c., so very heavily pretreated and often have obviously failed those therapies. So with that in mind, it'll hopefully give you a feel for the type of patient population we have. They are very, very high disease burden. But there's one other factor that we need to consider when we're looking at autologous versus allogeneic therapies, and that, because we're off the shelf, we are ready for patients to be treated rather quickly.
So we're often selecting an even sicker patient population than we are with autologous who may have to wait one, two, three, four weeks and beyond in order to receive the treatment. So I think we're looking at a very heavily pretreated patient population. With that in mind, the results we're seeing are very encouraging. We've seen what we've shared earlier for those initial three patients kind of gives you an idea of the responses we're seeing, again, in patients who often don't have any other treatment option available to them outside of the clinical trial. So I think they're encouraging. And let's not forget, that was at dose level one when we shared patients. We have now done dose escalation beyond that. So again, we're looking forward to being able to share that data package in 2025.
Great. What do we know about the duration of benefit at this point, directionally, and if at a higher dose, this can expand?
Yeah, it's a fair question. We know that with allogeneic therapies, one of the biggest challenges we have is ensuring persistence. Suffice to say, we believe our persistence is adequate based on what we consider to be the path forward from a regulatory perspective, so we believe our persistence is good enough for what we consider to be the likely endpoint for the trials we're choosing, so we believe in taking the unique properties of allogeneic therapy and making sure they're fit for the diseases we work in, so we are not in any way dissuaded by our persistence. We're actually very encouraged by it.
Great. And maybe talking a little bit about your tolerability profile, what can you tell us about ICANS, CRS, and then the sepsis case that you've had as well?
Yeah, so we are very encouraged by our adverse event profile. When we initially shared that data, we didn't have any ICANS, any CRS beyond grade 1, 2. We've continued to see a very well-tolerated product profile despite the dose escalation. So we don't believe that there will be any issue from a regulatory perspective when they review our safety profile. However, you know these are very heavily pretreated patients who often have had multiple high-dose chemotherapies, multiple CAR-T. And the patient that you're talking about, the grade 5 sepsis, that was a patient who, again, multiple lines of chemotherapy had had two infusions of KYMRIAH, blinatumomab, inotuzumab. When you get to these types of patients, they are frail, they are fragile. And unfortunately, we're going to have episodes like this.
It's incredibly unfortunate, but I think it's actually related to very much the need to lymphodeplete these patients, both for autologous and, of course, for allogeneic therapies, but also the rather frail high disease burden patients that we have. So an unfortunate case, but we don't believe that it's going to result in any real concern around the overall tolerability profile of the product.
Great, so since 2025, we'll get a big update in terms of data and recommended phase two. What are the next steps? How could a pivotal program look like, and when will we know more here?
Yeah, so we are approaching the end of our Phase I program. We believe, as we've touched on already, that we are very close to identifying our recommended Phase II dose. We also have plans in engaging with the regulatory authorities, both the FDA and the EMA, on our endpoint for our pivotal trial. We believe we understand our product well enough and are encouraged enough by the efficacy data we're seeing that this has a registration path. So I think throughout 2025, we would anticipate in the Phase I meetings with both the FDA, EMA, and our pivotal programs to have commenced.
Okay, great. Maybe switching gears to your other very interesting program, dual targeted CAR-T. Obviously, several benefits to having two targets here. UCART20x22, we had data at ASH last year. Could you just walk us maybe through that CAR-T program and what we saw?
Yeah, really exciting data. Three patients, three responses, two MRD negative responses, really exciting at dose level one, so really at the start. And these, again, were a mixture of patients, some very heavily pretreated, some very poor cytogenetics. So very exciting results we've seen in this dual CAR approach. And it's a very differentiated product with UCART20x22. We are encouraged by the safety profile. So we continue in dose escalation right now. And we look forward to being able to share an update on that during 2025.
Great. And obviously, with these dual target CAR-Ts, there have been some missteps in terms of the safety. Can you just characterize what we've seen on the tolerability front to date and as you escalate on the doses here, what are you expecting and how are you doing it?
Yeah, so throughout the dose escalation, again, we have seen some CRS, but low grade. We're not expecting, again, there to be a particular issue with this dual CAR. Broadly speaking, from an allogeneic across all our portfolios, we've been broadly reassured by our tolerability profiles, both in 22 and 20x22. So, we don't believe that we're expecting a sudden change in our safety profile that may be derailing all the programs.
Good. And of the three patients you presented, I believe all of them responded despite prior CD19 CAR-T experience. Can you just tell us how you're positioning your UCART20x22?
So I think, you know, while we're not going to share exactly how we're targeting, and I think it would be fair to say we're not just targeting the CD19 failures. We are looking at a much broader audience than that. We certainly won't be looking at the patients who would have had a CD19 escape and therefore would give you a very small niche of patients. We believe this product as a dual CAR has wide utility across the hematological malignancies. And as we touched on earlier, it's also got two validated targets within the autoimmune space. So we believe this is a really important product, has got great potential across both hematological malignancies and beyond. So again, we look forward to sharing that data sometime in 2025.
Great. So certainly it sounds like a much larger opportunity here as you potentially move it up in later stage development. What are the next milestones in the NATHALI-01 program? You've alluded to one data cut, I guess, in 2025. Anything else? Will we get any regulatory feedback, anything like that?
So from a regulatory perspective, we would think our lead feedback is going to be for 20x22. For 20x22, we want to just finish this current cohort. And we would anticipate sharing the data of that cohort after that sometime in 2025. We believe, based on what we've seen so far, that there's certainly efficacy. There is certainly a very acceptable risk-benefit assessment from our perspective. And yeah, we believe that there's a path forward for this. But again, not quite ready for the next regulatory interaction in terms of what would be our chosen indication moving forward.
Great. Well, thank you, Arthur, and thank you, Adrian. Thanks so much for joining us today. It was very helpful.
Thank you so much, Silvan. Always good to speak to you.
Thanks.