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

Good morning, ladies and gentlemen. Welcome to the Cellectis Live conference call, English session. [Operator Instructions] This call is being recorded on Monday, September 14, 2026. I would now like to turn the conference over to Arthur Stril, CFO and CBO. Please go ahead.

Good morning, everyone, and thank you for joining us. I am Arthur Stril, Cellectis' Chief Financial Officer and Chief Business Officer. Before we begin, please note that this presentation contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995, including statements regarding our strategy, development programs, financial conditions and potential future prospects. These forward-looking statements are based on our current expectations and assumptions and are subject to various risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. For a discussion of these risks and uncertainties, please refer to our filings within the U.S. Securities and Exchange Commission, including, without limitation, our 6-Ks, annual report on Form 20-F, our press releases and annual financial report prepared in French. Except as required by law, we undertake no obligation to publicly update or revise any forward-looking statements contained in this presentation. Here is our agenda and speakers for today. Dr. Andre Choulika, our Chief Executive Officer; and Dr. Adrian Kilcoyne, our Chief Medical Officer. We will walk you through Cellectis, a Gene Editing Company, our in vivo gene editing pipeline, followed by our strategic transformation. We'll then present our next steps and open the floor for your Q&A. I would now like to turn the call over to Andre.

Thank you, Arthur. Good morning, everyone, and thank you for being here. I'm Andre Choulika, Co-Founder and CEO of Cellectis. I want to share with you today is one of the most important updates in the history of this company, a deliberate science-driven turn towards the next chapter of Gene editing. I'll walk you through where we come from, where we're going and why we believe this is the right moment to make this move. Let me start with a simple idea, the one that has defined this company for a quarter century, Gene Editing. Cellectis was founded more than 25 years ago as a pioneer in this field. Long before Gene Editing became a household term, it is today. And our conviction has never wavered -- gene editing is not an incremental improvement in medicine. It's a paradigm shift. At its core, gene editing does one thing. It intervenes at the level of the genome to change how a gene behaves. You can do that in 3 ways. You can silence a gene, you can activate a gene or you can repair a gene. Keep those 3 verbs in mind, silence, activate, repair. This is what it's going to be all about. Why does this matter so much? Because genetics drives diseases, cancer, diabetes, obesity, neurological disorder, immune conditions, even the biology of aging. At the root, these are genetic variations in the genome, aberrant gene expression, polymorphism, gene doing too much or too little. The logic of gene editing is simple, fix the gene and you fix the disease. Now there are two ways to do that. EX VIVO, where we collect patient cells, edit them under controlled manufacturing conditions and infuse them back. That's the world of CAR-Ts, and it's the world where Cellectis built its leadership. And IN VIVO, where we deliver the editor directly into the body to the target tissue and do the editing inside the patient. This is the pivot in one sentence. We're building on our EX VIVO leadership to advance the next frontier in IN VIVO gene editing. Same expertise, same molecular toolbox delivered in a fundamentally simpler way. But let's talk about in vivo gene editing and why I'm so excited about it. The liver is the chemistry lab of the human body. And conveniently, it's also the easiest address for a lipid nanoparticle to find. Everything you inject intravenously ends up passing through it. The concept is simple. A single intravenous injection, product travels to the liver, editor does it work inside the liver cells and the effect is designed to last. No apheresis, no manufacturing per patient, no hospitalization for cell collection and preconditioning, one injection for a long-lasting effect. And what exactly is the product? It's remarkably simple. It's a messenger RNA that encodes a gene editor, all base editor. -- packaged inside lipid nanoparticle an LNP. It's a well-established, well-understood delivery technology. The messenger RNA is transiently expressed, it does a job and disappears, but the edit it makes in the genome is permanent. That's the elegance, onetime treatment, lasting effect, which brings me to the heart of today's news. We've made the decision to advance 2 preclinical candidates, both in dyslipidemia, diseases of blood lipids where the genetic drivers are exceptionally well understood. The first is HEAL-101, targeting the APOC3 gene in severe hypertriglyceridemia. The second is HEAL-201 targeting PCSK9 in severe hypercholesterolemia. Both are messenger RNA plus LNP products. Both go after targets that are exceptionally well validated by other modalities and both are designed around the same promise, a single IV injection with a potentially long-lasting effect. HEAL-101, this is gene surgery for severe hypertriglyceridemia. Severe hypertriglyceridemia doesn't get the headlines of cardiovascular diseases, but it should. These patients live with the risk of acute pancreatitis, a condition that hospitalizes you, is extremely painful and can kill you. They carry elevated cardiovascular risk. The quality of life is poor and their options are thin. 1 million to 2 million high-risk patients across the U.S. and Europe, not a rare disease, but a neglected one as APOC3 is a very small protein hard to address with the drug. Here's the program we've built for them. Here's HEAL-101 in a single frame. Severe hypertriglyceridemia at the high risk of pancreatitis. The target is APOC3. APOC3 has been validated twice over by other modalities. The technology is a TALE-Base Editor that disables the gene. The goal is to make a single treatment with a durable triglyceride lowering. We have already obtained preclinical data strong enough that we're heading to the clinic. Now let me explain how it works because the mechanism is where our differentiation really shows. HEAL-101 is a base editor -- rather than cutting the DNA, which is how first-generation gene editing works, it changes a single letter in the genetic code, a precise conversion of one base, the C to a T, at exactly the position we choose in the APOC3 gene. And this is the key point for safety. There is no DNA break. We're not relying on the cell to repair cut. We simply rewrite one letter. No double-strand break means the potential for cleaner, improved safety profile that matters enormously when you're treating patients in vivo. What does changing one letter accomplishes? It creates a stop codon, a stop signal inside the gene. When the cell reads the gene, it now stops early. The full APOC3 protein is never made. In plain term, we introduced one tiny precise edit and the gene that drives the disease is switched off. This is gene surgery. And here's the evidence. When we introduce HEAL-101 into human liver cells, we see highly efficient editing right at the target site in the left panel. Just as important, look at the right panel across the top putative off-target sites, we see essentially no modification -- high on-target activity, high specificity. This is exactly the profile you want to see before moving into humans. The functional consequence follows directly. As we increase the dose of HEAL-101, we see the frequency of disabling edit climb. And in parallel, the secretion of APOC3 falls. Editing goes up, disease-driving protein goes down. The biology behaves exactly as designed. Then we move into humanized animal models, mice engineered with human liver cells, and we see the full chain of cause and effects in the living organism, precise editing of APOC3, a clear decrease in the APOC3 protein and the outcome that matters clinically, a real drop in triglycerides. And the magnitude of that effect is what you -- I want you to remember today. In affected mice, a single administration of HEAL-101 produced at a 70% -- produces a 70% reduction of APOC3 and a 76% reduction in triglycerides, 76% from one treatment. This is the kind of effect that can change a disease, not just manage it. Now to our second program, HEAL-201, a slightly different, equally powerful type of gene surgery. The disease is severe hypercholesterolemia, high LDL cholesterol or the so-called bad cholesterol. LDL is the leading driver for atherosclerotic cardiovascular disease, and we know that lowering it reduces cardiovascular events, yet a large number of patients simply cannot get to goal. Even on maximum tolerated therapies, we focused on the highest need patients, younger, high-risk individuals who had a premature cardiovascular event and still have persistently elevated LDL despite everything available today. Again, roughly 1 million to 2 million patients across the U.S. and Europe. Here's HEAL-201 at a glance. The indication is severe hypercholesterolemia, the target, the PCSK9 gene, one of the most thoroughly validated targets in all cardiovascular medicine. The editing technology is different from the one I just showed. It's a TALE-Modulator that silence PCSK9. I'll come back to the silencing point later. The goal is onetime treatment for durable LDL lowering to reduce cardiovascular risk. And again, we've obtained promising clinical -- preclinical data supporting moving this product candidate into the clinic. And here's what I want to highlight the breadth of our platform. HEAL-201 works differently from HEAL-101. It's not the base editor. It's an epigenetic modulator. It doesn't change a single letter of DNA at all. Instead, it binds the DNA the gene and silence it epigenetically, turning the gene off while leaving the DNA sequence completely intact. Think of it this way. With HEAL-101, we edit a letter in the DNA. With HEAL 201, we simply flip the switch to off without touching the text, same company, same TALE backbone, 2 entirely different type of mechanism. That's what a real gene editing platform look like. And no DNA sequence change means, again, an additional safety rationale. The data backs it up with an epigenetic change alone, no sequence modification, we shut down PCSK9 transcription completely. The messenger RNA of PCSK9 dropped to near 0. The gene is effectively turned off at the source. And that translates to the protein. Over the days following treatment, PCSK9 protein secretion falls dramatically and stays down. The target protein is turned off, which is precisely what drives LDL cholesterol lower. Specificity is, of course, critical. So we looked across the entire Transcriptome -- every gene expressed in the cell. The result, PCSK9 is knocked down cleanly while the rest of the genome is essentially untouched in the expression. Gene surgery uses a scalpel, not a hammer, high specificity for PCSK9 and PCSK9 alone. And crucially, the effect is durable. This is the question everyone asks about epigenetic approaches. Does it hold? In biology, epigenetic pattern is stable over time, even over lifetime. Our data show a rapid and sustained decrease of PCSK9 that remains stable over time, rapid onset with a lasting effect. This is exactly the profile a onetime therapy needs. So -- when you will see the data, let me give you some time lines. And I would like to turn the call over to Adrian to walk you through our clinical plan for HEAL-101 and HEAL-201. Adrian?

Thank you, Andre. I will now outline our development pathway, which is composed of 2 parts. Initially, we have an accelerated path to first-in-human data through an investigator-initiated trial in China. This IIT is being run under the new regulations, which came into effect in May this year, requiring a comprehensive preclinical package. This first-in-human study in severe hypertriglyceridemia is focused on safety, tolerability and establishing that HEAL-101 will lower triglycerides, which we have seen in the compelling preclinical data, some of which has already been shared today by Andre. It is important to highlight that parallel IND and CTA preparation is ongoing to allow for a seamless transition from -- to the global Phase Ib/II by end of 2027 in the target patient population. This will also inform the path to Phase III. It is important to also recognize that the endpoint of lowering triglycerides is well established as a surrogate endpoint for reduction in the risk of acute pancreatitis. There will be no requirement for a cardiovascular outcome trial for either approval or reimbursement. This has a significant impact on the path to revenues compared with many lipid programs. I will now show the plan for HEAL-201. This plan follows the same strategic pathway as HEAL-101. That is accelerated path to first-in-human data and seamless transition to global Phase Ib/II trials. This Phase I first-in-human study in severe hypercholesterolemia aims to establish safety and LDL-C lowering, followed by a Phase Ib/II, which will focus on the highest risk population who would benefit most from a single-dose gene therapy offering durable long-term lowering of cardiovascular risk. These include younger high-risk patients, patients with severe genetic hypercholesterolemia, patients with premature cardiovascular disease and patients with persistent elevated LDL-C despite maximal therapy. It is important to highlight that LDL-C lowering is an established and validated surrogate endpoint that is accepted to support approval by both FDA and EMA, which, like HEAL-101, will enable an efficient path to market. Overall, we believe we have designed clinical programs that offer an accelerated path to first-in-human data that will demonstrate the potential of a single-dose gene therapy to offer long-lasting efficacies in areas of high unmet need. Our anticipated time lines are outlined on the slide now being shown. For HEAL-101, we expect the first patient to be treated in Q1 2027 with data readouts in the second half of 2027. It is important to highlight that early patients may demonstrate the expected durable responses by end of year, which could distinguish this as a product with best-in-class potential. As stated earlier, HEAL-201 follows the same strategic pathway. We, therefore, anticipate that first patients will be enrolled in the second quarter of 2027. The first data readout is expected in the first half of 2028, with again, early patients having the opportunity to demonstrate durable responses. In parallel, we continue to accelerate all activities, including IND and CTA-enabling activities with early engagement with the FDA and EMA. Our goal is also to ensure manufacturing is ready to support the demands of global supply. In summary, we have 2 first-in-human-ready clinical programs with preliminary clinical data expected in the second half of 2027 and the first half of 2028, respectively. Each offers the potential to be best-in-class products with long-lasting efficacy in areas of significant unmet need. I would now like to turn the call over to Andre to present our world-class gene editing capabilities.

Thank you very much, Adrian. Now let me step back up to the platform because these 2 programs are just the first expression of something bigger. This is what sets us apart. Most gene editing companies do 1 or 2 things. We have the full toolbox. With our TALE technology, we can act as a Nuclease, as a Base Editor, as an Epigenetic modulator and as a Transcriptional regulator. TIL-101 uses the base editors. TIL-201 uses the epigenetic modulator and the same core competency span across all columns. Let me make these advantages explicit because it is central. First, a broad toolbox, nuclease gene editing, base editing, epigenetic editing and transcriptional regulation, any modality from one single platform. Second, strong differentiation at the molecular level. Our TALE editors bind DNA without nicking it. with precision down to the base pair and a 32 base pair recognition site that gives us an exceptional specificity. And third, we can combine these tools for the same indication, any modality, any hybrid combinations of them for safety, to finesse the biology of each diseases. This is a meaningful competitive advantage. So let's talk directly about the pivot, the strategic decision itself and the discipline behind it. The heat pump landscape have changed and has changed for good reasons. In B-ALL frontline blinatumomab consolidation has cut relapse rates from roughly half to 15% to 25%. In NHL, Cema-cel in frontline consolidation is driving deeper MRD conversions. Bispecifics and ADCs are crowding second line and third line. And there is now an in vivo CAR-T rush in LBCL. In other words, patients are doing better earlier. That is unambiguously good news for medicine. It is also a smaller and more crowded pond for third-line plus therapies. But it changes the math for us. When relapses fall and competition rise, our enrollment slows, trial gets longer and more expensive and the registration moves further into a more crowded market. Put plainly, the opportunity for Lasme-cel and Eti-cel has narrowed. We looked at this landscape honestly and asked ourselves where Cellectis can create the most value. The answer was clear. So here's the pivot laid out plainly. Cellectis today has Lasme-cel in Phase II and Eti-cel in Phase I. We are making the disciplined decision to exit the internal cell therapy program while continuing to support our existing partners program, which remains valuable. And Cellectis tomorrow is an IN VIVO gene editing company advancing HEAL-101 and HEAL-201 towards the clinic backed by our partnerships. This decision also extends our cash runway into the fourth quarter 2027 into the second half of 2028. We are concentrating our resources where the science, the medical need and the value creation are the strongest. We're making 4 commitments. We accelerate our 2 lead IN VIVO gene editing assets with readouts, HEAL-101 with the first human readout in H2 '27 and HEAL-201 with the first human readout in H1 '28. We exit internal cell therapy development of Lasme-cel and Eti-cel. We continue our existing partnerships, AstraZeneca, Servier and Allogene and Iovance that the value doesn't go away. We realigned our organization around IN VIVO gene editing and extend the cash runway into the second half of '28. That's IN VIVO gene editing focused company with a full year of financing past its first human readout. Which brings me to where we are heading and to a world you've seen through today, HEAL. HEAL is more than a program. It's our purpose. Gene surgery is editing life for the better. We're not leaving our history behind. We're fulfilling it. With IN VIVO gene editing, we have the immense opportunity to transform medicine at its source and make a paradigm shift in the way patients are treated, a reality. And I hope you'll be part of this next chapter with us. With that, let me thank you for your attention and open it up. Arthur, David and Adrian are all here so we can read -- can be ready to answer your questions. Thank you very much for your time.

[Operator Instructions] Your first question comes from Amin Makarem from Jefferies.

This is James on for Amin. Congratulations on the strategic transformation. For HEAL-101, what would the program need to demonstrate to be meaningfully differentiated from existing APOC3 directed therapies, including antisense and siRNA approaches? And also just another quick follow-up. For both 101 and 201 programs, what off-target biodistribution work, liver safety work has to be completed for each program? And what remains before the first patients could be dosed?

Well, thank you very much, Amin, for these questions. And I'd like to turn the first question to Adrian and the second part of your question probably to David for all the preclinical work and before getting into the clinic. Adrian?

Yes. Thanks, Amin, for the question. As you've seen from the preclinical data, we get very strong efficacy. So we would expect our efficacy is at least as good as existing therapies. The really important differentiator for us is really based on the gene editing that is safe, but also very durable. We think one of the challenges is we've done market research on this. We've talked to many cardiologists, endocrinologists, et cetera, those involved in treating these patients. And they have identified a group of patients that they will feel would benefit significantly from a very durable patients. Now we've outlined those in the slides, which are those younger patients. But it's really that durability of response. And of course, the level of durability remains to be seen, but there's every anticipation that this will be a very long-lasting effect. And for young patients with significant cardiovascular risk or indeed patients with severe hypertriglyceridemia who run the risk of developing acute pancreatitis, the ability to not have to have repeated treatments for the rest of their lives is very attractive to clinicians and to patients. So I think really, the importance is the safety of our Gene Editing Technology and the potential for very significant durability of effect. In terms of the off-target, I'll hand over to you, David.

One of the things I would like to add to your question, Amin, here is, well, ASO, RNAi, et cetera, these are not long-term therapies. They can be lasting for a certain period of time. But the problem with most of these diseases is adherence of the patient to the treatment. And that's where the problem comes from. When you have no real symptoms and you have like to take pills on a daily basis, even on a weekly or monthly or sometimes like on 3 months basis, it is complicated for certain patients, especially when they're young, especially when they have like no symptoms, et cetera. Gene surgery is like the surgery concept. People prefer to have like one definitive action in order to fix a problem instead of continuing to go after the symptoms. And I think that this is something that where the medicine of 21st century is going to head at in the coming years and intervention on the genome is going to become one of the big changes where people will stop taking pills as, for example, normal surgery have changed the lives of a lot of patients in terms of certain type of treatments also. David, I would like to turn off like the floor for you.

So as for assessing off-target, we do that at 2 different levels. We assess the off-target at the molecular level for the TALE-Base Editor and TALE epigenetic modifier. And these are pursued essentially in a way that is quite similar to what we've made public for the TALE with a systematic unbiased approach. So we know where the strike will take place, and we're pretty sure that it does only what it's supposed to do. The off-tissue approach is essentially assessed through biodistribution studies made in animal models. And we actually pursue not only the detection of the lipid nanoparticle itself, the lipids, but also the payload and any effect thereof. So there's essentially a succession of models that have been classically used in the field, and we are going to pursue the same -- and we're pursuing the same path.

Your next question comes from Jack Allen from Baird.

Congratulations on the updates. I guess 2 quick ones from our end. The first is around the proof-of-concept data that we're going to get as early as the second half of next year from HEAL-101. How do you think about dose escalation here and what kind of dose you could potentially enter the clinic? Do you expect the initial doses to be effective doses? And what kind of proof-of-concept data could we expect as it relates to breadth and depth of that data set in the first half of -- or second half of next year? And then I have a quick follow-up as well on the delivery mechanism.

Great question. Maybe Adrian can -- like we've worked a lot on the dose, and I know that you've done tons of work with the physicians. So Adrian, please go ahead.

Yes. Indeed, it's a great question, Jack. Thanks for asking it. It's really important to us that we start at an effective dose. Now I think our preclinical work has demonstrated very reassuring safety and tolerability. So the group we're working with has done extensive modeling to enable us to start at a higher but safe and effective dose. So when we talk about dose escalation, we anticipate we're already starting at a relatively effective dose. So we would anticipate that the initial emerging data will also be giving us some strong safety signals. Yes, we may have to dose escalate, but it will be far probably less than we might have anticipated. So I think this extensive modeling with a center that has extensive experience in these type of therapies is allowing us to have that higher starting dose.

Got it. And do you have any context around what that dose might be as it relates to milligrams per kilogram? And then just very briefly on the LNP as well, where are you sourcing your LNP from? And is it a novel LNP? Or has it been put in man before? I'm just curious if there's anything to read into as it relates to the safety of that LNP aspect of the delivery here.

For the first part of -- I'll take the first part in terms of the starting dose, and I'll then hand over to David, who can take the second part. In terms of starting, we're not sharing our starting dose for some obvious reasons. But in due course, that will come out. So we'll share that later following the emergence of the first clinical data. But David, you can talk about the LNP in a bit more detail.

Thank you, Adrian. So we are using the latest generation lipid nanoparticle technology with the latest generation ionizable lipid. So the technology we've been using has been validated already in different context and has been optimized for the very targeting that we're pursuing, i.e., the liver with a dose range, which is commensurate with the needs that we've identified and that Adrian just referred to. Yes.

Just briefly to poke a little bit more on that. As it relates to the validation, I believe, has the LNP been in man and as their clinical experience? Or is it preclinical data that you're referring to there?

So both, but what we're essentially relying on is recent preclinical experience. Clinical experience is ongoing as well, but it's not pursued by us. So it's really essentially validated in models in primates and in other models.

Your next question comes from Lukas Shumway from Barclays...

A couple for me. Have you engaged with FDA at all already to see what the -- what kind of data they are going to want to see in order to bring this into trials in the U.S. And for HEAL-101, have you done any fate mapping for what the protein -- the truncated protein does within the cell? Because like the stop codon that you're introducing is still quite a bit into the protein. So you're still going to get some translation there.