Let's just dive into it. André, tell us a little bit more about Cellectis. So Cellectis is a biotechnology company. We're a gene editing company-based company at start, we essentially been developing gene editing for the past decades. I'm putting an S this, but technology agnostic. We have started with what's called meganucleases. There's, like, still some companies developing this technology, but we're quite technology agnostic. I think especially technology meant to be get obsolete at the time, so if you're totally focused on one technology, you might get out of trend at the time. We've started focusing on other technologies. We license TALEN technology from University of Minnesota and Iowa back, like 13 years ago, and we very much appreciated the this technology because of the precision, the easy access, et cetera, and we loved the way it worked. When CRISPR came in to, like, end of 2012, we jumped on CRISPR and started developing CRISPR technology internally. But given the underperformance of CRISPR compared to TALEN, we dropped it. Actually, we continue to use CRISPR sometimes in certain experiment, but we have a meaningful amount of patents because we started—I think the first patent was filed in March 2013. I think none of you have ever heard the name CRISPR at this time, we already filed the first patents. Okay. There was no company formed at this time in the CRISPR space, and we kept, like, working on TALEN, essentially. Now, we started doing therapeutics using gene editing in T-cells to develop the allogeneic CAR T. The concept of allogeneic CAR T-cells has been developed by Cellectis. Currently, we have three assets in the clinic in various liquid tumor application, acute lymphoblastic leukemia for UCART22, targeting CD22, one for non-Hodgkin lymphoma, targeting CD22 and CD20, so it's a dual CAR T. And last but not least, in acute myeloid leukemia, UCART123, targeting CD123. We have also series of collaboration. We have one collaboration that started initially with Servier, and then Pfizer, right after we signed an agreement with them, and on the CD19 CAR T that we had that was out licensed to Servier, and Servier gave the rights to Pfizer in for the US. So Pfizer had the US and Servier, rest of the world. And then finally, Pfizer decided to spin out the agreement between Cellectis and Pfizer into a newly formed company called Allogene. Mm-hmm. So Allogene is now one of the main collaboration we have in this space. They target, like, they're pushing series of trials in oncology, CD19 in DLBCL, essentially in the U.S., about trying potentially to get the rest of the world. Servier have essentially dropped or stopped working on CAR Ts. They're also developing in multiple myeloma BCMA. There's two assets from Allogene in multiple myeloma, from like BCMA CAR T that we licensed to them, and then finally CD70 for renal cell carcinoma. Besides this, we have one collaboration also in tumor-infiltrating lymphocyte, multiple type of tumor, solid tumors with a PD-1 knockout TIL that is currently in the clinic. I think that potentially I eventually give, like, an update on this, CAR T. We have one collaboration also with, with Cytovia. Cytovia is developing NK CAR T, that are resulting from, like, iPS cells, so iPS-derived NK CAR Ts. And, we also, started venture with Hibiscus, venture fund, private venture fund called, Primera. Primera is developing also gene editing solution to fix genes in some mitochondrial, mitochondria, for mitochondrial disease. And then finally, we recently announced also an agreement with, AstraZeneca on three different fields. So it's a cross-board agreement between, you know, gene, like, rare genetic diseases, immunology, and, and oncology. So that gives, like, a pretty- Yeah, good. Great! That's a great overview. Great overview. Just, obviously, your platform centers around TALEN. Mm-hmm. Can you maybe just, kind of discuss, you know, why TALEN, and what are the pros and cons of using TALEN vis-à-vis some of the other kind of gene editing technologies? You mentioned CRISPR. There's, you know, a couple others as well. Okay, it's a good question. Let me, let me start by the cons. Okay. Okay? Okay. Why not to use TALEN? There are two main reasons. The first reason is that we own most of the IP- Okay ... in the space. Okay. Okay. Or licensed- Okay ... exclusively, and so it's pretty difficult to get into the space with FTO, but there are, like, other companies using it, essentially, people working with us, sometimes not. Okay. The second reason is why not using TALEN is if you're not a protein engineer. If you have no clue how to engineer proteins, it's difficult to do it. If you're good, we're protein engineers, it's super straightforward. Why we're using TALEN is that it's by far the most precise technology. The constraints you have to place a cut on DNA is zero almost. It means you can place a cut exactly where you want it. For most of other technologies, you have more pattern constraints that you have. For example, let me give you one example. For CRISPR, you have a motif on the guide RNA. Right ... called the PAM sequence. So you have a triplet that is needed to have a good cut. If you don't have this triplet, then you have to go and find a triplet somewhere else. That reduces the space that you can target to one cut every 70 base pairs. Okay. So if you want to place your cut just right here and don't have the PAM, that's tough. The third thing that we like, we like it because it's a protein. It means you—a protein, you have 20 amino acid that you can play with in order to strengthen the tightness between the protein itself and DNA. So you can re-engineer the protein up to refine it, to drop off all potential off sites, and have a very high on-target cleavage with exactly the property that you have, and that's something you need to be a protein engineer. It's very quick. You can snap it like this. You can design the protein in, like, the—in, like, few seconds, and you can have very rapidly your in vivo experiment or in vitro experiment done in less than a week. It's 5 days to go from, like, the ID to the experiment itself, so it's quick. It's quicker than a CRISPR, which takes a week to more than a week, 10 days to get the guide RNA and do all the tests. And then, last but not least, it's a protein that wraps up on DNA in a very balanced way on both sides, where it's going to clip the DNA. So it release the-- it cuts DNA and release DNA with the same speed on both sides. So it leaves the DNA naked on both sides with the same speed. So the recombination can occur in a very balanced way. So to do targeting, it's more accurate. I know it's, like, very technical, but the problem, for example, that we saw in CRISPR-Cas binds to DNA like this and clips DNA just at the tip. So this tip is released very quickly- I see ... with a very high KD. Okay. The other is a very low KD and stay bounded to it. Okay. And so this side can recombine, and the other cannot. So when you look at most of the paper in this space, you see a conversion on one side of the DNA, and the other is blocked. Interesting. That's not good. Okay. Interesting. And what about off-target editing? 35 years of experience on my side on DNA recombination. One topic that's like, you know, is come to I think be very important from a regulatory perspective that we've learned with the CRISPR technology as we see the first genome editing product potentially be approved. Yeah, it's great news. Right? From Vertex and CRISPR, was just the concept of off-target editing. So how does TALEN do? How does it stack up on off-target editing? Well, I remember a very long time ago at the J.P. Morgan conference. I shouldn't say J.P. Morgan. The conference in San Francisco. Another conference. Another, yeah. Like, the conference in January in San Francisco, where I was invited outside the conference to a debate with some other people, and there was, like, a CEO of a CRISPR company that's not the CEO anymore. It was like, yeah, maybe 10, like, not eight or seven, eight, or eight or nine years ago, and the question was, "Does TALEN technology have an off-target?" I say, "Of course, every technology has an off-target." If you cut DNA at a place, you always have some activity, and the more you raise the quantity of protein in a cell, the more you're going to have- Right ... off-targets. It has to be handled. You need to know. We don't see any off-target in the product that we have in the clinic, 'cause we worked a lot on the protein, but there's always a risk. So handling this is not easy because you see essentially off-targets at places where you have a repeat cutting. If you have some off-target cutting like this, you cannot see them. But I think the stress should be taken down. As in the room here with the radioactivity that there is, we always have breaks in our DNA. We have, I think, 1 million breaks a second in our DNA on a permanent basis, and this can raise up, if you have, for example, sun or some natural radioactivity, or if you do an X-ray, et cetera, it enhances the number of breaks. The body is tuned up to fix this. For example, if you have a p53 deficiency, that might be risky. But if you have, like, a normal body, then we can fix this. So all of these nuclease technology have a background of off-target cutting, and the DNA breaks naturally and is fixed. However, the body is tuned to fix this, and I think that this is why I think it's a good news that the product has been approved by the UK, and I hope that's going to be approved worldwide, and I think there is many other technologies that- So you think that there's too much hype around this whole concept? It's normal that we have some stress because you don't want something that shears the DNA into pieces, but I think that the body know how to handle a little bit of breaks. ... Yeah. And what is that level of breaks relative to what you're talking about, just kind of everyday life activity? It depends of people. Okay. For example, when the Russians were making some, you know, nuclear bombs tests, they were sending a truck just after blowing a bomb to make some measures. All the guys that went to make these measures in Semipalatinsk died. But one of them did not die. He went there many times, being irradiated totally, and lived up, like, 30 or 35 years more after. He had, like, a genome that could handle all these breaks in the DNA, and I think that probably that was tough. But it depends of people. Some people can, and some cannot handle the number of breaks. Okay. Interesting. Okay, you've talked about—we'll just quickly go into your portfolio, but you've talked mainly about, like, T cells. Would you consider other kind of editing, other kind of cells as well, NK cells, for example, maybe others? No. Okay. We're not gonna consider NKs, first of all, because I think the proof of concepts are still very weak. Okay. We've been like, we've been in the T-cell space for now, like, more than 10 years, and I've been hearing NK cells forever. Okay. I still think that there is a problem with the use of NKs, is that they don't expand. It's almost like you have to inject billions of cells, if not trillions, and that's not enough. For a T cell, and you will see at ASH the data that we show, we inject, for example, for UCART22 or UCART20x22, a very minimal number of cells, less than 50 million for UCART20x22 as a dose level 1, and at the peak of expansion, you have over a trillion cell, and that you cannot obtain it with NKs. And if you want to melt down pounds of tumors, which is trillions of cells, you need T cells. So no. What about macrophages? Well, no. First of all, like, we're a small company. We need to focus. Okay. I think it's extremely risky. I remember when there was, like, iPS-derived NK cells. Everyone got excited. A lot of our shareholders were, "Why don't you do this, and why don't you do that?" Et cetera. Have to keep focused, and Cellectis is kind of like a nerdy company. Okay. I know we're not in the space of- All, all biotech companies are nerdy, let's be realistic. Not always, no. Some of them, like, follow trends, and Cellectis is not this kind. Actually, why don't you do CRISPR, et cetera? We think we're on the right path- Okay ... and these products are getting into approval at a time, and I'm like quite—keeping focused is something that's important. Macrophage seems interesting, I think. It's still there. The problem of like expansion is, and sorting these macrophages will be more complex. Let's talk about some high-level concepts, 'cause we don't have a ton of time. But, Mm ... how do you design your edits? What are some of the key features that you try to embed in kind of the edits you're making? So for the CAR T's that have been in the clinic for now, from us and the ones we licensed to Allogene, it's a plain platform. Avoid GVHD and avoid host versus graft rejection. Mm-hmm. GVHD is handled by TCR alpha knockout. Suppresses GVHD. We have no GVHD. Okay. We suppress CD52, and preconditioning the patient with alemtuzumab, which is CD52 monoclonal antibody, Campath, Lemtrada, that maintains the immune system down. That works, it's rock solid, and we like it. It's going probably to be the first CAR T-allogeneic CAR T that are gonna be approved, and I'm excited about that. Now, like, the next gen product, for example, we presented recently a product called MUC1 for triple-negative breast cancer and ovarian cancer. We're excited by this. So it's more sophisticated. It's like TCR alpha is a constant. Always? Okay. TGF-beta receptor, TGF-beta, that is a negative feedback loop. We knock it out, the receptor, to suppress this negative feedback loop. We replace PD-1 by IL-12. PD-1 is activated upon T cell engagement and releases IL-12. No PD-1 anymore. And finally, for rejection, we do a replacement of beta-2 microglobulin by HLA-E. Okay. It's four knockouts, three knockins- Okay ... plus the CARs, of course. What's the max you can do with your count? I don't know. Actually, we've done more, but- Okay ... it's the thing is that we have our own electroporation technology, so we own it. Okay. We bought in 2010 a company called CytoPulse back in Maryland, and we've been developing this, electroporation technology, and now we can series the electroporation one after another, and you can pile them up. Okay. The thing that is important is that you have to be gentle with the cells. If you electroporate 1 billion cells, you want to have at least 1 billion, like, not at least, 1 billion cells, close to 1 billion cells, post-electroporation. If you go from 1 billion to 100 million cells, it's not great. So, that's the gentleness of the electroporation is a key component. How do you hope to, you know, differentiate from the field? One thing I forgot to say. Okay, okay. As we own our gene editing technology, we've been protein engineers, one thing that you can do is multiplexing. Okay. If you want to make a knockin, it's better to cut DNA and open the DNA to place a gene inside. If you want to knockout, the thing that we do now, we multiplex using base editing- Okay. Okay ... and- Oh ... gene targeting. If you just want to knock out a gene, you base edit it, and so you don't open this, and you prevent having translocation. So the combination between base editing and gene editing is something that is definitely, very differentiated in Cellectis's approach. Okay. How we differentiate ourselves from others? Yeah, other allogeneic kind of companies. Well, I think that Cellectis is ahead of the race in this. We're probably going to have, like, our first allogeneic CAR T approved between us and our partners, Allogene- Okay ... and I think that's, like, going to be a big differentiation for Cellectis. And plus, I think the next generation CAR T is, with the sophistication I'm showing, is something there is only companies such as us can do that today. Great. So just give us a view into 2024 for Cellectis. What are some of the key things we can look forward to? So 2024 is going to be an interesting year. First of all, because 22 and 20x22 are going to go for an expansion, and I hope that this expansion, at least for UCART 22 and ALL, is going to be converted as a pivotal in trying to push this product into a registration. So that's it, and we'll get some additional proof of concept in the space, showing that these products are definitely on a straight line for approval. Great. Well, thank you for your time, André. Thank you very much.