Editas Medicine, Inc. (EDIT) Earnings Call Transcript & Summary

Thanks, everyone, for tuning into the Innovation and Cell Therapy Panel. I'm Yigal Nochomovitz, one of the biotech analysts here at Citi. With me is my colleague, Mohit Bansal, also one of the biotech analysts. [Operator Instructions] So with that, it's my great pleasure to introduce our distinguished panelists. We have from Adaptimmune, Mark Dudley, the SVP of early-stage development, and also other members of the Adaptimmune management team; from Atara, Pascal Touchon, the President and CEO; from Cellectis, André Choulika, Chairman and CEO; from Editas, Cindy Collins, the CEO; and from Fate, Dan Shoemaker, the CSO. So welcome all of you. Looking forward to a great discussion.

Obviously, the cell therapy space is advancing rapidly, and there are a lot of technological advances and changes. So I think to start the conversation, it would be great if each of you could sort of go down the line and just give a few comments as to how your cell therapy platform is differentiated from others in the field. What are the unique advantages that your cell therapy platform brings to the table and perhaps also some of the disadvantages? Maybe we could start with Mark from Adaptimmune.

Sure. Adaptimmune is a company with aspirations to be a fully integrated company, and that means all the way from a deep pipeline to commercial execution. And we are -- currently, we have 3 different assets in clinical development. We have -- all of them are TCR T-cell therapies. So they are differentiated from CAR therapies in that TCRs can recognize quite a broad spectrum of antigens. We think that could be a big advantage going into solid tumors. In addition, we're a company that is engaged in innovation in the following sense: we know the value of a fully integrated platform. We have manufacturing, very deep analytics and the capacity to take new knowledge and implement it in clinical trials rapidly. And from that, we have had responses in 5 different types of solid tumors with our first-in-human TCR therapies.

Okay. Great. Pascal, do you want to give us a few quick headlines about your platform and how it's differentiated?

Yes. Thank you, Yigal. And good morning, good afternoon, everyone. So Atara Biotherapeutics is a company dedicated to serve patients with unmet medical need through the platform and pipeline of allogeneic T-cell therapies. We have a very advanced pipeline in the sense that we have a Phase III asset, tab-cell, which is now in pivotal study, and for which we expect to be able to initiate the BLA by the end of the year. And this is addressing a very rare but very severe, deadly cancer called PTLD. We have also another program of allogeneic T-cell immunotherapy that is in Phase II right now, addressing multiple sclerosis, with encouraging early data in progressive MS. So these are the 2 most advanced programs, addressing EBV-driven disease because this allogeneic cell therapy are, in fact, leveraging the natural biology of EBV T-cells from healthy donors that we can then activate and select to be able to treat EBV-driven disease. But at the same time, we're also leveraging the natural biology of EBV T-cells in terms of having safety, resistance, trafficking, cytotoxicity to be able to add a CAR, chimeric antigen receptor, to this EBV T-cells to make an allogeneic CAR-T. And we have 2 such programs in the IND-enabling studies: one addressing CD-19, the other one, mesothelin. And just a few days ago, we announced that we're entering the clinic with the mesothelin CAR-T, the first version being an autologous one, to be able to address solid tumors with a unique set of features on this mesothelin CAR-T with a PD-1 dominant negative receptor and a new costimulatory domain called 1XX, invented by Michel Sadelain at Memorial Sloan Kettering in New York. So very new next-gen technology for CAR-T, applied to this unique platform of allogeneic EBV T-cells to either address EBV-driven disease or to address any type of solid tumors or liquid tumors based on the addition of a CAR to B cells.

Great. Thank you. André, you want to offer some thoughts? André, are you there?

I'm muted. Sorry, I was on -- I was muted.

That's okay.

Well, thank you very much, Yigal. Good afternoon, everyone. So Cellectis is a gene-editing company at the basis. We have a series of assets in the clinic currently in 6 different trials. Three of them are partnered: one with Servier on acute lymphoblastic leukemia with UCART19, targeted -- CD19 target; and one with a Allogene bio, ALLO-501, in DLBCL. Both of them are like, what, -- the first of them is in an expansion trial and the second one in dose escalation with Allogene. And the third one is in multiple myeloma developed by Allogene, targeting BCMA, and is also in dose escalation currently. The wholly controlled assets are UCART123 in acute myeloid leukemia, also in dose escalation. The other one is UCART22, targeting CD22 in acute lymphoblastic leukemia. And finally, the last one is currently in hold by the FDA, and hopefully, we'll resume the trial quite quickly. It's UCARTCS1 that is targeting multiple myeloma currently. All these trials -- like 6 trials, are currently developed in the United States and a bit in Europe also, for UCART19. Besides this, Cellectis is very much focused on essentially CAR-T in liquid, and potentially, in solid tumors in the future also, but have a very strong platform in gene editing and also is developing its own manufacturing plants.

Okay. Great. Cindy?

We have 2 focused areas for our engineered cell therapies, hemoglobinopathies and oncology. And within hemoglobinopathies, our lead program is EDIT-301 for sickle cell disease. And based on the preclinical data that we presented at EHA earlier this year, we expect our approach to induce higher and more durable levels of hemoglobin and to more robustly repopulate all blood lineages, most importantly, red blood cells. The data showed that we can efficiently edit hematopoietic stem cells from sickle cell patients and these edited cells improved properties indicative of reducing sickling propensity. We also have showed cells from healthy donor-derived hematopoietic stem cells were maintained in vivo and had elevated in pan-cellular fetal hemoglobin expression with EDIT-301. As we've said in the past, we believe editing at the hemoglobin beta G1 promoter instead of the BCL11A enhancer with our nuclease is the safest and most effective approach available now and will be potentially curative for patients. And we are on track for filing an IND later this year. Within oncology, our lead candidate is EDIT-201, an edited healthy donor NK cell medicine for the treatment of solid tumors. It's been designed to be used as an adjunct therapy for PD-1 nonresponders. And through our partnership with Sandhill, we're accessing the NK cell expansion technology called BINATE to expand NK cells. And this is going to be critical in successfully developing and commercializing EDIT-201. And we plan to share preclinical data on this program at a medical conference this year. And then down the road, we believe we can differentiate ourselves within immunotherapy by developing highly edited iNK cell medicines to address the broadest range of tumors with the highest quality and lowest cost. We've already made some substantial progress. We've successfully generated iPSCs from fibroblasts and peripheral blood cells, and we've achieved efficient editing of iPSCs. And finally, we have differentiated iPSCs into functional NK cells with potent killing activity.

Okay. Great. And last but not least, Dan, from Fate.

Right. Good afternoon, everybody. So at Fate Therapeutics, we're pioneering a novel manufacturing paradigm for cell therapy, which uses clonal highly edited iPSCs as a renewable starting material for scaled manufacturing of NK and T-cells. We currently have 9 INDs cleared by the FDA, and we're exploring both hematologic malignancies as well as solid tumors. If I do distill it down, the 2 key advantages of the platform is the -- first, is really taking advantage of the cell line properties of an iPSC, which opens the door for achieving complex editing strategies. And we used to have the same struggles when you do 3 or 4 edits of heterogeneity, but the ability to do single-cell cloning and screen through hundreds of candidate clones and find the few pristine ones that have all the on-target edits and none of the off-target or translocations. And then that single clone then becomes a master cell bank, which, again, serves as a renewable starting material for scaled manufacturing of NK and T-cells. The second key advantage is once you have your master cell bank, it really now simplifies your GMP manufacturing, where you simply take a vial out of the freezer, and whether it had 0 edits or 4, 5 or 6 edits, you go through the same 40-day procedure in a GMP facility where you could really get a million-fold expansion, create thousands of doses, low-cost of goods and high levels of homogeneity. But it's really unlinking the gene editing and clone selection with sort of the repeated GMP manufacturing that, I think, allows us to achieve unprecedented low-cost of goods and scalability, which is, I think, a strength of the platform. Right now, we're very committed to exploring both NK cells and T-cells. We think they both have unique advantages, especially as we start introducing dual-targeting traffic in an overcoming tumor microenvironment. Again, across the 9 approved INDs, we're really exploring clinically the different attributes and just really trying to increase accessibility and tap in innovation as a whole field as we really understand the barriers that cancer has put up in front of us that we need to overcome. I think we're big believers, ultimately, that having access to highly edited, cost-effective, broad and accessible immunotherapies will be a big secret, not only in solving hemalignancies, but as we think about the much higher hurdle of overcoming solid tumors. So that's sort of what we're up to.

All right. Great. Thanks for the intros from everyone. So obviously, some of you are developing cell-based therapies from healthy donor cells. Others, as mentioned, are using very potent stem cell platforms. So it'd be great if you could -- if each of you could talk a bit about, for your respective programs, what are some of the key hurdles or challenges that you face in either developing a healthy donor-derived cell bank, or in the case of the iPSCs, what are the key challenges that you face in developing an iPSC master bank? I don't know if you want to -- maybe you can start, Dan, on your -- on Fate.

Yes. No, so this has been a journey. We filed our first IND about 2 years ago for FT500, which is a nonengineered NK cell. And that opportunity really allowed us to build a relationship over many years with the FDA of the rigorous manufacturing, in addition to the quality control. I mean, looking for residual iPSCs in the final product was huge, really understanding and then maintaining your clonal master cell bank and demonstrating genome stability with a variety of very rigorous tools, and then fine-tuning the differentiation protocol and really convincing ourselves and the FDA that we are making bona fide NK cells that behave as natural NK cells do in a variety of mass models. And now that we've entered the clinic, we've been able to build on that safety profile across a variety of clinical studies. But it really has been a journey. Fate's been working on iPSCs for the better part of a decade. This -- the last 4 years has been really committed to creating NK and T-cells. And -- but just the rigorous quality control, release criteria, as you start doing gene editing, having very sophisticated tools to assess -- as you screen through candidate clones to find the right ones. And it's also just been a really important partnership with the FDA as we sort of built this CMC package over the years. And now we're absolutely building this platform in a stepwise fashion. Again, we started with a nonengineered NK cell, then introduced product was one edit, and now we just have products that our IND's are about to go in with 4 different edits for multiple myeloma. So we're big believers in dual-targeting, putting cytokine support into the cells. And I think, as we look down the road a little bit to solid tumors, I think there are traffic in the tumor microenvironment, recruiting other immune cells. I think just having access to really good editing tools and then a platform that allows you to build multiple edits and pick a clone, I think, is going to be the key to making significant progress, especially in solid tumors. But again, it all starts with safety, feasibility. And again, that is -- we've learned so much in our clinical trials with FT500, giving 6 doses of an allogeneic iPSC-derived NK cell therapy and looking for the patient's immune response. Is there an anti-product, either T or B cell-mediated program that gets elucidated? So there's a lot of the doubles in the details, but I believe those come back to manufacturing. And now we're starting to get clinical trial results back, being able to take those learnings and build that learning and the design of future products. But yes, so that's sort of the high level -- a few of the lessons we've learned.

Okay. Pascal, what about you for your donor-derived EBV cell therapy? What are some of the challenges in producing a high-quality cell product?

Yes. We have developed a very robust and well-tested type of supply and delivery chain now. We have inventories, not only of starting material from healthy donors or PMBC, but also intermediate T-cell, B cell and final product. And this supply chain has been tested with COVID-19 pandemic. Because I can tell you that between March and September, we have been able to deliver a few hundreds of shipments on time within 3 days in the U.S., so from order to delivery at the hospital, 3 days, and these are really allogeneic T-cells that can treat patients there. So that's been a very robust thing. At the same time, we've been able to scale it now. We know, for example, with ATA188 or allogeneic T-cell immunotherapy for progressive MS, that from one leukopak, we can then make the product into bio-reactions, real-time bio-reaction, and we can make up to 40,000 doses from one leukopak. So a huge improvement in terms of manufacturing yield there. And then at the same time, we have also clarified -- since we are doing partially match type of delivery of the product to be able to ensure persistence of the cells and functional persistence of B cells, we know that we have a very limited number of cells line that we need to keep. For tab-cel, it's about 40. But in MA, it's only about 10. And for allogeneic CAR-T, it's less than 10. So we mastered completely that. And the fact that we have now 2 products in the clinic, and one at very advanced stage where we are making commercial manufacturing today for the CMC testing, we are making PPQ lots as we speak. And I think nobody else at this stage is making PPQ lots with allogeneic T-cell therapy. That means that we have a very robust, very well-controlled system. And as I said, we are able to deliver to patients across the world within 3 days of orders, these allogeneic T-cells. So very excited about being able to deliver to patients this very efficient system of allogeneic T-cell coming from healthy donors.

Got it. Maybe, André, if you have any comments on the challenges and -- that you faced with the TALEN-based cell therapy and how you've solved them?

Well, the TALEN is essentially like the gene-editing technology that we're implementing in allogeneic T-cells for numbers of reasons, like the robustness of the technology and the efficiency, also the precision that it delivers. Not only this, but also it's very versatile technology that allows to do gene insertion, but then, as well, replacement or versatile edits in any kind of genes. One of the challenges we're facing currently in the manufacturing is the robustness and the consistency of batch to batch. And that's what Cellectis has been able to achieve. Because the batch that you would manufacture today or the one that you manufacture a year ago and the one that you'll be manufacturing for the pivotal trial should be exactly the same type of product at the end. And the composition in there, it means a number of CD4 positive cells, CD8s, the gamma, delta, the central memory cells, et cetera, all of this, the composition, has to be always the same to give exactly the same chances to every patient. It means having one batch that is super active and the second one that is less active gives you a very whimsical data at the end. And finally, it doesn't allow to develop a very robust product, and these changes and the variability from batch to batch becomes, at the end, a problem. And so all the secret sauce behind all the process development that has been implemented and what we're doing is trying to have consistency from batch to batch and having something that would be always the same in order to have a very consistent product and have the best chances of success at the time of the BLA. Because I think this is going to be a real differentiated effect at the end. And then you know how many doses can give to the patient and how this product should be delivered and giving exactly the same type of results according to the tumor size and the type of tumor and discretion of the antigen. And that's essentially delivered by a very hard and tedious work that is process development on a regular basis and tweaking all the parameters to come to something that is robustified. It take us almost like 6, 7 years to come to the point where we are. And then we think that we have -- we're currently working on the final pivotal versions that should come to production next year. And we're excited about that.

Great. Cindy, what are some of the key challenges that you've overcome in the development of your cell therapy?

So one of the key challenges with NK cells that we plan to overcome with editing is the durability of therapeutic effect. With our lead program, EDIT-201, which is the allogeneic healthy donor program, we're knocking out 2 genes that we believe will improve the persistence of tumor-killing and help the therapy overcome some of the defensive mechanisms that tumors use to evade the immune system. The other well-known challenge is expanding NK cells to therapeutic dose levels. And we're overcoming this challenge by using the technology from Sandhill Therapeutics to expand the NK cell population.

Great. And Mark, did you want to add anything?

I do. I want to add 2 things. Currently, we're using all autologous cell therapy products. And I'll turn this over to John for the second part of this, he's our Chief Patient Supply Officer, to talk about challenges with autologous cell therapy. By far, our biggest challenge is getting responses in patients. And there's a real advantage to autologous therapies in the sense that every tumor is different, every patient is different. And when you make a new batch for every patient, you have this opportunity to do deep analytics and then to rapidly reflect your learnings back into the next batch, in some cases. So this is one of the most valuable learnings that Adaptimmune has taken away, is the benefit of rapid integration of new learnings and that possibility with many lots. So I'd like to turn it over to John to discuss a little bit about supply and manufacturer for autologous products.

Yes. And also allo -- the other thing to mention, we do have an allo platform we announced in January in partnership with Astellas that we've been working on for several years as well. Because all of the challenges that the panelists have mentioned related to manufacturing and supply that auto deals with are real ones. I will say that I think the gap between the operational execution of an autologous product, and ultimately, the allogeneic product is going to narrow. I think the cost profiles are going to narrow. There's a ton of innovation going on within the autologous space. And of course, those are the 2 that are on the market, which are starting to really improve the execution of the delivery of the therapy. So in my mind, it's kind of an operational race between auto and a scientific race between allo to see which of those can make it to market. I think that having the auto platform to help validate some of the targets is also very important for us as well.

Okay. Great. I wanted to talk a bit about CAR and K versus CAR-T cells. Not everyone has to answer, but whoever has an opinion on it. What are the advantages and disadvantages of CAR and K versus CAR-T cells? And could you ever see a situation perhaps where you'd want to dose both types of cells in a patient?

Well, I…

Maybe I could -- go on.

Go ahead, Dan.

Okay. So we feel very strongly about moving forward with both platforms. Clearly, the clinical validation is in the space of T-cells, and we're very excited about our recently cleared IND for FT819, which was the first iPSC-derived CAR-T cell that we've been developing in a collaboration with Michel Sadelain of Memorial Sloan Kettering over the past 4 years. And we're really looking forward to dosing the first patient with that product this year. And again, that has the 1XX CAR and the TRAC locus under the endogenous sort of the latest greatest bells and whistles that have been refined in the autologous land being deployed in an allogeneic iPSC setting. That said, I think NK cells are sort of building their clinical experience. And certainly, the 11-patient data set out of MD Anderson, out of Katy Rezvani's lab, with a -- I think, the first properly engineered CAR NK cell shows a pretty remarkable clinical efficacy results. And encouragingly, there's very little sign of CRS. So potentially, NK cells might offer this opportunity of efficacy with less toxicity, which would be fantastic. We also really love the ability of NK cells through their activating receptors to recognize and kill stress cells through things like NKG2C and NKG2A, NKG2B, and to tap into sort of multi-dimension targeting in addition to putting CARs on top of that already powerful innate targeting machinery. So we're very excited about moving forward with our CAR NK platforms and seeing how they do head-to-head against our iPSC-derived CAR-T platforms. Our background is actually in transplant where we've grown to know and love and appreciate the relationship between adaptive immune cells. And nature has absolutely designed these things to work together. And preclinically, we see evidence of mixtures of NK and T-cells doing better than either alone and really starting to understand the synergies there. So I absolutely agree with your statement that -- maybe not immediately, but eventually, I do see, especially with an iPSC platform where you can create really defined mixtures of NK and T-cells, I absolutely imagine that that's where this movie is going to end and just leveraging into these natural synergies between adaptive and innate immune cells. So I would say NK cells are that new kid on the block. Early data looks encouraging. We're certainly fully committed, and our iPSC, NK programs is about a year ahead of our T-cell programs. But ultimately, the clinical data is going to be the judge, and we'll see who the winner is.

Got it. Anyone else want to weigh in on the T-cell question? Go ahead, Pascal?

Yes. I agree with Dan that the CAR-T have much more clinical experience. I think that one of the challenge with CAR NK cells is that the clinical expanse is very limited. And there is a beautiful study, of course, that was published and commended a lot from Katy Rezvani, a great work. The challenge in that study, that -- it's only 11 patients. Out of these 11 patients, not many had a durable response. Only one had a CR over 12 months. And very importantly, these were not fully universal calls because out of these 11 patients, 9 were treated with partially HLA-matched and 3 are mismatched cells. So the 2 that were really treated with no HLA match, clearly a mismatch. One didn't respond. The other one responded only for 3 months. So the question on durability of response with NK CAR is still there, and the study, so far, do not answer that question. So -- whereas with CAR-T, we have clear evidence of the durability of response, the duration of response and this idea of functional persistence. So how long the CAR-T can be there and respond with expansion and activity to different antigen challenge there. So that's a very important aspect of CAR-T. And with the way, for example, we are developing our new CAR-T generations with 1XX and PD-1 DNR, we've been able to show that we can have, in animal models, up to 10 rechallenged with the tumors and still being effective there. So functional persistence is still more evident today with CAR-T than it is within NK CAR. And the more you can improve that functional persistence towards duration of response, the better.

Okay. Great. Go ahead, John.

I think it's interesting to hear, I mean, all the different technologies. I think you asked the question whether NK CAR was still something to consider. What's clear is that cell therapy is a therapy. And whether it's iPSC, allo versus auto, donor versus iPSC, NK versus CAR versus TCR, I think what we've discovered at Adaptimmune is that being an integrated cell therapy company that has the capabilities to understand the clinical outcomes, to investigate some of these hypotheses more broadly, when you have research, when you have processing, look at development, when you have CMC and manufacturing, clinical development, and ultimately, commercial, it's going to be the ability to try to understand and absorb all of these technologies and get them quickly into the clinic because of the learnings that we can have so quickly in the cell therapy space that are taking down one path versus the other.

Okay. Great. Quickly running out of time. So let me try to hit some other topics. Two I'd like to hit are lymphodepletion and redosing. So maybe some of you could talk about what your strategy is for lymphodepletion, how you're approaching that. And then for the allogeneic cell therapies, what is your view on the importance of redosing? And what do you anticipate as the challenges associated with redosing and allogeneic cell therapy? Anyone want to take that one?

Pascal, take it.

We have some experience there because we are reducing patients on a regular basis with tab-cel and ATA188. So we know that redosing is possible. It's safe with allogeneic cell therapy. There is absolutely no issue with redosing. And Memorial has done a very interesting experience, and they presented data a few months ago with an allogeneic EBV CD19 CAR, showing that -- not only they have a very long durability of remission. At the same time, most of the patients received 2 dose, the median was 2 dose, without any safety issue. So redosing is certainly a possibility depending, of course, on the type of cells. But with allogeneic EBV T-cell or allogeneic EBV CAR-T, redosing is possible. And then in terms of lymphodepletion, we have 2 types of experience. We have the tab-cel and ATA188. We don't [indiscernible] for that patient. Patient. The cells are expanding and persisting without lymphodepletion. Now in allo CAR-T, we plan to have some level of lymphodepletion. But due to the unique natural biology of EBV T-cells, we believe that the lymphodepletion will be limited there because they are naturally persistent and trafficking to the site of the tumors there. So the idea of functional persistence is something that is very important and can be addressed with redosing, but it can be also address from the ability of B cells to be persisting longer there. And that's something very important for the field toward B cells that can stay longer, remain longer and ensure to have durable remission there.

Okay. Good. And any thoughts on lymphodepletion regimens?

Actually, I -- well, I can say a few words about it. Actually, when we started in the allogeneic space, the idea was essentially to try to maintain the CAR and prevent host-versus-graft rejection. Like so you prevent that graft versus host, so the TCR knockout and the host versus graft. And the idea was to knock out the CD52 gene and to precondition the patient with a CD52 monoclonal antibody, which was alemtuzumab. That was produced by Genzyme, now Sanofi. And this technology is -- seems to be quite robust. And we've seen the data that were presented either by Servier at ASH or Allogene last ASCO. It's being proven very solid. One thing that we're also doing, we're using [indiscernible] for depleting CAR-Ts, such the one like CS1. CS1 is present on most of the immune cells like T-cells, NK cells, B cells, macrophages, et cetera. A bit more on CD8s and CD4s, but the hypothesis is that the CARs such as CS1 would deepen the lymphodepletion and cells can graft alone by itself up to the time it cleans the tumor. And then once the cells are exhausted, then they're rejected. You have also the option just to inject without specific preconditioning besides Cy/Flu or essentially to try to remove beta-2 microglobulin. But if you remove plainly beta-2 microglobulin, you open potentially an NK attack. And when you do a lymphodepletion with Cy/Flu, and you look what are the cells that picks up first, it's usually NKs. But I cannot agree more with Pascal. Usually NK don't expand the same way as T-cells. So potentially, this rejection might be less brutal than a T-cell rejection. So like the knockout of beta-2 microglobulin might be effective. It has to be checked, actually. There are like trials in this year with beta-2 microglobulin removal. Or you can just remove beta-2 microglobulin and replace it by an NK blocker, such as HLA-E, for example. And that might not only block the T-cells but also block a potential NK attack. And so there's a very broad range of different types of things to be done like a deoxycytidine-kinase knockout that gives you resistance to all PNAs, such fludarabine, et cetera. There's a wide array of things. One of the things I think is extremely interesting is [indiscernible] for depleting CAR-Ts, and that opens the gate to something that would be embedded in the CAR. And the CAR makes its place and makes some room and then disappears afterwards.

Okay. Well, maybe just in the last 5 minutes, if everyone could quickly just run through what the key catalysts or upcoming data sets are for each of your pipelines so investors have a sense as to what to expect over the next 6 to 12 months. Maybe we can just go down the line, starting with the Mark at Adaptimmune.

Thanks, Yigal. I'm going to turn this right over to our CMO, Elliot Norry.

Thanks. So a key catalyst for us are, we anticipate updating our CD8 alpha T-cell receptor, MAGE-A4-directed T-cell receptor in the fourth quarter of this year, our Phase I study. That's focused on 4 different solid tumors at this point, head and neck cancer, lung cancer, bladder and gastroesophageal cancers. And then we will also be providing an update on our sarcoma data set that was -- from our Phase I study that was presented initially -- well, in its current numbers at ASCO. But we'll be providing an update on the durability and translational data in the fourth quarter this year.

Great. Thanks. Pascal?

Three key milestones. In just 3 days, we are presenting at ECTRIMS, which is the main MS, multiple sclerosis, congress, a virtual congress: 3 posters, and one of them is very important in the sense that these are new data with ATA188, or MS-specific allogeneic immunotherapy. And here, we are showing the highest-dose cohort for 12 months results on improving symptoms in these MS patients. And then we are also having open-label extension where we have been able to show that the sustained disability improvement that we start to see in the highest-dose cohort are being maintained in the long term. So not only are we aware that patients that were improving at 12 months on disability, but now they're also improving at 15 months. So very encouraging that data. Next, we have the start of a new study with tab-cel in a multi-cohort study addressing a lot of EBV-related cancers. And this is an important study to expand the potential of tab-cel in terms of addressing new patient populations. And last but not least, we are now -- right now conducting our interim analysis for the first pivotal study of tab-cel. And then we plan to engage with the FDA up to a pre-BLA meeting by the end of the year. And if this engagement is successful, we can then initiate the BLA by the end of the year for tab-cel, which will be the first initiation of a BLA for an allogeneic T-cell therapy in the U.S. So that's hopefully a big first for the company in the field.

Okay. André, you want to hit the key highlights for the next 6 to 12 months?

Sure. Actually, it's quite simple. So by the end of this year, we should see data on DLBCL or the NHL trial for ALLO-501 from our partner Allogene, but also data from their new multiple myeloma trial for BCMA. We might see maybe 1 or 2 INDs from our partners. You have to remember -- I have to -- you have to remember that we have also Iovance, that we have entered a partnership like less than a year ago with them. We should potentially see data maybe from like the survey trial, but also one of our trial by the end of this year. We should start also the production of our GMP facility for the raw materials in Paris. And then following this, we'll start to see a comparison between with or without alemtuzumab cohorts for 22, 123 data for multiple myeloma trial for CS1. So 22 is for ALL, 123 for AML. And finally, mid-next year we should go live for our production capacity for CAR-T in Raleigh. And then after this, more surprises. But I'm stopping here. I think it's already a quite rich pipeline.

Okay. Great. And Cindy?

So we plan to file our IND by the end of the year for our sickle cell program and to initiate trials in 2021. In addition, our allogeneic healthy donor program, we plan to present preclinical data at a medical meeting this year and file an IND in the second half of 2021. And we'll continue to advance our iNK programs as well.

Perfect. And finally, Dan?

Yes. So some of the key milestones coming up, we'll be treating the first patient with FT538. Again, this is the first CRISPR-edited product for multiple myeloma. The IND is cleared. The manufacturing is complete. And so that's going to happen in the coming months. We're going to be filing an IND for FT576, which is, again, a dual-targeted, 4-edited product for multiple myeloma. That will happen in the fourth quarter of this year. And we're also looking forward to treating the first patient with FT819, again, the first iPSC-derived CD19 CAR-T cell that we developed in collaboration with Memorial Sloan Kettering. We're going to have some abstracts presented at SITC and ASH later this year. But certainly, 2021 is going to be a data-rich year at clinical conferences for us as we start reporting data across the 9 cleared INDs that we're currently evaluating and a variety of clinical trials for both hematopoietic malignancies and solid tumors. And so next year is really going to be a big clinical readout for us. But this year, it will be interesting as well. So…

All right. Perfect. Well, thank you all so much for participating, and good luck with the rest of the year and the rest of the conference.

Thank you very much. Goodbye.