CRISPR Therapeutics AG (CRSP) Earnings Call Transcript & Summary

Good morning. Thanks for joining us for another session at the 44th JPMorgan Healthcare Conference. I'm Brian Cheng. I'm one of the senior biotech analysts here at the firm. On stage, we have Sam from CRISPR Therapeutics. I will now pass the mic to their CEO, Sam, for a short presentation, followed by a live audience Q&A. Sam, the stage is yours.

Good morning, everyone. Thank you, Brian, for the introduction. We're very pleased to be here today to present the progress and updates for CRISPR Therapeutics. Before I jump in, here are FLS statements. We're nearly a decade into our mission of transforming medicine with gene editing by developing cures for patients with serious diseases. And today, we're very happy to be in a very strong position with progress across 4 franchises. With heme, we have an approved product on the market today, together with our partners, Vertex in CASGEVY, which has a multibillion-dollar revenue potential. We continue to expand the addressable population that CASGEVY can address. And we have efforts ongoing for in vivo gene editing that can significantly improve access for patients suffering from sickle cell disease. Beyond that, we have a tremendous focus on our in vivo platform where we're doing in vivo gene editing of the liver. We published transformative data for CTX310 in November last year, together with the publication, I'll talk more about that data for hypercholesterolemia. And we have a best-in-class RNA that we've expanded our platform with a partnership with a company called Sirius. And this is an siRNA targeting Factor XI that's in Phase II trials. Beyond that, we have a very exciting early preclinical pipeline targeting LP(a), angiotensinogen for hypertension as well as rare diseases like A1AT. We're actually very excited about our CAR-T platform as well. We presented some data at the end of last year towards the -- in December with zugo-cel, which is formerly called CTX112. Very, very encouraging response rates in DLBCL and oncology setting, but also very exciting in the autoimmune setting for SLE myositis and a whole host of other diseases where we can do an immune reset. We also have efforts, which may be new to most of you with in vivo CAR-Ts. And here, we have early data in the preclinical realm, which shows that you can actually achieve in vivo CAR-T with a single administration. And finally, with type 1 diabetes, we have proof-of-concept data from CTX211 in humans, which showed that cells can survive and be stealth in the body, and we're advancing CTX213 as a best-in-class islet-cell therapy for type 1 diabetes. Here's the pipeline and a snapshot showing the progress across these various franchises that I talked about. But let me start with hemoglobinopathies. CASGEVY was approved at the end of 2023 in a landmark approval. It's now approved in multiple jurisdictions around the world. Our partner, Vertex, has set a tremendous groundwork in commercializing this therapy by setting up more than 75 authorized treatment centers around the world. And what you see in this chart here is tremendous momentum for CASGEVY between 2024 and 2025. The number of patients that are initiated have gone up 3x, the number of cell collections, the first cell collections have gone up 3x. And now we're seeing that momentum translate into more cell infusions. We're very happy that we've reached the goal of over $100 million in revenue. The exact number will be disclosed by Vertex in a regular basis, usually in the regular communications. But the revenues are ramping up, and we feel very bullish about CASGEVY and its trajectory. And we want the momentum to continue in '26. One of the things that we highlighted in 2025 was the data in a pediatric population. One of the things with gene editing is you want to treat patients earlier and earlier. The earlier you treat these patients, the less organ damage, the less pathophysiological effects that may happen from the disease. And what we showed are the data are tremendous for children in the 5- to 11-year age group for both sickle cell and thalassemia. And that will significantly expand the addressable patient population as well. And what's been really reassuring is the payer coverage for CASGEVY has been good around the world. In the U.S., the CMMI pilot has been very successful and adopted now by most of the states that assures coverage for this patient population. And globally, I think we have very good coverage in Europe. And I think we're also seeing momentum around in other markets as well. In the Middle East, the coverage has been universally good in Saudi, Qatar, Bahrain, et cetera. So overall, we feel very good about CASGEVY momentum in 2026. One of the things we do, and this is the same philosophy that's shared by Vertex is to have continuous innovation. Once we're very committed to sickle cell disease and beta thalassemia, and we are advancing gentle conditioning agents that would expand the addressable population for CASGEVY. And I think these gentle conditioning agents based on ADCs or antibody drug conjugates will be very meaningful in the patient experience, how long the patients have to be hospitalized and ultimately, I think how many patients can get CASGEVY. Beyond that, we're also quite focused on doing in vivo editing of HSCs or hematopoietic stem cells. And here, what we're doing is taking the gene editing machinery encapsulated an LNP or lipid nanoparticle and directly injecting that into the patients. And that would edit selectively the hematopoietic stem cells. And if you're able to do that, you don't have to go through a conditioning or through an ex vivo transplantation. And that is a core focus for us. On this platform, we've made tremendous progress over the last 2 to 3 years. And here is example data that we're showing in NHPs with a single dose of an LNP mRNA, and we show editing hematopoietic stem cells. And what you see here is that the editing is durable and kind of reaches its plateau of around 50%, which we believe is best-in-class for HSC editing. And if we're able to translate this, and I think the translation usually pretty -- it's not very difficult from NHPs to humans, although we have to go through many more manufacturing steps, et cetera. What this shows is a proof of concept that you could do in vivo editing of HSCs, and that can expand the addressable population meaningfully, not just for sickle and thalassemia but for a number of other indications. There are many indications where you can directly edit hematopoietic stem cells. And these range all the way from diseases like SCID or the bubble boy disease to more larger diseases that are not rare that can be addressed with hematopoietic stem cell editing. Now going to the in vivo vertical. What we presented data on November 8 last year with ANGPTL3 at the American Heart Association, and we had -- we garnered a lot of news because we're entering a new world in the world of heart disease. We published simultaneously in the New England Journal of Medicine. And what we have is a patient coming in and getting a single infusion over 2 to 3 hour, maybe 4 hours, and you get this infusion off the gene editing components and your liver cells are edited, in this case, for ANGPTL3. And within 2 to 3 weeks of that editing, you see a dramatic reduction in this case, in your cholesterol measures, LDL and triglycerides. It's a onetime paradigm-changing treatment to treat severe hypercholesterolemia, severe hypertriglyceridemia and many of these conditions that ultimately lead to heart disease, MIs and heart attacks, et cetera. And so not surprisingly, got a lot of coverage. And the basis for this type of edit comes from natural history studies. On the left is this picture of a village in Italy, Campodimele, where there was a publication where they saw that nearly 50% of the population had a naturally occurring mutation in ANGPTL3. And these people all had hypocholesterolemia or low cholesterol levels of LDL and triglycerides. And there's an association that they all live longer. So it turns out that they have less heart attacks, less MIs or less cardiac events. And the same thing was seen in the 2010 publication, which showed that for both heterozygous and homozygous mutations in ANGPTL3 control for other mutations that were not occurring in these patients, you could see that the LDL cholesterol is lower with 1 gene that's impacted and then 2 genes that are impacted, you get even lower LDL. And you want to be at that 50-milligram per deciliter target for LDL cholesterol and similarly for triglycerides. And so what did our data show? We did a dose escalation study with 15 patients. And what we see is that at dose level 3.5 and DL4, which is 0.7 milligram per kilogram of the gene editing material, you get almost complete editing of ANGPTL3. Now 80% is about the max you can get because ANGPTL3 is produced both in the liver and other organs. So the liver production is about 80% of ANGPTL3. And what we're seeing is we're saturating edit, titrating the edit at about 0.7 mg per kg. And what that led to in these patients is a dramatic reduction in LDL and triglycerides. At the highest dose, you had almost a 50% reduction in LDL cholesterol. And for those -- I don't know how many in the room will have or those listening have high cholesterol, but people try all sorts of medicines, statins, et cetera, you get 10%, 15% reduction. Sometimes it goes away if you're not consistent. Here, you do a onetime "Procedure" gene editing and you have a 50% reduction in LDL cholesterol. This is very, very powerful. And similarly, we saw a 55% reduction in triglycerides at the highest dose. Now some of the data are jumpier because the baselines are different for different patients. Some patients may not have -- may have high triglycerides, but already had low LDL, so you wouldn't see a further reduction in LDL. But what's very remarkable in these data, one, is that even some of the patients had a PCSK9 therapy ongoing, and they still saw a dramatic reduction on top of a PCSK9 therapy, showing that ANGPTL3 is very synergistic with PCSK9. The second point is there were patients -- one of the patients had over 1,000 milligram per deciliter of triglycerides, for instance, which is very hard to control with siRNA. There's an absolute limit to how much you can reduce triglycerides with an siRNA because it's that absolute limit. But gene editing, you don't have that absolute limit. And you saw dramatic control for even patients that have very, very high triglycerides. And overall, it's very safe. There were a couple of patients that had infusion reactions. There was -- were patients -- there was one death, but that was not deemed related to the therapy. It was well after the patient was treated 180 days later. But -- and this shows that the patients are very serious. They all are -- have had secondary -- the risk of secondary events for these patients. But having a very safe approach for editing where you can have a onetime reduction of LDL and triglycerides, it's quite remarkable and paradigm changing, and I think it's going to change how we think about heart disease. The markets -- obviously, the market is huge because every patient with high cholesterol or high LDL or triglycerides could be eligible patient for this type of therapy. But for us, even in the near term, if you look at the very severe patient population, SHTG with triglyceridemia, the homozygous familial hypercholesterolemia or the heterozygous familial hypercholesterolemia and you take a subset of those patients that are very serious, for instance, those that have very high acute pancreatitis events, even that is a very, very big patient population. So I think what we're sitting on here with CTX310 is it could be a multibillion-dollar opportunity and something that could have a dramatic impact on the cardiovascular landscape. Next, we're coming to LP(a). This is another one which is less known in a way. When you go to the doctor, people measure LDL and triglycerides, very few doctors measure LP(a). And it turns out as more and more studies emerge that LP(a) is 6x more atherogenic compared to even LDL cholesterol. And this has been shown with natural history studies, population studies and reducing LP(a) hopefully should alleviate any risk or secondary risk. Now there's a major trial ongoing by Novartis, which is called the HORIZON trial, which is the first sort of trial that has a pharmacologic intervention with LP(a) reducing siRNA or ASO, and we'll see what the data show us from an outcomes basis. But what we did is we developed CTX320, which is our first-generation LP(a)-reducing agent, and we saw up to a 73% reduction in LP(a) levels from CTX320. Now we have the benefit and luxury of time before the HORIZON data come out and we can decide what our path forward is for a Phase II or a Phase III. And so what we've done is actually develop a second asset, which we call CTX321, which was in preclinical studies shown to be twice as potent as CTX320. So if HORIZON trial shows that about 70% reduction of LP(a) is sufficient to have benefits and outcomes, CTX320 is there. But in parallel, what we'll have is CTX321, which should get us to 80% or 90% reduction of LP(a) levels. If you do the cross comparison between CTX310 and 320 and 321 based on NHP data or preclinical data, basically CTX321 can be projected to have much higher reduction of LP(a). And so that will dictate how -- at the end of this year, how we proceed forward with Phase II or Phase III studies, obviously informed by HORIZON trial. Then we have 2 additional programs that are very, very exciting. One is CTX340 targeting angiotensinogen. And this is probably the only agent that has shown this level, 53 millimeters of mercury, this level of blood pressure reduction in this mouse model. No siRNA or no other agent has been able to do that. This is a dramatic reduction in blood pressure. And it doesn't happen when there's no high blood pressure. It only happens if there's high blood pressure, you get this reduction. So this is going to the clinic soon, and we'll have data on this not in the too-distant future. The second one I want to talk about is A1AT. We have a new platform called synthase editing, which does very precise editing of the A1AT mutation that causes A1AT, which is the E342K. And this is very, very potent. Even at 0.1 mg per kg dose, we're seeing substantial editing and saturating editing at 0.5 mg per kg dose, which is lower than what we saw with 310, CTX310. And what you're seeing is a complete reversal from the Z-AAT, which is the pathologic version with the mutation to M-AAT, which is a normal version and on the right side there. And I think this is a best-in-class therapy for A1AT from a gene editing standpoint. And then I'll talk about our siRNA platform, which is a new platform for us. We did a deal with Sirius Therapeutics in 2025. And with that, we acquired CTX611, formerly known as SRSD107, and this targets Factor XI. The anticoagulation market is a $20 billion market, but there hasn't been much innovation in this space for a long time because some of the DOACs that target Factor Xa have been very good at anticoagulation, but that comes with severe bleeding risk. And there are many, many patients that cannot access DOACs and still rely on heparin or other agents, including vitamin K because they're not eligible for DOACs. Factor XI only works on one of the pathways that relates to thrombosis, but -- that relates to hemostasis, but if you target Factor XI, you can prevent thrombosis. And that opens up a huge opportunity where you could have an siRNA agent, it's once every 6 months that does the anticoagulation part without any of the bleeding risk. And that becomes the holy grail in the space of hemostasis and thrombosis. The data presented by Sirius are incredible. This shows that nearly 6 months out, you get 93% reduction with 95% peak reduction in the Factor XI antigen. And with siRNAs, it actually is reversible as opposed to antibodies. And that gives us another big advantage over antibodies as well in this class of medicines. I'll skip forward. This is the clinical trial design. We have a Phase II trial that will have a top line data hopefully, end of this year, in the second half of this year at some point, and that will be the gold standard in the TKA study, the total knee arthroplasty study. We also have a [indiscernible] design with the CV study, which informs dosing paradigm going forward for this therapy, which also will generate a lot of data this year. And I don't have to belabor the market opportunity with this therapy. This is in the billions of dollars. This is a very, very large market opportunity. It will be competitive, but I think we have a best-in-class siRNA. And then going on to CAR-T with zugo-cel, if you look at the CAR-T, it's almost -- it's over 13 years now since Emily Whitehead story and the emergence of CAR-Ts. And CAR-Ts originally developed in oncology, started with autologous, then there was allogeneic with healthy donors, allogeneic with iPS-derived, and then we have in vivo going from viral and nonviral approaches. And I think the blue areas of what CRISPR strategies are. We went with allogeneic with healthy donor, and that's what zugo-cel comes from, and the data looks very, very good. Because we use editing, they're almost as good as autologous, but with the cost of goods is much lower and the ease and convenience of an allogeneic. And with in vivo, we're going with nonviral approaches because we think ultimately, that's what's going to win compared to viral approaches. So this is the design of zugo-cel and the 2 potency edits, the Regnase 1 and TGFbetaR2 make these very, very potent and almost autologous-like in its phenotype. And these are the expansion data. So if you look at expansion data, when you put the CAR-Ts, zugo-cel in patients, one of the key things is how do they expand. And what we show here is expansion in NHL, which is in the oncology setting compared to expansion in the -- with SLE patients in the autoimmune setting. And you see comparable expansion. And the expansion here is much higher than any of the other allogeneic CAR-Ts or CAR-NKs out there. And you're seeing deep B-cell depletion on the right side. And this is just in line with autologous therapies where you have about a 90-day median for B-cell reconstitution in these patients. This is very, very important. If the B cells come back in 20 days, you don't have the immune reset. You need to have a deep immune reset, similar to autologous therapies that we've seen data for. And here are data, and there's a couple of elements that are new here. We had -- in December, we showed patient data for one of the SLE patients who was in drug-free remission up to 6 months. And here, we show that, that patient is still in drug-free remission at 9 months. And the second SLE patient also has gone down to SLEDAI score of 0. And by the way, these patients are severe patients. These patients have tried 9 or 10 other agents and not gotten better, right? And they take 1 dose of zugo-cel and they're SLEDAI 0, and it's an amazing improvement in their lives. These patients are young, young females who've had a dramatic change in their life after treatment with CAR-T. In oncology, here are the baseline characteristics, very severe patients, all high risk, several primary refractory, all with SPDs above 2,000 millimeter square. And in these patients that are very sick, that -- many of them have actually gone through T-cell engager therapies and not responded, one even went through an auto CAR T before and then they were treated with zugo-cel and they had complete responses. This is remarkable. I don't think there's any other allogeneic therapy out there that has shown responses after auto CAR T. And what we have is a 70% CR rate with zugo-cel in the oncology setting, which gives us a lot of confidence in moving this forward. At the same time, the safety profile is very tolerable with a 17% CRS rate, Grade 3 CRS rate. And what we're doing is further embellishing the prospects for zugo-cel in oncology by doing maintenance with pirtobrutinib. And we have this agreement with Lilly now to do -- to use a BTK inhibitor because what you're doing is you're doing complete B-cell reduction with zugo-cel and then you're preventing maturation of any remaining B cells, and that can give you very sustained and durable responses. And this -- there was an autologous CAR-T data set released last year that showed that this combination can be very powerful. And I think this is something that could be a very important option for patients. There are a lot of elderly and frail patients, for instance, that cannot take R-CHOP even. They do mini R-CHOP. There are patients that are not eligible for auto CAR Ts that don't have access to auto CAR Ts. And I think doing this type of model where you do a deep depletion and get them to CR with zugo-cel followed by pirtobrutinib can be very important. And finally, what I'll leave you with is our in vivo CAR-T approach. It's a very proprietary LNP system with proprietary mRNAs sequences and modifications that we've made for both transient CAR where we put the mRNA expressing the CAR in the LNP and you express the CARs that last a few days and deplete the B cells or any target that you're going after, but also integrating CAR-Ts that can have permanent CAR-Ts based on LNPs without using any viral elements. And here are some snippets of data, and we'll have a lot more of these data over the coming year. But here is a monkey experiment where we express GFP instead of the CAR. And we show that day 1, day 2, day 3, nearly 50% GFP expression in 50% of cells express GFP. And these are T cells that are targeted. And that is actually best-in-class for NHP studies, showing expression for transient CAR. And what we show is very targeted. On the right side, we show in mouse experiments that if you do the same thing with the liver targeted LNP, you see a lot of expression in the liver or with -- but with the control or the LNP that we have, which is targeted towards T cells, you have no expression in the liver. So it's directly targeted immune cells and you get very high expression. And this is data for transient CAR, but we also have permanent CARs we can make with the same solution where we actually integrate the CARs into the T cells. So that's very exciting. And then finally, with our type 1 diabetes effort, with CTX211, we saw really encouraging data where in 5 patients, we had C-peptide production out to 12 months. And you saw that means the cells were surviving without any immunosuppression out to 12 months in patients after implantation. Now -- but we were doing this in a device context and the device did have fibrosis. So I think we want to get away from that device fibrosis and do directly injected cells. And we have CTX213, and here are data with CTX213 in an STZ mouse. This is a mouse that has artificial high levels of glucose. And you see glucose control within 14 to 15 weeks after implantation. You have C-peptide levels that are in the 1,000 picomole range with a pretty low dose of cells. And you already worked out the [ stealthal ] elements of this with the CTX211 trial. So I feel very confident about CTX213 and moving this forward, and this is probably best-in-class in terms of C-peptide production. So final slide here, we have a lot to look forward to. We just have -- one of the things people say with CRISPR is we have so many things going on. But the good news is the technology is so powerful that we can actually do all of these in a very cost-efficient manner across franchises. We'll have updates on CASGEVY. We'll have updates on in vivo HSC on the heme franchise. On the in vivo side, we'll have data for 310. We'll have data for 611, 340 and 460 will enter the clinic. And obviously, with the LP(a), we'll see how 320 and 321 stack up in comparison the HORIZON trial. And finally, with our CAR-Ts, I think we'll have data for rheumatology, but also we expanded that trial now to include ITP and wAIHA and similar to oncology. So it's going to be a very exciting '26 and actually a very exciting few years to come. And thank you for the opportunity and happy to answer any questions.

Well let's start the Q&A session. For those who are in the audience, if you have any questions, feel free to raise your hands. For those joining us virtually, you can submit questions on the portal. Sam, lots of data updates in this slide deck, lots to digest here. Let's start off with more of a big picture question. How should we think about 2026 focus? There are multiple catalysts in front of us. Which component in the catalyst timetable do you think investors really need to take a close look at? Which program are you most excited about?

Yes. I think if you think about the value of the company, you can actually think about it in 3 parts. There's CASGEVY and the commercial aspect, right? And we'll have continuous updates on that. There are 3 Phase I assets that have shown exciting data so far, right? 310, we have 611, which is our siRNA and we have zugo-cel. And for all 3, the question is a little more data, but also what's the regulatory path forward? And what's the pivotal trials we're designing for those. I think that's as a company, those are things that we're working through right now, especially with the FDA and regulatory agencies around the world as to what that path forward is. So that's the second part of the value. And then we have this third tranche of value or a third set of value drivers, which is all the preclinical assets that are going to become clinical assets soon. Like A1AT program could be a crown jewel for us, for instance. It's a best-in-class program that's better than any solution out there that will go into the clinic soon. AGT is something I was talking to some of the KOLs after our American Heart Association presentation for 310. And they were very, very excited about AGT because refractory hypertension is very hard to treat and is actually one of the main reasons for mortality for patients that are older. And so that's another program, for instance, that's in the preclinical realm. And so that's sort of the framework for how we think about '26 as sort of this stepping stone pivotal year that tells you what the Phase II of the company is going to look like.

So since you mentioned pivotal trial for some of these early proof-of-concept indications, let's start off with AAT. I think this is where it gets interesting. You start to hear a little bit more clarity on the regulatory path forward there. What's your take for your AAT program as you start to really think about what that's going to look like 2, 3 years down the line? And just layer on top of that, how do you see your program differentiating from others?

Yes. One thing I'll say on the regulatory front is this FDA, I think, has been very, very supportive of gene editing. I've had a number of interactions with the leadership of the FDA, and they're very forward leaning. And you saw that with one of our peers' disclosures this morning about a pivotal trial that has 50-ish-odd patients, right? I think that's a very good sign for how the FDA are looking at gene editing. And I think you'll probably see a similar path forward, not just in rare diseases, but also common diseases like autoimmune. We have to work through that. But I think that's -- I suspect that as the year unfolds, we're going to see a lot of regulatory clarity for a number of programs for us. On A1AT, the big question is, I think a lot of these types of diseases are going to get treated earlier and earlier in life. And what you want, if it's your child getting treated or someone you know, you want the best possible solution for that patient or that person suffering from this mutation or this disease. And what you want is as normal phenotype of AAT production as you can get, which is in the 20 to 25 micromolar range. And so we'll see where our data stack up. But from a preclinical rat models, which are very predictive, it shows that we may be the best-in-class. If you take the same dose, 0.5 mg per kg and say how much M-AAT production is happening in these rats and just look at everyone else's data, we're far superior. So I think that's why we want to be -- we do think this is a very important value driver in our portfolio.

So I think if you look back at a year or 2 years ago, when you look at the same field, competition once to get at 11 micromolar, that's sort of the magic number that people want to aim at. As we think about the bar, I think certainly, the investor community has really shifted away from 11. We're shooting for higher. Where do you think the bar is now for your program? And ultimately, how do you win from the biomarker perspective? Is it 20? Or is it 25? Where do you think ultimately you want to show?

Yes. I mean there are a number of KOL calls and things that have happened in the last few months. But the closer you get to 20, the better off you are. Now does that mean that if you get to 18 micromolar, that's a bad solution for patients? Probably not. I mean that's actually a pretty good solution compared to where they are now, which is 4 to 5 micromolar of AAT production, right? And you want to do it earlier in life because you don't want any of the damage happening in the lungs. And so the higher you get the better. And I think that's what I'm saying is if you have a program that gets to about 15 micromolar versus one that's 18, I think patients are going to choose the one that's 18. Now you have to put everything else in context, what's the safety profile, everything else, et cetera, what's the body of evidence on this trial versus another. But I think our goal, and that's the beauty of the CRISPR platform or gene editing is you can try to get near physiologic levels and get better and better and better. So that's our quest with every program. We want to make it better and better and better as we go along.

And then switching gear into the in vivo side of the story. The cardiovascular space, you're really moving forward with ANGPTL3 and LP(a). LP(a), the hurdle seems to be waiting for what HORIZON shows, then you pick the winner to move forward. Do you see the path forward here as kind of a pick one scenario where you're deciding to pick ANGPTL3 versus LP(a)? Or do you ultimately think that you'll pick one and then partner off the other assets?

Yes. I mean it's a good question. This is one of the things -- if you think about the 3 assets I talked about that have shown encouraging Phase I data, right, we have 310, we have 611, we have zugo-cel and we have LP(a). Can we develop all 4 on our own? Probably not. I think we'll probably need to partner one or the other. But I think we have the luxury at this point with our balance sheet to continue developing these to a point where we have to make that decision, which is not -- may not be in '26. But that said, pharma interest is definitely on the ascendancy in terms of cell and gene therapy again. There was a period of time in 2018, 2019, everyone was very excited and interested. Then we had a few years where there wasn't as much interest from big pharma. But I think as we get into beyond rare disease into common diseases, we definitely are seeing a lot more pharma interest. So I think we'll have more optionality than people imagine in terms of what to do with these different programs.

And any questions from the audience?

My name is Charles Bruce, I'm from Mayo Clinic. I have a sort of broader question. How will society afford these? And how are you impacting early development with ultimately being able to afford all of these life-changing treatments?

Yes. One of the interesting things here is we're actually trying to reduce the cost of health care to the system. If you -- and we're working with Mayo Clinic on trials, for instance, with the first-generation programs like CASGEVY, they are expensive because they're very expensive to make. But if you look at our cardiovascular programs, it's not hard to imagine that these could be priced sub-$100,000. And if you look at siRNAs that are priced at $10,000 to $15,000 per year, and this is a onetime solution, you're actually creating pharmacoeconomic benefit to the system by using gene editing. So same with our allogeneic CAR-Ts. Our allogeneic CAR-Ts now are on a per patient basis, truly less than $10,000 per patient. In fact, we're doing trials now in India with an allogeneic CAR-T because they just can't afford autologous CAR T. So I do think onetime interventions sort of gene editing procedures will reduce the cost eventually. But we have to be able to continue investing in the near term to get to that point. It's not going to be an immediate switch.

Dr. Diana Ramos, California Surgeon General. This is very exciting. My one question is, are there any outcomes and differences compared for race and ethnicity? I know there's some response differences for black communities, specifically for hypertension medications. Do you see any of that with the medications or with the CRISPR technology? Or are you looking at that?

Yes, absolutely. There are lots of differences. In fact, if you look at PCSK9 and the identification of PCSK9 as a risk factor, there was a parallel research going on in France and from -- with a physician in Montreal, who is a scientist out there in France and then one in Dallas. And the Dallas population had a lot of the -- had a higher proportion of black participation in that trial. And there's -- what we've seen is there's SNPs that are out there that are specific by race that render risk differently to different populations. And so this is something that's going to -- as we get more and more sequencing, we're going to learn more and more about. And in fact, the thalassemia that you're seeing in Thailand is very different from the thalassemia that you're seeing in the U.S. And so we can actually treat all of them differently now as opposed to sort of a blanket trial that says, here's a dose based on a general population versus a tailored solution.

Neil McCallum, nice to be here. I'm just curious your take on AI and clinical trials.

Very, very broad question. And it's -- well, I'll just tell you is what AI is doing in the world of CRISPR. It's actually generally in the pharma world is impacting efficiency of trials, how we think about reducing the cost of trials, et cetera. But for us, the places where it's coming into play the most is protein folding, but now also mRNA folding and mRNA secondary structures when we design mRNA for CRISPR. Then the third one is guide selection or where to interrogate in the genome and AI is helping. The data sets are not as big as some other areas, but it's getting bigger. So those -- our AI efforts right now are largely focused on the preclinical realm and not yet going into the clinical, but eventually will.

I'll ask the last question here. When you look at the cell therapy space, I think your peers have seen a lot of challenge in getting the credit for things like autoimmune and B-cell lymphoma. What's your take on that? And how do you see zugo-cel kind of breaking that barrier where we sit today?

Yes. I mean I think it's for a good reason. I think a lot of the allogeneic therapies, the first-generation ones were not as good as autologous therapies, right? And I think we want the best solution for patients. And in the oncology setting, if you kill 99.9% of the cells versus 100% of the cells, the cancer is going to come back. And what we did is our first generation similarly was not as good as autologous. But what we did is continuously innovate and now we have zugo-cel, which is a second-generation product that seems to be as good as autologous with all the convenience. And I think that's when you're going to see credit as we can generate more data. And in the autoimmune setting, you get 99.99% of the cells. That's actually still a very good outcome because it's not a tumor, it's not going to come back as easily. So we are very, very bullish in the autoimmune space. We're expanding trials. We mentioned ITP and wAIHA, but we're going to go in targeting other indications as well. I think the immune reset concept is going to be a major way we treat autoimmune diseases.

Thank you so much for your time. That's all the time we have. Thanks for joining.