I think we'll get started now. Thanks everyone for joining, CRISPR Therapeutics presentation at day two of JP Morgan's Healthcare Conference. I'm Wonhee Oh from JP Morgan's Healthcare Investment Banking team, and it's my pleasure to be introducing you to Dr. Sam Kulkarni, CEO of CRISPR Therapeutics. Please be reminded that there will be a Q&A session at the end of this presentation, and there'll be mics passed along, so please reserve your questions for the end. Thanks.
Thank you, Wonhee. We're delighted to be here today at this JP Morgan conference, presenting our corporate overview and our 2024 priorities. Before I jump in, here are some forward-looking statements, which you can also find on our website. It was 10 years ago that Dr. Emmanuelle Charpentier and Dr. Jennifer Doudna did the seminal work to elucidate the platform CRISPR-Cas9, that has proven to be revolutionary in the field of biomedicine, and we're proud to be here today, to have translated that revolutionary platform into an approved medicine in this very short amount of time. We're also very proud to have built a company with a diversified portfolio, with pillars in oncology, cardiovascular medicine, and diabetes, with several data catalysts to come in 2024, which I'll talk about.
Our ethos is to continuously innovate on our platform and keep improving on next-gen editing and next-gen delivery to enable even more therapies in the future. And finally, we continue to run a very disciplined organization and disciplined operation with capital efficiency in mind, especially in this macro environment. When I joined CRISPR in 2015, we had grand ambitions to become the next Genentech and maybe even more. But our formula was simple: One, relentlessly focus on the first indication and bring it to human POC and maybe even to approval. But two, parlay those competencies into a broader portfolio, and three, that's when you can dream of becoming a sustainable biotech company and becoming the next Genentech, and we have done all that in the last eight years. In stage one of the company, we picked sickle cell disease and thalassemia as our first indications.
We worked relentlessly in a focused manner to bring this to approval in what is a record time if you compare it to other platforms that have gone from discovery to an approval, and we've done industry-leading deals to support and finance everything we're doing in our portfolio. We've now diversified into multiple different franchises, particularly as we advance our CAR-Ts in the immuno-oncology franchise and also autoimmune, which I'll talk about, but we now entered into the in vivo realm as well, with our first in vivo approaches entering the clinic late last year and now in clinical trials in ex-US.
In the meantime, this may not seem very important, but what's really important for companies in the cell and gene therapy space is to establish your own manufacturing, and we've established our own in-house manufacturing facility, which won the FOYA Award last year, which is the Facility of the Year Award. Typically, it's been big pharma companies that win this award, and we've built a facility that is the state-of-the-art in cell and gene therapies, with ability to scale not just for commercial in the U.S., but the entire world. That sets us on a path in stage three, as we advance, towards becoming that sustainable biotech company where we can be profitable but continue to finance an innovation engine that produces one or two INDs every year to take on more and more diseases, where we can bring a transformative, curative therapy to patients.
The approval of Casgevy is historic in many ways, not just for the field of biomedicine, but for humanity in general. Sitting here in the Bay Area, we talk about AI and singularity, but the fact that we, as a humankind, have figured out how to edit our own genome to fix our own diseases is another form of singularity, and we're proud to have achieved it in a record amount of time, as I mentioned before, from discovery of platform to bringing this as an approved medicine. And we couldn't have had a better partner than Vertex to help us commercialize this drug and bring this to patients worldwide. We see a robust support system for Casgevy in the U.S., but I would want to highlight the opportunity ex-U.S. as well.
There are a tremendous number of patients that suffer from both severe sickle cell disease and thalassemia in the Middle East, in parts of Europe, and in Asia, and you just saw that more and more approvals are coming in. Vertex just announced an approval in the Kingdom of Saudi Arabia. We already have approval in Bahrain, and the unmet need is very high in several of these markets. More to come on Casgevy, as we launch and as Vertex takes the helm to bring it to patients around the world. But we're not resting there. One of the priorities for us is to increase the addressable population for Casgevy, and we're doing this in two ways.
One is by developing a targeted conditioning agent, which is much gentler than the current transplant conditioning agents, and that would enable 3-4x the number of patients to be eligible for Casgevy than we have right now. But what's key is developing this conditioning agent in a very targeted manner for this particular application, which requires high on-target potency, but very low off-target systemic toxicity, which have been the bane of some of the companies that have tried to develop this in the past. We're making good progress with our c-Kit-targeted antibody conjugate, and we'll have more to say in the coming years, months and years, as we bring this to the clinic.
We're also very focused on in vivo editing of HSCs, or hematopoietic stem cells, in the bone marrow, and we're developing delivery systems to edit these HSCs directly in situ in the patients. We have a $15 million Gates grant to support this work as well because this is the only way we can bring this to the 1 million or so sickle cell patients around the world who won't be able to afford Casgevy in its current form.... 2024 promises to be a pivotal year for the company beyond Casgevy as well. We're proud, as I said, to have developed three additional franchises, one with our IO and autoimmune franchise, one with cardiovascular, with our in vivo approaches, and one with type one diabetes and our cell therapies there.
What we have is probably the world's most sophisticated engineered cells for our CAR-Ts against CD19 and CD70 that we've developed with several edits that I'll describe. And these CAR-Ts have promised not just in indications like lymphoma, but CD19 positive lymphoma, but also in autoimmune indications. With our in vivo approaches, we showed some data late last year in preclinical models, which shows best-in-class in vivo liver editing, and we're bringing those forward in a number of indications. Right now, we've named two indications or two targets, ANGPTL3 and LPA, but we're doing work for many more targets beyond that, should we show that our platform for delivery is safe and effective. With type one diabetes, we probably have the most advanced edited cells that are islet cells or beta cells that produce insulin in response to glucose.
We've started clinical trials with CTX211, and I'll talk more about that trial, but this is a major change in how we think about medicine. You know, the entire field of regenerative medicine, where we can take organs that are mass-produced and don't have to be autologous, but then are edited so that they can be immune-protected, can change the way we think about not just type 1 diabetes, but kidney transplant, heart transplants, and many other organ transplants. I'll start with our autoimmune and oncology franchise. CD19 CAR-T, I know, as we all know, is a crowded space, yes. There's autologous CAR-Ts, there are bispecifics, but yet a very small fraction of patients receive these autologous CAR-Ts, given the complexities of autologous CAR-Ts and the time it takes to manufacture them and the cost.
We had our first-generation allogeneic CAR-T, CTX110, that we put into clinical trials, and we showed that you can actually have durable responses or durable complete responses in patients with lymphoma, and some of these patients we followed over three years now. And we showed that we can get almost 19%-20% durable CR rates. These are six-month CR rates with the form of CTX110 with a single dose. That's a pretty huge accomplishment for taking a new concept like a healthy donor-derived allogeneic CAR-T and putting it into initial trials. But then we advanced from there to do multiple doses, and we did a regimen where we had two doses of CTX110. We improved that six-month durable CR rate even more.
And now we're very excited about the next generation CD19-targeted allogeneic CAR-T, CTX112, which has more edits, and I'll talk a little bit more about these edits that we've discovered, and they're very proprietary and came out of large CRISPR screens that we've done. And that has the potential, based on early preclinical data, but also in early data from human trials, to have much better efficacy and parallel that of bispecifics or maybe even YESCARTA. So more to come on this trial, which is ongoing, and/or dose-escalating right now, but we're very excited about our CD19 next gen CAR-T, CTX112. Now, the biggest idea for the year for us, and the biggest upside may be in autoimmune diseases.
If you went to the ASH conference last year in December, the news that was disclosed, the data that were shown for patients suffering from lupus with autologous CD19-directed CAR-Ts was remarkable. There were complete disease remissions in these patients that has never been seen before. It showed that if you can take CAR-Ts and reset the immune system by depleting all the B- cells, that immune reset can actually completely cure the disease, and not just for lupus, but for other autoimmune diseases as well. What we're thinking is that our CD19 allogeneic CAR-Ts actually have similar data in terms of B-cell depletion. On the right side here is data from our human clinical trials in the oncology setting, but it shows B-cell depletion following CTX110 infusion in nine patients.
What you can see is all the cells, T- cells and B- cells and NK cells, all are depleted initially after the LD chemo regimen and the CAR-T treatment. But over time, the T- cells come back, and then NK cells come back, but the B- cells don't. So you do have this extended period of B-cell depletion, and that sort of B-cell reset effectively can do the same thing that we saw with autologous CAR-Ts and that data that was shown at ASH last year. And not to mention that allogeneic CAR-Ts here will have several advantages. It's off the shelf, it's easily administrable, and in fact, you may not see some of these safety issues that you see with autologous CAR-Ts, like the T-cell malignancies that the FDA wrote about.
So a lot of advantages here, and this may be the place where allogeneic CAR-Ts have the greatest competitive advantage relative to autologous CAR-Ts. So we're moving with urgency on this indication, and we hope to bring it to the clinic in the first half of this year. In solid tumors is the home run opportunity for our company, can change the complexion of what we do as a company. CTX131 is the CAR-T that has the most edits out of any efforts ongoing among various companies or various academic institutions. We've made edits beyond CTX130 and CTX131 based on the observation that with CTX130, we did see responses in patients with renal cell carcinoma, and it's very encouraging to have seen the first complete response in a solid tumor with a CAR-T ever in this world.
But what we did see that those cells in the tumor microenvironment were getting exhausted beyond a certain day. And the key problem to solve was to make sure that these cells do not get exhausted and continue to be effective and cytotoxic in the tumor microenvironment, despite the, the, the various molecules secreted in the tumor microenvironment, including TGF-β. So the edits that we've made to CTX131, in addition to CTX130, are on TGF-beta R2, to prevent TGF-beta-mediated silencing of the effect of the CAR-Ts. And the other one is on a lesser-known target called REGNASE-1. But REGNASE-1 is a very interesting story.
This is a target that emerged from a very large-scale CRISPR screen that we had done at CRISPR, but we hadn't heard of the target, so we were surprised to see it emerge at the top of the list as the best edit you can make for CAR-Ts. Then we ended up, you know, having partnership discussions with a smaller company that had also done a big, large CRISPR screen, and they had come up with REGNASE-1 as also as the top edit. And very recently, Carl June, who who pioneered the entire field of CAR-Ts, did a very large screen and came up with REGNASE-1 as the key edit to make CAR-Ts better.
And so we've incorporated this edit, and we have all the IP around the use of REGNASE-1 edits in CAR-Ts to develop CTX131, and we're dose-escalating in solid tumors right now, especially in RCC, and we hope to have data there as well this year as we continue the dose escalation. Beyond that, we have an autologous effort against the target named GPC3, where we're doing this in partnership with Roswell Park, which is an academic institution. But this is, again, a very sophisticated CAR-T. What's encouraging is companies like AstraZeneca have shown very interesting responses in hepatocellular carcinoma with a similar construct against this target. So we're pushing this forward as well, and we hope to file an IND in the first half of next year in the next 12 months.
Other targets as well that we're pursuing that's on the shelf, and if this platform starts working, we have a very scalable platform where we can bring many more targets into play and push go in a very resource-efficient way. Owning manufacturing gives us great flexibility. This is a picture of our facility in Framingham, Massachusetts. This is the facility that won the award that I mentioned earlier. But in this facility, which is not very large, we're able to produce not just commercial scale for the U.S., but commercial scale that allows to supply globally, and even take India and China, for instance, to expand our CAR-Ts into, at a very low COGS.
You know, in fact, our COGS are down 4x from CTX110 when I compare it to CTX112, and that is a combination of process engineering, process controls, and yield improvement, but also biologically, the edits that we've made that allow these cells to be much more robust and expand in a much better way during manufacturing. So this notion of, you know, this, the fact that we have very low COGS now helps us bring this medicine to patients globally, but also gives us a lot of flexibility, and the fact that we have all this manufacturing capacity means that we can move very quickly in clinical trials. Now, let me move on to the in vivo platform. We have a plug-and-play platform where we have access to best-in-class lipid nanoparticle for delivery to the liver.
We showed preclinical data where we showed 70% editing of the liver in NHPs, which effectively means 100% editing in hepatocytes, because hepatocytes make up about 70% of all the liver cells. Given these data, we're advancing that into the clinic for the first two targets that are validated. One of them is ANGPTL3, and the other one is LPA. And we have many other targets we're working on, including PCSK9, where we're ready to go as soon as we prove that the platform is safe and effective. This, you know, these targets may seem like, you know, the, there's siRNA and other types of therapies against these targets, but a gene-editing approach is gonna change the paradigm of medicine.
Imagine a one-injection approach at the right time point for high-risk patients, where your cholesterol, bad cholesterol is 50% lower for the rest of your life. That's paradigm changing, especially in a world where the compliance is so low for these patients. There are patients who don't like taking injections, and even if it's a siRNA, that's a once every six-month injection, a one-and-done treatment will ensure sustained decrease of bad cholesterol or any risk factors versus a seesaw effect that you see with siRNA. The first of these targets, CTX310, we're proud to say that we're in the clinic now and have begun the clinical trials, but this target has plenty of validation from people who have a natural loss of function on this gene. So there, these patients or people are completely fine and don't have any side effects.
In fact, they have very low LDL-C triglycerides and lower risk of cardiovascular disease. So we're recapitulating this effect that's seen in natural variants in the population, just like we did with Casgevy. You know, in Casgevy, the original thesis around BCL11A, an answer was that there are people with those edits, with high fetal hemoglobin, that we can recapitulate using CRISPR-Cas9. And we're doing the same thing here with the ANGPTL3. And what we showed in NHP data is that you can have a sustained reduction of ANGPTL3 with the high editing rates I talked about before, and that leads to nearly 60% reduction in triglycerides.
We're starting these trials in patients with high risk, in HoFH populations, in patients that have very high triglycerides, and we quickly wanna move through dose escalation here to get to the right and optimal dose. Similarly, we've moved very rapidly to bring our CTX320 program to the clinic, and we've begun clinical trials here, and we're the first gene editing effort to enter the clinic against LPA. And this also follows a well-established correlation of high LPA levels with higher risk of cardiovascular disease or cardiovascular events. And on the left side here is a chart that shows different percentiles of LPA levels, and when you compare the high LPA levels in the orange and red to the low LPA levels in green, you see a significantly higher risk of cardiovascular events and cardiovascular risk.
And that's what we're trying to control by effectively knocking down the LPA, by editing the LPA gene. And we've shown that we can do that at a very high level and also, you know, shown a durable reduction, a 95% reduction of plasma LPA, over a sustained period of time in monkeys. So more to come in the human clinical trials here. In diabetes, we have parallel efforts here. We have our CTX211 program, which was formerly VCTX211, and we recently had ViaCyte opt out of this program, which provides operational flexibility and ease as Vertex and us both navigate the many programs that we have developing in diabetes.
So what we have now is CTX211, where we control the program, and if we're successful, we pay royalties to Vertex, and we also have provided a non-exclusive license to Vertex, where if their programs are successful, we get royalties from their programs. We're also making efforts on a device-free approach using these cells, and more to come on that front as well as we continue the trials on CTX211 and provide more updates. Next-gen editing, we've talked a lot about the various forms of editing. A lot of what we see in next-gen editing is parallel to what we saw with antibodies in the 1980s. You know, initially you had recombinant proteins, then you had antibodies come to the fore, and people started improving upon those by humanizing the antibodies, then creating fully human antibodies.
We're seeing similar improvements by tethering different effector proteins to the Cas9. But what I'll point out is, are two things. One is, we have the foundational IP for any effector protein tethered to a Cas9 to make any edit in the genome or any modification in the genome when it's directed by a guide. And second, we are not tied to one or the other. We're not tied to base editing or a certain other form of editing. We're trying all of these, and it turns out that based on which indication and which target you're trying to address, one may be better than another. So we don't want to be stuck with one platform. We're going to do all of these things.
So we're gonna we have our own base editors, we have our own editors that use reverse transcriptases, we have our own editors that use integrases and transposases. And we'll talk a lot more about all of these, but we hope we're laser-focused on bringing them to the clinic in the not-too-distant future. More so, we're going to manufacture all the component parts that enable this, like mRNA in our own manufacturing facility, that gives us that flexibility, and develop our own LNPs that help us target not just the liver, but other organs, and de-target the liver. So this is a big focus of our effort, not just in Boston, but here in California as well, in Mission Bay, and more to come on this front.
So in summary, we have probably the broadest portfolio in gene editing across different franchises, in hemoglobinopathies, IO and autoimmune, in vivo, type 1 diabetes, and other targets we're partnered as well, and we're progressing all of these forward. Thankfully, we have very strong balance sheet to support all of this. But what's most important is, as we look here at 2024, we have, beyond Casgevy, five assets in the clinic with seven different clinical readouts. That's more clinical readouts than several other companies combined, and we've listed them out here. With CTX112, we'll have data in lymphoma as we progress our trial. We'll initiate our trials in lupus. With CTX131, we'll have data in solid tumors, but also we're going to start trials with heme malignancies.
With CTX310 and CTX320, we talked about their respective targets, and we'll be doing dose escalation there. Finally, with diabetes, we continue to dose patients. Then what we've also said is that we will disclose new targets that we're going after with both our CAR-T and our in vivo platforms in certain part of the year, this year. Plenty of work going beyond what's the visible pipeline. To conclude here, you know, it's been a amazing 10 years for the company to get to this point and have the first approved CRISPR-based medicine in the world, and we're so proud to be at the forefront of that wave, and we believe that the CRISPR wave is just starting. You're going to see tens of indications, if not hundreds, that ultimately can benefit from having a gene editing approach.
We've built a strong and diversified pipeline beyond that, an effective operating engine, and supported by a robust balance sheet to support us in this next wave of growth for the company, regardless of the macro environment and regardless of macroeconomic forces. 2024 is just an exciting year for the company, which will dictate, based on the data, which way we push on the resources and where we add our resources and where we continue to press the accelerator. We look forward to disclosing these data to you, but all in all, we're, we feel very good, and we're well-positioned to build a sustainable, great biotech company on the basis of this great platform. Thank you all.
Thank you, Dr. Kulkarni, for such a comprehensive presentation, and just wanted to take this chance to thank the broader CRISPR team for your leadership and execution in introducing transformal, you know, transformational therapies to the broader market. Let's just open up for Q&A for the floor as well as online. If you have any questions, we'll be passing along the mic, so let us know if you guys have any questions.
... I was just wondering, the CTX211 that does type one diabetes, can you also apply it to type two diabetes?
Yes. A good question, and the answer is yes. We can apply to type two diabetes, because the fundamental concept is you're replacing your faulty islet cells with new islet cells. And, you know, if you think about your pancreas, it's about a banana-shaped organ, but a very small fraction of that are the islet cells that produce insulin in response to glucose. And by making these cells that are immune-evasive in a small device or even free cells, you could just produce insulin, and you can take on type two diabetes as well. Now, that said, from a regulatory standpoint, we do have to move through the severe type one diabetes patients before you get to a broader type two population.
I'm sorry, once that will be much easier. Sorry. And once that, it'll be much quicker to do the type two diabetes, I would assume?
Yes, because we've shown some proof of concept data, and we've shown the mechanism works.
So, for Ex vivo and the in vivo gene editing, what's your main point on the different application in clinical trials? That's the first question. Second question is, in terms of competition with other modalities like RNA, what's your think will be the future and the potential of a CRISPR?
Yeah, I'd tell you, the first question was Ex vivo versus in vivo opportunity? Yeah, this is a hotly debated subject in the field of gene editing. A lot of people believe that in vivo has a lot more opportunity than Ex vivo. But in my mind, I think we're just getting started. I think, you'll see equal opportunity across both Ex vivo and in vivo. And as I was saying, you know, Ex vivo regenerative medicine has tremendous potential. You know, if you look at the number of patients waiting for kidney transplants that don't have it, that number is huge. The unmet need is great. And so if you can create organs off the shelf, Ex vivo, that gives you, that can address several diseases.
Then in vivo, of course, you know, the more we learn about diseases and sequence patients and populations, we're coming up with the new targets. Now, there are targets that we can knock down for obesity, that you've seen with siRNA. So it's, it's just expanding from rare to many more common diseases. And then, you know, again, for in vivo applications and knockdown, the big question is gene editing versus siRNA and RNAi, especially as you get to once-in-six-month or once-in-12-month dosing. But I do fundamentally believe that we're gonna change how we think about medicine. You know, right now, everyone will prefer a pill over an injection, for instance. But the world is changing.
You know, four years ago, people said we may not be able to enroll any patients in our sickle cell trial, and now there's a line out the door. And because we espouse these new technologies, and I do think you're gonna get to a point where people say, "I just want it to be one and done, especially if it's safe. Why do I want to compound toxicities with repeat injections from siRNA?" And so, it remains to be seen, but we feel very bullish about gene editing versus other modalities.
Last question.
You said that you're doing a lot of the manufacturing internally. You have a facility that does that. Is that mostly the, like, the ingredients, like the mRNA, or are you doing the full formulation for the actual GMP product for clinical trials?
It's all the formulation. In fact, you know, for our cell therapies, the key is cell handling. That's where the expertise is, that's where the competitive edge is. And so when we make our CAR-Ts, you know, little things like how we separate the CAR-Ts, how we let it expand, how we let it rest, all those are key know-how items that we wanna keep in-house, and I think that gives us the ability to make healthier and healthier CAR-Ts. In terms of in vivo, we're developing that capability. Right now, our mRNA is manufactured by our partner, CureVac, for the in vivo indications that we have licenses for, and our LNPs are manufactured externally. But I think as we move forward, we'll eventually have the capability to manufacture mRNA and LNP ourselves.
Thank you. Wonderful talk. Can you speak a little bit more about your capabilities on LNP, discovery, if you would expand?
Yeah, so this is a more recent capability that we've built. We've built a dedicated LNP group that is looking at delivery not just to the liver, but beyond liver as well. Interestingly, you know, we think we've found an LNP that has very good delivery to the eye. We'll talk more about that throughout the year. We also have LNPs now that can detarget the liver and get to other organ systems. And of course, HSC editing with LNPs is a key focus. So you know, it's not rocket science with these LNPs. They're the same set of components that we're mixing and matching, but empirically finding what's best is the way to get to the answer in terms of the best delivery vehicle.
And there are good animal models now to test thousands of LNPs, because synthesis of LNPs is not the limiting factor. It was the finding the right models to figure out which ones are the best, and that's something we're doing. Now, that said, you know, we're happy to look at other companies that are developing LNPs and license those in or work with them because we don't have the, you know, not invented here syndrome. We just wanna make good medicines for patients, and so we'll take the best of technologies and put it into our medicines to address the patient needs.
... Maybe just one from my side on BD activity and collaborations. You spoke a lot about, you know, deep pipeline, robust pipeline coming in in 2024, as you replicate success from the past year. How are we thinking about sort of further partnerships amongst your portfolio right now, and what is the right selection criteria in looking at the right partner?
Yeah, thank you. You know, this is something that we've always been good at, is very, you know, doing very good BD deals. Our partnership with Vertex has been an excellent one. We had other partnerships as well. The question now is we have the money, so we don't need the money for, for our programs, but I think it does make sense to look at potential partners because if all seven of our trials succeed, we may not have the bandwidth and the capacity to prosecute all of them all the way to the finish, in which case, we would start looking at potential partners.
You know, interestingly, at this meeting here at JP Morgan, we had to rejigger our schedules because we ended up having a lot more BD meetings than we anticipated outside of investor meetings, because one of the things that people have been complaining about in cell and gene therapies is pharma's not jumping in. But in fact, I do think that pharma's interest in cell and gene therapies is increasing rapidly. Almost every pharma company now wants to have a cell and gene therapy strategy, and there is tremendous interest in some of these targets, especially LPA as a target, is emerging as an important one in the space. And second is, you know, the application of CAR-T in autoimmune is a very large opportunity for big pharma that we've seen a lot of interest in.
Mm-hmm.
So, we're continuing to have BD discussions, not nothing impending, but I think we'll carefully think about what to partner and what not to partner based on how the data develop over the next three to four months.
Maybe just one more question on the in-house manufacturing facility. Obviously, your work is being recognized by a lot for having in-house, which is creating efficiencies, but are there any lessons from perhaps wanting to have that sort of outsourced rather than having it in-house?
Well, when I say we have in-house manufacturing, it's always a hybrid strategy. You know, it's never fully in-house because it doesn't make sense for us to, for instance, make our own guide RNAs. You know, it's a relatively commoditized technology, not fully commoditized, but relatively.
Mm-hmm.
There are suppliers that can make it. So, you know, it's more efficient for them to do it versus us to do it. But there are things where, you know, putting it all together into the cells, and cell handling, for instance, is a key capability where we can't afford to have mistakes. And I think controlling that and doing it ourselves has been a very important part of our strategy. Similarly with mRNA, you know, it's one thing to do the mRNA for a SpyCas9, which is sort of a standard sequence, and so we do it with our partners. But as we go into next-gen editing, you know, every different editor, it's gonna have a different sequence.
So then you have the flexibility to make different mRNA for each application, and these mRNAs are even larger than what we have for the standard Cas9, SpyCas9. So I think, you know, what we have is a very bespoke strategy, and I think, you know, as we think about the different components, we want to retain the high-value components, which give us competitive edge, but then be efficient with everything else so that we have a proper allocation of resources.
Thank you. Any more questions online or on the floor?
Okay.
Thank you again, Dr. Kulkarni and the team. This concludes the session for CRISPR Therapeutics.
Thank you very much.