CRISPR Therapeutics AG (CRSP) May 12, 2026 Conference Transcript

Hello, everyone. My name is Alex Janahan. I cover CRISPR Therapeutics at Bank of America. Thanks for joining this session with CRISPR. And I'm pleased to introduce Sam Kulkarni, the Chief Executive Officer at CRISPR for this 30-minute fireside. Thanks for being here, Sam.

Thanks for having us.

Yeah, great. Well, maybe just to kick off, you've described 2026 as kind of a stepping stone year, some pretty important early readouts from six programs in the second half. I guess, how do you sort of prioritize the focus within the company on the earlier stage versus supporting, you know, Cash Jevy? And, you know, where are you sort of directing investors sort of in the remainder of this year?

Yeah, it's an exciting time for the company. We've been around as a company for about 11 years, The first phase of the company was all about Caschevy and bringing that to the market to patients that really needed a drug that were suffering from sickle cell and palestinia. And upon the completion of that phase, or as we got that to the end of the clinical trials and to commercialization, we started a number of other programs. And at this point, we're in the second phase of the company where these assets are starting to mature and we're seeing more data. So we have six assets, as you said, that will all have data in the next 12 to 18 months. And those are one bucket of that is in cardiovascular. That's with CTF310 that targets ANG-PTL3. This is a program that can reduce your LDL, cholesterol, and triglycerides by almost 50% of the single injection. We have Zugocell, which is a cell therapy for autoimmune disease, and a single infusion of that can reset the immune system and treat not just one or two, but several autoimmune diseases. We have CTX-611, which is a long-acting sRNA that basically is a promise of a blood thinner, efficacious blood thinner, without the risk of bleeds. So that's another powerful concept that could be a $20 billion market. And then beyond that, we have this extension of some of these programs like CTS-340, which is a program that treats hypertension by targeting angiotensinogen, which is upstream of the ACE-R pathway. And that is an important target that can actually reduce your systolic blood pressure by over 10 millimeters of mercury. So that's a powerful concept. And, of course, we have LP little a, which is a highly watched event in the industry. This is the Horizon trial from Novartis that can inform which way LP little a goes. And finally, we have a foray into rare diseases with alpha-1 antitrypsin. And we think we have a best-in-class product for that program. So, yes, our plates are full with a number of these assets. And by the way, we have preclinical platforms as well that we're moving forward. How do we think about resource allocation? I think, you know, Caschevi over time, we expect the spend on Caschevi to keep going down at some point will turn profitable. And then we have to get to what the phase threes are for these assets that we just talked about, and then advancing the preclinical to clinical. So, you know, it's hard to put exact numbers on this, but, you know, right now it's 40, 40, 40, 20. It probably becomes more, you know, 30, 50, 20 over time. But I think we're keeping a careful eye on all this. And we get to gain tremendous efficiencies by doing a portfolio of products versus one.

I guess when we think about Casjevi and sort of how that's helping you build a growing base on the top line for supporting the rest of your clinical investments, I guess maybe at a high level, like how is that launch tracking with your expectations? What are sort of the trends you're seeing end of last year and the beginning of this year, sort of on the scripts and any other comments coming out of the 1Q print that you'd highlight?

Yeah, it's gaining a lot of momentum. It's very different from typical launches. You know, typical launches, you can start tracking new RXs or total RXs right away, and patients are getting treated right away. Here, we're talking about a one-year lag between a patient coming into the program, per se, and saying, I want to get Kastchevi, to ultimately getting treated, and then for revenue recognition. And the reason for that is you have to collect the cells, manufacture it, get it back. Now, that causes a sort of a – it takes time to build up. So initially, when you build the ATCs up and you have this time period between initiation and infusion, revenues sort of take a while to start ramping up. But you're seeing that ramp now. And if you think about the funnel in terms of three different parameters, one is the number of patients initiated. And what that means is the patient has gone through a referral, expressed an interest in getting caschiavi. Oftentimes, they're already preauthorized from an insurance standpoint. Then those patients then move to the next step of the funnel, which is self-collection, and then finally to infusion. And there's a time lag between all of these. But if one starts inflecting, if initiations start inflecting, you're going to see a quarter, two quarters later, you're going to see an inflection in collections, and a quarter or two later, you're going to see an inflection in revenues. And what we said in this recent OneCube grant, as you called it, which is in the first year of launch, 2024, we initiated about 100 patients. This is our partner, Vertex, leading commercialization. The second year of launch, 25, it was 300 patients, over 300 patients. So it's a 3x increase. And in this 1Q update, we just said that we have over 500 patients initiated. So you're seeing, you know, almost exponential progression in terms of patient initiation and that momentum continuing, which should translate to greater revenues. And the other thing is, we're establishing this around the world. We're continuing to get tailwinds. For instance, we've now submitted for a pediatric label. Right now, the approved label in the U.S. is 12 and above in terms of age. We'll get it down to 5 and above. Because you want to treat kids early before there's any damage to their vascular system, any damage to their organs, that's a tailwind. That's going to help. The second thing is the reimbursement. We just announced a reimbursement agreement in Germany. And that, of course, was one of the hardest ones where a competitor of ours had tried to go in there and withdrew their product because they couldn't get reimbursement. But with Kastchevi, we have a reimbursement agreement. So those tailwinds will start to add up and continue the momentum well beyond what we're seeing right now.

Great. And I guess when we think about the conversion of patients in the funnel to revenues, I guess, what kind of visibility do you have? And what's sort of the timing around that exponential growth, as you said, in the new patients going on or, you know, getting the cells extracted, right, for the manufacturing? How does that acceleration kind of then accelerate the top line growth?

Yeah, I mean, I think that's why I say, you know, it's probably there's some lag, whether it's two quarters or three quarters from initiation to the revenues. It's hard to say at this point, but it's a certainty that it all falls through because you're not seeing patients drop out of the journey. So it's just a matter of time. And over time, that timeline won't matter because, you know, you're going to have a constant shape of the funnel, if you will. There's equilibrium around that timeline from initiation to launch or to getting infused in recognition of revenue. So, overall, I would say, you know, we have forward visibility. Our partner Vertex was very bullish on the expectation, or I guess they didn't guide to the exact number, but generally positive guidance around how they expect Caschevy to do. And I think from what I hear from physicians and patients, the words getting out there, you know, this is without sort of the classic DTC marketing and all that stuff. All the patients know about it. And more and more patients are interested in getting therapy, which is great for the entire population.

Yeah, that's great. And I know you're also developing, I guess, gentler conditioning agents and pursuing in vivo HSC editing to sort of broaden the access further. I guess, how material a difference could gentler conditioning make in real-world uptake? Has this been sort of a barrier from your experience? And I guess, when could that data be available?

Yeah, I mean, you know, we haven't guided to when gentler conditioning might come into play, but it will be a major tailwind for the product. And the reason for that is it expands the population. You know, you go from just the most sickest of sickle cell patients to saying even the ones with moderate disease should actually get Caschevi. And what you're looking at then is just potentially a three-day hospitalization. So that's why it's called gentler conditioning. And it's very targeted depletion of the cells of the HSCs to make room in the marrow. So we feel very good that that's going to be the next leg in the life cycle of the product. And that's going to expand the addressable market almost 3x if we can show that this using gentle conditioning can lead to the same results that we saw with the full busyl fan conditioning.

And I would expect that the value of the product would significantly go up whenever we fully disclose the timeline of gentle conditioning that's coming into play. and i guess as we think about the the commercial um landscape there there are i guess alternatives for patients with beta thal and sickle cell disease in practice when you know physicians are choosing between caschevy and say like a lentiviral approach you know what are sort of the key decision factors there and you know is crisper winning those conversations yeah i think Right now, ex-US, Kastchev is the only option.

You don't have any other products available for patients. So that conversation is different, obviously. It's just, do you want to do a curative therapy, and when do you want to do it? In the US, in some of the sites, both Kastchev and Lifjeni are available. And you're seeing some share split at the moment. But generally what we're finding is that the physicians, now that they understand that, you know, Caschevy has a lot of manufacturing support, there is, you know, strong companies behind it with Vertex and us, and it's a reliable sort of partner to deliver the drug product to patients. I suspect that you're going to see more and more patients shift towards Caschevy. And one simple reason, because, you know, when you have a viral versus a non-viral product, I mean, you're safer picking a non-viral product because you just don't know the unknown unknown of having a, you know, retrovirus-based product. Now, not every patient will care about that, nor every physician, but I think you're going to see a share shift towards Caschevi that that will be palpable.

I guess, you know, circling back on the pediatric review, you've got a commissioner's NPRV, I believe, for that. So that could be available soon, right, if they're true to their word on sort of the expedited review there. How do you think of that as a TAM expander, getting patients? Like, is there a higher demand in younger patients for sort of a one-time treatment like this, from your experience?

Well, it's just another bolus of patients, right? And I hope with the agency, we get that approval soon to go into these younger patients. The other thing is, you know, you're going to get a number of other centers into play in a big way. You know, a lot of children's hospitals are actually very good at doing these types of procedures, and they can start bringing their patients into the mix and become some of the higher prescribes centers. And so the pediatric expansion definitely will be a tailwind, not just from expanding the number of patients available in the bolus, but from a center activation standpoint as well, or the center velocity of treating patients. So we expect that to be a major positive.

Any other tailwinds or headwinds that you think could impact Cacheve this year? I know we saw 43 million in 1Q, but is sort of the way that the street's thinking about the escalation in sales, is that realistic?

Yeah, we don't see any headwinds at this point, really. Our partner, Vertex, is doing a wonderful job executing against the program. And a lot of it is operations with supply chain, with all the, you know, patient handling and everything else. So they're doing a great job. And I think I only see positive momentum with the program. So it's hard for me to say what the three expectations are. You know, there's different analysts who cover CRISPR versus Vertex, et cetera. But generally, we feel comfortable about the trajectory of the product.

Okay, great. Great. Well, I do want to maybe shift gears here and talk about the pipeline, which I'd say is, you know, equally or even more exciting for sort of the future growth for the company. But maybe just starting with CTX310, this is your LDL-lowering NHPSTL3 asset. I guess you showed a single-dose reduction in LDL triglycerides, safe early profile. you know, what sort of response thresholds in, you know, homozygous FH and severe hypertrite edemia would be maybe sufficient to design a registrational trial? Like, what do you think is sort of the bar for investing further in this program?

Yeah, for those who are not familiar with the program, we showed some landmark data in a late breaker at American Heart Association last year and these data were for 15 patients that received ctx 310 and one the lmp-based delivery was very safe you know we barely saw any elevation of liver enzymes and even if there's some elevation it self-resolves within you know very quick period of time so it's very safe so you have this prospect of going out there get sitting in a chair for a three-hour infusion and your liver cells are edited, and you're going to have 50% lower LDL or triglycerides for the rest of your life. And that's a pretty powerful concept in how medicine may evolve for cardiovascular, to treat cardiovascular risk or prevent cardiovascular events based on some of the risks that are seen earlier. So where does this take us on the program? Obviously, something like that is momentous, but people are still trying to get their handle around how is gene editing perceived by the physicians etc and this is where i see a big disconnect you know if you look at our inbox on the info at crisper we get so many requests from patients around the world wanting to do gene editing for their triglycerides or ldl cholesterol physicians are universally excited about what the prospects are here and by the way this is not going to be an expensive million dollar therapy it's going to be much actually going to save the system money at the end of the day by doing it one and done. So I see, you know, something, you know, 310 having unlimited, uncapped value, but it may take some time for the value to be recognized. And I think a lot of that will be based on going to the FDA or the international agencies to say, what is a path forward for a phase three? And to your question, you know, for HOFH, which is homozygous familial hypercholesterolemia, the bar is very low. All you have to show is that there's further reduction of LDL cholesterol post agents like PCSK9. And we've already showed that for two patients in the initial data set. For severe hypertriglyceridemia, which is a large population, by the way, much larger than people think, again, the bar is not very high because you're already seeing a lot of triglyceride reduction. We just need to do it in a few more patients and put the data it together and go to the fda and say you know this type of registration trial makes sense here or not and um i suspect you're going to see a favorable opinion from the fda in terms of how big a trial needs to be and how fast we can go so that that'll be the unlock on 310 and similarly for 340 uh is to get regulatory guidance around what a path to registration might be And that'll come soon enough.

And I guess on 340, different target here, but I guess when this enters the clinic in the first half, you know, what is sort of a twice yearly, or what does a CRISPR edit offer over like a twice yearly SI RNA in this indication? Is there kind of a minimum efficacy or blood pressure reduction that you'd want to see?

Well, the benefit of a gene edit for blood pressure is, let's say, you know, people have varying degrees of high blood pressure. You can just basically reduce everyone's blood pressure by 10 to 15 millimeters of mercury and still modulate with the different medicine, right? The problem with sRNAs, you know, you have one that's every three months. You may have one that are once every six months or whatever, right? But towards the end of the dosing period, you're going to get a creep up in their blood pressure. And that's kind of dangerous for these patients because, you know, all it takes is one hypertensive event and something fatal could happen or something bad could happen to the patient. So what you want is a consistency of blood pressure so you can manage these patients. And that's the promise of CRISPR gene editing. Even with the best sRNA out there for LP little a, you saw that after two six-month cycles, only 80% of the patients remained in control for the entire period of time. So towards the end of the dosing period, you're seeing people, you know, be out of control from what's recommended. So I think at some point this question is going to flip and say, why not do gene editing because it's safe? And why would you take years? If you're high LPA, for instance, and you realize that when you're 15 years old, why would you take twice a year sRNA for the rest of your life when you could gene edit? It does not make sense. you could have compounded toxicity for putting a lot of RNA material into your liver over a long period of time. You don't know what the effects of those are. So I do think that this question will flip and primarily led by the physicians because they all see this as a better way to treat patients.

Yeah, that was actually something I was thinking of too is like which patients actually derive the biggest benefit. These are large disease areas. Is a patient with you know 30 40 years of life ahead of them is that kind of the ideal patient group versus say a 60 year old with you know hypertension or or ILDL like is there a way to sort of like break down the market opportunity here would you even want to do that at this point yeah I think we're doing a lot of work on that I think it's gonna one of the access is going to be attitudinal as well whether it's a 30 year old a 50 year old or 70 year old there is an element of you know a patient saying i'll take the risk and do gene editing right and that's how this what happened in our sickle cell patients and trials it wasn't that all the patients that came

in were the sickest of patients you know some people who said i'll take a chance because i can't live with my disease anymore and you're going to see that i think over here as well one of the access the other access is you know you're going to get for genetic conditions like lpa you know pretty early in your life that you have high lpa and you know if you have high lpa some people have high lpa levels above 300 milligram per deciliter you probably want to take care of it sooner rather than later so you want to do it as young as possible uh with hypertension you're likely to get it more later phase of your life so you're going to be older but some people have very high uh blood pressure that's uncontrolled and they won't have a choice but to do it right and then you have ldl which is a different ball of wax where you have to segment the population many different ways you know do they have high ldl and high triglycerides do they only have high ldl have they tried pcs canines what it's going to be but the thing is whichever way you slice and dice it's a huge market um and so we're playing in you know major markets in a way, a global scale, where we could, you know, benefit all sorts of people at different levels of risk.

It's not like you'd have to break that down preemptively to run, like, a pivotal study that you could wrap your arms around, right? Thank you.

Yeah, we don't have to. I mean, I think, you know, like, if you can do a severe hyperthyroidal serenomy trial based on pancreatitis events, that is a registrational path that could get us there and get us a label. And beyond that, I think you can, you know, the label and the marketing will all, you know, we can obviously influence it, but I don't think we need to a priori determine exactly what the market's sizes are and the market potential.

Yeah, makes sense. Maybe shifting gears to autoimmune and oncology, I think Zugacel, great name, by the way, that's a new name.

No coincidence, because we're based in Zug, Switzerland, but, you know, that just happened.

Oh, I see the connection. Yep. I guess, you know, are the CR rates in DLBCL sort of tracking with what you would have hoped? And, you know, you're expanding into multiple autoimmune indications. I guess, how do you prioritize these different arms of development? And is there maybe a minimum data set you need before you have, you know, registrational conversations with the FDA? Absolutely.

I think Zucocel is the best-in-class allogeneic CAR-T for CD19 because of the edits we've made to it. And it's autologous-like efficacy, but with the convenience of allogeneic and the cost of goods like allogeneic. So in oncology, we showed nearly 70% CR rate with Zugocell, which is at least two of the patients at the time of data cut who were past 12 months, so it's durable. Now, what we've done also is start dosing patients with a BTK combination, vertebruninib, And it's seen from some of the investigator-initiated trials that somehow the BTKs actually potentiate the CAR-Ts even more. So we end up with, you know, in that study, it was almost 80% CR rate. So we can push that up even more. We could be better than autologous therapies. But I think our strategy in oncology is to, you know, potentially get an approval off a single-arm trial in late stage and then pick off patient populations in front line that perhaps cannot, are not eligible for auto, that are failures on bispecifics, et cetera, because we did show a really good response rate on bispecific failure patients as well. In autoimmune, our goal is to lead the pack and become the predominant or preeminent player in autoimmune disease, and that's our number one focus. Our chief medical officer, Namish Patel, came from Sanofi, where he was leading the autoimmune franchise there. And we're translating a lot of the learnings into how fast we can move in autoimmune indications with ZugoCell. This could be an Argenix-like platform. Any disease that's B-cell mediated, you could have a one-time reset that gets rid of the disease. And so we started with this trial called EID500, which we were dosing patients with lupus, myositis, and scleroderma. Now we've expanded into two other diseases, ITP and YHAB, where we're dosing patients, and now we've just opened an IND for neuroimmune, because we've seen all this hyperon, you know, in vivo CAR-T, we haven't seen those CAR-Ts go into the CNS system, whereas ZUGO cell, we have evidence that it goes into the CNS system, actually can eliminate B cells in the spine or in the brain. So that has tremendous implications for indications like multiple sclerosis, NMO, et cetera. So we've started that trial for neuroimmune indications as well. So it's literally all systems go for us on ZugoCell. And we now said we've dosed 14 patients for our 1Q update and we'll provide further updates as we go along.

That's great. Obviously, autoimmune CAR-T space is heating up and it's quite competitive. Do you see, is that kind of a fire lit under you guys to really accelerate things and push forward? Or, you know, how do you sort of maintain your lead given the wealth of development going on?

Well, I think we're in a good position because the auto parts, you can only go so fast, right? There's a natural governor on how fast you can go. And so we've seen that whether it's a big company like Novartis or BMS or a small company like Governor Cavaletta, you know, even though they had a three-year lead, they can only go so fast and we're patients. I suspect that by the end of this year, we'll have dose more patients than some of the autologous companies because we can go damage faster. And so we'll catch up to the autologous players. Now you have a second set of threat in terms of the TCEs, and they can move equally fast. And you've seen some of that, but we don't think it's going to be a one-time reset in an elegant, beautiful way that we can do with CAR T's. So we have comparative edge over TCEs that may require, you know, multiple dosing and, you know, you still come to the risk of CRS, et cetera. And then finally, the in vivo space, in vivo CAR-Ts, we're working on that as well. We have our own in vivo transient redosable CAR-Ts that showed complete B-cell depletion in monkeys with one or two doses. But I think it still has, you know, there's more work to do to get that to patients and see what the effects are on patients. So at this point, I think we're in pole position. As long as we execute, we can actually lap everyone else, but we'll have to show that over the next months to a year in terms of execution. Okay, that makes sense.

I want to ask about your SIRNA collaboration with Sirius. I know we talked about the benefits of a one-time gene editing approach over SIRNA and LDL and those indications. This is a different application. Is this more just a right tool for the job or anything to read into your leaning into SIRNA through the function?

Well, I think the way this came about is we were building a cardiovascular franchise with, you know, NHPTL3 and LPA, and we were talking to all our steering committee members about what else is exciting in cardiovascular medicine. And factor 11 kept coming up. The promise is, you know, you have very effective blood thinners out there in the market. These are factor 10A-based drugs, but they come with high lead risk, right? And if you're on these blood thinners, like especially if you're old and, you know, you're taking it for stroke risk or whatever, you have an injury, you could bleed to death. So is there, you know, what's the holy grail is to have the same level of blood thinning without the bleed risk. Now, you don't want that for life. So you don't want to gene edit your factor of 11A because that'd be something that's unnecessary. Let's say you're doing this for an acute phase after surgery or something like that. But we do believe that all of medicine is moving towards long-acting. I don't think in 10 years you're going to be taking a pill a day. You're going to be taking once every six-month injections or once a year or generating for life. That's going to be the majority of medicines. And so we are going to play into that long-acting aspect with this factor of sRNA that right now seems like best in class. It could be once every six-month dosing. This is with our partner, Sirius. And there's so many indications you can go in, whether it's secondary stroke prevention or there's an AFib patients that are not eligible for DOACs, whether it's patients that are that have peripheral artery disease, post revascularization. So all these are trials that you can do. Now, of course, there are some, you know, any attractive space, there's going to be competition. there are some antibodies from Regeneron and Novartis that are also playing in the same space and a couple of small molecules. But I think an sRNA approach could be the most powerful approach, especially with its dose inconvenience.

Okay, great. Well, it looks like we're out of time. Plenty going on at CRISPR over the next 12 months. So looking forward to seeing the updates. And Sam, thanks so much for the conversation.

Thank you very much. Thank you.