CRISPR Therapeutics AG (CRSP) June 2026 Conference Transcript

Good afternoon. Thank you, everyone, for joining us. We're really pleased to have with us CRISPR Therapeutics, and with me I have Raju Prasad, CFO. Raj, could you start by giving us a brief overview of where your portfolio stands today, your updated strategic focus on the cardiovascular and autoimmune franchise, and how you're thinking about technologies as you bring in new modalities, including CERNA and InVivo CAR-T.

Yeah, absolutely, and thank you for having us at the Goldman Conference once again, and it's great to be here. You know, CRISPR is now over 12 years old. We're, you know, entering sort of our teen years as a company, and, you know, with that, in addition to, you know, Caschevy, which is our approved product with Commercial Partner and Vertex, which I'm sure we'll talk about, we really have been focusing on the pipeline and identifying what our next second, third, fourth programs are. And you mentioned cardiovascular and autoimmune disease. And, you know, we're looking at those therapeutic areas specifically in how we build sort of the clinical development apparatus of the company as well. And, you know, I think with regards to how this pipeline is going to shape up and how it will frame the next phase of growth for CRISPR as a company is that in the back half of this year, we'll have five clinical trial readouts across three programs. We have CTX-611, which is a siRNA program with a partner, Serious Therapeutics, and it's targeting Factor 11. Second, we've got CTX-310, targeting HPTL3. This is a cardiovascular program as well. And here we're looking to identify certain patient populations where we think we can provide a one-time treatment that can be... potentially be a best-in-class approach for an indication such as severe hypertricolous serodemia. And lastly, we have an allogeneic CD19 ZUGA cell where we'll have an update in both autoimmune diseases and oncology. And I think what investors should focus on out of all three of these programs and all these developments is how are we charting the trajectory of each of these programs into potential pivotal trials, which we anticipate starting in 2027. Now, you mentioned our ability to bring on other platforms such as InVivoCartee. We can talk about that more as well, but I think this was, InVivoCartee in particular, is obviously in a very interesting moment in time from an industry perspective, and there's still what we feel is opportunity for best-in-class where we have all the pieces given we're a globally integrated biotech where we really can pull together LNP, mRNA, and manufacturing at scale to potentially reach the promise of that as well. So we've got a lot going on, and I'm sure we'll go through most of it.

At this point, how focused are you on the allogeneic oncology platform for two reasons? It seems like there's an emphasis on cardiovascular and autoimmune, but also as you bring in in vivo, How do you think about the, you know, the focus that would play out with that vertical?

Yeah, I think, you know, the...

For oncology.

Yeah, yeah. As you know, you know, the beginning of allogeneic cell therapies was with an oncology focus, and in the last couple of years, we've now seen this amazing ability to translate this technology to autoimmune disease, where, you know, the initial data from the autologous patients are now in remission out four or five years. So it's truly a B cell reset for the autoimmune patients. And in our view, there are going to be significant value created for allogenic cell therapies in autoimmune disease. I think where we're trying to focus our oncology efforts is in areas where there's still an unmet need and where, for lack of a better term, the clinical trial process for approval isn't too onerous. What we're seeing in the autoimmune side of development is the autologous players are getting relatively sizable trials, say in that 25 to 50 to 75 patient single-arm trial sample size for approval. And on the oncology side, I think the trials are much more sizable, 250, 300 patient trials. And so when we look at the competitive landscape and our data set, I think it will be a critical strategic decision that we'll make in the coming months where, you know, do we go bigger in autoimmune disease where potentially you could bundle more indications for the same cost versus an oncology where if you run a big 300-patient phase three trial, are you really going to get the ROI on that? I think we'll have more to come, but I think you can kind of tell where we're leaning towards at this point.

And with five program updates expected in the second half, how should we think about the sequencing and relative importance of these catalysts in terms of both proof of concept and pipeline validation?

Yeah, and it's a concept that I'll probably come back to in other strategic questions, But, you know, we really look at our pipeline in terms of modality risk and target risk. And so with 310 and the allogeneic CAR-T, we're really taking more modality risk there. You know, CD19 and NHPTL3 are pretty validated targets. When we did the Factor 11 deal, you know, Factor 11 hadn't been fully validated in a Phase 3 trial. In fact, it was on the heels of the asindexian atrial fibrillation trial, which didn't hit its endpoint. Subsequently, S-indexians hit into a secondary store prevention trial, and so there has been some de-risking there. But I think factor 11 in particular is something where, you know, investors do understand the modality. They understand the value prop that we have with a potentially one-sever-six-a-month approach. There are several landscape readouts with milvexian, with avalestimab reading out, and then also Regeneron doing multiple phase three programs for two antibodies for factor 11. So I think that's going to be one in the second half of this year between outside data readouts as well as our own TKA study where that's going to be of fairly big importance. and not only from understanding our drug product profile but also understanding which indications we may go into in 2027. I think with CTX 310, Phase 1 update on durability, but the Phase 1B will be focused more on individual indications where the population is more homogeneous, and you can sort of compare our efficacy to other programs a little easier. So, for example, in severe hypertriglyceridemia, we've seen an ASO program with, you know, high 50% to low 70% triglyceride reduction. I think if we're able to get in that range in severe hypertriglyceridemia, we have the benefit of being a one-time only treatment that can differentiate from those RNA therapies. And similarly, with the allogeneic CAR-T update, you know, we'll have a meaningful number of patients. I'd say we'll probably have over 20 patients treated across our BASCA trial, and we'll have a sense of where we're going to take that forward in Phase 3 development as well. So really the cadence of these readouts in the second half will not only be data that I think is analyzable in the context of other modalities or other indications, but also will inform multiple pivotal trials, which we'll likely initiate in 2027.

Great. Maybe starting here with the serious partnered Factor XI program. So this is currently in a Phase II study in patients undergoing total knee atheroplasty with top-line Phase II data in the second half. Can you frame expectations for the data, what the bar for success is in terms of Factor XI reduction and thrombosis prevention, and also in the context of what we've seen from the competitive landscape?

Sure. Yeah, so this is a pretty standard trial across multiple factor 11 programs, and I think it'll show that CTX 611 has a profile similar to these programs on thromboembolic rates, as you said. And so, you know, we've got it to a top line readout in the second half of this year, I think what you should expect there is a discussion of the percent of thromboembolic rates across the dose levels that we're testing. We're testing three dose levels of CTX-611, and then anoxaparin, which is the other trials that ranges in low double digits of 10 to 10. Really, we're looking at a single-digit percentage for the CTX-611 in our go-forward dose versus a double-digit percentage with anoxaparin. I think in addition to that, we are running a multiple dose trial just to look at a regimen of once every three months and once every six months. So the plan is by the end of this year, we'll have our data, we'll have the readouts from competitor programs, which will tell us is this going to be in DOAC and eligible patients, which we think is around 2 million patients, is it going to be a DOAC, sorry, an AF all comers population, which in atrial fibrillation, we think that's roughly 8 million patients, and that could be a $15-20 billion opportunity, and then will both the Movexian trial and the Abilassaned trials hit, which will really define our pivotal development for this program. But the TKA study, I think, is an important trial for us to hit just to show that 611 is sort of on par with those other assets.

Noting a, you know, multibillion-dollar TAM across all of these indications here, how will you prioritize the indications that you look to advance with regard to phase three development?

Yeah, I think from a PTRS perspective, the cancer-associated thrombosis and some of the venous indications are relatively de-risked. I think where the questions arise for factor 11 is on the arterial indications, and, you know, S-indexion from Bayer hit a wonderful secondary stroke prevention trial that started de-risking these programs on the arterial side. Again, there's two major readouts. Milvexian will have an atrial fibrillation trial against DOACs, and then Abolacimab will have a DOAC-ineligible phase three that reads out early next year. And I think the way we see it is cancer-associated thrombosis is sort of a low-hanging fruit, high probability of success, but lower market opportunity, say about a billion-dollar market opportunity. The DOAC and eligible patient population, I mentioned 2 million patients, so it's roughly, you know, 5 billion market opportunity. And if the Milvexian trial de-risks the full atrial fibrillation market, that's roughly 8 million patients, 15, $20 billion market opportunity. So you can see, like, there's sort of three levels of value capture that we can have, and a lot of it will be de-risked before we have to make our decisions, and I think that's how we strategically planned it out when we did this deal.

Great. And you also have an option to nominate two additional candidates with Sirius. Just maybe share details around the potential targets I could play out there.

Yeah, I think, as you astutely said earlier, you know, cardiometabolic and autoimmune is sort of where our strategic focus from a TA perspective is going to be for the future. And so you can imagine that the SRNA programs will be sort of in that vein. You know, the good thing about that aspect to the partnership is, you know, we've got a certain time point to name targets. We've got reserve targets. So, you know, what we want to do is make sure that we have a best-in-class asset that we're pushing forward, and Sirius has a great research engine with multiple companies' expertise. So they've got folks from Dyserna, Arrowhead. So it's a really good team. and so more to come on that, but it just goes more toward our strategic shift in our portfolio to being a TA-focused company and having diversification of modalities. Right.

For your in vivo gene editing program in cardiovascular disease, can you frame expectations for the second half in terms of patient numbers and follow-up for CTX310 and what profile you're looking for across the homozygous and heterozygous FH populations, but also SHTG, to inform the go forward decisions?

Yeah, I think, so we had a phase one trial at the American Heart Association last year. We had a concurrent New England Journal paper. We've gotten significant positive feedback from that data set, and both from the PIs as well as the patient community, and that's been fantastic. I think what we should expect from that trial is just more follow-up, where we're looking specifically at the ANHPTL3 reduction. And for just sort of a reminder, we saw about 80% ANHPTL3 reduction, which we think correlates to all the liver ANHPTL3 in those patients at the DL4 dose. And I think in the back half, we'll have a phase 1A update where there'll be longer duration of follow-up there. The Phase 1B, again, is in different indications, and we're going to be having about, say, 10-ish patients in certain indications. I think where we're strategically looking at now specifically is, you know, the SHTG population. We think that we might have differentiation over the APOC3 target, and I think if you look at the core, core 2 data, they did see an increase in hepatic fat fraction as well as an increase in LDL in the patients. What we know from the ANHPTL3 target is that we do get a significant reduction in LDL. In our phase one, it was about 50% across the basket study. So we have that, and then there's also other ANHPTL3 therapies, RNA therapies that have shown reductions in hepatic fat fraction. So those two plus the one-time, one-and-done approach, I think, gives us a unique profile to differentiate.

And it seems like you had, based on prior data, a synergistic LDL reduction with PCSK9 therapies. Just any thoughts there from the KOLs on how to think about that from a clinical standpoint on the floor?

Yeah, we definitely think that there's a mechanism that could be synergistic between PCSK9 and NHPTL3. We've thought, we've given some thought into a PCSK9 refractory population. At this point, you know, we like the setup in SHTG, just given that the core core tube trial on AP was very statistically significant. with 800 patients, you know, the Arrowhead trials are going to have, I think, 400 patients or 500 patients. So if that looks very good, like, it'll help us statistically power our trial, but we're hoping to have a more manageable enrollment criteria in our phase three that, you know, could potentially be a, you know, a low investment for a high return in that I think with PCSK9, refractory patients, I guess the question with LDL always is, with payers, do you need a CVOT? And I think if we can avoid doing a large, as a company of our size, if we can avoid doing a large CVOT to get significant commercial adoption first, we'll go with those indications. So, you know, we're leaning towards SHTG for that reason, with something like a PCSK9 refractory FH population maybe being an add-on indication later on.

Could you speak just with regard to SHTG about the competitive dynamics here, given you've got an RNAi and an, you know, oligonucleotide both in the market here?

Yeah, I think, again, the AHPTL3 target is going to be a big differentiation, we think. But we've always felt that there's a continuum on small molecules, antibodies, RNA therapies, and gene editing. And you can see from the patients, and some of them have actually come out in NBC and some major media outlets, And you can see the profiles of the patients that are starting to develop for our therapy now. And so this one article was about a father and son that they both got the therapy in Australia. And, you know, I think from the son's perspective, you know, he knows that his father's had multiple heart injuries, heart attacks, and got this therapy and did well. He was facing, you know, 30, 40 years on therapy and chose to get this approach, whereas the father had multiple heart attacks, you know, was probably worried about, the doctors probably worried about compliance on therapy and the potential for another one to occur. And so having this ability to sort of, you know, live a normal life and not worry all the time about taking medications, particularly medications where you don't feel much different, you know, if your LDL is higher or lower on a day-to-day basis. So I think those two case studies, those two profiles are sort of where we think the early adopters can be. There are young patients that don't want to take 30 years, 40 years of therapy, or older patients that have had issues with compliance.

On the next-generation LPLA asset, 321, what are you looking to learn from the Horizon data to inform development here, and how will the gene editing asset be positioned versus competitor approaches?

Yeah, I think the Horizon study is going to be one of the biggest readouts in the back half of this year. I think between that and factor 11 in the cardiovascular space, those are probably the two most important targets that maybe de-risk. But with the Horizon trial, I think us and I think everybody else that's looking at LPA as a potential new biomarker for ASCVD is looking at the Horizon trial to see both the 70 mg per deciliter cutoff as well as the 90 mg deciliter per cutoff and see whether or not the, you know, it's a significant study. There's so many ways that this could go, it's hard to lay out all the scenarios, but I think with regards to our development, you know, we really need to see in that particularly that high-threshold cohort if that hits significance. With regards to our programs, you know, 321, we do believe, based on preclinical studies, that it's a more potent guide RNA and we can get a more potent LPA reduction. Now, whether we need that or not, we'll have to see. But I think it'll be very interesting to see this Horizon trial, and then there's also the RNA trial coming out soon after. But again, similarly, this is just an area where LPA is known to be something that is genetically derived. it does fit the profile of something where a gene editor would get adoption, where, you know, you know your LPA from an early age, and either you're staring down 40, 50 years of therapy or you take this one-time opportunity to cut your risk reduction significantly. So it's definitely, you know, we'll all be waiting with bated breath. I think you cover this. We'll cover this as well from multiple angles. So it'll be a very interesting trial for not only the sector, but for patients as well.

Yeah, definitely. And you have Phase I study initiations this year that are planned for refractory hypertension with 340 and 460 in AATD. Are those still on track?

Yeah, they're both on track. You know, just staying on the cardiovascular side first, I call the refractory hypertension trial probably the biggest disconnect between PI enthusiasm and investor enthusiasm. But I think, you know, knocking down angiotensinogen and being able to make patients normotensive, particularly in this refractory hypertensive population where they're on five therapies plus a diuretic, it could be pretty meaningful. And so we'll have more data. We're running some preclinical studies with some preeminent leaders in the space that will be published as well at some point. But I think that there's real opportunity here to change the paradigm of how we think about hypertension. I think, you know, LDL and triglycerides, as you mentioned, there are other therapies out there. But here, you know, to potentially make people normotensive, I think, could be very interesting. And, you know, I think at some point the data will tell the story for us. But we're very excited about getting that program into the clinic, and so are our PIs.

I want to – sorry, go ahead.

I was going to talk about 460 as well, but, you know, just quickly here, this is almost the opposite of our issue in cardiovascular disease because I think there's a general consensus that gene editing will be taken up commercially in alpha-1 antitrypsin disorder. And so what we wanted to do is if we were going to bring a program forward here, we wanted to have a best-in-class approach. So our synthase editing technology, we think, is more efficient and more potent than approaches that are out there. And we're really aiming for that, you know, 18 to 20 micromolar of AAT production to get to normalization. And I think, you know, we're very excited about the opportunity there. We're leveraging our LNP from the cardiovascular program, so we have a good sense of where our therapeutic window is from an LNP perspective. And so we've modified the payload or we've developed this payload where we think we can get to those levels, those types of levels with this data. But the initiation for that trial is going to be in the middle of this year, so not too distant future we'll have human proof of concept there, which I think could be a significant value-generating event.

Before I jump into the autoimmune portfolio, just curious here, given the breadth of your cardiovascular portfolio and then this additional autoimmune, How are you thinking about, you know, taking these assets forward by yourself versus partnering them out?

Yeah, this was sort of a reason why we did an opportunistic fundraise earlier this year as well, was we never want to be in a position where we have to make a decision on any of our assets based solely on resource allocation. And I think we've put ourselves in that position where now we have over $2.4 billion on the balance sheet. And I think, you know, we have the ability to take these forward. Again, I think if we want to do a broad-based development in cardiovascular disease, to your point, there's, you know, SHTG, HOFH, HEFH, PCSK9. There's a lot in potentially CVOTs. If we decide we want to go in a broad-based development over there, maybe we do go find a partner. Similarly, if 611, if the factor 11 space hits on the Milvexian trial, that's a huge market opportunity. There's probably several pharma companies that would be interested. I think in allogeneic CAR-T, I think it's probably more of a bite size that we can take. So we just need to see all these cards play out. But I think there is a world where, you know, we do look for a strategic partner to do some of these things because we're not running 8 to 10 pivotal trials next year, but we will be a pivotal phase company next year.

Pivoting here to ZugoCell, which is your allogeneic CD19 CAR-T program, over 14 patients have been dosed across multiple autoimmune indications, and the first two SLE patients remain in durable long-term remission. What stands out with regard to this drug's profile, and what gives you confidence that it can be competitive with the autologous and in vivo CAR T's and TCEs and autoimmunity.

Yeah, I think what we really want to show with this first data set is can we recapitulate the autologous profile? And the first two patients that we've put out data on are directionally trending that way. As you mentioned, the first patient is now in door submission through 12 months. The second one is through nine months. We've dosed 14 patients. We've gotten through this chasm of the enrollment, which I think initially there was a bolus of companies developing in this space that's come down now through runway issues and strategic priorities for other companies. We've been able to bridge that chasm. In the back half of this year, we anticipate having over 20 patients in that data readout across the basket trial. I think where we stand in the context of the landscape and a lot of hype for TCEs, We do believe that allogeneic CAR-Ts can be used in indications where there's a high severity, as well as potentially CNS indications where some of those other therapies may not be able to as readily cross the blood-brain barrier and have a therapeutic effect on the scale of a cell therapy. You know, the benefits of aloe over autologous from a supply chain, from a cost perspective, of those, everyone knows those, you know, we think at the dose that we've got those remissions, the cost of goods for Zugacel will be 10K or less. So, in autoimmune disease, again, we have this benefit of a low cost of goods, high margin product profile, even at a reasonable price point. And so, we'll have to see where, you know, the in vivo car team, we have our own efforts I think that's a very exciting place. I think Alucarty will have its niche and its markets where it is the leader. Again, we're looking at myositis and scleroderma in addition to lupus. With scleroderma, for example, there's a 40% mortality rate with that disease. There's some pretty, you know, severe forms of that disorder where patients have ILD as well and lung function deficits. So if we're able to expand into those populations as well and actually have a maintenance of forced vital capacity or lung function, like that gets really interesting as well. So more to come on this, but I do believe that the CD19 allergenic CAR-T product is a multibillion-dollar opportunity.

And can you frame expectations for the data in the second half here? How many patients? What length of follow-up could we see across the various autoimmune indications?

Yeah, so the patient with the most follow-up is the one we have previously 12 months, so back half of this year, say 18 months, ballpark. I think with regards to numbers of patients, we'll have over 20 patients dosed by then. There'll be some SLE, some scleroderma, some myositis. Again, we're looking at sort of the normal biomarkers, MCRIS scores, TIS scores with myositis, and then DORS remission criteria. We'll also have some description of B-cell depletion and recovery, as well as some other cell markers. But overall, what we're really trying to show is we're recapitulating what we've seen with the autologous therapies from an efficacy and safety benefit, and then directionally where we're going to take this forward into pivotal.

You also initiated a third phase one study here looking at autoimmune neurologic indications and maybe speak to what supports the assets activity in CNS disease and when we could expect first data from that study.

Yeah, so when we had patients in oncology with CNS involvement, we did see reductions with our first-gen program. So we know that the allogeneic CAR-Ts do cross the blood-brain barrier. I think when we were thinking about strategically where an allogeneic CAR-T could benefit patients where a TCE or in vivo CAR-T may not be able to, I think CNS popped up as an area where that could happen because of the blood-brain barrier. So we've initiated that basket trial. We're enrolling patients, and so when we have that data, we'll share it and talk through if we do end up going in those indications as well.

Great. Maybe one last question here. So as you look to the Ford, and we didn't get time to touch on these, but touch on the multiple in vivo CAR-T efforts you have. You have a transient mRNA and a non-viral integrating CAR, and how you're thinking about this whole portfolio in the context of path to profitability.

Yeah, so, again, being at the scale we are, Envivo Car T was just a way where we were able to leverage all the aspects of our business, including the manufacturing. I think that's going to be the key differentiator long-term. Can you create a scalable Envivo Car T that can really have superior binding, superior biodistribution, and efficacy and safety? And so we don't think that that profile has been fully generated yet, and so we have the ability to catch up and create a best-in-class profile there. With regards to profitability, and obviously we have Keschevi with Vertex, you know, we do think that for us at this point it's a question of when and not if we will reach profitability. You know, we've got $2.404 billion on the balance sheet. We have the ability to get multiple programs through Pivotal and into commercial discretion at our choice. And so we'll be able to supplement via BD deals and things of that nature, both on the buy and sell side. We have a lot of optionality, and we think we have a runway to profitability at this point with no need for opportunistic – no need for fundraising. We can always be opportunistic about it, obviously. But we find ourselves in the position right now, 13 years in, where, again, coming to the beginning, I think we're going through that growth phase. In the next 12 to 18 months, we really will understand our second, third programs, our path to profitability, and how we really get to that next level of $10 to $15 billion market cap that really defines a leader in biotech and not just a gene editing leader.

Great. Well, with that, Raj, thank you so much. Thank you so much.