Hi, everyone. My name is Mitchell Kapoor. I'm a senior biotech analyst at HC Wainwright. Today, I'm pleased to welcome CRISPR Therapeutics, and I'm going to have a fireside chat with the CFO, Raj Prasad. Raj, thank you for joining us. Just to jump right in, maybe those who are not familiar with the story or who are not current, maybe you could just kind of give a company overview, what you're working on today, and.
Yeah, absolutely. CRISPR Therapeutics is almost 12 years old now. The company was founded on the Nobel Prize, now Nobel Prize-winning work, from the Milchart MTA, where they showed that they could edit human cells. We have taken that initial technology and we have applied it to Casgevy, which is an approved product, the first approved CRISPR product, which is now in eight different countries and jurisdictions to treat sickle cell and beta thalassemia. Us and our partner, Vertex, are taking that program forward. Vertex is leading the commercialization of that program, which we will talk about a lot more. We are now in this second phase of our company where we basically took revolutionary technology. We were able to apply it to get a medicine approved. Now we are working on getting the second, third, fourth programs approved.
We are solidly financed with $1.6 billion on the balance sheet. What we really want to do now is focus on making transformative gene-based medicines that can change patients' lives. We also want to do that in a capital-efficient manner, obviously, given the markets. We were able to find an opportunistic deal, which we announced yesterday, hopefully for this conference. We did a deal with a company called Sirius Therapeutics on an siRNA platform with a lead program in Factor XI, where we have a 50/50 co-development, co-commercialization partnership, where we lead the US commercialization. Sirius handles China commercialization. We also had the ability to license two additional siRNA targets, which we'll disclose in short order. We are really excited about what that program adds to the complement and the suite of toolbox modalities that we have now at CRISPR.
We really wanted to show the street and obviously show everyone that we have this ability to think more globally about what we can do as a company. We are very excited about that deal. We can also touch on that as well. Aside from Casgevy and the Sirius deal, we also announced top-line data from CTX310. This is an in vivo LNP plus mRNA platform, the first program in our platform offering here, where we saw what we think is best-in-class data with 82% knockdown in triglycerides and 81% knockdown in LDLs. Really best-in-class data from the early 10 patients that we put out data for. We will have more data there in the second half. As if that was not enough to do, we also have a CV19 allergen in CAR-T in autoimmune and oncology, which we will have an update for in the middle of this year.
We have a diabetes and a solid tumor program as well we'll have updates for. Really a value inflection next 12 to 18 months for us, where in addition to Casgevy, we will have several readouts. Now we have the Sirius platform as well to integrate into the company.
Yeah, that's wonderful. Hopefully, we can touch on as much of that as possible because there's so much going on at CRISPR. Okay, great. Starting with the most topical, the Sirius deal, can you just talk about, being a gene editing-focused company, what does this deal do for your platform with sRNAs? Is this a diversification play? How do you see the future of CRISPR?
Yeah, so I think we set out about a year ago to say, okay, if we were modality agnostic, if we were just looking at what are some interesting assets out there, we have enough capital to get us, we think, all the way to profitability. We have the ability to look at sort of different assets in what I consider a buyer's market right now in depressed valuations. What would be complementary to what we're doing internally? We found sort of Factor XI in sort of this broad strategic look at the landscape. We looked at Factor XI in particular and we said, there are certain indications where it doesn't make sense to have a one-time permanent knockdown.
We think anticoagulation is one of those spaces where we're going to be running a phase two trial that we initiate in the second half in total knee replacement, where you don't want the patient to have Factor XI gone forever. Factor XI is a great target in that it gives you this anticoagulation effect, but it reduces your bleeding risk. It is different than the Factor XA inhibitor, along with the DOACs that are available. In this massive market, Factor XI gives us an interesting point where we don't want to have a gene edit, but we found Sirius and their long-acting siRNA, which gives you six months of durability, significant target coverage, or 95% Factor XI reduction. We think that it can compete with some of these massive products that we see in the competitive landscape.
The way that it sets up for us from a strategic perspective is we'll run our phase two trial. At that point in time, Novartis has a product that they acquired from Anthos Therapeutics, abelacimab. They'll be running some phase three trials. Bristol Myers Squibb and Johnson & Johnson have a vaccine and oral molecule. They'll be running some phase three trials where the target will be de-risked in some of these larger indications. Basically, we'll have a good sense of how to clinically prioritize the siRNA asset, SRSD107, in that time frame. I think if you're thinking about this 12- to 18-month time frame, it gives us an immediate value-creating catalyst that I think has been validated not only by pharma as well as by some deal activity.
Okay. So what are the key days to watch for that program?
Yeah.
Externally and.
Yeah. So I mean, we'll obviously be watching the Novartis and abelacimab readouts. But for us, it's just an initiation of the TKA study or TKR study in the second half of the year.
Got it. Okay, great. Then moving to Casgevy, could you just talk a little bit about the launch performance to date? How has that been trending? What does that look like in terms of your confidence for uptick in demand? When might we see some sort of inflection point? Is there some gating items before we can get to that inflection? How would 2025, 2026 look in CRISPR's vision?
Yeah. So we're thrilled with the launch. We're thrilled with the job Vertex has done. 2024 was a foundational year where we were focused primarily on ATC activation. As of Q1, we have 65 ATCs. We have 90 cells collected. We have $14 million in revenue. We're getting revenue in multiple geographies. We're very happy with the way the launch is going. We're seeing Vertex and their press release has guided to significant inflection in patient initiation, which is the top of the funnel and the beginning of the demand curve that we see. We're also making combined manufacturing investments that Vertex and the press release put that they're getting along the Portsmouth online as well to basically support this demand that we see. We're targeting 75 ATCs. We think that that will be the right number to cover.
We see a huge multi-billion dollar opportunity. Again, we're not, neither us nor Vertex is in a state where we're well capitalized. Again, we don't have to worry about a quarterly revenue number to raise money or whatever from the CRISPR perspective. We're focused on the opportunity here in getting a transformative therapy to as many patients as possible. We continue to have a tremendous amount of faith in both our partner, Vertex, as well as the value creation that Casgevy can have in commercialization.
Okay. Very helpful. The cell collections just being kind of a leading indicator of that funnel you're talking about, top of funnel. Talk a little bit about how that's been trending. In terms of geographies of where you're getting these cells, is there anything you can say about that? Is the Middle East typically playing a big role in where those cell collections happen? Is that a big focus for the launch? Just kind of help out with the.
Yeah. I mean, the numbers that IP that Vertex has put out, 35,000 patients in the US and the U5, greater than 23,000 in the Gulf countries. We think that the Middle East is going to be a huge market for Casgevy. I think that they obviously have pressed some of the first patients that have been infused. It's been phenomenal to see those patients get approved. I do think that at the end of the day, the 75 ATC coverage, we believe, is the right number. I think over time, you're going to see those ATCs get more and more comfortable with administering the therapy. You're going to see this intra-ATC growth being the driver for revenue sort of inflection as the sites finally get online.
Okay. Got it. Yeah, getting close to that 75 number, that target 75 number, what are those things you think with the intra-ATC growth that are going to drive that, closing the gap between cell collections and dosing of patients? Obviously, that cell collection number is growing, but that transition point.
Yeah. I mean, again, a lot of the, at this point, a lot of what we've seen is going to be anecdotal because we're early in the launch. Over time, when we build scale, I think you're going to see cell collections, some of the clinical trial, there's a low attrition rate to infusions. Again, we believe in the multi-billion dollar opportunity here. We're excited about the execution thus far and where we stand in this field.
Okay. Is there anything that you've been able to say on cell collections to infusion, that timeline to get a patient on therapy, has that narrowed or lengthened at all or anything you can provide color on?
Yeah. I mean, again, I would love to sort of yield to Vertex on sort of the color commentary here. I think right now, anything we would say would be anecdotal. It would not be a trend at this point. From what we've seen, I think we're seeing a steady increase in growth in ATCs. We're seeing a growth in cell collections. We're seeing a growth in infusions and revenue. We are very excited about the trajectory and how it's going thus far.
Okay. Is preconditioning, the preconditioning regimen that goes along with Casgevy, is that something that you've heard is a barrier to uptake? Is there anything you're doing to help patients become more comfortable with that? Is it something where the more patients that get dosed and they go through that, they're telling the field, like, "Hey, this is how my experience was, and that's a snowball effect." How does the preconditioning regimen play into that?
Yeah. I mean, the market opportunity is still big with Casgevy as it is now. I think to expand the TAM, there will need to be an RNA conditioning regimen. We have a CD117 approach. Vertex has their own approaches. Both come into the collaboration where we have the 40% net profit split for CRISPR. We're taking this CD117 ADC approach with sort of a short half-life, a quick hit, as we call it, because you don't want the long half-life like you would for Ergocardias, some of those other companies, those other programs. Yeah, we're advancing that program, but we'll have to wait and see to see how that all develops.
Yeah. Makes sense. Okay. Moving away from Casgevy and into the pipeline now, you had some exciting data. You mentioned briefly CTX310, AngPTL3, first in vivo data. Can you just recap that data, what it means for CRISPR? Just talk about the dose levels, the trends you saw, the dose response, anything else that you think is important to investors?
Yeah. Yeah. I mean, as everyone knows in biotech, there's just a long lead time from when you make a strategic decision to build a program or build a platform or build a vertical and then seeing the clinical human proof of concept. No different with this. I think there were some other folks in the gene editing field that have shown compelling data in the in vivo space. We took the approach of going into cardiovascular disease where compliance is a huge issue. We selected AngPTL3 to be first just given we thought the competitive landscape there was preferable to, say, another target. We presented our press release top-line data from the phase one trial earlier this month. In DL3 and DL4, we're seeing robust reductions in both triglycerides and LDL.
I mean, it's still early data, but numerically, we think it's best in class. We're seeing an 82% reduction in triglycerides, 81% reduction in LDL. The triglyceride patient in particular, the triglyceride reduction was in a patient with severe hypertriglyceridemia. And in this patient, they had over 1,000 microdeciliter at baseline. If you look at that in a vial, it's a very thick layer of sort of milky white in addition to blood, right? That patient now is down below 200 microdeciliter. The consistency of the blood looks much more like blood. It's really a transformative effect. If you think about the current standard of care in severe hypertriglyceridemia in particular, I think that that makes it pretty impactful.
With regards to AngPTL3, again, the fact that we have this dual effect on triglycerides and LDL means that you can take it into a hyper-dyslipidemia population. The fact that we're seeing these massive reductions in LDL as well is very exciting. Some of the siRNA products that have put on data recently have shown liver fat reductions via MRI. We think that bodes well as well for the target. We'll have data and medical meeting in the second half. Again, I think our strategy now is we really want to get investigators globally, more eyes on the data and more interest in the data and grow the platform. Again, as I mentioned, now we're in this stage where we're really looking to develop what the next drug is.
We're really trying to figure out what are we going to take forward as the next asset to the commercial space for this company.
Okay. Very helpful. Yeah. And SHTG is obviously a focal point for the genetic medicines field in general right now. I'm not going to. You had a mix of different patients, different disease subtypes. Trying to interpret that, obviously, it's early for us. Investors always want more, trying to understand it. When could we get more in terms of understanding what it means per disease? What could that look like? What should set our expectations?
Yeah. I think the next step is to finish the dose escalation study. Following that, there will be a dose extension study where we'll go into sort of disease-specific cohorts. I would just say from a high level that, again, severe hypertriglyceridemia, they don't have a good standard of care right now. As you mentioned, there are some later-stage programs in development that have a decent effect on triglycerides, but they don't impact LDL in the same way that our AngPTL3 data looks like it does. We think we could have a superior profile. Again, this mixed dyslipidemia population is multiple millions of patients where they have both elevated LDL and triglycerides. We think that that could be another indication as well that of interest. We do have ATFH and HOFH as well in the phase one trial.
Stay tuned for, again, I think we need to get more data, talk to our advisors, get the medical meeting out, and then sort of take the holistic view and sort of decide what we're looking for.
Okay. When you present the data second half, could you just set the stage for the numbers of patients we'll see? What could change from what we've seen so far in the follow-up time?
Yeah. I mean, we'll obviously have additional durability. I think the data cut off for the top line was in April. We'll hopefully finish the dose escalations and DL4 cohort. Stay tuned. I think it's going to be pretty exciting. If we can show this profile, we could have a best-in-class cardiovascular program with the most development.
Yeah. Yeah. Makes sense. All right. In terms of your second LPA that's coming up, CTX320, how does this data risk mitigate that?
Yeah. Yeah. I mean, it's always difficult to say they're exactly the same, or you can't say that. Obviously, different targets, different genes. But we do believe that the platform approach that we've shown that we can develop in LNP mRNA products and meaningful reductions. I think the competitive landscape for LPA is a little bit different in the fact that everyone's waiting on the Novartis Horizon trial to see whether or not you can therapeutically reduce LPA is going to lead to cardiovascular outcomes. I think us and the rest of the field, while we're propagating our trials or advancing our trials, that will be a very important readout, which is now in first half of phase six.
Okay. Great. So yeah, and your in vivo data set is coming up in 2Q, which is today or tomorrow or the next day. Can you help us understand what to expect then? Is it still on track for 2Q?
Yeah. I would just say the trial, we announced it about three months after, publicly announced that it was initiated three months after the 310 trial. Yeah, I mean, when we have it, it'll be there. You're looking at how with LPA, it's different than LDL where you don't want to get—the current literature says that it's more of a threshold effect than getting patients down to zero. I think what we want to do with our therapy is get patients in the range of control, which is basically below 25 millimol per liter. The fact that we can have a durable effect there, that does differentiate a gene editing one-time therapy from, say, another therapy where compliance is an issue. If you miss the dose, you all of a sudden get out of control until you get your next dose.
We think in these cardiovascular medicines, that one-time gene editing medicine can be in these lipid-targeting medications, that one-time medicine can be extremely transformative. That's the feedback that we're hearing from cardiologists as well.
Okay. To that effect, one of the questions we get a lot across our gene editing and gene therapy companies is about the applicability in broad diseases, vast diseases versus more rare diseases for gene editing specifically. How does CRISPR Therapeutics do that? How does that factor into your strategy, pricing dynamics, willingness for patients to undergo gene therapy, I mean, gene editing in these mass indications? What do you think the thresholds are and things like that?
Yeah. Yeah. I think an underappreciated aspect of this next suite of programs in our pipeline is the fact that we've made significant investments to ensure that the cost of goods is very low, in the low five-figure range, which means the price point for these medicines is not going to be seven figures. This allows us to be competitive with whatever therapies that are going to be on the market prior to while showing potentially a more durable benefit. This goes for not only our in vivo pipelines, but also for our allogeneic RTs, where if you're thinking about our four-angle autoimmune medicine, our autoimmune indications, which we're very excited about, also a 2025 update. We're talking about low five-figure cost of goods, and we're talking about antibody-type pricing. We can be very competitive.
Off-the-shelf modality where we're getting 28-day B-cell, 28-day PK from our oncology data. We'll get B-cell aplasia. I mean, I think we can have these durable responses as well. Yeah, I mean, I think the key issue for democratization of genetic medicines is being able to provide a high-margin product at a price point that can meet these primary care settings or these settings where the current standard of care is in the low six-figure range. We anticipate fully to be able to meet that criteria. If we're able to show disruptive benefit on top of that, I think we'll gain a significant market share.
Yeah. Definitely. The compliance advantage in some of these indications, especially cardiovascular, is a big factor for switching. Okay. Great. One of the last things I wanted to touch upon is with the series, since the series still was announced, what is the appetite for business development going forward for CRISPR? What kind of companies in terms of size or anything else you can talk about that might be of interest?
Yeah. Again, I still think with depressed valuations, it's a buyer's market. We'll be on the lookout. I think the feedback that we've heard thus far has been very positive on the deal. I think people are impressed at the price point that we were able to get a phase two asset, a phase two ready asset at, especially for a market opportunity that could be multiple millions. Sirius is going to be a great partner. They've got a significant amount of RNA expertise, siRNA expertise from both Dicerna and Arrowhead. We're excited about that. I think we're also going to be very active in discussing with our south side partners as well. I think in the next 12-18 months, we could have three or four multi-billion dollar products from our wholly owned pipeline.
I don't anticipate we'll be able to take everything forward. We do anticipate having those discussions. One thing this company has done very well historically is they've been able to strike partnerships that can create significant value, as referenced by the Vertex relationship, as well as not only in sickle and beta thalassemia, but we've done other deals with them to get onto the capital to be able to maximize the potential for some of our news and market platform. I think we'll do things similarly as well. I mean, I think, again, the Sirius deal was not only a deal of economics and value creation, but it was also a deal that we think is complementary and brings complementary expertise. I think it's one of the things that we do extremely well, and we're very thoughtful about it.
I think we'll be active under buying the south side in the near to medium term.
Great. Last thing, if there's anything else you feel like it's important that we didn't touch upon, I know there's so much in the pipeline, but anything you'd like to highlight for investors?
Yeah. No, I mean, listen, I think a question we do get a lot is, what's your next potential approved product? Obviously, SRSD107 is in the later stage, but we've seen some pretty exciting developments from some of the regulatory interactions that have been made public in autoimmune disease. So like a 15-patient study to get approved or a 100-patient safety database across indications. I think that is extremely bullish for the autoimmune space. I know it kind of a wave and has come down, but if you think about long-term provability and the knowledge of self-medicine, how many patients you can dose, how does everything do it? I mean, it's really a matter of just building trial sites, but I think that could be a huge multi-billion dollar opportunity.
Amazing. Thank you so much, Raj.