Hi, everyone. We're going to get started. I'm Sami Corwin, the Biotech Equity Research Analyst covering CRISPR at William Blair. Before we get started, I would like to direct everyone to williamblair.com for a full list of disclosures. I'm very pleased to introduce CRISPR's Chief Financial Officer, Raju Prasad, who's going to provide an overview of the company, and then if we have any remaining time, we can take some questions. Raj, thank you.
Great. Thanks, Sami. It's great to be back. Thanks to Sami and the rest of the team at William Blair for having us again. At CRISPR Therapeutics, we are focused on one goal, and that's to create transformative gene-based medicines for serious diseases. There's a forward-looking statement. Today, I think we've already done that once. We have an approved therapy in Casgevy, where our partner Vertex is leading commercialization. What we're doing with the technology, the gene editing technology now, is trying to get our second, third, fourth, fifth products up and going. We've got several clinical trials ongoing that'll have readouts over the next six to 12 months that'll really determine the future strategic direction of the company. Beyond that, we've got several preclinical programs. Again, having this expansive platform technology, we have the ability to apply it to multiple diseases.
Based on resource allocation, obviously, can't do everything, but we have the ability to really exponentially grow our pipeline and our offerings in the much longer time frame as we look to become a sustainable biotech. Currently, our vision for how we can prosecute the CRISPR technology, which again won the Nobel Prize, is we have four key franchises. In our heme franchise, we have Casgevy, which really anchors that franchise. We have some life cycle extension with being able to reduce the conditioning regimen, as well as what's known as an in vivo platform. I'll talk about that. We have a CAR T platform where we apply the CRISPR technology to T cells, and we have the ability to treat oncology or cancer and autoimmune diseases with these T cells.
We have an in vivo platform where, if you can imagine going to the doctor's office or a cardiologist's office and getting a one-time infusion that can reduce your triglycerides and your LDL for the rest of your life and reduce the risk of having a heart attack, that's what we're looking to develop with the in vivo pipeline and our clinical trials there. We have a type 1 diabetes franchise where, if you can imagine getting pancreatic islet cells that have the ability to produce insulin, you don't have to take insulin anymore. We're really trying to create the medicine of the future with these four franchises and, again, focusing on transformative benefits for patients.
This is sort of a pipeline, and I'll go through sort of each franchise and sort of the key programs where we anticipate clinical data in the near to medium term. Where have we been? Where are we right now? Where do we anticipate being? This slide sort of encapsulates how we view that. In the past, the foundation was really built by focusing on taking this transformational technology, this Nobel Prize-winning technology, and applying it to a tangible drug in Casgevy. We've also diversified the pipeline into these other therapeutic areas.
What we see at 2025 is an inflection year where we'll have clinical trial data, and we'll really chart the strategy for the next decade plus where we anticipate being a sector-leading biotech with multiple clinical trials, with multiple flywheels of regulatory filings, and the ability to be a sustainable biotech with a strong balance sheet of $1.86 billion. Another sort of topical update from the company was we had a business development deal where we were able to bring in an siRNA technology from a company called Sirius Therapeutics targeting factor XI. We're really excited about that. Hopefully, we can cover that in Q&A. We think that has a multi-billion dollar opportunity in the anticoagulation space. To talk about hemoglobinopathies, again, 2024 was a foundational year for Casgevy. Our partner, Vertex, and I are very thrilled with the launch.
I think the population and the effects that we're seeing in patients are transformational. We're seeing some patients that have been treated with our sickle cell disease therapy, Casgevy, that are climbing Mount Kilimanjaro, for example. A lot of our first patients in the trials are becoming advocates for the therapy and spreading the word on how much better their lives are. We really think the addressable market globally for Casgevy is 60,000 patients. At a $2 million price point, $2.2 million price point, it creates a very, very large multi-billion dollar market opportunity. This year, based on the foundation that we built in 2024, we really anticipate expansion and execution on this multi-billion dollar opportunity. We've done this in various ways. We have a CMMI pilot model where states are opting in now to get reimbursement for Medicaid.
We're expanding into these untapped ex-U.S. markets. Particularly, I think, to investors, the Middle East market has come as a pleasant surprise, with Saudi Arabia having the first beta thalassemia patient treated last year. We're investing more. Vertex is investing in manufacturing to support this global launch. In our most recent update, or Vertex's most recent update, there were 90 cell collections and greater than 65 authorized treatment centers activated. We do not want to stop there. 60,000 sickle cell patients or sickle cell and beta thalassemia patients is not the entire population. We are working on ways to serially innovate via targeted conditioning, or if we're able to provide, again, similar to our in vivo pipeline where we're targeting liver targets, if we're able to do the same where you have one infusion and you can address sickle cell disease, that would be the holy grail.
That would address not only the entire population in the U.S. and E.U., but also thinking about underserved populations in Africa as well. With regards to our internal wholly owned pipeline, we're extremely excited about the opportunity that we have to apply the CRISPR technology to what's known as CAR-T or T cell therapies. We're doing it in multiple ways. I'll focus most of the time talking about CTX112, which is, again, off-the-shelf therapy using the CRISPR technology where we're applying it to clinical trials in cancer as well as autoimmune disease. What we do with the CRISPR technology is we make some edits into a healthy donor that provides their T cells. We're able to make these edits to increase the potency. What we found with our first-generation technology is that they were working well.
There was an adequate safety profile, but we wanted an extra kick to really get patients with severe disease, both in oncology and autoimmune disease, to come into potential remissions. We ran a phase I trial in oncology. We put out data last December at the American Society of Hematology Conference. Early data looks really promising. We're seeing across the total population, 67% overall response rate and a 50% complete response rate. When we went back at JPMorgan this year and looked at sort of the higher dose cohorts, the patients that are getting more cells, we're seeing greater expansions. That's exactly the profile that you want to see. You want to see a dose response and patients being able to have expansions with DL3 and DL4 versus DL1 and DL2.
In addition, we looked at patients that had relapsed off of currently approved therapies for oncology. We were seeing that despite them relapsing on what are known as TCEs or T cell engagers, they were getting responses on our CTX112 therapy in this DL3 and DL4 cohort. In autoimmune disease, these results from oncology, we think, give us a best-in-class profile. We anticipate sharing this year. In autoimmune disease, there are various competitors out there. The way that we think allogeneic therapy or off-the-shelf therapy is going to win is threefold. We think that we have the ability for lower COGS and higher scalability. We have deep B cell depletion. We have proof-of-concept data from an academic group as well as other groups that show that CAR-Ts can actually get long remissions in these patients.
With the ability to have lower COGS and higher scalability, we have the ability to price at an autoimmune price point. If we can provide similar remissions that we've seen with the autologous CAR-Ts, we think that CTX112 has the potential to be best in class. In addition to CTX112, we also have CTX131 and a GPC3 autologous CAR-T with Roswell Park, an academic collaborator, that are progressing as well in trials. For our in vivo pipeline, another topical update we had here was top-line data from CTX310. This targets ANGPTL3. The beauty of ANGPTL3 is that it targets both triglycerides and LDL. If you go to your doctor, you get your blood drawn at a physical, you will see these two markers. LDL and triglycerides are both biomarkers that have been associated with the progression or the risk of having a heart attack.
In our phase I trial here, we tested various doses of CTX310 in patients with high levels of triglycerides, high levels of triglycerides and LDL. We saw very meaningful results. If you look at our 0.6 and 0.8, in the 0.6 cohort, we're seeing an average of 56% reduction in triglycerides and a 28% reduction in LDL. We had a patient in the 0.8 mg/kg dose cohort that had an 82% reduction in triglycerides and a 65% reduction in LDL. You can imagine for a patient, for example, this DL4 patient, they have 1,000 milligrams per deciliter triglycerides. If you look at their blood, you can see sort of a thick, foamy layer of triglycerides. Following our therapy, that number is down below 200 mg/dL. They're almost within the normal range.
Similarly, we had a patient in the DL3 cohort where they had an 81% reduction in LDL. They had a baseline of 256. That number is meaningfully below. This is the bad cholesterol, LDL. From our animal studies, we've been able to follow monkeys out durably over two years. We anticipate that these patients now have a significantly reduced LDL and triglycerides for potentially ever. We obviously have to follow the patients out to confirm that. This is a pretty transformative therapy. From a safety perspective, if you think about the cardiovascular space, safety is going to be very important if it's going to be in a larger patient population. We saw no treatment-related SAEs and no grade 3 AEs and no clinically significant changes in liver enzyme elevation. We're thrilled with this profile.
Early data, but the top-line data does suggest that we have potentially a best-in-class therapy that is performing numerically better than anything that's out there. The way CTX310 works is, again, there's a large addressable population. There's multiple indications we can go after. We'll share an update in the second half of this year. I mean, we can take it into everything, obviously. Prioritization will be important. Resource allocation, getting approval, and indications is going to be important just from a cash flow perspective. We're looking at various indications and how to progress the trial as we go into a phase 1B study. More to come on this in the second half.
Again, you can go from patients with HOFH, where it's a very rare disease population, to something like mixed dyslipidemia, where you can treat multiple millions of patients with these transformative benefits that we're seeing in the early data. Follow on to our CTX310, we have a therapy called CTX320, which targets sort of a novel biomarker called lipoprotein (a). And lipoprotein (a) is becoming more and more recognized. In ex-U.S., they test for it. In the U.S., they still have not adopted the guidelines. If you go to medical conferences, there are lines out the door to test your LPA. There's a very important trial reading out from Novartis in the first half of next year called Horizon that will basically test the hypothesis that if you reduce LPA, it can confer the same type of effect that we're seeing with LDL and triglycerides.
It reduces your potential for having a cardiovascular event. In our NHP studies, we're seeing, again, a very robust reduction, 95% reduction in plasma LPA. That is sustained for two years. This program is in the clinic as well. We look forward to sharing an update there. Again, similar trial design to the 310 study. Top-line data will be similar to what we've shown in the 310 study. We look forward to sharing that shortly. When you think about 320 and what it could do, elevated LPA is in a significant number of people. They say elevated LPA in general is in one in five people. We've estimated it at over 60 million U.S. patients. Because we have this scalable platform with in vivo, this is just a lipid nanoparticle and an mRNA. It's very scalable. It's very cheap.
We have two additional programs that are advancing towards the clinic. One is targeting angiotensinogen. This is being developed for patients with refractory hypertension. You can imagine there are people out there with high blood pressure that are on a lot of medications, these ACEs and ARBs. They're on diuretics, but they still have a high blood pressure. What we've been able to show in animal models is that we can normalize that blood pressure, again, with an infusion. We also have a rare disease program, CTX450. In diabetes, again, we're looking for the holy grail of providing islet cells that are edited that have the ability to produce insulin in patients and reduce the need for insulin infusions. We're advancing our CTX211 program. We have a follow-on program that is a direct infusion with iPS-derived cells.
We anticipate providing a type 1 diabetes update in 2025. If that was not enough, the field of gene editing is evolving. What we want to do is stay on the cusp of all the technology, in addition to our current clinical programs, really stay on the cusp of the technology innovations that are happening. We have developed internal groups called CRISPRx and a group for delivery technologies to really see if we can expand our toolbox or toolkit where eventually we are providing the best tool for a specific disease and hopefully have best-in-class data as well. In 2025, we see a significant year of value creation. We had the ongoing launch of Casgevy with Vertex leading that launch. We get 40% net income of the program.
We have a catalyst-rich year with, in addition to the 310 data which we put out last month, we've got several data readouts upcoming for the second half of the year across the portfolio. We have a strong balance sheet, $1.86 billion, which, again, in this environment, we're being very purposeful with dollars spent on a return on investment generated. Then, again, we did sign a business development deal with Sirius Therapeutics that we're extremely excited about where we see a multi-billion dollar opportunity in factor XI anticoagulation without the risk of bleeding. We do anticipate the story of CRISPR to evolve with the foundation of Casgevy, multiple clinical programs, and a platform engine behind it that will really carry us into a sustainable biotech for multiple years and hopefully decades to come.
Great. Thanks so much, Raj.
We'll go into some question and answer in the meantime while we have about nine minutes left. First, I would love to discuss the deal with Sirius. Very interesting, obviously, to have a gene editing company form a partnership with an siRNA company. So can you kind of describe the rationale behind that and how the deal came about and ultimately how you see siRNA and other genetic medicines fitting into CRISPR's technological platform?
Yeah. Yeah. I think one aspect of the deal was to say we think gene editing is a modality. We think RNA therapies are a modality, antibodies, and small molecules. And we think that there's a continuum where RNAs might be better for certain therapies and gene editing might be better for some. And factor XI hit that high hurdle rate we had.
With factor XI, again, this is a target where it hits the intrinsic pathway of coagulation, but there's no bleeding risk. If you think about factor Xa inhibitors like Eliquis, for example, there is a bleeding risk that inhibits its use in certain populations. Factor XI does potentially hit these populations and would be amenable for patients that are not on DOACs or factor X. In this target in particular, there's indications where you don't want a lifetime treatment. The phase two that we're running is in total knee replacement. In a total knee replacement, you don't want to have your factor XI reduced for lifetime. You want it in a more finite period of time until you've recovered from the surgery and you can kind of go on with your life. In areas like this, it hit that rate.
We have two additional license programs as well from the collaboration. You should think about those targets in a similar light where we're going to have this high hurdle rate where we're still committed to gene editing, but we also wanted to supplement our pipeline and have a complementary technology that hits this high hurdle rate of, "Okay, it's a value-creating asset, but gene editing might not be the best modality at this period of time." We're very excited about the deal. There are several competitors in this space that have important trials reading out. Anthos, which was just acquired by Novartis, has some trials reading out next year, which will be important for sort of laying out the value potential of the asset.
Great.
I guess, how should we be thinking about CRISPR participating in future business development deals, obviously, of the partnership with Vertex where you developed in-house Casgevy? Should we kind of think about CRISPR engaging in both in licensing of new technologies as well as partnering out your current pipeline?
Yeah. I think it's all part of this foundational year or value inflection year of what's our goal. I think our goal is to become a sector-leading biotech. With that, it requires bringing in assets. It requires potentially risk-sharing where we might not be the best in commercializing a certain therapy. We're in this transitional period now where we've had significant success with Casgevy. We anticipate that launch will continue. We're figuring out where are we going to be in the five, 10-year time horizon? How are we going to get to profitability?
I would anticipate us being very thoughtful about what we do. We have a high hurdle rate on both the buy and sell side. Yeah, we're definitely having conversations across the portfolio. You should anticipate us to stay active.
I guess I'm also curious if your proprietary lipid nanoparticles come into play at all in terms of an asset that could be out-licensed. What struck me about the initial CTX310 data was its clean safety profile in contrast to some other in vivo gene editing therapies we've seen. How are you guys kind of thinking about that and how that platform is differentiated?
Yeah.
I mean, what we basically the bets that we made with our next assets in the clinic is we were really focusing on how do we bring a low cost of goods asset that can be priced competitively with the standard of care and you can deliver this transformational benefit. With the in vivo pipeline, as Sami mentioned, the LNP mRNA combo is relatively cheap to make compared to Casgevy, for example. We have the ability to maximize the platform potential of it, to your point. I think what we're seeing is that some of these programs, there are certain aspects of whether it's formulation or indication that you go into where the data is going to read out differently between companies. There is some proprietary know-how into how we develop our technology versus others.
We think that it's pretty powerful based on the early CTX310 data. We'll have to see how sort of the clinical trial progresses. So far, so good. We're excited about the data set and the interest from pharma as well has been pretty solid in the platform.
I would love to touch on Casgevy real quick. Obviously, 2024 was very much a foundational year for the technology, getting those treatment centers up and running. How should we be thinking about 2025 and what would be viewed as a successful year, in your opinion, for that product? How should we be thinking about the implementation of CMS's Cell and Gene Therapy Access Program as a tailwind for the program?
Yeah. I mean, I think it's been a great experience to be part of the Casgevy launch. Again, the transformational impact on patients can't be understated.
Sickle cell patients with multiple VOCs are now hiking Kilimanjaro. Patients feel better. Patients with thalassemia are potentially transfusion independent. The benefit to patients cannot be understated. I think in 2025, again, 2024, as you mentioned, was a foundational year. 2025 is going to be a year of execution. Vertex is doing well. Ninety cell collections as of May 1st. We are generating revenues from cell collections as well. The launch is ramping. ATCs are almost at the target of 75. We do anticipate a multi-billion dollar opportunity here. Vertex's ability to execute in the rare disease space is bar none. We are excited about the partnership there. We do anticipate growth, significant inflection in initiations, I think Vertex said in their PR. We are excited about the prospect of that therapy for the long term.
Any specific geography where you would expect to see an acceleration in those patient starts? I mean, I would say all geographies are, I think we're approaching and getting approval and going through reimbursement access with some are in later stages. So hard to single out one opportunity. I think I would say the one that's probably been the most surprise to the investment community is the Gulf Coast countries. I would anticipate we're the only therapy out there in ex-US territories. As we grow our U.S. presence, and there's a little bit of a competitive dynamic there, we feel best positioned there. The ex-U.S. is just all green space for us. Greater than 23,000 patients, Vertex has said, is the addressable population in the Gulf Coast countries. We feel really good about, again, a multi-billion dollar opportunity.
Great.
And then you said you are generating revenue now with Casgevy. That combined with your already very healthy balance sheet, how are you kind of thinking about the current road to profitability for CRISPR?
Yeah. I think one thing the company has been extremely good about is not resting on its laurels with regards to the balance sheet. I think in this biotech tape in particular, being good stewards of capital is extremely important. It has separated us from a lot of our peer companies in the gene editing and cell and gene therapy space. You can imagine that we will be very careful with making sure that any dollars that we are putting to work are going to generate returns for investors. We stay very singularly focused on that as a public company, obviously. Yeah, the balance sheet will continue to be a source of strength for us.
We anticipate being able to run the business to become sustainable and profitable at some time in the future.
Great. Thanks so much, Raju. We are going to continue this dialogue in the breakout session in the mayor room upstairs. Thanks, everyone.