Good afternoon, everyone, and thank you for joining me at the third day of the Needham Healthcare Conference. My name is Gil Blum, and I am a senior biotech analyst with a focus on immuno-oncology. Today, I have the pleasure of having with us Sam Kulkarni, the CEO of CRISPR Therapeutics. As a reminder, any viewers who are watching through our conference portal are able to submit questions via the Ask a Question box.
Let's start with transfusion-dependent beta thalassemia and sickle cell. I think a lot of investors are pretty focused on this, and again, congratulations of the filing being accepted. That's I think it's a big move for CRISPR and for Vertex.
Yeah. Thank you, Gil, for having us at this conference. We're quite excited about where we stand today. It's hard to believe that we're nearly eight years into the life of the company, but only 10 years since the technology, CRISPR technology, was elucidated and developed for gene editing. To stand here where we filed the first BLA, of its kind in the entire world is, quite a proud moment for CRISPR, but also for an important moment for the entire field.
It does feel like 1985 when the first, you know, proteins or biologics were, brought to bear as medicines, which sparked off a whole category of medicines which now comprise over half of the entire pharma market.
We're quite excited, both Vertex and us, not just in terms of having filed a BLA, but the prospect of bringing these medicines to patients in need. We do think that, you know, there'd be a lot more patients that could benefit from this medicine than than how people are thinking about or handicapping it. There's a lot of work to do ahead of us as well. Anyway, all in all, very excited about where exa-cel stands, but also very excited about everything else that's coming behind that in terms of our pipeline.
Okay. A couple of technical questions regarding filings. It looks like regulatory process for exa-cel is a little ahead in Europe compared to the US. Are there any differing regulatory requirement in different jurisdictions ex-US?
you know, by and large, they're very similar, I would say between the US and the European authorities. I do think that, you know, there are some specific, there could be some specific differences here and there in terms of CMC matters, but generally very similar. I think, you know, the fact that we completed our European filings in December last year versus completing our filings in March for the US BLAs, it was just a matter of providing all the data that was necessary from each of the agencies.
Okay. Just to remind everyone, now that the filing is complete, what are the timelines for the review?
Yeah. Typically, you know, with the US FDA, what you have is a window of time, about 60 days, where they can review the filing and either accept it or not accept it. I think typically when they accept it, you also find out whether you have a priority review or not and what the PDUFA date might be. You know, we also find out whether there's potentially an AdCom required. That doesn't have to be at the 60-day mark. You can find out later. I think, you know, I think having the BLA accepted is a pretty important milestone.
I think in Europe, for Europe, I think there's ongoing dialogue after you file, and questions that you answer. Overall I think, you know, that timeline for approval, typically takes nine to 12 months in Europe. Given that this is a disease with a lot of unmet need, we're hoping that people act with a sense of urgency.
Okay. Maybe because we discussed it in brief here, any handicapping on a potential advisory committee? It is bit of a first of its kind.
It is a first of its kind, and, you know, an advisory committee is, it could be a good thing for us, because it would demonstrate, it would highlight all the risk, the way physicians think about risk/benefit, and, could provide tailwinds in terms of a potential launch. I think at this point it's very hard for us to say whether an AdCom's necessary or not, or the FDA will ask for it. Given it's the first of its kind, there's a, you know, I would have said that there's a good chance there will be an AdCom, but we don't know at this point.
Regardless, you will be fully prepared.
Yeah, absolutely. Absolutely. We do view the AdCom as a positive thing.
Okay. Maybe a bit of a, you know, kind of an outside-looking-in question. Do you see changes in attitudes, timelines, in the FDA, to OTAT? A lot of people have spoken about, you know, Peter Marks's involvement. I'd love to hear your opinion.
It's hard to say, you know, for one case-by-case basis. I think we generally I've always maintained that we've seen a very supportive agency, and the people of the FDA are trying to do the right thing, for these to bring medicines to patients safely. I think there are always gonna be some disagreement between companies and the agency in terms of CMC requirements or other preclinical assays and preclinical studies. Overall, I, you know, it's hard for me to say there's been any recent changes. I continue to see a supportive environment.
Okay. Maybe from a commercial preparedness side, what can you tell us about your inventory set up ahead of a launch, and do you expect there to be an initial bolus of patients? How do you see some of these dynamics?
Yeah, I think the key question is capacity rather than inventory. I think since it's a patient-by-patient basis of drug manufacturing, the only inventory we're talking about is, you know, Cas9 or guides or the necessary materials that go into a manufacturing. I think from a capacity standpoint, we do have the capacity to support whatever demand we may see in the launch, even if it's above what we expect. Over time, we're gonna continue expanding that footprint because if the capacity and, you know, we don't wanna build too much capacity off the bat, but at the same time, we never wanna be capacity limited.
Yeah. That all makes a lot of sense. What learnings do you say the company has garnered from others' experience, like bluebird bio's experience in this space, you know, things like pricing in Europe?
Yeah. I think, you know, lessons mainly I think on the clinical development and regulatory path. I think on the commercial side, I wouldn't say that there's much to work off of. You know, I think I'm not sure the bluebird bio experience in Germany is a big read-through on willingness to pay for a therapy like this. I think we feel very confident, so does Vertex, around the value that this medicine brings to patients, the pharmacoeconomic benefit, and I think there's gonna be support across the spectrum to bring this therapy to patients.
In terms of the clinical path, the regulatory path, I think, you know, my big take is gene editing is a much more reliable, consistent way of manufacturing, where the CMC requirements and the CMC needs are more facile than anything that involves a virus.
You know, I think we've seen this for lentiviral-based products. We've seen this for AAV-based products. You know, outside of the path that AveXis had, which was a pretty linear path towards approval, any other company going towards a BLA using viruses have had a bit of a tortuous path. That's not because any of these companies are good or not good. It's because, you know, with viruses, there's inherent variability from a CMC standpoint.
That's something that, you know, we're getting, everyone's getting a handle on in the industry, but it's not straightforward. Gene editing, on the contrary, is actually much more consistent. If you get the Cas9 and guide into the cell, into the nucleus, you get the edit.
You know, I think that gives you a level of reliability and a and very limited variability that will give the agencies comfort that everybody's getting the right product, and ultimately that you're not gonna see the same, you know, manufacturing-driven variability drive clinical variability in patients.
Maybe spending another moment here on pricing and benefit. I'm sure you've seen the recent published ICER report in this space that does suggest that a high premium is warranted. What are your thoughts there? You feel it's pretty supportive, I assume.
Yeah. It's very encouraging that even the draft report has the relatively high price point. You know, I think, they obviously will do the final report at some point this summer, and they're soliciting opinions and input. At the same time, I think, you know, the starting point's a very favorable starting point. It just illustrates what we've been saying all this time along, which is the pharmacoeconomic benefit alone can support a very high price.
Forget, you know, the entire value-based argument, and you layer that on with the value you're bringing to these patients and to society, and I think, you're gonna create net economic benefit, for the system from this in, you know, in a relatively unambiguous way. I think that's what's gonna garner a lot of support from the payers as well as we launch this therapy.
One last question that we do get often from investors, which goes back to capacity and how many patients can receive treatment per year on launch.
Well, I think, you know, I think what we're gearing up, you know, from a capacity standpoint, you know, like, and capacity, when I say capacity, it's twofold. Capacity of the qualified treatment centers to handle a number of transplant procedures per year and the capacity from our manufacturing standpoint to produce or manufacture the drug for all these patients.
I think from both those standpoints, we wanna get to a point where we can comfortably have capacity for hundreds of patients per year and eventually pave the way for even more beyond that, but that's what we're building. I think from a demand equation and the payer side, I think we'll have to see, you know, where it all comes out, but I do suspect the demand equation's gonna be stronger than people anticipate as well.
The one thing to know for everyone is that, you know, I think the revenue recognition comes at the point of infusion, so there's gonna be a little bit of a time lag between the time we launchBring the patients into the funnel, and by the time we actually infuse them. That, you know, regardless that the key marker to look for is how many patients are coming into the funnel where we harvest their cells. Because once their cells are harvested and manufactured, we suspect that there's very little drop-off from that point to patients actually getting infused.
That also makes sense. Another strategy to expand the market would be to use milder overall conditioning regimens. There's been some notable failures in this recently. What are your thoughts and how is CRISPR working in this direction?
Yeah. Both Vertex and us, have made this a top priority given the value we see with exa-cel to bring a gentler conditioning agent to the market. You know, the interesting observation I have is that over the last few years we've seen some failures. The reason for that is these agents were being developed for indications other than sickle cell and thalassemia. You know, the PK/PD profiles, were all designed to work in AML, or some rare diseases like SCID.
In sickle cell and thalassemia, what we need, are antibodies and, or ADCs that have a fast clearance so that you don't impact the drug product, but sufficient hit that you create enough room in the bone marrow to enable enough sufficient chimerism.
That's sort of the requirement which may be different than, say, what you need for allo transplant in SCID or for AML. I think that's why we're doing a very much of a demand spec-based build of the assets we're gonna develop here, and that gives us greater confidence that it's gonna work where others have not worked.
Okay. Maybe a broader question? There's significant investment involved in rolling out any gene and cell therapy, particularly on the CMC and manufacturing side. How much of a moat do you think from a competitive standpoint is having in-house abilities compared to, you know, companies that use contract manufacturing?
You know, it's a delicate balance. I think, you know, if you asked people three years ago, everyone said you have to build in-house manufacturing, and what we've seen is capital destruction. Everyone's built expensive in-house manufacturing, which now is selling for pennies on the dollar. I think what we did is, I think, should have been, that we wanna be bespoke. You know, I think the key knowhow is the process development and analytical characterization for the products. The actual manufacturing of the product is, you know, once you've figured out the process, it can be done externally without much issue.
We're gonna have a hybrid model where, you know, all the early products are developed, for instance, in our, in our own manufacturing facility, like CTX112 or CTX131, for the early clinical trials, and then they will be. Once they're, you know, fully established, we could do that at a CDMO because it's more capital efficient versus us doing it ourselves. You know, same for mRNA or same for AAVs.
You know, our manufacturing facility can produce all of these, but we don't wanna turn and turn, you know, be the ones operating at scale for manufacturing eventually because it's a different competency, and CDMOs are pretty good at it. We're gonna have this hybrid model. I don't know that it per se creates a big moat.
I think the biggest value add we see in having our own GMP facility 30 minutes away from our R&D headquarters is that the bench to bedside translation happens much faster. You know, as soon as we start making an asset at the bench side, we start thinking about how to manufacture it at GMP scale or at, you know, in a GMP environment. Our typical timeline from concept to IND in some cases has been less than 18 months, which is unimaginable if you're gonna do this at a CDMO.
Yeah. Okay. I'd like to switch gears and talk more about immuno-oncology. Let's start with B-cell lymphoma, CTX110 and One-twelve. The most recent data updates indicated about a 40% CR rate with about 20% of patients maintaining kind of long-term activity, and investors have noted that these results come in below what you would expect for autologous CAR Ts. I'd like you to spend some time differentiating the kind of patients that would go on an allogeneic therapy versus an autologous one. I know this has been a point of contention for investors, and I think it's worth clarifying.
Yeah. It's also apples and oranges when you compare the clinical trial data. You know, I think when the autologous therapies came out and did the early trials, you got patients that didn't have huge tumor burden, nor were they fast progressing tumors. You know, if you look at the intent to treat population for Kymriah, for instance, of the 170 patients that they published, only 110 got the CAR T. Of the ones that didn't get the CAR T, some were manufacturing failures, others were just fast progressers.
You know, in our instance, you know, we're getting much sicker patients in our trials. It's not really an apples to apples comparison to say that, the one in five durable CR that we have, the 20%, is far lower than autologous CAR Ts because in the real world, my sense is it's somewhere between one in four and one in three for autologous CAR T. Somewhere in the 27% to 28% range for durable CRs, okay? That's my own.
You know, it's not like there's been a systematic study done. That's my own take on what I've seen across different academic medical centers. That means that we're not that far away, you know, and we have all the convenience of an allogeneic therapy. Mind you, that data was with one dose, right?
Now if you have two doses, and we've shown the safety profile remains the same, odds are that we end up with better efficacy, or hopefully we end up with better efficacy, and that gets us even closer to this, to what we're seeing in the real world with autologous therapies. This is all in the CD19 context.
With our CTX112, I do think that those CAR Ts are gonna be much more potent, and you could end up even enhancing upon the durable CR rates that you've seen with 110 or with the first generation programs, which could be equal or better than on auto CAR Ts. So the limit of improvement on allo CAR Ts is a lot higher than the limit of improvement on autologous therapies.
That kind of brings me to the next question. If you had to set a bar for your ongoing pivotal study, where do you think that would be? Should we compare it all to autologous CAR Ts? Should we compare it more internally? What is the best way to think about this?
Well, the bar to approvability in my mind, I think where we are right now, the one in five or 20% durable CR rate is actually an approvable profile for CD19 allo CAR T, because there are gonna be a significant set of types of patients that are gonna benefit from that therapy being available. There's a market sensitivity. You know, if we're at 20% versus 25%, that, you know, translates to me to a difference of being a half a billion-dollar drug to a potentially a one and a half to $2 billion drug.
That's I think the commercial sensitivity in that efficacy. You know, I mean, if our worst cases were a half a billion-dollar drug, that's not a bad place to be because our profitability on allo CAR T is a lot higher than what you've seen with autologous CAR Ts.
Okay. kind of a last focus on 110 before we switch to 112. let's say everything goes well. Where do you think, 110 would slot in the, in the therapeutic algorithm?
Well, I think we're developing for relapsed refractory settings right now, but, you know, if I put my hat on, you know, future hat on and say eight years from now, what is that sequence of therapies gonna look like for CD19 positive malignancies, my suspicion is that, you know, allo CAR Ts and bispecifics are gonna move up in lines of therapy at the expense of auto CAR Ts.
You could very well have a patient get an allo CAR T for tumor debulking followed by a few cycles of bispecifics as maintenance as the first line of treatment, whether it's bispecifics or Rituxan as maintenance. You know, if it's early stage tumor, it doesn't justify doing auto CAR T and the expenses associated with it. You also wanna treat it right away, you know, to give it to.
You don't wanna wait too long. I think bispecifics are gonna be moving up in line of therapy as well. I don't know what the path is gonna be in terms of development, you know. You could go into high risk, frontline, et cetera. Eventually I think allo CAR T and bispecifics are gonna jockey out auto CAR Ts in the grand scheme of things.
Okay. Let's spend some time on CTX112. Recently saw the paper from Carl June's lab on RAG1, and it seems that both of the edits that are in 112 are designed to enhance the health of donated T cells and improve their expansion in tumor microenvironment. Just to help me understand, how important is suppression in the TME for a liquid tumor?
Yeah, it is important. I think there are two aspects to the its, to these edits. One is overcoming exhaustion because of factors in the TME that are suppressing the activity of CAR Ts. The second is just the CAR T's own health and robustness in multiplying and replicating, right?
I think what we're seeing, and we just presented these data at ACR, is that with the RAG1 edit and TGF-βR2, a much higher fraction of the CAR Ts were the central memory phenotype, and it remained naive several days into an animal experiment with exposure to CAR, with the tumor, right? What that tells me is, you know, we have a window of about a month before these CAR Ts are rejected by the patient's immune system.
In that time, if you can maximize the activity of the CAR Ts, that's what's gonna get us the most deep responses that could lead to durable responses. That's sort of the thesis behind it. That's why we're going after the edits.
In fact, it's, you know, RAG1 is getting a lot of notoriety with the recent publication from Carl June, but TGF-βR2 is also gonna get a lot more notoriety over the next few months because, you know, at ACR you saw a GPC3 auto CAR T with the T-TGF-βR2 disruption, which by the way is, we also have a program there, and that looked pretty interesting. There's another program, other programs which are also employing TGF-βR2 knockouts.
I would say TGF-beta suppression broadly because there's different edits you can make, whether it's TGF-βR2 knockout or some others to achieve the same desired effect. In all in all, I think the cytokine space in, as effectors of T cell activity or influencers of T cell activity is gonna become a much more studied field and much more in the news.
Okay. Assuming that CTX112 is successful, so do you see it replacing CTX110 over time or do you think maybe both of them are gonna be coexisting but in different patient populations?
It could. We don't know yet at this point. You know, I think what our thesis is we, you know, it makes sense for us to move forward full speed ahead on CTX110. You know, just going through that BLA is gonna give us a lot of experience, and actually launching in a market is gonna teach us a lot, even whether, you know, CTX112 works or not.
If CTX112 is much better, obviously we'd try to bring that to the market as soon as possible as well. This is a new paradigm in the industry because typically people pick one or the other. I think the synergies of working on both are, you know, quite important here for us and far greater than people imagine. We'll continue to push forward both programs.
Moving on to CTX130 and 131, just starting with the T-cell lymphoma space. We definitely saw some interesting activity there. Is there a likelihood of an expansion study becoming registrational? This is very high unmet need in T-cell lymphoma.
Absolutely. That's what we're trying to clarify with the regulators. You know, I think, you know, in T-cell lymphomas, there literally are no options for patients. You know, there's an agent that was approved 10 years ago on accelerated basis that never had a confirmatory study, for instance, or others that only treat CD30 positive T-cell lymphomas.
Yeah.
In that environment, a single arm study could certainly get us to you know, registration and approval. I think the numbers of patients required are not, you know, dramatically high. I think the treatment paradigm in T-cell lymphomas, we need to establish, you know, essentially the multi-dose regimen. At this point, we're seeing very encouraging activity, you know, much better than what the benchmark is. I think what we you know, our goal is to get to that point where we can say we're in a registrational trial sooner rather than later, but it does require a little more FDA discussion.
One of the challenges of targeting CD70 is it can result in T-cell aplasia. How is this being managed in your studies?
You know, we interestingly, we haven't, while there is some T-cell aplasia, we haven't seen an increased risk of infections, or any sort of, any of the effects you see when people are immunosuppressed. I think, we haven't had to deal with any of the, you know safety issues essentially, because of targeting CD70.
Yep. Switching gears to CTX130 and RCC, again, a really interesting study. Can you remind us what the T-cell expansion looked like in that one responding patient?
Yeah. We, we haven't, you know, first of all, we're super encouraged that we have the first demonstrated CR, complete response, in a solid tumor with an allo CAR T. In fact, the first demonstrated complete response with any CAR T in the world. It was a very interesting case, you know, I think. We're encouraged by the activity against the target in RCC. We haven't disclosed the T-cell expansion for that one patient.
You know, I think we do generally with CR as you do see the reasonable T-cell expansion, but it's not always predictive. You know, it doesn't always mean that if you have high tumor expansion of CAR Ts, that you'll get a CR or even a PR.
The reason for that is this all boils down to effector to tumor ratio. You know, when the tumor is very bulky, sometimes we see very high expansion, but we don't see responses because the tumor is so bulky, you know, and you don't get complete, or you don't get deep responses. But you do see some response. You don't see complete responses sometimes.
Sometimes the, you know, there's a sweet spot where the tumor is bulky enough, where you see quite a bit of expansion, but you also see complete killing of the tumor where you see CRs. It's a little bit hard to say, and in fact, this data, this has been borne out with all the autologous CAR Ts as well. You know, initially there was a thesis that expansion is the single biggest predictor of a complete response, and it's not been the case.
Yeah. It's more area under the curve... [crosstalk]
Yes.
The dynamics are slightly different, right? If you get a very high peak, Cmax is usually associated with tox.
Well, associated with tox, but also in the case we've seen, sometimes associated with quicker exhaustion. So it could, you know, you're right about the area of the curve, we have now data for, you know, CAR T expansion in about 150 patients across all our trials. The bigger data set than most other companies, involved with T-cell space. We're learning quite a bit about what cell, you know, what it means from a PK/PD standpoint how predictive things can be. We don't disclose all these data, but it gives us a big leg up in terms of how we develop the next set of products.
Yeah. Excellent. Going back to the two edits we discussed, do you expect them and CTX131 to support systemic expansion, support activity within the tumor microenvironment, maybe both?
Both. I think the, you know. Typically, when you infuse the cells, they have to go find the tumor to start expanding, you know. I think then they expand, and they come back into the bloodstream where they're measured. What we wanna see is greater expansion because the cells are somewhat more central memory phenotype, and then for them to be able to retain their effector activity for longer, even as those cells differentiate from early naive cells to the more effector-like state, that they can keep going 15, 20 days post-treatment, and that's what's gonna get us a durable response.
The longer term surveillance.
Yeah. I don't know if you wanna call it surveillance or, you know, to your point, just air into the curve, longer term killing, pressure.
Pressure. Longer term pressure.
Exactly. We may never get surveillance for three months, you know, unless we have other persistence edits. I think we would get it, you know, enhanced killing for longer than what we're seeing with our first gen CAR T's, which is about 14 to 15 days.
Okay. I'd like to spend a little time also on the regenerative medicine angle. You've had some interesting reports recently on a new deal with Vertex, a new partner... [crosstalk]
Yes.
N ext generation programs of VX-880 and VX-264. What can you tell us about this?
Yeah, no, we're very excited about our regen med franchise. You know, again, speaking of world firsts, we were the first, to my knowledge, to have treated patients with edited cells derived from iPSCs. You know, I think that's a pretty big feat, and that brings together the 2012 Nobel Prize with iPS-derived cells or creating iPS cells with the 2020 Nobel Prize on using CRISPR-Cas9. I think that's two major technology waves that have created, can actually create significant value. What we have with Vertex is a two-parts partnership. You know, on one hand, we're working in a 50/50 co-development fashion with VCTX211.
Mm-hmm.
The thesis here is that we take stem cells that are not fully differentiated, partially differentiated, but their fate are determined, and implant that into a device, and implant the device into the patient, sub Q. The goal is to get the cells to fully differentiate inside the patient's body and then produce insulin, endogenous insulin that's gonna reduce their insulin requirements and hopefully make them insulin independent. All this while without the need for immunosuppression, right? That's one part of the program.
Th e other part of the program, the partnership we have is that we've licensed our IP around CRISPR-Cas9 editing to Vertex to pursue, further pursue their own efforts with a different cell line, where they differentiate the cells to fully, to the full, you know, to what's called an S6 state or a fully differentiated state, or islet cells, where you can inject those cells either as naked cells or in a device,
to achieve the same end goal and the end result. I think, you know, having multiple shots on goal is a very good thing for us, and we look forward to advancing our programs as well as the Vertex programs advancing at the same time.
There should not be any read-through between these two verticals.
No, at this point, no read-throughs, read-through between what the Vertex programs are doing versus ours. I think we just wanna, you know, from both our standpoint and Vertex standpoint, I think the more shots we have in this very attractive market where we have the first-mover advantage, the better off it's gonna be.
Okay. Kind of on the data end, what should we expect this year from the earlier programs, so VCTX210 and VCTX211?
Yeah. We 210 was a safety run-in. I think this was, you know, as you said, as I said earlier, the first time that we put edited iPS-derived cells or edited stem cell-derived cells into patients. That's, you know, an important technological advancement, but we wanted to demonstrate the safety of it.
We worked with the agency to say that, you know, how do we do a safety run-in with the lower dose of cells in the device to prove the safety of this approach, which allowed us to move into 211. With 211, we have a higher dose of cells, and we have a more optimized clone to produce greater level of insulin in these patients. What we wanna see is data for a handful of patients with at least six months of follow-up.
The reason I say six months is, you know, it takes these cells about three to four months to differentiate fully inside the patient's body, and only then do they start producing insulin as measured by C-peptide production, which is generated when proinsulin is broken down into insulin. We do wanna wait six months for these patients to show what their steady state insulin production might be. That's the data set we're looking for. Whether we get there by the end of this year or whether it's early next year, I don't know.
Okay. I'd like to spend the last few minutes that we have before we take a couple of questions from the audience on your in vivo programs. Maybe you could shed a little light on the reasoning behind going forward with ANGPTL3 as your initial target.
Yeah. ANGPTL3 is gonna be a very important target in cardiovascular medicine. You have several pharma companies working on it now, and so is LP little A or LPA. These are both the risk factors that could be very important in cardiovascular disease, and especially in mitigating cardiovascular disease. ANGPTL3 is a protein that actually works by inhibiting lipoprotein lipase, which acts on triglyceride-rich lipoproteins.
Inhibiting that activity I think actually helps reduce triglycerides by almost 60% in some clinical trials, or by assessing natural history data, and also reduce your cholesterol levels, LDL cholesterol levels. Mind you, this is all with a single dose of CRISPR-Cas9 based medicine that could lead to this level of reduction.
We're moving forward very quickly on, as fast as we can on these programs. What I've said is we hope to be in the clinic, with our in vivo programs this year, for at least one program, and then quickly follow that with the second program in LPA.
Okay. Is the strategy to focus initially on smallish, kind of genetically well-defined indications and maybe expand later? Or maybe an agnostic approach?
No, absolutely. I think what we wanna do is, you know, start with indications where whether it's homozygous familial hypercholesterolemia or patients that have uncontrolled... [inaudible] [crosstalk]
Yeah.
Y ou know, with certain manifestations, where we can have easy or relatively easy biomarkers. I think people with very high LPA levels, that's what we're going after first so that we can hopefully have single arm trials that get us to approval and then follow that up with confirmatory trials.
All right. We are coming up on time. I do have one question from the audience, and this is specific to recent ICER report. The question is, where is ICER getting their information about the safety of exa-cel?
Yeah, You know, ICER doesn't have access to any of the non-public clinical trial data. They have an advisory committee where they have experts who may or may not be exposed or be part of the trials that are ongoing. Unclear to us what their sources of data are. I would say that they generally don't have access to non-public data.
Excellent. Sam, thank you very much for taking the time today. Great discussion.
Yeah.