Beam Therapeutics Inc. (BEAM) Earnings Call Transcript
September 3, 2025
Earnings Call Speaker Segments
All right. Good afternoon. My name is Sam Semenkow. I'm one of the Biotech analysts here at Citi, and it's my pleasure to be hosting Beam Therapeutics for a fireside chat. I'm joined by CEO, John Evans; and CFO, Sravan Emany. John, Sravan, thank you so much for being here.
Thank you for having us.
Absolutely. So why don't we just jump right in then. Tell us a little bit about Beam. Tell us a little bit about some of your programs that you have going on, and then we can just dive deeper into each of them from there.
Wonderful. So Beam is working on next-generation gene editing using CRISPR tools. Specifically, our lead technology is a technology called base editing, which allows us to precisely target the genome similar to other CRISPR companies. But once we get to the target site, we make a much more precise edit without needing double-stranded breaks and generally create a single base change. So this is useful in a lot of different context. We have two major franchises under our control. One is in hematology, working on sickle cell disease, lead program BEAM-101 for severe sickle cell disease. We think a best-in-class option for patients with this disease, followed by some next-generation versions, which attempts to deliver that same functional cure, but in increasingly acceptable ways, dispensing with chemotherapy in the case of non-genotoxic conditioning or just in vivo delivery directly to the bone marrow. So that's hematology. Then on the liver side, we're doing direct LNP injections to treat liver and edit the liver. Lead program is alpha-1 antitrypsin deficiency, BEAM-302. And that program also has shown very strong evidence of correction of the causative point mutation for alpha-1 and restoring patients to sort of a therapeutic range. And I'm sure we will talk a lot about that program, followed by BEAM-301 for glycogen storage disease and then what we see as a real scalable franchise of additional liver targeted genetic medicine programs behind that. Of course, many other places we can take this platform over time, but those are really the focus areas for now. Very well financed with $1.2 billion in the bank. That's cash into '28 and certainly sufficient to do a lot of different things with that pipeline through some really meaningful milestones.
Perfect. So you're correct. I would love to talk a little bit more about the AATD program. So there's some competitor data out this morning, but maybe let's just go ahead and start first with what you've shown to date and some of the context you've given even around some of the higher dose cohorts that you've run. And just maybe a high-level overview to level set.
Yes. So what we're trying to do with BEAM-302 is to correct and edit the causative point mutation in alpha-1. This is called the Z mutation. So this is a single base change where you have a G where there should be an A in the gene for this alpha-1 protein. And your body should normally be making alpha-1 in the liver. It then is circulating around the body where it will protect your lungs from degradation when you get infected, but also is being secreted out of the liver quite efficiently. When you have this point mutation, two things go wrong. One is you have a mutant form of the protein that builds up in the liver and causes liver toxicity. And because it is building up in the liver, it is no longer secreted, you have low systemic levels and that causes the lungs to be unprotected and they become degraded over time. You get emphysema and eventual lung failure. So our job with BEAM-302 is to go in and make that single letter change, the base editing is so good at and turn that Z mutation back into the normal, which is called M. So the normal is M, the mutation is Z. And that's exactly what we do. And so what we showed in March was our initial data out of our Phase I trial. It was over 9 patients, 3 different cohorts, a dose escalation as we give larger and larger amounts of the LNP. And indeed, at the third dose cohort that we tested, which was 60 milligrams, we saw striking evidence of therapeutic correction of this gene. We had seen it in lower dose cohorts as well. There was a dose response. It was quite clear. Specifically, what we saw was total alpha-1 levels get up to about 12.4. And of that total alpha-1, 90% of it was M, was this correct form and only 10% was Z. So very strong production of M and reduction of that toxic Z, the Z was down about 80%. So -- now why are those numbers important? Well, we know that patients with this disease, what we call ZZ patients, they have two copies of that bad gene. They generally live in the total alpha-1 level range of about 4 to 6, right? So they're mid-single digits. There are no ZZ patients who live in the teens, okay? So that's quite clear. And of course, it's all Z. There's no M. And so the fact that we've taken these patients into the double digits or higher, that it's almost all M. We look much more now like what I would consider a carrier, somebody who maybe had one copy of the bad gene, like the parent of a patient, okay? But those people are normal. They don't have the disease. And so that's how we know that the editing that we have produced has gotten patients to a therapeutic zone. On top of all of that, we also showed, of course, that the LNP we were delivering was well tolerated. The base editing was well tolerated. So the safety looks really good. That continues to be the case. And of course, this is a onetime durable correction. So we literally could treat the patient once and have them have a lifetime of benefit. And of course, that's something we're following now.
That's a good overview. In the higher dose cohorts as well, you have a 75 milligram. You qualitatively have talked about how you're seeing a dose response there above the 60 milligram, and you've also expanded to a multi-dose cohort for the 60 milligrams and you've added some more patients. How are you thinking about what the ideal dose could be for 302?
Yes. So building on the idea that we're clearly in a therapeutic range, and we think 60 milligrams could very well be a great dose. We still want to push and explore, particularly because we've been so safe, we think we have the latitude to do that, and we wouldn't want to leave efficacy on the table. And so what we're really doing is what I consider sort of late-stage Phase I development where you have one opportunity to really get this right. We want to thoroughly explore dose and schedule parameters even while we think about what the next step is towards registration. So that's going to take a few different forms. So we're expanding on the 60 milligrams. So we're adding more patients there. We have initiated -- and then there's sort of two axes we're going to explore. One is to go higher on single dose, and that is the 75-milligram dose, and we're adding 6 patients there. And the idea there is you're now going to push higher on the Cmax of the LNP, which can potentially penetrate the liver a little bit more. And then the second axis we're going to explore is AUC. So what happens if we add a second dose, but there's still 60-milligram doses. So now you see your Cmax' will be the same, but you're adding more total exposure separated by 8 weeks. And again, preclinically, we see that, that does indeed add editing. So a little bit of an empirical experiment, but it will help us really understand that relationship, I think, of safety, dose and efficacy. As you noted, just the early sort of qualitative read we gave at our last Q was that as we're dosing, we do continue to see good safety and tolerability, including the 75-milligram cohort. And yes, we are seeing signs of dose response where especially we measure this as sort of a fold change above baseline. We do see that climbing up at the 75 milligram over the 60 showing that there is still some editing still to be done in this liver. So all of that is going to come together. We're going to plan to give a data update in early '26, where we can hopefully present all of that data together along with dosing some of the -- what we call Part B, some patients with liver involvement and just check to see that the safety is the same in those patients. That should altogether give us a very clear idea of where are we going to be for future development as we push towards registration of what we think is clearly a drug.
And how do you think about -- or is there a way to sort of get an estimate of what editing level you're achieving so far with the 60 milligram? Because you noted that clearly 75 is showing you that there is more room to go. How much more editing could you achieve within the bounds of the clean safety that you're currently seeing?
Yes, it's a great question. It's something that until we do liver biopsies, we won't be able to know for sure. And we actually are going to do some liver biopsies in the liver patients that we're testing both as part of a safety test. Also, we can potentially look at editing. And of course, you're going to look at the protein aggregates. This is what builds up in the liver and then hopefully see some of that resolve over time, which we expect it will. But until we do that, we're really looking outside in. So I think that there's good evidence that we are -- we've edited a lot of the liver. I think we're clearly north of 50%. If you look at our MZ ratio, for instance, right, we're 90-10 MZ. A person who is a carrier, as I said, that threshold for not having the disease, they're generally at an 80-20 ratio, right? So we're north of that. On the other hand, there's still some Z around. And so clearly, we have not edited the whole liver yet. So being more precise than that, I think, is probably impossible at this point. I think frankly, we'll learn a lot this year from these additional dose cohorts that we're adding to see how steep is the further dose response? Are we -- where do we start to see plateauing? Or is there still a good dynamic range ahead? That will tell us how much left of the liver there was to edit, and we'll learn a lot from that.
Got it. And in the update in the first quarter of next year with the Part B, specifically the liver patients, what doses are you starting at? And what doses do you think we could -- would it be more than one dose that potentially ends up in that data readout? I'm curious because you mentioned about the biopsies. So I'm wondering if we can get a feel for that editing level at a couple of different doses in that readout.
Yes, great question. So just stepping back, so everything we've done to date has been in what we call Part A, which is patients who are primarily lung. And basically, what we've done is we've excluded the minority of patients who have really heavy liver involvement. Like livers are really sick. We wanted to get a sense of the tolerability of the drug without that factor, then go back and dose those patients. So those patients are in what we call Part B. It's really just a clinical experiment that we wanted to do to get a clear signal in both populations. We don't anticipate much of a difference. These patients have sick livers, but we have dosed LNPs to animals with heavily involved livers. The field has dosed LNPs to people with sick livers before, and it has been tolerated. So I think we're quite hopeful there. But that's a check that we want to do. If that's successful, I'd say the goal would be then to bring everybody back together again. So we don't check for liver status as we go forward. That's probably the base case expectation. This is probably 15% of the patients who have this kind of liver involvement. So in terms of biopsies, I think it would be unlikely that we'll have biopsy readouts by the early '26 sort of update. That would probably be some pharmacodynamic data we'd have to bring subsequently. But I do think we will have some number of patients dosed, and that will give us a sense on the safety question and how we're treating that population going forward. Part B is going to start at a higher level than Part A did. So we'll start at 30 mg. And from there, if that's tolerated, we'll likely go to 60 mg or something like that, and that may be...
Got it. Okay. And I wanted to talk a little bit about the Z protein. Obviously, you're decreasing it less than 10% of total. When you're seeing any level of Z in the plasma, it's not available anymore to become an aggregate in the liver. Is that correct? And then I guess the follow-up question would be, if you're seeing a higher percentage, let's say, closer to 50%, 30%, so anything above 10%, is there -- what is the risk then that you could still have Z aggregating in the liver?
Yes. So Z, we do think of Z as the bad actor here, and it poses risk both in the liver and systemically. So you can think of this almost as an analogy to in sickle cell disease, the sickle protein right? Which is, again, the bad actor there. You want not just protective fetal hemoglobin, but you want to get rid of Z as much as possible. Really, the same thing is happening here in alpha-1. We want to get as much M fully functional, normal protein as we can, and we want to eliminate Z as much as possible. Now Z in circulation, I don't believe, is going to go back into the liver. So I think at that point, the risk of liver is gone. But the Z in circulation you see is the small amount that got out. Any sign of Z, that's already after a whole lot of other Z got stuck and was creating toxicity and aggregating and causing a lot of harm. So certainly, any significant amount of Z is a sign that the liver is still potentially threatened and may still be sick, particularly when you get sick. And systemic Z has problems for the lung. So you can actually aggregate in circulation, right? So these aggregates can be inflammatory and they can travel around the body in bad ways. And it can have a kind of dominant negative effect on the function of the protein, right? So you're trying to inhibit neutrophil elastases, but it's less effective at doing so than the normal M protein, but it's getting in the way, right? And it can interfere. So people think of Z canonically as sort of causing that liver toxicity, but really, it has -- there's a lot of evidence that it has negative impacts on lung as well. And so the bottom line is, to the premise of your question, our goal is to get Z down as far as possible, both in the liver and systemically, and that will have its own benefit in addition to raising M as far as we can.
Okay. That's helpful. And then on the M piece, the 60 milligram, you've above 11 micromolar on average and all patients were above that threshold, I believe you said before. Is that sufficient to -- for one, regulatory perspective? But also, I'm curious about if you need to go higher? Like what are your thoughts on the benefit above 11 once you hit that 11 threshold?
Yes. So this is where we keep going back to the clinical genetics because that's nature's experiment, right? We can -- we know so much because there are tens of thousands of people who have these sorts of genotypes, and we know how healthy they are, right? So it's not that there's a magic number like 11, all that's been used in the field a lot, and we think it's a reasonable sort of benchmark to look at. It's not that there's a magic number. It's more that we know that patients who have liver disease, who have steadily declining lung function and who may ultimately get themselves into lung transplant, liver transplant kinds of situations, they live in the 4 to 6 range for alpha-1 levels. They do not have 9 or 10 or 11 or 12 or higher, right? So it's just not what you see. So I think the fact that we've gotten the total AAT up into the teens that we've gotten the M level up into the double digits. We also test functionality of the protein, right? And the functional AAT is a sort of very important assay, and our functional level was also about 11, right, about the same as the amount of M we were producing, which makes sense. So all of that, I think, is very strong evidence that we're already in a therapeutic zone. So then you say, is there a benefit in going higher? The answer is maybe. We're certainly going to go higher if we can and as we can so long as it doesn't cause any kind of safety questions. We love the safety profile of the drug, and we want to keep it there. It is not clear to me that you would ever be able to detect the difference clinically from, say, where we are with 302 at 60 milligrams and going higher. Because if you look at the genotypes, again, you have MZ, which is the carrier. You actually have one called SZ, where S is a kind of rare intermediate allele. It's not quite as active as M, but it's not as bad as Z. So if you have one of those and then one Z, even those patients do not have progressive lung deterioration, okay? So it's a pretty steep curve where if you can get out of that ZZ place, SZ patients with total AAT can live in the 8 to 12 range or so and maybe a 70-30 ratio. So anything there or higher, we think will be stable effectively. And so we're already there, and we think that we'll be able to show that. You would also finally asked the question about regulatory bar. I think there, again, I don't think there's a magic number on any one of these parameters that the FDA is looking for. There's, of course, history with augmentation therapy and other types of development efforts in this space, which we can build on. But fundamentally, we think we're doing something totally new, right? Nobody has ever had a drug like we have, which is fundamentally correcting the root cause of the disease and is causing the renormalization of the physiology of the entire AAT system across the whole body between total levels, M levels and Z levels across the board. So that, we think, opens a lot of doors because all of these changes are predictive of clinical benefit and will be lasting.
Got it. And so one of the things that came out from a competitor this morning was, I think, the first evidence that we've seen of a patient having an acute phase response. And it was interesting because we had a nice increase in both total and M. So thinking about what that data showed and about your product, how do you think that patients that have had BEAM-302 would respond to an acute phase? Because at the end of the day, protecting the lung during those inflammation events is the goal, right?
Very much so. So one of the beauties of our approach is that it will -- the gene that is corrected will be under normal regulation. And so when it wants to turn on -- when you get infected, it will turn on. And that is a very, very important paradigm shift because when you think about what we've had in the past, which is augmentation therapy, right, there, we're just putting in some exogenous protein. It is not produced by the body, so it's not regulated by the body. So basically, however much you put in, it's sort of washing out over time, you get to some sort of trough and then you have to redose, okay? And you're also not affecting the Z protein that is already being produced by the body. The body is still completely producing Z, we've added some M, okay? So that's augmentation. And that is somewhat effective. It has some benefit, but it is clearly not ideal from a bunch of different perspectives. So in our case, we will be regulated. And I think it was exciting to see the upregulation data that was shown by WAVE today showing that in an acute event, the levels do go up, and that is proof of concept that, that sort of thing is possible, and we expect the same is happening with us. Now in their case, they have a large proportion of Z still, and that's sort of a feature of that data set. So it went up to about 20, but about 10 was Z still and 10 was M. In our case, as -- if we get that induction event, it will be almost all M, right? So that's an important distinction. But it does highlight this point that unlike augmentation, where the levels you have are sort of your average and your trough, right? For us, it's really a floor, okay? So levels that we report are kind of your baseline and then when you need, it can go up higher. And that's -- it's just a fundamentally different sort of way to think about the numbers once you're in the sort of gene correction paradigm.
Right. And WAVE had -- well, I guess, the experience of having a patient that have an acute phase pretty early on in the study. I think it was patient 2. You have shown us 9 patients, I think, so far. Have you -- are you able to say if you've seen one of these events yet? Or do you think it's likely that we could see something -- some type of event like that in the data set in the first quarter of '26?
Yes. So we're monitoring it. I think we have seen evidence of regulation, I think. I won't give you specifics in terms of what you might see in early '26, but we're certainly confident that our mechanism is going to work in the same way. These are tricky events to catch. You have to really get patients at the right moment. But again, I think, it's a fundamental advantage of our approach, which is that we're correcting the gene in its normal location. One, that will be a permanent durable change. And second, it will be regulated normally by the body, including turning on.
Great. Okay. And then maybe we just talk a little bit about competition. You have yourselves -- I think you've definitely reported the most data, I would say, the most advanced dosing data at least. WAVE now has a considerable amount of data, at least for the first dose. We also have another with Prime editing in the mix. We have some other RNA editors, obviously, small molecules that do very different things. Where do you see your BEAM-302 really fitting into this from a commercial opportunity?
Yes, great question. So -- and this is evolving, of course. But we've had historically augmentation therapy, where you're just, as I said, exogenously putting in some more protein and then trying to maintain that trough level, but it's not regulated in an endogenous way, and you're not affecting the Z. Z is being produced normally. It's still circulating both in the liver and systemically. So there are new versions of augmentation coming, right, that we're interested to see those advance. But fundamentally, that same profile will be there. You then had us and probably RNA editing or the other kind of current sort of modalities that are most in view. So for RNA editing, I think, in general -- and we've seen some data today, right, from WAVE and there's others coming, where you clearly can create some amount of M. You're taking the pool of Z, effectively mRNA, the body is producing and you're editing it at some point so that now some of it is mRNA and then that will produce M protein. And so you basically get a mixture of Z and M. And look, I think it's great to see multiple mechanisms coming forward. I think it's good news for patients to have this much development activity, and it's such a big disease with so much opportunity, there's room for a lot of players. I think when I look at the RNA editing preclinical data, and I think it's, in some ways, reflected in the human data that was just released this morning. With RNA editing, you do get to a sort of a ceiling of effect in terms of the amount of mRNA that can be edited, the amount of M that can be produced and still having a fairly large amount of Z left over, right? And all for getting to total levels that are sort of comparable to what we've been seeing. So I think fundamentally, it's good progress, but I do think it leaves BEAM-302 in a strong position as a potentially best-in-class option where we're driving that M protein more strongly. We're really eliminating Z much more thoroughly. And of course, the most simple comparison between the two classes will be that RNA editing has to be redosed for life, right, because it's going to wear off because you're only editing the RNA pool. With BEAM-302, you're editing the DNA. So it's a permanent onetime change that you benefit from forever. So we think there's a lot of demand from patients. Again, they've been living with augmentation, kind of a chronic therapy that creates some M, but leaves them with a lot of Z for their whole lives. And we think that RNA editing is more similar to that profile. With DNA editing, we move beyond that to more of a onetime fixing the disease at its root cause sort of cure. Now to your other point, there will be more gene editing efforts coming on over the coming years. I think that there's a lot of enthusiasm for that. It isn't obvious to me yet what BEAM-302 leaves undone. We're editing a lot of the liver. We'll see if we can get towards saturation. I expect that we can. And we're producing really strong functional M protein and eliminating Z. So we've got a big lead there. But again, more options for patients is always a good thing. But I think that we are feeling very good about the leadership position we have relative to competitors with this really breakthrough [ target product ] profile, which is a onetime cure addressing both liver and lung and the root cause of the disease.
One of the criticisms that I do hear for base editing is the bystander edits. Can you just remind us what you've seen in terms of functionality, both preclinically and in the clinic for those bystander [ editing? ]
Yes. Yes, so this is a point that gets brought up by our competitors a lot because it's sort of a place where they can focus. So with base editing, what happens in, I'd say, a rare case, but in this case, it does happen, is in addition to the target edit where we're correcting the disease-causing mutation, we can, in some cells, create an additional edit nearby. And that is -- basically creates a variant of the M protein. But it's still M. That's the most important thing. And this is very predictable. So it happens in some cells. And so what you do in that case is you basically characterize that protein. You want to make sure we fully understand it. And this has happened over 3 to 4 years over the last year where we published on this. And the bottom line is that variant protein is still functional like M, right? So it is still secreted. It still inhibits neutrophil elastase. The structure is comparable to the M without the variant. So those are the same. And really, in all ways, we can detect, it is silent. It's actually also a position where there's a lot of basically polymorphisms in the human population, including the one that we make. So it is observed in humans, and there are others as well that have been observed. So bottom line is we think it's basically a silent ineffectual kind of effect. So -- and I think that's been clear with the patient, and physician community, it's clear with regulators as well. So although it is something that competitors can talk about, we don't see any unmet need there in terms of the profile and the outcome of the drug.
Understood. But then when you think about just from a patient and physician perspective for base editing therapies, permanent change, I think that can, for some people, be something that they need to think through very carefully. In your conversations with both patients and physicians, what has the appetite been for a permanent change wherein presumably if you were to get approval, we might not have enough or what everyone talks about, which is 10 years, 10 years of long-term safety data quite yet. So how do you think that the community will balance that?
Yes, it's a great question. I mean this is very much a spectrum that is dependent on the disease, right? So if you have no disease, no risk, right, then yes, people are going to be a little more cautious about things that are genetic. For instance, GMO foods, right? It's like they're not as enthusiastic about that in some cases. Once you start to be sick, right, you're motivated. And the sicker you are, the more urgent it becomes. And so in alpha-1, this is a very serious disease, right? You are declining constantly. And it's inexorable and you can't stop it, and you're literally losing your lung function as you age. And the end of that is you're on oxygen, you may need lung transplants, you've lost all your quality of life. So these patients are very motivated to get help and to get a cure. And unfortunately, they haven't had options that were actually that effective to date. And so I think for the most part, we hear from patients a lot of desire for this kind of curative approach. In addition, as I noted before, they've been given augmentation therapy, which again is a great option for them, but it's a chronic therapy. It's quite burdensome on their lives. They have to kind of get it constantly and mold their lives around getting the augmentation therapy. The idea of a one and done, therefore, for this population is very appealing, okay? Now in any population, there will be early adopters and late adopters. I think that's totally fine. But there are so many patients here, we have a lot to work through as we go. So if you think about it, there's over 100,000 patients in the U.S. who are ZZ genotype. Of those, 10,000 to 15,000 are diagnosed already and are quite well educated, quite up to speed on everything that's happening and quite motivated to get care. So that is a very large population that we can think about curing over a period of time. From there, we'll then have the diagnosis campaign to identify the rest of these patients. They're mostly living in COPD clinics or even primary care, where they're just not getting followed up and no one's thought to do the genetic test. But as with other conditions, once you have therapies available, once you have a reason to test, we think we can certainly drive that and start to uncover those patients over time. So I think that, that will really help. The last point you mentioned about follow-up, you're right that by the time we're reaching market, the specific follow-up on this drug will not be 10 years, but it will be many years. We're already a year plus into this. And so is it 3, 4 years by the time we're really treating patients. That's pretty good. And patients, again, are quite eager to see more of this. But then you put that in the context of the whole editing field, right? We'll have sickle patients on base editing out 5, 6 years by then, and there are CRISPR Gen-1 patients out a decade or more. So I think given the severity of the disease, the urgency and the motivation of this patient population, I think there will be a lot of strong demand. And in fact, we're seeing exactly that on the trial. We see a lot of demand. There's a waiting list for enrollment. Patients are quite motivated.
Got it. That's helpful. Is there anything that I didn't ask about that you wanted to talk about for 302?
Maybe the last comment would be path to market and filing. This is an area that investors are quite focused on and rightly so, partially because I think we've checked the box that we have what we all think, I think, is a credible medicine here that could be quite important. But alpha-1 is a field that has been sparse in terms of therapeutics. That means you don't have that many things to build on in terms of endpoints and trial design and things like that. So I can't give you guidance yet because this is still to be worked out, but we are thinking hard about how we will get this to patients. And one thing I've said frequently is that I think a drug of this profile where it's so clear what it's doing and all of the different changes are going in the right direction and start to look like a carrier for somebody who doesn't have the disease, and it would be very predictable clinical benefit. We really should lend itself to something that's more on the accelerated side, right? And whether that's a full approval or an accelerated approval with a follow-up, there's lots of details to work out. But certainly, that is our goal. And I would say, to a degree, my base case assumption. I think a downside scenario would be if the FDA says this is really exciting, but we want you to go do a randomized controlled trial before reaching market. If so, great, we have endpoints for that as well. And there's been a lot of progress in that front. Those trials are very doable. So one way or the other, we'll figure out what it needs to look like, but we are certainly thinking about this as how fast can we get this to patients. I think they're ready. I think the drug signal is quite clear, and we're looking to work with regulators to identify that.
And I recall that we should get some sort of guidance for what that could look like or at least an initial update in early '26.
Yes, that's certainly our aspiration is that part of that early '26 update is to give, obviously, the data, the dose information comparing all the dosing schedules that we're doing, but ideally give a clinical update as well, what's the next step in the trial. And ideally, that has a lot of regulatory input included in it for sure.
Absolutely. All right. So 302 has monopolized a lot of our time, but let's spend our last couple of minutes on 101 and sickle cell disease. I'd love -- I think we're all kind of familiar with your data. I think we all know that it looks better than Casgevy. But I'm curious on just the market for Casgevy and how that's progressing and where 101 would fit in when and if it were to get an approval?
Yes. So it's an unusual market, right? So -- it's so operationally complex, and we've always said this, that we've never felt we were going to miss out on the important first few years of the market. In fact, we think there's a lot of building to do that is currently happening that we will benefit from, right? So some examples of that are the treatment centers learning how to schedule these patients and move them through the Apheresis Clinic and then into the transplant. Reimbursement. Reimbursement today is still happening on a lot of what we call single case agreements, right? So importantly, it's important to note, and this is going to have read-through to sickle as well as alpha-1 and other places. Nobody is quibbling on the price, right? So the $2 million to $3 million price, it gets headlines and it's a large number. But society, Dr. Oz, who runs CMS said this publicly, right, that, that is a price worth paying because you're going to then not pay many more millions of dollars over the life of the patient in medical care hospitalization and other therapies that are used chronically. And ICER, the cost-effectiveness body of the U.S. said the same thing. So that said, you still have to make the reimbursement process more smooth, and that is not there yet. So in fact, there's a -- most patients on sickle are on Medicaid, about 50% to 60%. The Medicaid process to approve that reimbursement is just coming online. That's the CMMI CGT access model. And again, Dr. Oz of CMS is banging the drum, how excited he is about that, but it isn't even in place yet. So I think this is just an example of it is going to take a few years for these sorts of things to become more and more smooth. And again, I continue to draw on the CAR-T analogy. CAR-Ts were first approved in 2017, 2018, right? And the first few years were slow as the hospitals got oriented to it and the payment models got worked out. But now it's a multibillion-dollar a year category. We're doing 5,000 CAR-Ts a year, and that line is just going up. So we remain quite bullish about it. I think we obviously are watching the Vertex launch carefully to sort of learn what are some of the things that are real roadblocks that we need to work on. What are some of the things that maybe we're already going to improve upon relative to what is happening in the market, things like smoother manufacturing process, fewer cycles of mobilization, that faster time to engraftment. Some of those differentiation features also make it smoother for the hospitals to treat more patients. And what are things that are just going to get better over time and every year are going to be smoother and more predictable.
Let's talk a little bit about the ESCAPE program as well because that one is moving along, the CD -- I think it's 103, CD117 entering the clinic at the end of this year. When does that come online if you can -- if you're able to provide some sort of estimate post 101 approval and commercialization? And how does that improve the market?
Yes. So in addition to 101, which we think is clearly a best-in-class relative to the field of kind of what we call WAVE 1 gene therapies where you're still using chemotherapy for transplant, we're equally interested in these next-generation versions, first of which is ESCAPE, we call WAVE 2, you're still ex vivo, but you're now adding an edit, which allows us to use an antibody to condition, that's BEAM-103 to get rid of old sick cells. And then your graft will grow, but it is ignored by the antibody because antibody no longer binds that graft. This allows us to independently use a non-genotoxic conditioning agent like an antibody while the graft takes hold. So as you noted, BEAM-103 is that antibody that is on track to dose this year, in normal healthy volunteers, just a quick single-dose PK/PD study. And from there, we would be in a position to think about filing a patient IND for the clinical experiment, which we're quite excited about. So very important opportunity to expand and bring functional cure to more patients who aren't in that sickest population where chemo is a no-brainer. They're happy to do that. Lots of patients are just over that threshold where they would really rather not have the chemo. The third wave then moves all of this in vivo. And that's really bringing the threads of our 2 franchises together because now you're going to use lipid nanoparticle technology, which we do all of our liver delivery with, like 302 for alpha-1. And instead, we're going to retarget it to try to go to the bone marrow and now it reached those long-term hematopoietic stem cells in the marrow. That's an area of really intensive research right now. And I do think seeing some positive signs of progress in that field, we're quite bullish on targeted LNPs just in general, reaching a variety of non-hepatocyte targets within the body and HSCs is, of course, top on our list. So that one is coming as well. You'd asked about tying. I've generally said in the past that this is a life cycle plan. So it would be -- as 101 reaches the market, it would be several years before ESCAPE, WAVE 2 reaches the market and then potentially several years after that for in vivo. In vivo is moving quickly now. So we'll kind of see how that timing plays out. But I think next-gen versus Gen 1 is still a several year gap, and that's why we're developing both fundamentally.
Right. I'm looking forward to hearing more about the in vivo piece moving along nicely in our next conversation, but we're unfortunately out of time. So John, I just want to turn it back to you for any closing remarks that you have.
No, it's been a great conversation. We're -- we couldn't be more excited about the progress that we're making. Obviously, the technology is working. We're helping patients. Enrollment is going very swiftly and smoothly. Despite all of the uncertainties and noise, the regulatory interactions actually have been clockwork and quite predictable. So I think gene editing generally is a field that's working and it's growing. And we do think ourselves positioned to be a leader here with some really significant commercial franchises that bring this technology to patients who really need new options.
Great. Well, thank you so much for being here. It's a great conversation.
Thank you.
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