We good? Okay. All right. I'm Eric Joseph, Senior Biotech Analyst with J.P. Morgan. Our next presenting company is Beam Therapeutics. Presenting on behalf of the company is Chief Scientific Officer, Pino Ciaramella. We'll be doing Q&A in the room after the presentation. There should be mic runners around for those who want to ask a question from the floor. If you don't, you can also submit a question via the digital conference book, and I'll work them in where appropriate. With that, Pino. Thank you.
Thank you very much, Eric, thank you very much for giving me the opportunity to give you an update on behalf of Beam Therapeutics, a precision genetic medicine company that utilizes next generation gene editing technology known as base editing. Usual cautionary notes. Our vision is really to provide lifelong cures for patients suffering from serious diseases. With our technology, we have the potential for generating one-time curative therapies that we plan to deploy not only on rare diseases where the field and us are starting, but also increasingly so on more common diseases as the safety of our products is demonstrated. Importantly, the platform that we're developing has the ability to rapidly develop program number two, three, and four, once program one has been optimized and de-risked.
Base editing really exploits the, and builds on, the success that has been made using the programmability of CRISPR, whereby a simple change of a small guide RNA, a sequence of about 100 nucleotides, allows that protein to actually land on a different spot on the genome, actually with incredible precision. Actually modify that technology such that we do no longer make a double-stranded break, which we believe brings some unwanted consequences to that. In addition, the base editor is actually a fusion protein that incorporates directly an enzyme that directly catalyzes the chemical conversion of one nucleobase to another. As a consequence of that enzymatic activity, the editor is actually very efficient and does not need to rely on the dividing or non-dividing state of the cell.
Therefore, it can be deployed, actually on a variety of different cells and can be very versatile in the way in which it can be used, not only to make the change that corrects a point mutation, but also to do other things like introducing stop codons as well as upregulating promoter regions, for instance, like we do in our BEAM-101 program. Importantly, though, in addition to the editor and the cargo, of which obviously base editing is the one that is developing the most because it's so efficient and effective. However, Beam has developed arguably one of the more deeper toolbox of gene editing technology available, which we have our own proprietary nuclease. For instance, we also have access to RNA editing as well as exclusive access to prime editing for certain fields.
Where a lot of the innovation has been applied, particularly most recently in the company, is really in the ability to deliver this technology in a variety of different ways. We can obviously do autologous cells as well as some allogeneic cells. We can manufacture mRNA and deliver in vivo with LNP technology that we have been developing and optimizing, thanks to the acquisition of a company called Guide Therapeutics two years ago, as well as developing some novel viral vectors. The third part of the strategic deployment and investment that the company is making is really building our own capabilities for manufacturing.
We believe that this is a very strategic asset for any gene editing technology, but in particular complex drug products like ours, because it gives us the control of the quality as well as the timeliness of that. And we have a facility being built in North Carolina, which is 100,000 sq ft of utilizable space and potential for going even beyond that, and should be come operational later on this year. So having developed that platform, it allows us the opportunity to really to deploy this base editing to a very extensive portfolio of opportunity that span not only ex vivo approaches in the hematology, but also in immunology and oncology, but also in in vivo delivery to deliver initially and also other tissue as the delivery technology mature.
We've really focused our portfolio on three main franchises. There is a hematology franchise, an immunology, oncology franchise, and genetic diseases in general, which liver is the starting block. In each one of these franchises, we have a series of programs. The lead programs at the moment are such they've developed and picked such that the probability of technical success is highest within that. We have a series of additional programs that are coming behind the first lead program that as the technology and that particular franchise is optimized and de-risked, that we can deploy very rapidly to really expand the patient population that we will be able to tackle too. We have finished the last year, 2022, with very significant momentum across each one of those franchises.
In hematology, we have enrolled the first subject for the BEAM-101 trial. This is for the treatment of sickle cell disease. We have made significant progress in what we call the ESCAPE technology. This is an improved conditioning regimen that overcomes hopefully the toxicity that Busulfan currently leads and refocus the additional programs in the hematology pipeline so that they can exploit that particular technology for the future expansion of sickle cell disease treatment and other hematological disorder. In immunology and oncology, we have cleared successfully the first IND for the BEAM-201 program by the end of the year following a relatively brief clinical hold, and this is a treatment for CD7 positive TALL and potentially AML for the future.
Treat a set of patients that have left behind somewhat given some of the challenges of targeting antigens that are exposed on T cells. The BEAM-201 is able to overcome that by delivering essentially four simultaneous edits, which is to our knowledge, the first in the field. We also believe that there needs to be an investment at the research level to generate really truly allogeneic approaches, which we believe that so far it has been a challenge in the field to be able to do that. What we do know is that what you need to do in order to accomplish that, even though the biology can be challenging, is for sure the ability to edit several genes at the same time.
The base editing and the ability of base editing not to make double-stranded break is ideally suited to generate highly engineered cells of that type, and we're making very good progress in the preclinical phase. For the genetic diseases, we have initiated and enabling studies for BEAM-301. This is our product that aims to cure GSD1A, particularly the R83C mutation that is the most prevalent and also the most severe form of the disease. Actually, we nominated BEAM-302 as a development candidate. This is a program that aims to correct for the first time, to our knowledge, the mutation that causes Alpha-1 Antitrypsin Deficiency. This is a single mutation that causes this protein, basically accumulate in the liver, causing liver toxicity as well as lung disease.
Finally, we have expanded our strategic partnerships with a deal with Pfizer, as well as a deal with a new company that has been formed called Orbital Therapeutics, that aims to generate the next generation of RNA-based therapies. For 2023, we are excited to aim to complete the Sentinel cohort, or the enrollment of the Sentinel cohort, and also initiate the expansion in our BEACON trial. This is the trial basically to develop BEAM-101. We have made some changes so that we believe that this program can actually be accelerated such that we will be positioned in 2024 to present some clinical data on multiple patient as opposed to a single one. We plan to dose the first patient in the BEAM-201 trial.
We believe mid 2023 is a realistic opportunity there. For the genetic diseases, we aim to submit the regulatory filing for BEAM-301 by late 2023, beginning of 2024, and by the beginning of 2024 for BEAM-302, the Alpha-1 program. Let me just give you some snippets of data on some of the key programs that we're moving forward, starting with BEAM-101. In this case, we are making, we're using the precision of base editing to make single point mutations in the promoter regions of the gamma-1, gamma-2 genes that prevent the repressor protein from binding. As a consequence of that, we can up-regulate hemoglobin F to very significantly level.
In fact, if we are able to reproduce the preclinical data in human, we would have a best-in-class profile where we have the highest level of hemoglobin F, in excess of 60%, and the concomitant lowest level of hemoglobin S, because there is a regulatory control that the higher the F you generate, the less the hemoglobin S. That reduction of hemoglobin S in itself has the ability to be clinically relevant. The BEAM-101 trial is to our knowledge, the first clinical base editing program in the U.S. Thanks to the optimization of the protocol, we aim to accelerate this program significantly such that, as I mentioned, in 2023, we can not only enroll the Sentinel cohort, but also to initiate the expansion phase.
In this case, is a trial aimed at enrolling 18 to 35 years old with severe vaso-occlusive disease. Importantly, in addition to look at some critical safety profiles like engraftment time and potential, we are going to explore many biomarkers of disease in addition to vaso-occlusive crisis. Obviously, vaso-occlusive crisis are very important for the life of the patient and contribute clearly to the disease, but they're not the only thing that contributes to the disease. We plan to look at this very intensely with a variety of different biomarkers, including the quality of the blood, the hemolysis, and many other parameters that are signs of progressive organ damage, which ultimately is what kills prematurely the patients.
The way we see the sickle cell franchise is obviously the Busulfan conditioning. We believe that that is a commercial valuable opportunity where our preclinical profile, as I mentioned, if confirmed in the clinic, has the ability to be best in class. Where we see the opportunity for significant expansion is in what we call wave two and wave three of the programs. Wave two is where we would deploy an improved conditioning over Busulfan that does not carry the toxicology, the safety, and, you know, consequence of that, like for instance, sterility, which really prevents many patients from actually accessing this particular transplant. We have this opportunity that I will show you in a moment that we call ESCAPE.
We're also developing LNP technology that can actually overcome altogether the need for transplant and potentially deliver the editor directly to the stem cells in the bone marrow following an IV administration. We've shown some data, positive data in non-human primate targeting the stem cells last year, to a range of about 20%. The improved condition that we're looking at uses this technology that we've named ESCAPE. Again, it uses the ability of base editing not to make double-stranded break that enables our ability to do multiplex editing, whereby the same editor is used to not only make the disease-correcting mutation, in this case, the BEAM-101 correction. Also, thanks to an additional guide, can make a single amino acid change in an epitope that is recognized by an antibody that we have specifically developed.
This is an antibody that targets CD117, it's an antagonistic antibody that prevents the binding of the ligand that activates basically the stem cells in the bone marrow. Because of the editor that we make in our cells, the edited cells are essentially stealthy to this antibody. Even if the antibody is present in the body, it does not bind the edited cells. As a consequence of that, it creates a survival advantage for the towards the edited cell, such that you are able to populate very effectively the bone marrow. The graph on the, on the right-hand side shows some data that we have generated in mouse, where essentially proves exactly that. As you increase the dose of the antibody, you can see increased chimerism of the edited cells versus the unedited cells in these animals.
Moving on to the genetic disease franchise, BEAM-301 is a liver-targeting base editing technology aimed at correcting the single-point mutation that causes GSD1A. This is a R83C, and as I mentioned earlier, is the most prevalent mutation that causes disease. This is a very high unmet medical need disease. Basically, the mutation causes the glucose-6-phosphate enzyme to essentially be unable to manage glucose homeostasis. As a consequence of that, unless you are fed on a very regular basis, every three hours or so, you risk basically a lethal hypoglycemic attack. The, as you can imagine, is very impactful to the quality of life, not only of the patient, but also their family.
We have generated transgenic mice that in the homozygous setting, are actually lethal within few days of being born, even when you give them, you feed them glucose. We've shown basically that we have a long-term preservation of vitality, basically, in these animals when we treat them with base editing. In case of BEAM-302, this is the additional liver-targeting base editing program that we have generated, where we are aiming to correct the single-point mutation that causes essentially Alpha-1 Antitrypsin Deficiency. This is called the E342K mutation, all of the patient carry this very same mutation. Typically, between 60,000 and 100,000 patients are estimated to be in the U.S. alone.
Because of the fact that this protein is naturally produced in the liver, we are able, in the liver, to correct it to its wild-type state, and as a consequence of that, restore the ability of this protein to be correctly folded and released by the liver into circulation, where it goes to the lung and does its job of protecting the lung from the attacks of elastase and other proteases. Therefore, in this way, restoring the normal function and system for Alpha-1 Antitrypsin. In particular, correcting both the liver and the lung disease, and the lung disease arguably is the one that affects the most patients in this particular setting. We have achieved editing rates that if reproduced in human, would be in excess of 11 micromolar.
In fact, probably will be close to about 20 micromolar restoration of levels of Alpha-1 Antitrypsin, and 20 to 50 micromolar are levels associated with the normality. The BEAM-201 program. This is the multiplex-edited CD7-targeting CAR T program. As you can see, we are essentially making four simultaneous edits that not only eliminate CD7 from the surface of the cells, essentially preventing the ability of the cells from killing each other. Also, we eliminate CD52, which allows us the ability to use Campath potentially as a lymphodepletion agent and therefore achieving allogeneic in this particular setting. We also eliminate the endogenous TRAC. This basically eliminates the endogenous TCR, which prevents the graft versus host disease and basically also eliminating PD-1 receptor to prevent premature exhaustion.
You can see that the efficiency of the base editing allows us to have in excess of 90% of the cells carrying all four mutations. The program, the clinical trial, which we're calling BTXL 001, basically is targeting a population of 18 to 50 years old, where there will be a dose expansion phase. Once the dose has been selected, there will be further expansion to different cohorts, including hopefully pediatric population of one year and older, following review with the FDA of the data. Here, basically, we're looking at complete remission as a prelude to essentially enabling transplant, which is the standard of care in this setting. Finally, we've continued to expand our strategic part-partnership, not only obviously with Pfizer, which I mentioned earlier.
We have an ongoing collaboration with Apellis for six programs looking at a complement pathway. We had a deal with Sana where we outlicensed our Cas12b nuclease. Obviously we have opt-in rights to the three programs that Verve is prosecuting, two of which are disclosed, the third is not. Opt-in right after the phase I data has been generated. We have exclusive access to prime editing for certain fields, which include basically the transition mutation as well as sickle cell disease. This new partnership with Orbital Therapeutics, that is a next-generation RNA and delivery company, utilizing amongst other technologies, circular RNA and viral-like proteins.
Last but not least, we are extremely proud of our team that has come together, you know, as a real with real camaraderie and with a lot of experience, frankly, in developing and launching programs and projects in a variety of different fields, but importantly also in new technology as partner. I'll leave it at that, and happy to take any questions.
Okay, great. Thanks, Pino, for the presentation. I guess while, I guess, mics get positioned and so forth, I can start out. I think I'll start with BEAM-101 and sickle cell disease and really just kind of. Well, you know, recently we saw a clinical setback with another cell therapy-based competitor in this space. I guess it would be helpful to sort of have you distinguish the approach that you're taking with 101 relative to perhaps that program and just sort of how, I guess, how you would give investors comfort that, you know, you're going into clinic with a favorable tolerability profile from the get-go.
Maybe I'll jump in here. I'm John Evans, CEO. I think the, we often get the comment that the sickle gene editing space is very crowded. There obviously are a lot of entrants. I think, though, if you step back and look at the data that's starting to roll in from the various players, we can actually start to differentiate what we're seeing and, I think identify, you know, those companies that are gonna hopefully, you know, rise to the top and then some that are obviously struggling a little more. Obviously, the Graphite data is very disappointing. I'm sure they are all over that. We obviously, you know, think about the health of the patient as much as possible. You know, that's a challenging approach.
Obviously, trying to make HDR work in long-term engrafting hematopoietic stem cells, that's been a challenge. It looks like it still is one. You know, I think at the end of the day, we look at the field as Bluebird will get there, clearly. Vertex and CRISPR are gonna file soon, and we expect them to reach market as well. You have another set of nuclease companies that are coming, and then there's us. You know, we're really coming along with what we view as next-generation editing technology. It's non-viral, it's non-cutting, so we're not using a nuclease. We make very precise changes in the case of 101 to turn on directly the fetal hemoglobin genes and deliver that very high level of editing and of F that Pino described. We think that'll be very competitive.
Okay.
Maybe the only other thing to add is that really what is important to understand is that even though the CD34 is a starting patient population, actually the only proportion of targeted cells that are ultimately going to engraft for the long term is a very small proportion of that. It's usually about 1% or so. Really, the ones that you are aiming for is the long-term stem cell progenitor cells. Those cells are importantly in the context of HDR, are typically very poorly replicated. They don't replicate very well. Therefore, HDR is a disfavored pathway in those cells. Fundamentally, what you're doing with HDR, you are selecting and editing in the population that is not your target population.
In fact, what, my interpretation, what they've seen is actually a secondary engraftment that they've seen, which likely stems from the fact that you can get engraftment thanks to the short-term, stem cells. Actually, if you don't manage to engraft significant number of long-term stem cells, essentially what you see, you will see secondary engraftment failure. That, you know, is my interpretation. I haven't seen the data, of course. There may be other factors as part of that, but certainly it's something that we would have predicted could be likely to happen in the clinic.
It won't be until next year where we might see initial data from the BEACON study. That being said, how should we be thinking about updates from the study, particularly as it relates to certain safety checkpoints in the trial? Just the nature of updates from enrollment progress over the course of the year.
Yeah, you will see signs of progress. I mean, I think that, you know, I think the most significant... We did guide that we expect to have data in 2024 on, you know, multiple patients. We wanted to have a really robust data set because this is about communicating the depth of our science in that program with the sickle community and getting them excited. We want to make sure we do this in the right way at a scientific meeting. That said, this year it's going to be a pretty active year. What we've guided is that we will, we basically accelerated the first part of the trial as we talked about last fall. That we can, as Pino Ciaramella said, complete the enrollment of the Sentinel cohort this year and initiate expansion this year.
I think you'll have a sense as all that is happening, that things are, you know, hopefully on track and that they're moving quickly, even if we haven't shown you the data yet.
The other thing that we are investing significantly on, as I mentioned earlier, Eric, is on the manufacturing capabilities there. 'Cause, you know, as you know, obviously the editing is important, but the entire process of manufacturing is also a strategic importance in this particular process. We're optimizing a process that right now is already pretty much closed, which means it's, you know, really automated and very close to be essentially the commercially viable program that we want to be. You will see also, hopefully, some updates in the manufacturing component.
The, I guess, couple questions related to wave two. It's a really elegant approach that you're taking with ESCAPE. Still would be interested to get a sense of what makes CD117 sort of an attractive target for myelosuppression, myelodepletion, and sort of how your approach might differ from... I guess we've seen other anti-CD117 approaches, some of which have also had sort of clinical separate. I guess, how is yours perhaps differentiated from them?
Perhaps I can give a couple of, you know, important consideration there. First of all, the CD117 and in particular, the binding of the ligand, which is called the stem cell factor to that receptor, is essential for the expansion of the stem cells. It's a critical part of the biology that enables essentially engraftment. The antibody that are being developed are antagonistic, so that basically you cannot no longer bind to that to some extent. The issue with the other approaches, though, is that they need to ensure that that antibody is out of the body by the time the edited cells comes in, because otherwise it will kill the edited cells as well as the unedited cells.
They have a relatively narrow window of opportunity, as well as a PK profile that is limited in dosing, because obviously the higher the you dose, the longer the antibody is gonna stay in the body. By creating edited cells, which are stealthy to this particular antibody, we have the ability to allow the antibody to be present even in the presence of the edited cells, and therefore, creating really this competition opportunity that favors the edited cells above the others. This actually happens in a preclinical animal model, which is the NBSGW mouse, where there is a hypo, you know, hypoactivity of CD117, thanks to an amino acid change. You can see that there we can achieve very high level of engraftment with the human cells.
We already have a system in preclinical setting that shows that that competition with a less than active CD117 can lead to successful engraftment. The important thing now and part of the pharmacology studies that we'll be doing during the course of next year is to demonstrate that we can achieve that condition essentially that we see in the preclinical model in also higher animals like non-human primates.
It's essentially like a, it's a, I mean, it's kinda two products in one here, right?
Yeah.
How does the pre-IND process work? How far advanced, I guess, how far advanced with non-clinical models with CD117 do you have to go? Then let me also ask sort of how close you are towards DC, development candidate selection for, let's say ESCAPE 1.
We haven't provided any guidance in terms of timelines, but it's a very high priority program, so it's heavily, you know, funded, as you can imagine. Importantly, we will be doing some pharmacology studies in non-human primates, which we think are really important to understand, really what is the clinical profile that we can aspire to have. Once we have that, I think we will be much, much closer to a development candidate and moving forward because it gives us the idea around the dosing regimen, the frequency, the levels of engraftment that we can expect to see in a, in what is essentially a kinetic, you know, in a way, fight between the edited and unedited cells in the bone marrow.
Maybe if I could riff a bit on your point about multiple programs here, because I think it's an important point. As Pino Ciaramella mentioned, we have these pillars. Each one has sort of near-term assets and these long-term expansion opportunities. In hematology, it really is all about ESCAPE and then in vivo delivery as a pair of ways to change the calculus for patients, right? Right now, a busulfan transplant is a good option for severe sickle cell disease, but not a great option for moderate sickle cell disease or other hematologic conditions. If we can bring ESCAPE forward, now you make that transplant much more tolerable. Now many more diseases are potentially targets for gene editing, and we can move there then quickly.
I think it is a critical piece that opens the door to, both, you know, a lot more success within hemoglobinopathies, but a lot of diseases to follow beyond that.
Any plans to take ESCAPE beyond sickle cell? Ostensibly, you could, you know.
Yeah. You could do ESCAPE with other therapeutic edits for other diseases. You could also do ESCAPE on its own.
Right.
Right? Just to bring the benefits of autologous transplant to patients who would benefit from resetting their blood system at certain points. You know, ESCAPE, the ESCAPE edit on its own could be a product on its own. Lots of opportunity if this, if this pans out.
Pause for a sec for any questions from the floor. Maybe just on the liver-targeted programs, I guess how much editing do you, are you achieving right now with BEAM-301? Sort of where do, I guess, you know, how much editing do you think is achieved in order to have a clinical benefit?
Yeah. BEAM-301, actually, there is several models that would suggest actually that the threshold above which restoration of activity of glucose-6-phosphate would be enough. We think that something in the order of 10%-11% would actually be enough. It's a relatively low hurdle, if you will, in order to eliminate the physiopathology essentially of the disease. We're way north of that. We typically see 30%-40% editing at very clinically relevant doses. You know, we think that that is, you know, certainly an achievable target.
Does the sort of the baseline function of the patient's So these patients have elevated glycogen levels in their liver, is that at all likely to have an impact on the base editing efficiency or either delivery efficiency?
Yeah, it is, it's a great question. Obviously to some extent we're not gonna be able to have that until we expose this to the clinic. The good news though is that we have done editing actually in fibrotic animals, and we see same levels of editing whether they are fibrotic or not. It is not necessarily exactly the same thing, but it's certainly a surrogate for a dysfunctional liver that has some toxicity associated with it. We don't see any impediment or difference, frankly, of editing rates between fibrotic and non-fibrotic.
Okay. In terms of, well at least within GSD1A, your lead program targets one particular mutation. There's another mutation, Q347X that's also prevalent. I guess as you get to clinic, I guess effectively speaking from a development standpoint, how much of a priority is developing a Q347X editor? Would there be the opportunity, do you think, to develop it in parallel with 301? I guess when might you get regulatory feedback on the, on that potential?
Yeah. We've got, I mean we have a very rich liver pipeline. I think we're obviously focused this year on BEAM-301 and BEAM-302. As Pino Ciaramella mentioned, you know, BEAM-301, you know, regulatory filing is on the horizon, you know, towards the end of the year, maybe early next. Obviously Alpha-1, we've brought in a lot to the early 2024 in terms of its filing intention. Those are right next to each other. That is our number 1 focus is just getting those filed successfully. These are, to our knowledge, you know, 2 of the first industry efforts to do in vivo correction of mutations that are causing disease. Not, you know, knocking out or turning on, but actually literally fixing the thing that's wrong in the body in vivo.
We couldn't be more excited about that. Beyond that, for sure we have this another GSD mutation, Q347X. I think if we can show that R83C works.
Mm-hmm.
That would of course be very de-risking for that program. It's a, you know, slightly smaller population, but still a meaningful population that really needs therapy. We of course also have our Hepatitis B program, where we've shown some very interesting early data. You know, many, many other liver targets are possible. The beauty of the system, as Pino said, I think in his opening remark, is the programmability, right? Once we've shown the ability to deliver to the liver with an LNP carrying our editor, it is, you know, relatively straightforward to just swap out the guide RNA and you have an entirely new medicine. You know, many, many targets in the liver could potentially be the platform for a lot of opportunity to help patients from there.
Yeah. In the context of GSD1A in particular, you know, one of the opportunity that we may want to explore is this concept of umbrella INDs that the FDA has recently introduced, where fundamentally the, you know, with minimal change, you may not necessarily need to reproduce the entire package. We will see to what extent the FDA basically will work on that. GSD1A is an ideal program to be able to explore that kind of, you know, regulatory paradigm.
Okay.
Can I ask a quick question about?
Can you just wait for the microphone, please? Thank you.
Yeah. Sorry. Thanks. Beam-201, there was a clinical hold lifted, I believe in December. I know there was a clinical hold also on a Verve Therapeutics product also lifted. I'm curious if there's anything you would say about the FDA's approach to base editing therapies, if there's any similarities between those two programs? Just I guess in general, if FDA is in your view being more cautious than some other regulators with respect to these therapies.
Yeah. Maybe one I could say, first of all, the two hold items were between 201 and Verve were unrelated. 201 were specifically around T-cell characterization, which we disclosed in a, you know, one of our SEC sort of a disclosure there. What we're finding in general is that it's not base editing per se that, you know, it's what the FDA wants to see, particularly in vivo. I think there are some additional, you know, considerations one needs to make from a safety point of view that needs to be demonstrated. In fact, actually our BEAM-101 sickle cell disease, well the IND was basically cleared within 30 days, we didn't have any issue.
That is a base editor as well. It's not really related to that. In vivo, there are really two aspects that the FDA is rightly concerned about. One is how do you adequately characterize the off-target biology, not just in your target organs, but also presumably with an LNP technology or any other delivery, you are going to go into different tissues. They want to make sure that whatever off-target biology you see in your target tissue is mimicked in non-target tissue, or if it's not, you know, to what extent it's not. Then the other one is obviously they want to prevent the fact that the edit would actually be transmitted to the progeny, you know, to the children. Obviously we share the sentiment that it's important to be able to do that.
The good news is that the biodistribution of the LNP technology we use is consistent with the fact that being an extremely low risk, but even being low, you just have to confirm and generate the dataset that that is the case. That takes a little bit of time. It's a matter of more of a depth of the data
Rather than a fundamental impediment that says you will never develop a gene editing product in U.S., right? Because I definitely don't believe that that's the case.
Maybe just a last question on the Pfizer partnership and just business development in general. I guess the first question being, when do you expect to learn a little bit more about the programs within that collaboration and, you know, just appetite for additional partnering or business development over the near term?
Yeah. Pfizer partnership's going great. They've been incredible partners. Obviously they just had a restructuring in their rare disease portfolio, that does not affect us. I think they remain very enthusiastic and we look forward to continuing to work with them. As Pino mentioned, we have a wide variety of different deals that we've done, both in terms of larger partners, where there's cash coming into us, and then we, you know, generate new programs and new spaces for them and with them, and then obviously these more innovator deals where we've shared technology directly. There's no question we will do more of both kinds, I'm sure.
you know, I think that having built the integrating platform that we've, that we've pulled together at Beam, there's always the conundrum of how do we unlock more value out of this, and how do we reach more patients than we can really do ourselves, and that's where BD plays a role. We have not yet partnered anything in our internal pipeline. That means everything is wholly owned still for us.
At some point, we may consider even that. I think the point would be it would be done not from a financing perspective, but primarily from a strategic perspective, where we say, "Hey, this program could reach even more patients, go even faster if we had a world-class partner on our side." That goes a little bit to our decision-making over the next few years about where are we gonna commercialize ourselves? Where would we think we could benefit from having help? That'll also go into the equation. You know, at the end of the day, we also disclosed today, we've still got about $1 billion in cash. That's cash into 2025.
It covers all of the milestones that Pino mentioned and the investments in our next generation platform opportunities like ESCAPE, like allogeneic, you know, highly edited cells, like the in vivo delivery. We feel great about, you know, what we're able to do under our own steam, but always open to new opportunities. I think pharma in particular is paying more and more attention to gene editing. They're positioning themselves and thinking about how that plays into the future of their portfolios. There's so much opportunity here, we're eager to engage in that.
Great. All right. I think we'll leave it there for time. Thanks so much, John and Pino, for your time this morning. Great.
Thank you.
Thank you.