All right. Thanks again for joining us at our healthcare conference. I'm Eric Joseph, Senior Biotech Analyst at JPMorgan, and our next presenting company is Beam Therapeutics, and it's my pleasure to welcome John Evans, CEO, to tell us a little bit about the company. Before I hand it over for the presentation, I just want to note that there is a Q&A after the presentation. Please feel free to submit questions by clicking the Ask a Question button, and I'll put all those in on your behalf. With that, John, thanks again for joining us today.
All right. Thank you, Eric. Hello, everybody. Great to be here today. Sorry not to be in person in San Francisco, but nonetheless excited to be entering a new year in 2021. I'm going to walk you through a little bit about Beam today. I'll be referring to the slides, which I know you have access to as well. Beam is really trying to create a new class of precision genetic medicines using base editing, and I'm going to tell you about that technology today. I will be making forward-looking statements today.
On slide three, our vision is really to provide lifelong cures for patients suffering from serious diseases. We really believe that we are on the cusp now as an industry of a new era of one-time curative therapies. This, of course, begins with gene therapy. It's moving into gene editing, within gene editing, base editing is rapidly emerging. This will include gene editing for both rare and common disorders. Ultimately, as we have seen with the mRNA vaccines, we're building a platform to create rapidly programmable precision medicines.
Once we get this engine set up, we can very quickly print out new programs with very rapid timelines to exploit new biology. On slide four, really the gene editing field to date has been characterized by what we call nucleases. These are the scissors of the genome. This includes TALENs and zinc fingers, also more recently and famously, CRISPR. What these tools can do, which is amazing, is you can target a single address within the genome out of three billion bases. Once you get there, you only can do one thing, which is to make a cut.
That blunt double-stranded break occurs and really it's up to the cell to put the pieces back together again at that point. The targeting is really good, but the ability to control what you do to the gene is relatively limited. With base editing, what we want to do is something that's more precise. We want to be the pencil of the genome, where we can erase any letter we want, write in a letter in its place, and you didn't disrupt the sequence around it. The targeting, the precision, the control, and the efficiency of what we're doing is going to be much higher. That's exactly what we can do with this base editing system.
On slide five, we can show the construct itself. This does use CRISPR, for targeting, which we think of as CRISPR's best feature. Shown here in gray is the CRISPR protein, and that is exactly the same as many CRISPR applications. We target it with a guide RNA, and that guide RNA encodes an address of 20 bases in the genome where we are going to search and then bind. Now the differences appear. We have changed the CRISPR so that it no longer creates the double-stranded break. It merely binds at that recognition site and opens the DNA up.
We have tethered to it a second domain called a deaminase, and that's shown here in blue-green. These deaminases that we use can only edit single-stranded DNA. They will leave alone all of your double-stranded DNA. Once they're presented with a short segment of DNA as the CRISPR binds, they'll edit very efficiently. If we use an adenosine deaminase, we will edit As. If we use a cytosine deaminase, we edit Cs. Those are the A-base editor and the C-base editor that we have in our portfolio. The advantages of the system are quite numerous.
First we're directly editing disease-causing genes, within the coding region. The applications are very versatile. Of course, gene correction is of interest. Point mutations, where you have a single letter misspelling in the gene, are by far the most common class of mutation-causing genetic diseases. Things like sickle cell anemia, alpha-1 antitrypsin deficiency, we would aim to directly fix that gene by just changing the one letter that's wrong. Equally, we can do a lot of other things with this tool as well. We can activate any gene by targeting regulatory regions.
We can silence any gene in a variety of ways with a single letter change, all without cutting. We can also do multiplex editing, where we can edit simultaneously across multiple positions in the genome. Without cutting, we don't worry about the chromosomes being put back together again in the wrong order, we can push the boundary of multiplex editing quite significantly. Specificity is really attractive. We have loads undetectable off-target profile with this system. Just in general, it is a gentler edit. The cell almost doesn't know it's been edited, because it can't detect the editing event.
Primarily, that's because we avoid the double-stranded break that's inherent in the nuclease editing. Finally, efficiency. This is very efficient. It's partially because it's chemistry. Once we're in the cell, we will bind to the DNA, we'll open it up, and then this enzymatic reaction is a natural and very quick one that we can even tune and optimize. We get very high levels of editing efficiency, anywhere from 70%, 80%, 90%, often even more efficient than what's possible with a nuclease. Ultimately, a very differentiated proprietary next-generation gene editing technology in base editing.
Slide six shows you how we have adopted a strategy to really bring this forward ambitiously across all of the different delivery modalities that are currently available in genetic medicine. That includes electroporation of cells outside of the body. This would be blood cells in hematology, and that will bring us into sickle cell disease. T-cells in CAR-T, to treat cancer. Here we're doing, initially, some leukemias.
Non-viral vectors, which will go in vivo, now to the liver initially, where we're treating alpha-1 antitrypsin deficiency and glycogen storage disorder, now precisely correcting the point mutations in those disorders. Finally, viral vectors like AAV, which can bring us to the eye, the CNS, and many other places, initially targeted Stargardt disease, for precisely correcting the most prevalent point mutation there. All of these programs are moving forward in parallel, and moving quite quickly. Significantly, we're the only company that has gone this broad in delivery.
As each of these delivery modalities comes online, we now have the ability to double down on each of these tissues, so that next generation programs can quickly advance with much higher probability of technical success once these initial programs in each area have succeeded. Obviously, ex vivo is moving a little faster because there's no vector to engineer, as is true with the in vivo portfolio, but really all of them moving now in parallel and making quite rapid progress.
In terms of milestones on slide seven, 2020 was an amazing year for Beam. We achieved, I think, more than I expected, honestly, in terms of our ability to move forward. We have three development candidates now named in our ex vivo portfolio, BEAM-101, for the upregulation of fetal hemoglobin in sickle. That is also now in IND-enabling studies. BEAM-102, really the first industry program to directly correct the sickle mutation itself, over 80%, a really unprecedented result, also a development candidate, and moving forward just behind 101.
BEAM-201, a CAR-T program with four different edits to provide additional functionality in that program, as well as in vivo proof of concept that we published late last year. All of these programs now moving forward quite quickly in parallel. BEAM-101, we continue to be confident is an IND filing in the second half of this year. That's moving forward quite quickly. We've been to the FDA, we've gotten good feedback from them, and it's quite clear which way we need to go. BEAM-102 and 201 are moving along just behind that, and not far behind.
Those will be next into IND-enabling studies, and we'll be able to give additional feedback on IND filing timelines as we get it. For the liver portfolio, in vivo editing, we've shown in vivo proof of concept of direct correction of alpha-1 and GSD. Next steps for that will be show LNP data this year, which we expect early in the year of prime editing, which we're quite excited about. That would set us up to deliver our first liver development candidate out of the liver portfolio later this year.
The AAV program is moving forward, and that will also be into primate studies early this year in collaboration with the Institute of Ophthalmology in Boston. Before I dive into the portfolio, let me just step back a little bit and tell you about where we're going with Beam. Ultimately, we are establishing what we think of as the leading platform for precision genetic medicine, and we're so excited about this vision. Of course, base editing is a big part of what we do, highly differentiated technology. It'll form the dominant part of our portfolio for the long term.
That said, we have other editing systems as well. We also have a nuclease family called Cas12b. We can do RNA editing. We have access to a new system called prime editing. Already we have one of the broadest suites of editing technologies in the industry. That said, none of this matters unless you can deliver these technologies. Here, again, we have one of the broadest suites of delivery technology already. We can do autologous cell editing as in sickle. We can do allogeneic cell editing as in CAR-T. We can do mRNA at a very pure level and a very high sophisticated level.
Of course, we can do non-viral and viral vectors. Finally, none of this matters unless you can manufacture it. We announced last year we're going to be building our own 100,000 sq ft manufacturing facility. This is going to be in North Carolina. It'll be open by 2023. This is again, the largest manufacturing capability that we believe is available in the editing space. When you put all this together, and it will establish in Beam really the full stack of capabilities that you need to create any precision genetic medicine you want for any biological situation.
We're very excited about this. It'll allow us to go very deep into franchise areas that we want to win in, such as sickle cell, alpha-1, and others. It'll allow us to break new ground in new tissues using these delivery technologies, where again, we can identify high-value programs that we can develop ourselves. Also it makes us a one-stop shop for partnering, either with other innovator companies who may have expertise in biology, or disease areas, or with larger pharmas who want to establish a footprint in this space. We think the power of bringing all of this together under one roof is quite significant.
We've already made incredible progress on the editing side, and we do expect to increase our investment on the delivery side over time over the course of the next year. All right. Let me dive into some of the programs now. On slide nine, for ex vivo delivery, here we're taking cells out of the body, electroporating them, and putting in the editing machinery. This includes the guide RNA to target within the genome, and then the editor RNA, which will encode for the editor. All of our programs are using mRNA.
We think it's a really attractive, synthetic, and scalable way to deliver our editors into these cells. On slide 10, in sickle, we're going to be doing what we call autologous cell processing. Here we are taking diseased cells out of the body. We're editing them using this electroporation technology. We then ablate or condition the patient to get rid of the other old cells, and then we reinfuse these corrected cells for long-term engraftment to really repopulate the blood system.
In sickle cell disease, slide 11, of course, this is the most famous point mutation in all of genetics. A single T is misspelled as an A, and this causes a new form of the globin called sickle globin to occur in the cell, which then polymerizes, deforms the cell, and creates these painful crises and organ damage, and ultimately early mortality. A very significant number of people suffer from this disease. We have two best-in-class approaches for editing sickle cell. BEAM-101 is the first. Here we're taking advantage of human genetics to create point mutations in the regulatory regions of the fetal hemoglobin genes.
Now, fetal hemoglobin upregulation has been practiced by others. It has clinical proof of concept now. It's clearly going to work and be transformative. In our case, we can do it much more directly than others because we aren't cutting. We can go directly to the on/off switch of these genes and put in these point mutations that turn them back on. In this case, these same mutations are actually found in people who have persistently high levels of fetal hemoglobin throughout their life. If they also happen to have sickle mutations or beta thal mutations, they're protected from those diseases.
We're leveraging that clinical genetics for the strategy we take here. It turns out that using a base editor to install these point mutations is quite efficient. On slide 13, we show you that data. We're well over 80% base editing at these two different promoter regions. By definition, this is a multiplex edit because the same guide will bind to each of the promoters of these two duplicated genes. In addition to the high editing, we get a very robust biological response. We see very high levels of F, over 60% editing. That is, as far as we know, the highest level of upregulation of F that's been reported in the field.
The combination of these two things, a high number of cells that has been edited, and in each cell, a high level of F, is going to give patients the most robust protection from the activity of that sickle globin from causing polymerization, because this fetal hemoglobin basically blocks that polymerization. At the same time, by switching so heavily to the fetal form of this globin, we are also simultaneously switching away from that mutated version, as you see here on the right. We are actually lower than 40% levels of HbS.
That is again, the strongest lowering of HbS among the fetal hemoglobin approaches that we have seen in the field. We have recapitulated these results in vivo, shown on slide 14. Here we do editing of human cells, and then we engraft them into mice long-term, and we track them over time to make sure that engraftment is helped. On the left-hand side, you see very strong engraftment, over 90% human chimerism after 16 weeks. You see very tight error bars. This is a very robust and reproducible process. Particularly, you see no difference between edited and unedited cells in engraftment.
That speaks to that milder edit that we make, which really preserves cell viability. In the middle, you can see the very high level of editing on all of the different lineages within this cell population, including all the ones that contain the stem cells. That again speaks to base editor's ability to really uniquely be consistently applicable in any cell state, dividing, non-dividing, any type of biology that's active in the cell, that the edit will still occur. Finally, we, of course, recapitulate the high level of F upregulation here, over 65% F with the A base editor.
We're very excited about BEAM-101 moving now rapidly towards the clinic and will be an IND filing later this year. BEAM-102 on slide 15 is our second approach. Here we're doing, of course, what you'd like to do, which is go directly at the sickle mutation itself. In this case, we don't have a base editor that can go A to T and revert to the form of hemoglobin that many of us have. Luckily, our A-to-G editor can still turn out an edit that produces a form that is normal, and it's called Makassar or HBG. About 0.1% of the human population has this. It is normal. It binds oxygen normally.
It does not polymerize or form sickle. With this editor now for the first time, we are literally creating cells that no longer have the ability to create sickle. They're eliminating the mutation itself. You can see that editing data on slide 16, over 80% editing of this direct causative point mutation. When we go a layer deeper and look at the allelic burden of these cells, we can see that actually over 70% of the time, we're actually editing both copies. We're fully removing the sickle mutation from these cells altogether.
In the next 20% of the time, we are editing at least one copy, and that would be more of a profile like a patient who had sickle cell trait who also don't get disease. That means that over 93% of all the cells are potentially cured of sickle, and that is again, an unprecedented result. When you look functionally at what this does on slide 17, you see what you would expect, which is that as we dial in the edit on the left-hand side, we are again one-for-one replacing a new copy of that gene with the old mutated copy. By the time we've gotten to 80% editing, we're down around 10% sickle globin.
Again, an unprecedented lowering of the causative protein in these cells. Of course, on the right-hand side, you can see at low oxygen conditions, we are indeed eliminating the sickle phenotype altogether. Very excited about this as a potential cure for sickle.
I would say in both cases, not only are we moving forward to the clinic and we'll be doing kind of the standard trial using standard busulfan conditioning to ensure we can establish proof of concept, but we're quite excited as well about the ability to move on to next-generation conditioning regimens and improve the ability to deliver these editors to more people in a non-toxic way. We think the entire field is going to move in that direction, and we are hard at work to make sure that happens because we think it'll pair really well with our best-in-class editing.
Okay, slide 18. Let's shift gears now to the CAR-T and T-cells. Obviously, CAR-T has been a revolution in cancer care, the ability to take immune cells and retarget them directly towards the tumor itself. Beyond a couple of really notable early successes, we have more that we want to do. What we'd like to do is make many more edits in these cells and engineer more function into them. What that'll mean is knocking out things on the surface of these proteins using editing. Now we're silencing, and we're silencing in a multiplex fashion.
On slide 19, what you can see here is when we do a single electroporation, we put in the RNA for the editor once, and then we put in as many guide RNAs as we want to target within the gene. It's a single reaction. We don't do this in serial. It's all one parallel single electroporation, and as many guides as we put in, we will then simultaneously edit once these editors are expressed in the cell. It's a very powerful approach for multiplex editing, putting in a lot of functionality into these cells, and then, of course, we bring them back into patients.
In this case, these will be allogeneic products, so we're going to take cells out of a healthy donor and be able to freeze them and then ultimately give them to many patients as soon as they need them off the shelf. This is indeed the future of cell therapy. Slide 20, BEAM-201 is our candidate here. This is the first quad edited cell in the industry. We're making four different edits to prevent graft-versus-host disease, to make the cells allogeneic, to add efficacy by avoiding immunosuppression. Ultimately, the target here is CD7. In this case, the antigen we're targeting on the tumor is also expressed on our T-cell.
If you don't edit that target out, which is the fourth edit, then you have what's called fratricide, where your CAR-T cells are killing each other before you have a chance to infuse them and hopefully kill the tumor. By knocking it out, they will ignore each other, and they will only target the tumor indeed. This program is moving forward very nicely, and you see here the dramatic efficiency with this system. Four edits at the same time, single reaction. Each edit is in the 96%-99% range efficiency for knocking down these proteins, and over 90% of the cells receive all four edits. That is a remarkable result.
The cells are very potent. You can see on the right-hand side a very aggressive in vivo tumor xenograft of these T-cell leukemias. You can see a beautiful dose response of beginning to eradicate these tumors. Very excited about what this program can do. Now, on slide 22, you can, in theory, knock things out with nucleases as well, and other companies are doing this, and it can be efficient. The challenge is when you make multiple edits at the same time. You get two issues with that.
On the left-hand side, if we make simultaneous triple edits to three genes with a nuclease, and then you detect for translocation, so this would be the cell putting the pieces back together again in the wrong order. You can readily detect those chromosomal rearrangements when you use Cas9 nuclease. With a C base editor, we find none. That makes sense because we're not making any double-stranded breaks. Furthermore, on the right-hand side, as you add edits going left to right, going from one to two to three edits, with a nuclease, you start to see a decrease in viability of these cells.
Whereas with a C base editor shown in blue, we don't see any decrease. That's, again, because the cell doesn't really even notice the editing is happening. There's no detection of it. Whereas we create double-stranded breaks across the genome, those are genotoxic events, p53 pathway turns on, the cells will start to arrest and can even die. Both of these problems get much more acute the higher you go in the number of edits. Whereas again, with base editing, we don't face that issue. We think that base editing is a really powerful paradigm for cell therapy for the future of highly engineered cell products.
Now on slide 23, we're going to use lipid nanoparticles for non-viral delivery of base editors. Here we are formulating the RNA encoding the editor and the guide RNA into that synthetic lipid nanoparticle, infuse it directly into the patient. It will travel at least to the liver. There may be other places we can go as well over time and edit. This is scalable. In this case, you can also think about redosing, if you ever need to. Our lead indication here is alpha-1 antitrypsin deficiency. This is again, a huge population, very significant unmet need.
Again, as with sickle, every patient has the exact same single letter misspelling in their gene. They have an A where there should be a G. Now our A base editor can revert that back to normal with a single A to G change in that coding region of the gene. If we can do that, we can create two important benefits.
First, we will stop this gene from creating mutant protein that builds up in the liver and creates toxicity and ultimately can lead to liver failure. At the same time, for every copy we correct, not only is it not creating toxic protein, it is now creating normal protein that can be successfully secreted, which is what the liver is supposed to be doing, and it would then travel to the lungs where it will protect the lungs from degradation.
In patients with this disease, because of that loss of protection, have gradual emphysema, loss of lung function, and can even end up with double lung transplants. Ultimately, base editing is a potential cure that can address both sides of the equation, the lung phenotype and the liver phenotype, and that is unique in the editing field.
For editing, on slide 25, you can see our editing target. It is this blue A in the gene sequence. For every time when we can successfully edit that A back to a G, we will create a beneficial effect. In this case, we can occasionally, a minority of the time, hit a second A as well, given the window of editing that we have on this editor. We call that a bystander edit. As long as we hit the blue A, even if we hit that second A, we still get a beneficial allele. It is a functional gene. It does not create toxicity of the liver, and it can successfully secrete, go to the lung, and prevent degradation.
You can see here, 45% beneficial alleles are created, and this is in patient fibroblasts carrying both copies of this Z mutation from human patients. Again, remarkable level of editing here. We've taken that in vivo, an initial experiment in the disease model with alpha-1 antitrypsin deficiency shown here on slide 26. Here we've got about 16% editing initially after a single delivery of an LNP with a Beam formulation of this editor. Over time, those cells appear to have a selective survival advantage, probably because of the lack of toxic protein buildup. This has been seen before in other settings.
We actually see those cells grow out as a population within the liver over time and reach about 30% of the cells by the end of this measurement period. In addition to editing, we can look then at the functional consequences of this correction. Indeed, we do see on the left-hand side of slide 27, reduction in liver aggregates from the correction. On the right-hand side, we can see an almost fivefold increase in circulating normal alpha-1 antitrypsin protein in these mice because that gene has been corrected.
We do believe that this level of correction and upregulation of the normal protein would be sufficient to have a transformative impact on these patients, and get them up into a normal range of alpha-1 antitrypsin. You can see also the power of the biomarker that we will have in clinical development, where very quickly after editing, we ought to be able to detect levels of normal protein for the first time in these patients' blood systems. Very excited about this program, highly differentiated, and could be a first-in-class approach to a cure for alpha-1 antitrypsin deficiency.
On slide 28, our second program in the liver is glycogen storage disorder, a devastating disease where patients can't fast, so they can't reprocess sugar back out of their liver. They need to eat basically every three to four hours. That includes overnight. You literally can't sleep through the night, you have to wake up constantly and keep your sugar levels high. If you miss a feeding, then you can literally die of hypoglycemia. It's very sudden. A terrifying disease. In this case, we can target the two most prevalent point mutations in this disorder. Both are directly correctable back to normal with the A-to-G editor.
On slide 29, you can see in vivo results, again, showing 70% correction and 40% correction, respectively, of these two different mutations. Clearly, that'll be in excess of therapeutic threshold for cure, which we believe is around 11%. Unlike gene therapy, here, we don't worry about this wearing off over time. This would be a true durable edit. It would be endogenously regulated because we're fixing the gene in its normal position in the genome. Significantly, we can also treat very early in life, because as the patient grows, their cells will divide, they'll carry the edit with them.
With a gene therapy like AAV, that signal will be diluted out, so you can't treat infants or very young children. A significant number of advantages for this approach over gene therapy and a potential cure for patients who need more options. Finally, let me wrap up with our viral portfolio. Here we're delivering with AAV vectors. AAVs have a packaging capacity limit, and our base editors, which are a little larger than CRISPR, are going to be a little too big for one AAV alone. Fortunately, what we can do is we can actually split it into two pieces. It's using a technology called split inteins.
What happens is you put each half into a different AAV, you co-transfect, and then as they are expressed at the peptide level, the two halves then rejoin and form a single editor, and then the editing occurs from there. This actually works very efficiently. We're exploiting this in the eye as well as in the CNS, and in other places where AAV can work. Initially, our first program is targeting Stargardt disease. We are looking at the most prevalent point mutation in Stargardt, where we're going to directly correct it again back to normal. We think there are over 5,000 patients with this single mutation in the U.S.
Here you can see dramatic editing efficiency of 75%. This is using that split AAV system to deliver the editor. It's delivering into retinal cells, and it's delivering using a dose of the AAV that is comparable to what Spark has used with LUXTURNA or other AAV retinal applications. This, again, would be well in excess of what would be required to arrest this disease and prevent any further loss of sight, which we expect to be around 12%-20%. Very excited about this program.
There was also a recent publication in "Nature" from David Liu's lab showing use of this AAV delivery system, to do a base edit on progeria, targeting the point mutation that causes progeria. Again, we see very exciting applications emerging, and we see a lot of applicability of this kind of delivery technology to other tissues outside of the liver. On slide 32, just to talk a little bit about our strategy. Having established this platform where we have all of these different components under one roof, it gives us a lot of flexibility.
Sometimes we will, of course, choose to develop medicines ourselves, and take them all the way. That's true in the case of sickle or the T-cell malignancies or liver alpha-1. Equally, we can do partnerships. We pride ourselves in being creative here. We have done what we call innovator-innovator partnerships. Something like Verve Therapeutics, where Verve is really an expert company in cardiology and wants to use tools like base editing to permanently lower cholesterol and prevent heart attack.
We did a very creative deal with them, where we gave them base editing and some of our other technology, and in return, we'll have a share in the U.S. rights in their program, and they're making incredible progress. We want to do more program deals like that, where we continue to work with innovators who can use the suite of technology we've built and exploit it even beyond what we can do ourselves.
Magenta Therapeutics, a very important relationship we have where we're working on next-generation conditioning regimens, again, to improve transplant options, and expand the use of our curative therapies for more patients within the hematology field. Wrapping up, just to say a little bit about the team. It's an amazing group of people, united by this mission. We take a lot of pride in the fact that these are people who have worked on novel modalities before, filed many INDs, and have delivered approved products.
For us, the finish line here is to get a new class of medicines approved at the FDA and have a sustainable engine for new precision medicines that we can move forward, both near term but also for the long term, as this engineering campaign continues. With that, let me thank you very much for your time, and couldn't say more about how excited we are about where we're going, both in terms of the pipeline and where this platform can be expanded over the long term to create new options for patients. With that, I'll pass it over to Eric, and we can maybe have a couple questions.
That's great. Thanks, John, for that presentation. Maybe just a couple of questions to start on the sickle program, so the SCD programs, which is really I think the editing efficiency that you guys demonstrated taking a base editing approach compared to CRISPR is sort of well laid out. I'm just curious about sort of the opportunities for clinical differentiation with this approach compared to the CRISPR-mediated assets.
What we've seen so far presents some pretty high clinical comps, low patient numbers, but I'm curious to know whether, at least maybe perhaps looking beyond F levels, there are avenues for differentiation with your asset compared to the first movers using CRISPR.
For sure. I think, at the end of the day, first of all, we're so excited about where the field is, and it's moving really quickly. It shows us that this is likely to work, and we have a high probability of success, and that's really encouraging. There's no question the editing efficiency being higher, the F level being higher, these are proxies. These are going to be biochemical results in the cell product that we expect to show differentiation over the long term in the clinic. There's no question that eradicating VOEs has been very successful for Bluebird and for CRISPR.
Nonetheless, I think there's definite opportunity for improvement. We're watching markers of hemolysis. Have we really eradicated that underlying hemolytic event with cells that are still sickling? Time to engraftment, how viable are these cells, and how gentle has your editing process been, and how quickly can we get those cells engrafted? Patients are very fragile in that transplant setting. Ultimately, the longevity and durability of these edits. I'd say the next generation as well is going to be to move beyond just these readily measurable markers as well.
There's a big movement in the field to go beyond vaso crisis. Of course, VOCs will be an approvable endpoint. That's great for the field, and we'll take advantage of that. Ultimately, the goal here is cure and to change mortality. We think that there's more to that than just pain crises. Ultimately, that's going to be about organ damage, and there's going to be an effort in the field to go deeper and to begin to show some of those deeper markers of the disease impact. That's work that we're going to do with the field.
Again, given what we think is superior nature of the editing that we're doing, we're confident that we will be able to show some of those clinical outcomes as well. The final thing I would say is that, remember that there's more going on here than just editing. Ultimately, it's about the payload that you're delivering to these cells, and the editing outcomes, of course. Equally, it's going to be about changing the way we deliver these programs.
I think the field is also going to go through some generations, where we're all going to begin on this busulfan conditioning regimen, which we know is efficacious and can work, and that's going to provide us a path to approval. Ultimately, we're interested in improving that regimen with non-ablative conditioning and other delivery avenues to make this a less toxic and more accessible regimen.
For us, where we want to position ourselves ultimately in the field is to provide both that best-in-class edit, cleanest, most precise, non-cutting, non-viral, highly efficient, with the superior regimen for delivery and conditioning and transplant. I think at the end of the day, that product profile is the one that will treat the most patients.
When it comes to conditioning, I guess, is there any part of that that can really be proprietary or better served by your product candidate, perhaps, driven by the phenotype of cells or maybe the quantity of cells you need to dose with?
Yeah
that proprietary and modified conditioning regimen.
It is very possible, and we're working hard on that. I think that is a belief we have, to be honest. One of the things about these next-generation conditioning is, you're going in, you're a little more surgically precise. At the same time, it's not as much of a sledgehammer. The question will be, can you deeply enough eradicate the old stem cells to create enough room for your new cells to go in, when there will be more marrow around? You haven't wiped everything out.
It's going to be a slightly higher bar. I do believe that may have an advantage for base edited cells, where you haven't created a double-stranded break, right? It's, again, that very mild edit, where the cells may have a higher viability heading in, to then engraft quicker and compete with what may still be there from the conditioning.
Okay. Got it. Maybe just pivoting to the in vivo applications, AAT and glycogen storage disorder. Well, actually, in one of the earlier slides, you outlined timelines to bring a lipid nanoparticle formulation to NHPs, and would sort of enable these programs early this year. We've seen some initial NHP data with a partnered asset.
Yep
Right? I guess, are you planning to move forward with a similar lipid nanoparticle? If not, do you need to sort of individually tailor lipid nanoparticles depending on the asset, the base editor, or the disease application that you're pursuing?
Right. You wouldn't need to individually tailor LNPs to each editor. Once we have an LNP that delivers this kind of construct, an mRNA of the editor plus a guide to hepatocytes, we won't need to recreate that every time. That's a really important feature of these systems where, again, with very minor changes in the new guide RNA, you have an entirely new medicine and a new program. That said, the first time you do it, you do need to get to that right formulation. LNP is a place of great expertise for us. We have people from Moderna, from Novartis, some of which technology went into Intellia.
You can look around the field and see that it is possible. Intellia has made great progress here. Verve is the company I mentioned earlier. They've shown really nice editing results already in primates using base editing. You can see that it's possible today. They showed long-term durable follow-up of those edits in the liver of those primates. We are doing similar things. We actually have a comparable lipid to what Verve has. Beam is doing its own formulation work around that, which is proprietary. We, over the course of this year, expect to be able to share some of our primate editing data using these LNPs.
From there, you can kind of see the editors are ready to go, and they just drop into the LNP, and that becomes a potential development candidate. We ought to be able to unleash a wave of in vivo programs as that LNP engineering work is done.
Maybe the last thing to say is that I think we're also pretty intrigued by the opportunity to take LNPs beyond the liver. They're synthetic, they're easily scalable in manufacturing. You can redose them. I mean, there's a lot of advantages there. We do think that liver is the low-hanging fruit, but there are going to be abilities to move that into other tissues over time. That's an area we expect to invest in as well.
Okay. Got it. I guess looking beyond sort of LNP selection, how should we be thinking about the in vivo directed program sort of advancing to final DC selection and IND-enabling studies?
I think if we stay on track with LNPs this year and can share that data, then we've guided that we'd have at least one development candidate this year. Again, we think there's at least three in view, in various phases of late-stage lead opt . The primary work here is LNP. That's the critical path. Once we have that, we'd be at that DC stage and then we expect a pretty predictable path to IND after getting to DC.
Okay. Great. I think we'll have to leave it there for time. Thanks again, John, for your time this afternoon and getting us up to speed on the story. Thanks everybody for tuning in to the webcast. Everybody have a great afternoon.
Great. Thanks, Eric. Thanks, everybody.