Beam Therapeutics Inc. (BEAM) September 2026 Conference Transcript

Great. Thanks everyone for being here. My name is Yanen Zhu. I'm one of the biotech analysts here at Wells Fargo. It is my great pleasure to be joined by John Evans, CEO of Beam Therapeutics. Thanks, John. Thanks, Yanen.

Thanks for having me.

Wonderful. I was just wondering, can you kick us off by providing an overview of the company and its initiatives? Yes, sure.

So Beam is a platform company developing a really novel and innovative technology called base editing. So here we're doing genetic correction of genes at the single-letter level. We use CRISPR to target flexibly within the genome, and that's a quite powerful system. And if you change the guide RNA that does the targeting, you have an entirely new mutation that you can target using the same machinery. But then unlike old CRISPR, we don't make double-stranded breaks, so we're not editing by sort of cutting the genome, we're editing instead by using a deaminase to do single-letter changes, so very precise modifications, and that gives us the power and the uniformity and the predictability of modifying the genome one letter at a time. We're using this in a wide variety of different places, delivering to blood, we're treating sickle cell disease, initially ex vivo with our Ristosol product, that'll eventually hopefully move in vivo over time. Then the liver, using lipid nanoparticles to deliver, we're treating alpha 1 and 2 trypsin deficiency, very high in metany disease, where again a single letter misspelling causes the disease, so it's a perfect application for base setter to go in and change that one letter. And then we're looking at other metabolic disorders, including PKU, GSD1A, and others, where, again, we're going to go in, find single letter misspellings, turn them back to normal with the base editor. And all of these treatments are potential one-time functional cures for these patients so that they get the therapy and that's it. They shouldn't have the disease anymore if we've done our job.

Great, great. Thanks for that overview. I think this morning you presented some new data at ERS and also at a company event. Could you share with us what are the incremental data presented today?

Yeah, broadly consistent. This was, we gave a top line version of this data earlier in the year in April, May timeframe. This was our first visit to an academic conference, so now communicating with the investigators and the treating physicians in this field. So I think, you know, major headlines are, you know, drug continues to look like we are getting patients into that functional cure zone that we want. So we're getting patients above what's called the protective threshold in alpha-1. So the disease is characterized by deficiency in this protein, alpha-1-netrypsin. And so, you know, patients are living in the mid-single digits for their micromolar levels of this important protein. And this important protein is needed to protect your lungs from degradation. We're getting patients into the mid-teens, okay? And every patient is at or above this protective threshold, which is 11 micromolar. And where that comes from is we know that there are no patients who have this disease who live at 11 or above. They're all in the single digits. So we know we have relieved that issue. You know, today, we basically were able to give a thorough summary of the dose escalation phase, part A and part B, with single-dose treatment. And we're showing now durability of these effects across 18 months or more with these patients. So consistent with that idea of this is a one-time intervention. We're showing dramatic reduction of the toxic protein, the Z protein, over 80%. And we're now able to show additional functional parameters. So we had functional data in today's update showing that the AT that we're producing, the normalized forms called the M form, is fully functional. We showed that. We also showed reduction in human neutrophil last days, which is a measure of this potentially problematic process that we are lowering by having the protective M around. We also showed reduction for the first time in Z polymers. So Z is commonly thought to be a problem in the liver. It builds up to toxic levels and causes liver toxicity. But unfortunately when it's secreted, it also polymerizes in the body and those polymerized forms can also cause systemic damage. They cause inflammation. They also interfere with alpha-1's ability to inhibit elastase activity. So all of that data set is now really coming together to show strong functionality of the blood we're producing. And in general, we're getting, you know, over 90% M and under 10% Z, so the shift from an all-Z patient to now dominantly an M patient is quite dramatic. So anyway, all of that came together into the update today.

Got it, got it. In terms of AAT levels, compared with what you've shown in the April-May timeframe, You know, the number back then was 16.1, I think, and today's number was 14.4 for the 60-meg patient, part A patients. So I was wondering, does that reflect a change in level, or is that just a measurement unit or something?

Yeah, you know, a little bit of both. Our original report, I think, for 60 milligrams was in the 12 and a half range, right? And then we were at 16, now 14 and a half. I think, first, this is a protein that moves around. I mean, there's a fair amount of up and down in levels in patients. We're also going, you know, mixing multiple different assay formats, okay? So today's update was in turbidimetry, which is the classic thing that investigators are used to. And so for an academic conference, we felt that was appropriate. it, but we've, you know, last time that 16 number was with LC-MS. It's just a different assay. That'll ultimately be the thing we also use for filing with the FDA, because it's a quantitative assay. It's also what we use when we want to discriminate the M and the Z forms, okay? But all of that together said, I think at the end of the day, we think this is the same data.

You know, we're clearly in the mid-teens every patient is at 11 or above I don't think it's like there's a meaningful difference between 14 1⁄2 and 16 and I expect these numbers to continue to fluctuate over time but the by and large the the level we're reaching is looks very durable and I expect it to hold okay got it got it you also reported part B data this was quite a quite a lot more data compared with last time right these are the patient with the liver manifestations right yeah can you talk about in liver disease patients whether the efficacy has any difference that you can tell also touch on safety and give us a sense of how

prevalent liver disease really is yep so so really probably every patient with alpha-1 has some amount of liver involvement because they're all they're making is Z and we know that Z is not secreting and it's sort of building up in the liver and causing toxicity. We know that in most patients the lung phenotype leads and the liver trails and that may be because the liver is able to regenerate itself to some degree it's a fairly plastic organ whereas lung tissue once you start to lose it it's gone. You asked about the market or the kind of of the prevalence, by and large, only about 10% of patients with alpha-1 are kind of pure liver phenotype. It's kind of an unusual population. So 90%, we would say, have some degree of lung involvement, and then a range of liver involvement below that. So out of that, I would say maybe 15% or so are lung and liver, kind of equally severe, and then the rest are mostly lung with some lower liver burden. So it's a minority. But, you know, we're addressing with an LNP. It's a population that we want to study carefully and just make sure that the safety, you know, looks consistent. Then obviously efficacy-wise, are we getting to the hepatocytes in the same way, etc. So I think if you look at the data we revealed today, so as you said, there's five patients, so it's a pretty important increase in the number of liver patients. FC looks very similar, right? So we were getting, you know, again up into the mid-teens, I think in the thirteens range, and that's up from a baseline of about 4.7, so you're just about tripling the alpha-1 levels, and that's similar to what we see in the lung patients. Safety, you know, by and large, very well tolerated. All grade 1 LFTs, with one exception, we had one patient who had a grade three LFT and you know these are biochemical findings and so just to unpack that a little bit patient basically went up in their ASD LT within a few weeks they went back down there was never any bilirubin so there's no liver injury signal never hospitalized this is just you know sort of lab findings so no change to the to the you know path forward for the drug There's no different monitoring needed, so it looks good.

Okay, okay, so yeah, so with this, you know, this is the first grade three finding for liver enzyme, is this related to the fact that the patients already have underlying liver condition? And when you think about enrolling more patients in the future, what kind of consideration of this brain?

Yeah, I mean, I think this, so a liver patient, you know, like the Part B patients that we're studying here where that we've done FibroScan and we know that they have a more severely burdened liver, let's say, you know, they generally live often in the grade one, you know, they kind of, they sit above usually the upper limit of normal just as a background, whereas I think the Part A lung patients are usually high normal, but they're probably still below the upper limit of normal in general. So this was, you know, one of our liver patients, and then, you know, from there you put a bunch of lipid in and, you know, the liver can show you that kind of biochemical response, and that's what we saw here. Again, I think in general, as long as it's just AST-ALT, right, you're just detecting those enzymes, you're not seeing bilirubin change, which is the functional measure of liver function, right? As long as it's just those lab tests, then, you know, grade three and below is very much, you know, in the noise for these sorts of, you know, LNP therapies. I think, you know, grade four and above, you start to consider things, and then obviously bilirubin is a big deal. So we obviously didn't see that. So, you know, again, no, as I said, no change to how we're proceeding and continue to enroll all these patients in a cohort C. Got it, got it, got it.

Is there anything to be considered in terms of the timing of the observation?

Not really. It's within the kind of mix of what we've seen for, you know, the grade ones that we've been seeing as well. You know, it started, you know, a couple weeks into the dose, then resolves, you know, a couple weeks after starting. And again, no intervention, no hospitalization, outpatient completely.

Okay, got it, got it, got it. Yeah, so also I was wondering if you can comment on some data from other companies also presented at ERS, this is your text data, they had a poster there, can you share your thoughts on that data?

Yeah, so I think we've sort of shown that I think DNA editing is going to be a very attractive category and base editing is obviously a perfect fit for this disease. We do expect there will be competition and that's standard so I think we're you know we have a good couple year lead here but we're starting to see these newer entrants start to come on the scene. Yoltec is one, there's also Tessera and then you know behind that just filing now would be CRISPR and then Prime. So there will be there will be a set of these. With the Yoltec data they They are using base editing, which of course is the technology that we have pioneered and where we have a really leading position, I think, so that's quite important. They have at least one patient who has nice high AT levels in the maybe mid-20s. Their mean was lower, maybe around 20, which kind of implies that the other two patients are probably in the teens, more comparable to what we're getting. So I think it's too early to tell exactly where they're going to land, but I think at the end of the day, it goes back to, I think once you're at where we're at, where you're getting everybody above 11 and in the teens and, you know, you look like not a patient but maybe the parent of a patient, right, so a carrier, I think you've achieved all the clinical benefit there is to achieve. So I'm not aware of any clinical argument to going, you know, any higher, and I don't know how much higher those other players are going to get either.

Got it. Thank you. So let's talk about your pivotal cohort effort. So you dosed your first patient in July in the pivotal cohort. Oh, sorry, if I can backtrack one step. I think in Part A, you also have Part A expansion for the 60 mig. There are six patients there, right? So, you know, now that you're enrolling your Pivotal cohort, what purpose does that cohort serve and will we see data from that expansion cohort?

Yeah, great question. So yeah, we basically, when you're doing an accelerated approval push, you sort of want to keep the machinery rolling constantly and so we have these expansion cohorts where we can keep adding patients, so that's been ongoing. Now, of course, we're gonna mostly direct patients to the Cohort C, which is the Pivotal cohort. So, yes, at some point, we'll have some of that data, you know, to share as well. There's no expectation on when. Today was really the kind of full story of the dose escalation phase and how we got to the dose and sort of where we're going next. I think at this point, we've treated, you know, quite a good number of patients. So I think the signal is very robust. I think the safety understanding is getting quite strong. And it puts us in, again, I think a good position to now confidently go into that pivotal cohort. and enroll okay great great can you comment on the progress in your enrollment into the pivotal cohort yes so it's going well so we have our first patient dosed in July we had guided the second half so obviously there's a lot of enthusiasm there I think the operations is in great shape we have I think 14 sites in six countries again investigators are very eager to participate we've had a lot of waiting lists patients raise their hand for interest so going well I think you know at the end of the day in terms of expectations for enrollment I think we can't give guidance just yet but you know I always say that you know the beacon trial took about a year to enroll once we got out of the sentinel cohorts and you know so this will be a similar number of patients and out of a similar sized population I think we might be to be able to go faster than that, given what I'm seeing, but we'll see.

Got it, got it, got it. So in terms of the patient's willingness to get a one and done therapy, do you get some feedback from the ground?

We do, we do. I think this has probably exceeded expectations, honestly. We've always felt that a DNA curative edit here would be popular, but also there's a lot different classes of agents and a lot of different people trying to bring new solutions to this field. And I think what has become clear to me is that the idea of a one-and-done, as long as you have the profile we have, which is getting you to a protected level, lowering your Z, increasing your M, inducible, we haven't talked about that, but just the ability that when you're sick it goes up even further to give you even more protection. That's the way the gene normally works and given that we're correcting in its normal location we get that and we showed that in a patient who got an upper respiratory attack infection. So you put all of that together and that is a very popular profile with patients. You know, if you think about these patients who are diagnosed, they have been living on augmentation their whole lives since diagnosis and this is a weekly infusion, very burdensome to their lives to kind of maintain what even then is is actually an inadequate amount of protection. They're getting total AT kind of mid-teens, they're adding about 11 of M, they're not reducing Z, and it's not inducible, right? So when they get sick, they're stuck with what they have, they can't go up any further, unlike us. So for us, we're inducible, we're lowering the Z, those are quite improvements. And so these patients are really, frankly, sick of it. It's been a long time. And so I think any chronic medicine has been a little bit of a hard sell. The one and done looks very attractive. Now, within that, obviously, there will be early adopters and late adopters and all the normal, I think, cycle will play out. But the overall enthusiasm level, I think, has been pretty striking.

Okay, great, great to learn that. Let's do talk about the bar for success again. I think you talked about this before, but it's been since JP Morgan when you aligned with the FDA, right? So it's been a half a year, half a year. Can you remind us or provide any update with your more recent FDA interaction regarding the primary endpoint and what's the bar for approval?

Yes, so I think as we said back at JP Morgan we do have alignment with the FDA for an accelerated approval path here. I think they are working with us in a great way and and and by the way it's been very consistent you know a similar team you know consistent reviewers so we're just so appreciative of what they've done I'd also say very consistent today as it was then I mean there's been there's been a good amount of consistency there we haven't as you know disclosed the specific ordering of endpoints and exactly what what that agreement is just that's such as from a competitive intelligence perspective of something we're holding to our vest, but it is really the constellation of all of the things we have talked about together. So obviously, total AAT matters. You know, your M, your Z levels, your functional AAT, inducibility, like these are all things that are important, and then many other of the functional assays that I have mentioned become relevant as well. And the reason all of it together is important is because they tell a story that, again, as I said at the open, we've clearly taken a patient who has the profile of a diseased patient, a ZZ, with all 100% of their AT is Z protein, and it's in the mid single digits. and we have really converted them to what's clearly at least a carrier phenotype, where they're now total ATs in the teens, they're 93% M and very little Z is left, Z has been reduced by 83, 84%, and then it is clearly inducible and it's clearly all functional. So I think what that tells you when you're at FDA is you're looking for the evidence that you can then use to to predict clinical benefit. That's what accelerated approval is. And so it's really that profile that we know from the genetics should no longer be a diseased profile. It should now be a stable profile. And so that's, I think, the basis for the confidence that they need to work with us on accelerated approval.

Got it, got it. That makes a lot of sense. Thank you. So maybe switching gears for the PKU program. You announced this program fairly recently and you already, this is IND cleared. You are in a clinic. Can you talk about the level of your excitement with this program and how big is the opportunity and how do you think Beam 304 can be positioned in the treatment landscape?

Great question. The level of my excitement is high I think you know this really becomes I think the third leg of the stool for the company from a commercial perspective that's important you know we clearly see the sickle franchise as having blockbuster potential alpha one clearly has blockbuster potential but so does PKU and and that's really important for a company like us where we're looking to make gene editing into a sustainable business. It's also a very efficient path in the clinic. So we will be starting dosing patients around year-end, early next year. That goes, you know, a few cohorts of dose escalation to establish safety, right? So that, you know, will be an important first step. But once we've established a dose, we should have a path directly into a expansion cohort, which could be registration-enabling, right? We will try to treat, you know, some number of patients, maybe it's another 50 or so, and here we're just measuring phenylalanine lowering, which is the deficiency here, they can't process phenylalanine, and then some amount of di-normalization, and that's a full approvable endpoint. So no confirmatory trial, this is just, that would be the whole journey. So that's a very efficient and predictable clinical pathway. As far as I know, we're the only DNA editing players in PKU right now and so it's a perfect indication for us and then really cool about PKU as well is we're using this novel platform approach with the FDA so we got the IND open which we announced mid-year and here the FDA for the first time as far as we know in industry is doing this sort of new kind of rules within CRISPR and genetic medicine where we actually have multiple editors in the same product. So that depending on which patient you are, depending on which mutation you have, we give you one of two different editors. That's the initial IND we have now. And we can add to that. We can add a third, a fourth, a fifth. And all just be part of one package, not have to redo things every time. And so that's really exciting because it allows us to increasingly create individualized curative therapies for each patient while treating the same disease. right and the FDA's plausible mechanism pathway guidance really talks to this and and so I'm quite excited about that so our first two editors cover we think about 45% of patients would have one or the other of these two alleles it's the R4AW allele and then there's one more but again we think we can add more alleles over time into this package and treat more and more patients within this community and then as with cyclone alpha one this would be a one-time intervention to potentially give you lifelong normalization, ideally, of your phenylalanine metabolism.

Okay, got it, got it. I guess you haven't guided on potential timeline to first-hand human data on this program yet, right?

We have not. We have not. I mean, obviously, you know, it's open-label trial, so we'll be accumulating it over time. I generally say, you know, give an average 12 to 18 months before even starting to expect data is usually a good rule of thumb but you know we'll see as we get into it got it and maybe talk about bar for success on efficacy right so there are approved therapies out there so what is the bar here yeah so this has been one of these diseases where like alpha one where it really needs better therapies and it hasn't been easy despite a lot of effort. You have Kuvan, right, which is like a cofactor, but that only works in the milder cases of PKU. More recently you have Cefiance from PTC, which can maybe get you more out of any functional enzyme that you have left there, but even that is not curative. You still have some amount of diet restriction, and not all patients are in control. So I think there's real room here to improve, and And if you look at our preclinical models, which we have shared, at a relatively low clinically meaningful dose, around 0.3 mg per kg, for instance, we were getting full normalization with stability and durability of phenylalanine levels. So I think we'll see what we get, but my ambition here is to provide as close to a full normalization as we can. That's the promise of gene editing.

Got it, got it. That's great to hear. So that sounds like there's some, you know, efficacy advantage to look forward to.

Yes, and as with all of our other programs, again, not giving guidance yet on when the data might arrive, but it is true that the first data set should tell us not just safety, right? These are precision medicines. So the very first data set should show us how is it tolerated, but also is it working?

Because we're treating patients with intent to cure from the very beginning so the first data set you know ought to be pretty informative as to whether we have a drug in a franchise right right just continue on for the in vivo editing friend franchise GSD 1A I think you have data coming this year help us understand the the study design and what What data could we expect?

Yes, so GSD1A, our beam 301 is editing the RA3C mutation, again, a single point mutation in this gene that we're trying to correct back to normal. This is a really terrifying disease where you can't fast because what's broken is the machinery to take stored energy from your liver in the form of glycogen and turn it back into blood sugar, glucose. And we all use that every time we fast between meals and when we go to sleep for eight hours and we're not eating, your liver is keeping your blood sugar up. So these patients can't do that. So they're basically constantly crashing and going hypoglycemic. And so they have to eat something every couple hours. And particularly they take this sort of cornstarch that's a slow digesting source of glucose. And so their glucose levels are just crashing and then spiking and crashing and spiking. And if you literally, if you sleep through one of those feedings overnight, you can die. You slip into a coma and you never recover. So it's a crazy situation. And, again, a relatively low amount of editing would restore the ability to do that glucose production out of the liver, and we see that in animal models. So this is the most prevalent mutation in this population. It's an ultra-rare population. You know, we think there's probably 300 patients with this mutation out of maybe 1,000 total. And what we would like to see, we'll have a couple of cohorts worth of dose escalation, so, you know, stay tuned for that. And again, you know, the goal here is to show some real impact on the metabolism of these patients. You know, we look at things like cornstarch utilization, right, that was used by the ultragenics drug. Ultimately, the gold standard here would be time to hypoglycemia, right? That's the fasting duration. So at baseline, if you take them off cornstarch, how long until they go hypoglycemic? It's generally a couple of hours. And then after the treatment, you know, do you extend that? And so that's what we'll be looking for. And that, again, should be ultimately an approvable endpoint for full approval.

Got it, got it. So I see. So in terms of the data points that we will see this year, can you outline those endpoints for us?

Yeah, so I think, again, the ones I just mentioned, so it would be sort of corn stretch utilization, time to hypoglycemia I think those are the you know gold standard endpoints here and would be could be comparable to other agents in the field which will be hopefully helpful to it to investors and then obviously safety you know you know how it's performed okay okay obviously there is the the autogenics the gene therapy approved as you mentioned earlier do you think there's room to improve with the gene editing approach? Yeah I do I think I'm so happy that product did get approved I think this is a population that really needs more options and and as you noted I we're only coming to at least initially treat one mutation which is the RD3C there are other patients who don't have that mutation so the more options for these patients the better. All that said you know I think that product does leave some room to improve so it's an AAV product which means some patients will have pre-existing immunity which blocks them from receiving it. That's not the case with LNP therapies like ours. And then for those treated, they got a 44% reduction in cornstarch, which is a real improvement. But you can see the FDA is thinking of this as potentially an accelerated approval, and then they need to come back with more data to convince them for that full approval. And that's because the cornstarch reduction, I think, is a maybe a softer endpoint, and maybe the effect size is something that's maybe the FDA wants to see a little bit more and so I think that's where I think both cornstarch reduction but also time to hypoglycemia is maybe you know the endpoints that we'll be looking for got it got it super helpful let's do talk about sickle cell so this this is the program that you already we have, you know, you will file by your end.

So, let's talk about what are the items remaining for the filing and then also touch on the commercial experience for Kaskavi so far and, you know, what are the lessons learned and how do you foresee your launch?

Yeah, great question. So everything is going well. We're doing validation runs and PPQs and all of that, very much on track. The timeline is really driven by, you know, we've treated 50 patients, but we think it's the 30 patients that were similar to the Kaschevi label that we need. We treated number 30 July of last year. 15 months to measure the VOC12 endpoint puts us into October. That's your data cut, and then you basically write it up as fast as you can. So we think it's, you know, around December. That's hence the guidance of end of year. And, you know, we'll see if we can hit it. I think we're in good shape, too. I think that we then would be positioned to enter a market that is actually starting to grow. Caschevy's doing better now. Genetics with Lovgenia, I think, is doing quite well. They announced they were profitable this year. So they're making money with that drug. Patient demand is really high. and yet we do hear from sites that they do want more. I think they're looking for new options, particularly there's been a lot of difficulty with manufacturing some of these products, and that's real-world issues that they're working through. But we know that Wristocel has real advantages there. Our vein-to-vein time for the median patient for the start of mobilization to when we deliver them a dose and they dose it in the transplant has been four and a half months. So we think that's quite a bit faster than what is being seen with other products, and that was with our own manufacturing facility, our own team releasing the drug, and that will continue to be the case on the commercial market. And then on top of all that, we get higher levels of F, lower levels of sickle protein, faster time to engraftment than what has been reported before. So I think in general, it looks like a best in class profile for a market that's just beginning to really get into gear, and we think can be quite meaningful.

Got it, got it. And you're ready to, or do you plan to launch it yourself? And build a sales force?

Yes, we're fully ready for that. But it's just not that big an effort. We need to scale up the North Carolina production line a little bit and then grow it over time as capacity in the market increases. There are 50, 60, 70 centers that we'll be focused on, a small team can do that. We'll be doing that. We did a financing, a really exciting financing with Sixth Street, where we have access to a $500 million facility. We're projecting we'll take down about $300 million of that, about $100 a year, and that fully covers our commercialization buildup costs for the product, and the product can then fully pay back the cost of that financing and the principal later. So it makes Ristocell effectively self-financing, which we're, you know, we're quite pleased with. And this, you know, this will launch by the end of next year and be making money, you know, in the end of the decade. And for a company like us, that's quite important. And then from there, you know, we're also hard at work on next gen products. You know, this is to treat really the 10% of patients who are sick enough to go through a transplant but from there we have an in vivo program that we're quite excited about that will be coming at some point and that of course can then create access to genetic cure for hopefully all sickle patients and that would be a hundred thousand patients in the US so again we think that the sickle franchise is a very important one for being future as well yeah that definitely look forward to progress on the in vivo front unfortunately that's all the time we have today, for today, so maybe another time.

Thank you, John, for a very, very helpful session.

Thank you, Yannick.

Thanks, everyone.