Beam Therapeutics Inc. (BEAM) Earnings Call Transcript & Summary

I'm Sam Semenkow, one of the senior biotech analysts here at Citi. And it is my pleasure to be hosting Beam at Citi's 2026 Biopharma Back To School Summit. I'm joined by John Evans, CEO; and Sravan Emany, CFO. John and Sravan, welcome, and thank you both for being here.

Thanks for having us.

So why don't we just start by level setting. You've made a lot of progress across the pipeline this year. Just tell us where the company stands today and what we can expect through the end of the year and beyond.

Yes. Great. So Beam has made a lot of progress. We're moving very quickly now across a broad range of programs, all building off of this very dynamic platform that we've created. Using base editing, of course, next-generation CRISPR 2.0 technology for more precise gene editing, but then building that into a delivery and manufacturing machinery that is now quite mature. So doing both ex vivo cell therapy but also now in vivo lipid nanoparticle part programs and manufacturing all of that internally. So it's a very significant capability we've built. The programs are now moving very quickly. So Risto-cel, our sickle program is really awaiting its final data cut from a now fully enrolled and dosed BEACON trial that will become a BLA filing right around the end of the year, which will be our first BLA. So that will be an update we're excited to share. Then in vivo programs, on the liver, we have been 302, alpha-1 antitrypsin deficiency. We just have shared sort of new data there, showing really dramatic consistency of that program as we continue to add patients. That's now a pivotal cohort. We're enrolling patients. We dosed our first patient in July. By the end of the year, we hope to have significant progress on enrolling that 50-patient cohort and continue to move that program forward towards patients. Behind that is BEAM-301 which is a program for glycogen storage disease 1A, the R38C mutation. There we'll have first data, first in human data this year on a couple of dose cohorts for that program, another sort of metabolic type of mutation that we're going to try to correct. And then finally, also Vivo PKU, BEAM-304, we now have an open ID. So we're now opening sites as we speak and hope to begin screening patients towards the end of this year. And obviously, then that will become a clinical program to follow. So lots going on, lots to talk about, but we're seeing this flywheel continue to gain momentum on both the payload technology and our delivery manufacturing capabilities.

Yes, absolutely. So as you said, lots to get into, why don't we start with AATD. So yesterday, you did share data an updated data cut. And our takeaway kind of what you said is that it seems to be quite durable in that the level of AAT and MAT induction that you're achieving just continues to be within the range of that protective NZ phenotype. So maybe it would be helpful just to hear a little bit of the feedback from ASR. Walk us through how physicians are viewing the data, how impactful they believe achieving these levels of AAT and MT are for patients.

Yes, it's a great question. So there's been a lot of enthusiasm and I'd say ERS is no exception. We're hearing from physicians around the world, certainly our investigators, but more than that, that this looks like the profile they've been waiting for. There's been -- this patient community is really overdue for some better therapies. And when you ask them sort of what is the ideal outcome, they will say, well, we need something that raises our AT into the protective -- above the protective threshold -- teams into the teens because that is the place where there are no patients who have those kinds of levels. We want to raise it by creating M, the norm protein, which we know is functional, and we'll protect their lungs. At the same time, we want to be reducing Z as much as we can -- that's a toxic protein, both for the liver, but we've learned a lot more recently about its disruptive effects systemically, causing inflammation and interfering with the protection of normal you want to be inducible, right? So when you get sick and as you could go up and we have shown that. And then, of course, you want it to be durable. Patients -- these patients have been on chronic therapy, their whole lives, taking weekly augmentation. They're very hungry for a onetime cure, and that is what we believe we're offering. So lots of excitement, I think, as the physician and patient community, and we continue to see that operationally in our BEAM-302 trials.

And so one thing we heard after the presentation yesterday is maybe a little bit of confusion on the assay used to quantify AHV and MAT. It can make cross-trial comparisons perhaps a little difficult and maybe even comparing your own data cuts difficult. So maybe just talk about whether Tuburdity or LC/MS is better assay. Why are you using both? And maybe clarify if we're seeing a decrease in AAD levels or if it's just an assay difference.

Yes. Great question. So there are multiple assays available. And I think the important point is to step back and see that they're actually telling the same story across the board. We do change back and forth between the bits. So turbidimetry is the classic in the deal. This is literally taking protein in liquid, shaking it up and seeing if it disrupts light scattering. So it's a fairly crude sort of old assay, but it is used by the clinicians very frequently. So that's the standard. If you're going to get diagnosed with ATD, you're going to use turbidimetry to do so. But they don't check AT levels very frequently. It's kind of a one-off. So for our first academic conference presentation, which yesterday, we thought turbidimetry makes sense because it could be familiar to the clinicians, and they would fully understand it. LCMS is different. That's, of course, mass spec, and we need LCMS to discriminate between the kinds of AT, right? So if you want to see how much you have, how much Z you have turbidimetry can't do that. So we need LCMS at least for that. And so you've seen some of our LCMS data reporting that. Our expectation is ultimately, even things like total AT level for the FDA, they will also want LCMS. And so we have been bridging our way over to that assay. I expect we will -- you'll see more of that from us in the future. Right now, we're validating it for pivotal stage but it gives fairly similar answers. There is definitely for these assays, there is a 10% wiggle as you think about sample to sample and also AT levels themselves drift up and down for these patients on that order of magnitude. So I definitely don't see -- there's no change in our levels, I think that you should interpret here between 16%, 14.5%. It's all basically mid-teens. And as we have seen, it's quite durable. So once you see those set points, I think you'll see them sustained.

Right. Okay. What patients tend to achieve is what they tend to keep?

Exactly.

And so then looking forward, there's a lot of competition in AATD. The space has quickly become quite crowded. You remain well ahead of competitors entering pivotal studies. But other companies are also developing gene -- therapies. And so how do you see 302 positioned outside of being first to market against all the competition?

Yes. So I think the success of BEAM-302 is definitely going to invite competition, and they will be coming. We have the fortune of being well ahead. So we've been up against some different costs of medicine. So RNA editing is one that we've been facing. I think we're now moving past them in operations, we're now into pivotal trials or any editing is still more of the early stage development. By and large, the numbers they've produced have been positive clearly for patients, but maybe numerically not where we're at in terms of both level [indiscernible] amount of being produced, the amount of production in the -- so then you look to the DNA editing field. And as I said, I think the DNA editing is maybe more where the ideal target product profile lives for the patients and for the community. And they are, as you noted, BEAM-302 is in pivotal trials. We will have a clear first-in-class advantage. We're about 2 years ahead of our most advanced competitors, but there are going to be others. By and large, it isn't clear to us where the opportunity for differentiation clinically really lives. There will definitely be a competition around who can maybe have the higher AAT level and that will be something that people focus on. The reality is all of our patients are already above the protective threshold, right? So there's no evidence that there's any clinical difference once you get to that state or going a little bit higher, it also isn't clear to me exactly how much higher you can go. I think we'll learn as we see some of the competitor data. But I think it's clear to me that editing a lot of the liver in these patients. You can get patients to that protective threshold. You can get them into the teens. I don't think it's going to be possible to get people to 30, which is kind of where normal would live. But again, it's all good because patients are protected now. Beyond that, I think BEAM-302 is doing everything we needed to do. So I think we're looking forward to pressing on the accelerator and staying certainly ahead of the competition and bringing a new product to patients as quickly as we can. All that said, competition is good for patients. We're always welcoming of more entrants. They certainly deserve more options.

And just maybe double-click on that a little bit about the AAT level. I mean, do physicians recognize that there -- it's going to be difficult to clinical differentiation, say, if you have 2080 versus your 14, 16, depending on the asset. Like how do you think it will be viewed by physicians when they're trying to make treatment decisions.

Yes. I think it's got quite well understood. So these physicians have thought a lot about the clinical genetics here, right? So ZZ is the profile of a patient. They live in the 6 -- 5, 6 range in terms of their [indiscernible] levels and their parents, right, the people who are carriers who maybe have 1 copy of Z, but the other is of M, they are in the teens. And this is called MZ. And so an alpha-1 expert intimately knows what ZZ patient is like versus an MZ carrier, and then, of course, MM is the normal. And there's been extensive literature that these community groups have done to understand what is the relative risk of each of these groups. And it is a very settled question that MZs do not have progressive disease, they're perfectly stable where they may have a little bit of high risk is if they are heavy smokers, for instance. So if you have a second hit you can see a little faster decline, but that's really the extent of it. So I think at the end of the day, I think if we're all in sort of the MZ neighborhood or better, I think that that's going to be a wash from a competitive perspective.

Got it. Okay. And then how important is it to lower Z levels? Z have its own pathologic effects?

It does. And I think that is actually an increasingly important part of the story here where, of course, we want the total [indiscernible]. And then we like the fact that it's inducible so when you get cyclical even higher still. But it's really the quality of the AAT that was being produced in the body. Meaning, in our case, we're getting 93% M circulating and only 7% Z. And that's because we have lowered Z by about 84%. That's really helpful. It's helpful obviously to the liver. Z is the thing that's building up in the liver and causing toxicity. But it's increasingly clear and Dr. [indiscernible], who is on our call yesterday morning was speaking to this that Z is a bad actor systemically. It causes polymers. And those polymers are basically inflammatory and they lodge in tissues and they cause the local inflammation. They can also bind to and actually inhibit the natural AT from doing its job to stop [indiscernible]. And so they can actually frustrate them from doing its job. So I think there are lots of sort of emerging ideas that the less you have the better systemically. And so our ability to do that is an important part of the product profile.

And so how is enrollment going in the pivotal cohort? I feel like you've commented that it's going quite well. I'm wondering if you could just speak to some of the engagement that you're hearing from your investigators based especially on the back end of this updated durability data?

Yes. It is going well. I think we have great enthusiasm. We're at 14 sites across 6 countries now. We've been adding more sites in the U.S. in response to demand. And yes, as I noted, there's -- almost each site has a list of patients who are interested and are willing to travel for this therapy. I think it's very clear we've gotten on the map with the community. So nothing more to say other than what we feel confident in the enrollability of the cohort, and it's moving quickly.

How long does it take to get a patient off the list and into the trial? Is that site dependent on their capacity? Or is it your ability to like be able to dose them? How does that work?

Yes. It's more the -- I mean, the site obviously has capacity. I have to work through it. The patient has to go through screening, I mean, that's probably the biggest thing. So we just want to make sure they meet the inclusion criteria that they're stable and all the right medical things are at. You then have to wash them out, right? So they're generally on augmentation, particularly in the U.S. and we are washing those patients out. So you want to get the augmentation out. That then gives you a clear view of their true baseline in terms of alpha-1 levels, all Z, of course. Then we take a baseline phase, right? So then we're going to take a series of measurements to make sure we have a good average of what their set point is. And then you can treat. So I think there are definitely a few steps to go before the dosing. But as I said, -- we're already in the dosing phase. We had our first dose in July. So this has all been ongoing now throughout '26.

And it's a little early to maybe start this conversation about the commercial strategy. But how are you thinking about initial launch strategy? Where are these AATD patients typically treated? Are they concentrated in centers of excellence? Or do you need a community referral program? Or are they all of the above? How are you starting to think about actually targeting this in a commercial way?

Yes, it's not too early at all. I think we actually think about this a lot. So there's probably at least 100,000 patients in the U.S. are ZZ genotype, that's our target population. Of those, we know about 10,000 to 15,000 are diagnosed, okay? So it's a largely underdiagnosed disease still and of the 10,000 to 15,000, maybe 9,000 are on augmentation, something like that. So the large majority are taking therapy, but everyone is pretty educated about their disease that they've got the diagnosis. So that's your initial addressable market, right? And that launch will be primarily through the academic key opinion leaders, the AATD treatment centers, these are specialists, right? This is still a rare disease. And that's clearly a very biotech friendly kind of launch. We know these folks. We're working with them now. They're partners with us. So we feel quite capable of moving there, and that's a large addressable market, right? If you think about 10,000 to 15,000 patients at gene therapy pricing. From there, though, we were not done yet, right? So we need to think about how do you find the other 85,000 to 90,000 patients who are not yet diagnosed. Now some of them may be ZZ but not yet symptomatic, right? And that would be a group that we'd want to find and treat before they get the disease, right? But many are symptomatic, but they've just not completed the diagnostic odyssey. So they may be living in a respiratory clinic, may had COPD diagnosis. They may just be primary care and be complaining about fatigue. There's an awful lot of that out there. And so that is more of a diagnostic campaign that would happen over the subsequent years. I think of the analogy to like a TTR CM, right, where you have you have to go find those patients, educate them, get them to the right centers and then you can treat.

Got it. Okay. That makes sense. And that's a really large opportunity if you can improve those diagnosis rates over time ATTR.