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

Great. Good morning, everyone, and thank you for joining H. C. Wainwright's 27th Annual Global Investment Conference, September 8 to September 10, 2025. My name is Patrick Trucchio. I'm the senior healthcare at H. C. Wainwright. It's my pleasure to introduce our next company, and next speaker. It's my pleasure to welcome Beam Therapeutics, a biotechnology company, leveraging its fully integrated precision genetic medicine platform to bring lifelong cures to patients suffering from serious diseases. Beam's suite of gene editing technology is anchored by base editing, a proprietary technology, that is designed to enable precise predictable and efficient single-based changes at targeted genomic sequences without making double-stranded breaks in the DNA. And with that, it's my pleasure to introduce the CEO, John Evans. Welcome to the fireside chat today.

Great to be here. Thank you.

So first, maybe you can briefly introduce Beam's base editing platform, how it differs from first-generation gene editing and what it enables clinically?

Great. So Beam is working on a next-generation version of CRISPR gene editing. It's called base editing. And with gene editing in general and CRISPR specifically, we have the amazing ability to target the genome very precisely. We can choose one spot across 3 billion different letters of your genes, where there's an error and go in and try to fix it. What is different about what we do is that once we get to that target site, we have the ability to make precise single letter changes to rewrite the DNA at a single base pair level rather than just the cutting, which has been the characteristic of previous generations of technology where you can't control the sequence, you're going to get out of the other side of the edit. So that precise editing is really important because it opens up a lot of new therapeutic territory for us that hasn't been available before. So one is to make more precise and efficient changes, things like upregulating fetal hemoglobin into more uniform and potent way, which we are doing with BEAM-101 in sickle cell disease, but also to rewrite the genome to correct mutations. So a single letter misspelling can cause a lot of genetic diseases. We can now take that single letter, turn it back to normal and leave you with a functional gene. That has not been possible in the past. We deploy that in, for instance, our BEAM-302 program for alpha-1 antitrypsin deficiency, where we correct the single point mutation that drives that disease in the vast majority of patients.

You've demonstrated clinical proof of concept in both ex-vivo and in-vivo base editing. How does this validate the broader platform vision?

Yes. So the beautiful thing about these platforms, these genetic medicines are very complicated to make work. But once you get them to work, they start to work again and again because they're fundamentally programmable. So once we tested in a cell that we can deliver the editing machinery along with the targeting element that takes it to the right place in the genome, and we can detect that we've made the right kind of single letter change, then if we change the targeting element to alter a different part of the genome, it should work and indeed it does. So the repeatability and the predictability of these tools is quite significant. The same is true of delivery. So in the human body, once we know we can take the blood cell out of the body, put our editing machinery in and correct those cells and put them back in and it works, then we should be able to do that again and again with other blood disorders, same thing in liver. So once in the liver, we do in-vivo deliveries. So now if we take a lipid particle, to package our editing machinery. We can deliver that successfully in an infusion to the liver and treat a patient, then we should be able to do that again and again. And so what it does is it really sets up a platform, allowing us to make a large number of medicines over time where the investment and maybe the risk we're taking on the first such programs in each of those areas is maybe high but then it gets dramatically lower for programs 2, 3, 4, 5 and 6. So this is really important because what it can do is it can fundamentally change the math of building a drug company and creating a pipeline of medicines, right? Because now we don't have to guess for programs 2 and 3, are they going to work? Will they get to the target? We know they will, and we can build on the derisking that's already been established in these other areas.

So just moving on to BEAM-101. This is ex-vivo base editing in sickle cell disease. Can you walk us through the therapeutic hypothesis, the edit and how it's intended to work in sickle cell disease?

Yes. So in sickle cell disease, we are creating an upregulation of fetal hemoglobin. This is the protective form of fetal hemoglobin. And we do that by making precise single letter changes in the promoter region of these genes that are known to turn on the fetal hemoglobin. We do it so potently and so broadly across all these cells, they were also really turning down the amount of sickle protein that is being produced. That's the protein that causes the sick cell disease. And fundamentally, base editing has enabled a deeper resolution of the genotype so that we are getting the blood of these patients farther into the normal range than has been seen before.

So EHA 2025 reported that all 17 evaluable patients that trait like HbF/HbS ratio. Can you expand on the significance of that finding?

Yes. So trait is what we call a carrier in sickle cells. So this is somebody who has 1 copy of the mutation and then 1 copy normal. And they don't have the disease, that's very important. So in genetic disease, we usually look at the carriers as the threshold for where we want to get a patient to because then they would no longer be the disease-carrying patients. And so in sickle cell, a trait person, somebody who has that characteristic, generally has about 60% normal globin in their blood and about 40% sickle globin in their blood. And that's the bar we got to. We have -- we are actually over 60% fetal hemoglobin, which is protective under 40% sickle globin. And when we looked at a whole wide variety of other exploratory assays, testing the blood under low oxygen conditions, things like that, in all cases, we saw that the blood of the corrected cells that we had edited was performing like a trait person's blood or better.

And then anemia resolution EPO normalization were also reported. How do those markers relate to long-term functional benefit?

Yes. So I mean, anemia, sickle cell anemia is of course the original name of the disease. So we clearly want to resolve anemia, and we do. And I think some of the other programs in the field, maybe aren't quite getting full resolution in all patients of getting up into the normal range of hemoglobin. So that's important. EPO is a sign of adequate oxygen delivery to the body. And so you want to see that come down. That's a sign that, again, the blood is functioning better. It's delivering the oxygen where it needs to go, and the body is reaching homeostasis. So just all different signs that we can look at that suggest that the drug is working. Of course, along with reduction of vaso-occlusive crises. These are the pain crises sickle cell patients go through and these gene therapies have been really transformative there. We, of course, have not seen any VOCs either here with BEAM-101. So really, the constellation of medical outcomes looks like we are achieving so far, a very robust transformation of these patients.

Right. So no VOCs to date. So I'm wondering how will that translate into your registrational strategy?

Yes. So the registrational strategy here is quite simple. There are a couple of drugs already approved, which we think are really strong with LYFGENIA and CASGEVY. In the case of CASGEVY, that was approved on a single trial with a patient cohort of about 30 patients followed for about 15 months to just test how many of them would have these VOC events. And we believe that same registration path will be open to us. And so something very similar is planned. So we're doing a single trial called the BEACON trial, where we will ultimately treat about 50-plus patients, but the 30 patients, the first 30 will really form that same core data set that was available for the CASGEVY approval, and we've already dosed the 30th patient, that happened over the summer. So at this point, the clock has started now. We're going to be following those 30 patients that will most likely, we believe, set the timeline to having the data we would need to file.

So can you discuss the timeline more specifically and whether the BEACON trial could support a BLA filing?

So we believe it could. Of course, lots of confirmation still needed over time. But we are certainly planning in that direction, and I think all of our regulatory interactions to date have been supportive of that idea. And so that would mean that once this sort of 30-patient cohort had gotten out to 15 months, we're in the latter part of 2026 now. You would then have all the final data you would need to start writing the BLA and think about getting it on file.

How do you see BEAM-101 ultimately competing with the approved sickle cell disease treatments?

It's a great question. And again, the approved treatments are -- have been transformative for the field and are true breakthroughs for patients. We think BEAM-101 can provide meaningful additional options for patients and a best-in-class profile. So what we bring to the table are potential improvements in manufacturing. We've worked very hard on that. We have a low number of cycles of mobilization. That's the way in which the cells are collected. And so the fewer cycles you go through, the shorter the time between beginning the process to get into your dose. We have, so far, rapid time to engraftment. That means that when you go into the transplant to get your edited cells, how long does it take you for the new blood to turn on and to start creating immune cells so that you're not vulnerable to infection, creating platelets, you're not vulnerable to bleeding. And so far, we've seen a very rapid onset of drugs. We hypothesize it may be linked to the gentleness of base editing and the lack of gene toxic stress because our edit is so gentle leaving the cells in a really viable state ready to engraft. And finally, of course, the hematology side, we have the strong 60-40 ratio, the resolution of anemia, et cetera. So we think it's a great option for patients that were eager to see -- reach them. And that said, there's obviously going to be a strong role for the other programs in the field. This is one where I think the industry as a whole is going to need to build up supply and I don't think we will struggle to gain share with the profile that I've just mentioned, but still more to come.

Great. And then just now shifting to ESCAPE. Can you introduce the concept behind BEAM-103 and BEAM-104?

Yes. So with sickle, maybe I'll step back. So everything I just described with BEAM-101 and CASGEVY and LYFGENIA are treating what we consider to be the most severe patients. And in our minds, that's about 10% of the population, where there's -- disease is severe enough where they are going to seek a transplant with chemotherapy because it's the chemotherapy that allows you to get rid of the old blood cells and so that your new edited cells can engraft and take hold. And that's about 10,000 patients in the U.S. So it's a big market that is ready now for treatment. Our ambition is to go beyond that. We would like to treat all 100,000 patients with sickle cell disease in the U.S., not to mention the millions globally who have this disorder. But to do that, we have to get rid of the chemotherapy. And so we have two basic ideas to do that. So one is to create another ex-vivo version, which is just like BEAM-101, but instead of using chemotherapy, we're going to use an antibody much more precisely to get rid of the old stem cells, replace them with the new ones. But to do that, we have to make it so that our new edited cells don't get hurt by the antibody, right? And so we have a technology called ESCAPE, which does this. And so with ESCAPE, what we do is we add a second edit to the cell. So one edit is fixing the sickle cell disease. The second edit renders it invisible to that antibody. And all you're changing is a single letter back to base editing, single amino acid, which changes the epitope, the place where that antibody would bind on your edit itself. So now it can no longer bind there. And so now can independently have the graft growing within the body and the antibody suppressing old cells. So BEAM-103 is the antibody, BEAM-104 is the cell product. So that is moving forward. So BEAM-103 is going to be starting a normal healthy volunteer study just to get the sort of PK/PD parameters on that antibody that will start this year. And that would put us in a position for a filing for a patient IND potentially next year. In addition to that, we have what we call a Wave 3, which we'll be looking at putting all of that in-vivo. So we would like to just -- now we're using our lipid nanoparticle technology from the liver side of our company to see, can we do an infusion, get to the marrow and do the editing there. And we do see real traction on that and promise on that wave as well. So I think very exciting times to come. I'm quite hopeful. And the bottom line is we're not going to rest until we find a way to get this kind of curative technology to everyone who can potentially benefit from it, well beyond the initial severe population.

And so if ESCAPE is successful, do you envision it would eventually replace BEAM-101 or are these programs complementary?

It's a great question. We don't know. So I think at the very first level, it expands the market for curative therapy because the other 90% of patients will get no gene therapy, right? And so they're just waiting. And so I think it will certainly expand the market. The beauty of ESCAPE is in theory because you're selecting and you're driving away all the old cells, hopefully, as much as possible, you should be able to reach a very high level of efficacy. And if we do, then I think ultimately, it would cannibalize BEAM-101. If we fall short of that, if we're sort of in the middle on efficacy, or if like an in-vivo set of programs as possible, but reaches only mixed chimerism, that would be therapeutically meaningful for the other 90% of patients. But the very severe patients might still really need that 90% plus cure. And so I think whether it would fully cannibalize or they would live alongside really depends on the efficacy level we achieve for these next-generation programs. With ESCAPE, our ambition is to get to full BEAM-101 like efficacy.

Right. So before we move on to BEAM-302, are there any questions in the audience in the sickle cell program?

Yes. Can you talk about the cost of these therapies and for example, it is the new technology, is it more expensive, less expensive? And then sort of related to that to approvals and that kind of thing.

Yes. So cost is important subject in gene editing, obviously. So the currently marketed therapies are in the $2 million to $3 million range which is high, but it is a really clear value story for the healthcare system. So these are patients who are constantly sick. They're constantly in the hospital. They have certainly lost productive years of their lives and they're on chronic therapies, which are often expensive. So you put all that together and the lifetime cost of a sickle cell patient, who is severe, is in the many millions of dollars, okay? So ICER is the U.S. cost-effectiveness research body, and they already came out with a report saying that a price of $2.1 million was justified based on those lifetime costs. More recently, actually, Dr. Oz, the Head of CMS, was out making statements about this exact point and made the point again that, yes, these are high prices, but they're worth paying because we're getting patients to a healthy state, and they're no longer going to spend $5 million or $10 million over their lifetime on medical care, okay? So that's important. So there is actually really broad alignment across the government, across payors to organize around these kinds of payment models, but it's because we're not going to do this for life. We're going to do this once and then you're going to be healthy. So like that's the trick. It has to be a good bargain for society and for the families as well. And we think clearly that this is. So I think there's a lot of tailwinds actually for this pricing model, at least for the severe genetic diseases.

What is the potential for reducing costs? I imagine it is not really [indiscernible] to comment on scale, but maybe you can talk to that.

Yes. No, the costs will go down over time. The cost of goods on an ex-vivo therapy are high, but not nearly $2 million, so there's a perfectly reasonable business case here. The percentage cost of goods is actually pretty normal for a biologic. And over time, we've seen this in the CAR-T therapies that can go down because as you get up to scale, you do this more and more regularly, you can continue to drive that down. And then as we move into things like in-vivo therapies, those are even more scalable, of course. And I would also acknowledge, I think, the business I just described of a high-priced therapy, ex-vivo in hospital settings, that will primarily be a business in the U.S., in Europe, Middle East, it's for the developed world. I think the other kind of point is that as we get to more and more scalable technologies like in-vivo, that will be required to go global and reach everyone with these diseases.

In-vivo, just in general.

Yes, it's a lot less because you're making 1 batch and then you have vials, right? So it's not 0. It's still complicated technology. But at some level, our in-vivo therapies are the same technology as is in the mRNA vaccines, right? So it's actually pretty scalable to a very high degree. Of course, we give a higher dose, and so that does drive differences.

Do you expect the [indiscernible] where you see that going [indiscernible]?

Yes. So I think, again, I think the general biologics margins are achievable. So are you in the 20%, 25%, 30% range for a while. I think that's a reasonable place to be. Because again, I think it has to be a sustainable business, right? So we need to be able to treat these patients and move on and treat more patients. It has to have value for society, right, where we're going to be helping the system save money over time by helping cure these patients and the technology has to be scalable enough to reach the patients who need it. Those are the constraints that I've seen.

So I did want to get on to BEAM-302 with some of the time we have left. So maybe you can walk us through the mechanism, mutation you're targeting, what makes this a dual action therapy? And then maybe you can talk us through some of the initial data that's been generated and why it's so promising?

Absolutely. So BEAM-302, as I said, is correcting the single point mutation in alpha-1. It is a dual action therapy because what we're doing is we're treating the disease at its root cause, right? So we fixed the single letter that's wrong in the organ that makes this protein for the body. That's the liver. And so you have two toxicities of this disease. One is it creates a mutant form of the protein that builds up in the liver and causes liver failure. And because of that, it's not secreting, you have low level systemically and the protein is less functional, so you're not getting protected. Your lungs are actually vulnerable when you're infected to degradation and you get this emphysema, lung failure. So simply by editing the gene and fixing that 1 letter misspelling, we simultaneously stop making mutant protein that will hurt your liver and start making normal protein that will secrete, raise your blood levels and will protect your lungs and stabilize your lungs. So it is a dual mode of action. It's also, of course, going to be normally regulated, which means it will turn on and off in the body the way that it normally would because we fixed it in its normal location in the genome. So we've already shown at our third dose cohort of our trial, we showed this in March. At 60 milligrams, we got patients into the double digits for their total alpha-1 levels. They generally live in the maybe 4 to 6 range for alpha 1. It's all Z, the mutant protein. And we got patients up to 12.5. Anyone in the 10 to 20 range looks like a carrier, so similar to the sickle story, that's a person who should not progress and should be safe for the long term. And of that 12.5, 90% of it was the normal protein as opposed to the Z toxic protein. So that's a really major transformation of the profile and the normalization of the AT physiology that we think looks like a curative therapy. We're now in, what I consider, late-stage dose escalation, sort of trying to optimize the dosing schedule and make sure we have all that correct, get the right balance of safety and efficacy before we think about moving forward to hopefully registration.

So program received RMAT designation. I'm wondering if you can talk us through the regulatory strategy and what your conversations with FDA will look like from here?

Yes. So RMAT is the breakthrough therapy designation for gene therapies. We've received one for sickle cell BEAM-101 and one for BEAM-302. And the FDA looks at the data before they give you that. So you can interpret from that, that they're at least enthusiastic enough about the data to talk to us more because that allows us to have more frequent interactions with them. And generally, I think the goal here is with them to identify what that path to market is. There's a variety of options ahead for us. I think we have been pretty open that all things equal when you are a precision medicine like this, you know who you're treating, you're right on the fundamental disease mechanism and you have the kind of dramatic results we've already seen early in Phase I. Generally, as a drug developer, I think that sets itself up well for something that is more accelerated. And there's different flavors of how to do that. And that's certainly what we'd like to explore. Of course, also over the longer term, generating the kinds of longer functional outcomes that, of course, are interesting to regulators as well. So that's the zone where we're working. I think we'll be working with the regulators frequently over the near future. We hope in early '26 to be able to give both a next data update, but also potentially give some insight into where we've gotten with the regulators on the path to market. But I'm pretty bullish about finding a path to patients for this pretty exciting drug.

Great. And then maybe just briefly on BEAM-301 for the audience, if you could introduce this program and just sort of what's the status of this program?

Yes. So BEAM-301 is another liver program. So back to where I started. Once we've done it once, it should be easier and easier to do it again and again. This is the same LNP, the same kind of editing, just a different targeting element to take us to a different part of the genome where these patients have another single letter misspelling that we can try to correct. And in this case, patients can't fast. They can't turn glycogen back into glucose from their livers, including when they sleep. And so they're constantly going hypoglycemic and that can literally be fatal. So it's a terrifying situation at kind of constantly eat cornstarch every few hours to survive and we would like to normalize that and cure them. So this is a much more orphan disease than alpha-1. Alpha-1 has about 100,000 patients. Here, there's hundreds in the U.S. with a single mutation, but we're testing it, and we hope to see something dramatic there. This, again, would set up for then future liver programs. And we have a pipeline coming of other liver diseases that we think would be curable with the same approach, always using LNP delivered to the liver and base editing. So again, once you get the variables out, you're starting to do the same thing again and again, we think we can move faster and faster and treat hopefully, a large number of people with some severe disease.

And just as a final question, what should investors be watching most closely for the remainder of 2025?

Yes, great question. I think for the remainder of '25, we have, obviously, our ASH update, so we'll get another look at BEAM-101 in sickle. I think the -- just operational progress across the board continue to move forward on 302, we're quite excited about. And then sort of where I landed at the end, I think maybe not this year, but hopefully, sometime in '26, we can give a little bit of insight into some of the other things we're working on and where this platform is going to take us because we do see a really dramatic potential to impact a lot of people.

Terrific. Well, thank you so much, John, for joining us. Thanks to Beam. Thanks for everyone. It's great to see you at the conference.