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

Thank you. Good morning, everyone. My name is Gena Wang. I'm [indiscernible] biotech analyst at the Barclays. Welcome to our seventh gene editing, gene therapy summit. It is really great to have this happened again. I wanted to take this opportunity to thank all the investors companies, and also especially our event team and the corporate access team who made this event possible. With that, I would like to introduce our next presenting company, Beam Therapeutics. With us today, we have John Evans, Chief Executive Officer. John, thank you very much for giving us this opportunity.

Thank you for having me.

Yes. So maybe before we dive into the specific questions, do you want to give a quick overview.

Sure. Yes. So Beam Therapeutics is a next-generation gene editing company. So we're working on a new form of CRISPR called base editing, which we think improves on what is possible. It uses CRISPR to target within the genome, but not to edit. The edit is then made by a second component called the deaminase, which basically does a very precise chemical modification of the DNA to alter 1 letter to another at a very programmable spot, which gives us incredibly flexible and versatile tool to make very precise, very high efficiency changes within the genome, doing everything from silencing genes, to turning them on, to modifying their function, to correcting them if there's a spelling error in them. And we have taken a very broad strategy to exploit this technology and bring it to patients wherever we can, looking at delivering it outside of the body in blood cells and T cells, delivering it into the body using with lipid nanoparticles or viral vectors and building a real integrated stack of capabilities from the editing, to the delivery, to even manufacturing, a facility that we're building internally to try to have all under 1 roof, all the things we need to make a really compelling set of medicines that could be potentially onetime cures for patients suffering from serious diseases.

That's great. So maybe we'll start with your lead indication BEAM-101 in sickle cell disease. I know the first patient enrolled in November '22, and recently was [drawn] due to nonmedical reasons. Can you elaborate a little bit on how that will impact your data updated timing?

Yes. So this is patient #1. So yes, unfortunately, in Patient #1 had to withdraw. It was truly idiosyncratic. There was basically just a very dramatic life change for this person that made it impossible for them to continue. So the investigator then withdrew them. It wasn't like if we waited a month, they could have come back in. It was bigger than that. As you noted, it was not related to the drug. We haven't treated them yet. It wasn't related to the procedures we were doing. It wasn't even that they had changed their minds about seeking therapy or gene editing or anything like that. It was truly on the personal side. So we wouldn't expect this to happen again. It was a kind of one-off, but unfortunate. We had been through several rounds of mobilization with the patients, we actually have cells. So there will be a conversation about could we ever treat this patient in the future? If they could come back, we'd like to, they obviously went through a long journey with us, but not right now. So in terms of the impact, the -- we had already enrolled 2 more patients. So they were, of course, going to be Patients 2 and 3. Now 1 of them will have to serve as Patient 1. So the first dose will come later than it would have. And I think that's the impact. The good news is that we had been working since the fall on really accelerating and broadening the BEAM-101 program, basically taking advantage of the fact that it looks like vertex is sort of showing that there is a path to market with 1 trial, as we would have hoped, and we can design, and we have a designed Beacon really to achieve that. So we're powering this not just for the [indiscernible], but really for the full expansion. So since then, we've been really building this out. So we have already 5 sites open. I think we'll have double-digit types of sites by the end of the year opening. We have patients now in view and looking to get into the trial. And we can do a lot of things in parallel, right? And so we can literally enroll multiple patients. We can think about the screening, the transfusions, the mobilizations, just getting all of that done in parallel. And the bottom line is, I think if we can do this right, we can make up the times that we really aren't much later, if at all, into the expansion phase. And certainly, the final BLA filing doesn't have to be much later either. So that's our current assessment. Obviously, the first dose will come later, but through going in parallel on multiple patients, I think we can we can keep the time lines in. And so we've sort of said, continue to think we will fully enroll [indiscernible] this year. We will add more patients this year who will then contribute to the expansion phase, and we will be able to have data in '24 on multiple patients. So that's been our guidance, and we're able to reiterate that.

Okay. That's good. So you mentioned that you wanted to -- and especially we have a President of say, Vertex CRISPRs program, see how they quickly evolving into the pivotal program. So 1 key data point is, 1 is the number of patients, why 45-ish, and the other is the primary end point. So when I look at -- I think last night, I look at [indiscernible], the primary endpoints did not change. Like do you need to change your primary endpoint in order to VOE events and then like the CR rate in order to be aligned with approvable endpoint with the agency? And maybe have you discussed with the agency? And do you plan to do that at some point?

Yes. So we absolutely would discuss it with the agency. So what we have done so far with the BEACON trial is we've put in everything we can think of based on what we've seen outside in of what others are doing in terms of both number of patients. Clearly, it's about a total end, maybe we've guessed 45. Within that, there's clearly a kind of a benchmark analysis of a certain number of patients who have gone for a certain amount of time follow-up. We've estimated it's anywhere in the 20% to 25% range for 12 to 15 months it's just a ballpark. And then obviously, the choice of endpoint itself, building around [indiscernible] prices reduction. There are nuances around that, which we would potentially be able to update. And the good news is we'll basically get a beautiful view into that by the end of the year in terms of the Vertex FDA interaction for approval, potentially bluebird as well. So we will be able to basically take that information and incorporate into the trial and make any tweaks we need to. Also, of course, as you say, we will talk to the FDA as well at some point and get their final input. But I think we will -- it will be pretty close to what this looks like. I think that those sorts of tweaks don't slow down the trial in any way. We'll just sort of make those modifications. And then we continue to be fairly confident that it should then, me be true, that we have a rapid path to the first filing based on BEACON as the data set.

And you mentioned also bluebird, and we -- now I can think of like bluebird CRISPR, and we have Editas also already modified all these endpoints and moving also very quickly. So it is a very competitive space. So any thoughts like how would you differentiate? and how every program, when they present is that ours will be the best. So like how would you differentiate especially giving, say, maybe third or fourth to the market like how do you differentiate and take some market share?

Yes. I mean, first of all, just to say, I think competition is great for patients, right? It raises the bar, they will benefit. So I think there's nothing bad about that. It is a crowded space, but it's a lot less crowded than it was, right? So even in the last 6 months, we've obviously seen Sangamo, Novartis and Intellia and then Graphite drop out. So it is narrowing actually. And I think no healthy drug category has fewer than 3 or 4 entrants in general in it in my opinion. So we welcome the competition. I think that our base case view of the world would be that both bluebird and CRISPR will get approved, CRISPR Vertex. So they will start to build this market out. We will obviously enter several years later. Editas is definitely there in the mix, and they -- as you say, they are going fast. Again, that's kind of the optical illusion of these trials. They seem very slow to start, and then they have seem very fast later. And it's just because of how it sort of gradually builds up. So we expect the Editas sort of pattern to play out with us as well. I think, obviously, in the case of Editas, you have another nuclease relative to the Vertex program, you have a different target, which is the HGB locus, which is also what we're targeting, but they're using a cutter for that. So far, the clinical data looks fairly comparable to the Vertex program, but we'll have to see more follow-up more data there. I think in our case, obviously, we do believe we are bringing a best-in-class editor forward that will have clear differentiation. So we have -- very clearly in the preclinical models, we have higher levels of editing than these players. We're up above 90%. We have higher levels of F, which is the up regulation we're aiming for over 60%. We have, therefore, lower levels of sickle protein down to 40% or lower. So we're just having effectively a deeper cure than what others may be able to offer. We then would look for, obviously, not vaso-occlusive crises, everybody is sort of fully getting rid of those, which is good news. But for differentiation, we would look to things like hemolysis, blood markers, markers of inflammation, then things like pain, stroke, organ damage or sort of some of the longer-term ideas where we would expect that a better editing product will have some of these visible clinical markers. And as a reminder, patients aren't dying of vaso-occlusive crisis, they're dying of all these other things accumulating over time. So we do think that deeper cure is going to be important here. And then, of course, there's an entire next stage of the story for us, which is our next-generation versions where we're going to bring forward better conditioning, which uniquely builds on base editing's ability to do precise modifications to do the ESCAPE technology, which lets us use an antibody conditioning agent to selectively get rid of old cells, but leave alone new cells. We think that is another potential game changer where really base editing has a unique advantage. And then we may be able to put all of that in vivo delivering the initial edit using a lipid nanoparticle, but then, again, maybe using the antibody in combination with it to select for those cells. And so we see this as really a 3-wave life cycle strategy and BEAM-101 is just the beginning of it.

Okay. Very good. I'm pretty sure you've also done [cancer for] marketing as well. And when we talk to some doctors, and it seems like patient willingness to take this new drug class is a little bit hesitant. So like how do you see this -- and we know that the total population actually is very big. But the patient willingness and even also the doctor as well, like maybe lack of understanding, like how do you see this will evolve over time?

No, I think that's exactly accurate. I mean, so if you think about it, the cure is great. Everybody wants to get the permanent change in their genes, and they're very excited about that. The challenge is the transplant and the use of chemo. And I think everyone is very clear about that. So busulfan is the chemo we all will use. And it is chemo, right? So it's the standard of care in transplant. It's a great trade if you have a very severe disease and you are very motivated to get rid of that disease. But a lot of patients with sickle are maybe more moderate, and they can survive for longer without needing to feel like they need to do that. So that's where the hesitance will come in. So I think we've always sort of said that this wave 1 with busulfan is a minority of the market, but it's not 0. There are a lot of patients who are desperate to get out of their disease and for whom that chemo transplant process is very exciting. And they are lined up for our trials and they're lined up for therapy. So the real question that we will all answer over the next several years is exactly how many of those people are there and what size is that market? I would just note that the pricing, looks like it is lining up to be anywhere in the $2 million to $3 million range based on even ICER, let alone competitor dynamics. And it doesn't take that many patients a year to potentially contribute to a potentially a multibillion year market of even this sort of first-gen chemo. And I think we do anticipate something like that playing out. Now I think, for the commercial launch, I would say we're cautious. I don't know that it will be an S curve launch, I think it will be more steadily grown as Vertex and Bluebird and others sort of start to establish the footprint of sites who are capable of doing this through referral networks, much like the autologous CAR-T field has evolved. But over time, we do expect it to grow and then be a kind of sustainable model. Nonetheless, there are 100,000 patients with sickle in the U.S. So clearly, despite everything I just said, there's going to be a lot of patients left to still treat, and that's what we are aiming for with our Wave 2, Wave 3 products.

Okay. Actually, going back to your -- say, we've won the current conditioning regimen, the pivotal registration trial readiness. How is the preparation regarding the manufacturing part, regarding CMC and then also, say, aligned with the FDA potency assay, the lease assay?

Yes. Yes. So 1 of the other things we said in the fall as we -- this commitment to bring 101 forward. We're basically doing all of the registration-enabling work now. [Some] as middle of development, you sort of say, "Oh, I'm going to go for it and now I have all this work to do to finalize the commercial process, get those assays done," and then you have to have a certain number of patients who are on those final assay forms before you can file and so it creates a delay. So we're going to try to avoid that. So we're doing all that work now. So yes, all the assays are in process that we need. And then manufacturing, we're currently using an external manufacturing facility, but we have built North Carolina up, and we do anticipate moving to that by the end of the year as a GMP-ready operation to do the sort of cell processing and manufacturing. And in the process, we're going to kind of lock down those final validation forms of our process so that -- which would be kind of commercial grade. And the beautiful thing about that strategy is basically North Carolina is also a potential launch facility. I mean we can basically start manufacturing and now do much of the expansion cohort out of North Carolina. And then basically the exact same process would be what we would launch with. So there would be no comparability questions or bridging processes you need with the FDA. And I think, again, that is all designed to make the BLA stage of this program as smooth as possible.

So for North Carolina site, like how many patients or percentage of, say, 45 patients, how many patients do you think you need to treat in order to be able to clear with the FDA?