Conference Transcript - PRME 2026-09-15

Arthur Herr, Analyst — H.C. Wainwright

Good morning, guys. Let's get started. Thanks for coming and joining a conversation with Alan, the CEO of Prime Medicine. My name is Arthur Herr, a senior biotech analyst at H.C. Wainwright. So, Alan, welcome. Thank you, Arthur. Thank you for having us here. So, I guess, first of all, for the investors who are new to the story, Could you give us a quick overview about Prime and especially like explain a little bit like what Prime editing can compare to the CRISPR and the base editing? What do you guys, the specials?

Alan Ryan, CEO

Yeah, well, yeah. So Prime is a gene editing, Prime editing is a gene editing technology that was founded out of David Liu's lab. So this is a groundbreaking technology that really, you can think about it as the most versatile and the safest way to edit the genome. So to answer the second part of your question in terms of looking at other gene editing technologies, we think there are obviously incredible advancements, right? Nuclease CRISPR-based technology was Nobel-winning technology at this point. But what that technology is really, really good at is that sort of search function as you think about getting to very precise places in the DNA that you want to make a change. And it uses a nuclease and with a double-stranded break is very, very effective at finding the very specific point in your genome, making that double-stranded break. So if you're looking to knock out a gene or knock something out, it's very, very effective at that. But as a result of double-stranded breaks, you can get different potential kind of off-target issues. You can get translocations, chromosomal rearrangements. Ultimately, when you're doing that type of editing, you're going to get a lot of indels or other stuff that gets kind of added where you make the edit. But we've seen it be very effective at knocking out for different targets. And there's some drugs that now one's approved, and we've seen a number that are getting to registrational studies. and more will be approved soon. With base editing, also out of David Liu's lab, for the first time he added an additional enzyme to the mix, so now he's added a deaminase, and where for the first time, instead of just knocking something out, you can actually change the genome. It's limited to kind of changing, it's limited to four changes. It can change one base pair to another, and it can do that very effectively. instead of a, it uses more of a Nikke, similar to prime editing, where it's a single-strand break, which is a lot more gentler and doesn't lead to the same rate as these other issues you see with a double-stranded break. It does cause, at times, something called bystander editing, so it can lead to not just wild-type protein or what you're trying to accomplish, but it can edit edit some of the other base pairs that are sort of adjacent to the one you're trying to correct, which is a liability in some of their programs. And then with prime editing, we use a different enzyme, it's called the reverse transcriptase, and we use the RNA templates, the same guide that's looking kind of search and find the exact point in the genome that you want to edit. We could actually put a template on there that now gets written directly into your genetic code. So we can do everything that nuclease-based editing can do, everything that base editing can do, but really so much more. We can fix transition mutations, transversion mutations, so any type of missense mutation, frame shifts. We could do what we call hotspot editing, which is kind of larger edits that cover multiple mutations. We could edit exercise repeat expansions. you know it's it's and we can do large gene inserts that are very specific with something we call landing pad with our passage technology so it's incredibly versatile it's incredibly safe we think compared to other approaches as well and really excited that we have treated a couple patients with our lead program in cgd and about to treat additional patients with our in vivo programs awesome so i i recall you guys always uh kind of emphasize how the liver lmp platform can be universal um so you you're leading program with the western and alpha one could you give us a little bit of color like what can be carried through between these two programs yeah i think there's an incredible amount of leverageability as we go from program to program, and I'll give you a few different examples here. So one, as we go to different mutations within one program, so let's take Wilson disease. The first mutation that we're going into is something called H1069Q. The second mutation that we're going to be going into is our 778L. And we can do, we've got feedback from the FDA, we can do multiple mutations in the same IND. So that's an incredible amount of leveraging we can do from one to the other. And that enables us to leverage the majority of the IND enabling studies, including tox, biodistribution, et cetera. Because really you've got your LNP drug product that's going into the patient that's composed of the RNA guides. We have the mRNA that codes for the editing enzymes. But all you're really changing is the guide, right, or the guides. So sort of minimal changes that we don't think have any impact on safety or anything else. So you might have to do a kind of small off-target package for each editor, right? But that's, you know, a minimal amount of work. You'll probably want some in vitro, in vivo proof of concept work. But it really is a minimal package we expect to go from one mutation to the next. But then as we go from disease to disease, for alpha-1 being our second program we're going to the clinic with after Wilson, we were able to leverage a lot of the studies from Wilson for alpha-1. As we go to additional liver indications, we expect to leverage even more as we go from disease to disease, where ultimately, once we have true proof of concept in the clinic of our LNP, we think it can be very cost effective and very fast to go into additional indication. It really is a flywheel that we think is gonna create a tremendous amount of value as we look to additional indications. Beyond the IND enabling work, there's also a lot of manufacturing synergies because we're using, again, it's the same LNP. We don't have to do kind of, you know, it's the same LNP that we're using. At times, not always, it could be the same mRNA. So again, it's really just the guides that you're changing that fill finish that you're doing at the end with the new guides, that is going to be different.

Arthur Herr, Analyst — H.C. Wainwright

Awesome. So let's stick a little bit on the Wilson disease. So now you had the CD and the IND in hand. So what's the gating factor between the start of getting initiated and the first patient dosed for Wilson?

Alan Ryan, CEO

Yeah, I mean, I think as you've seen with gene editing, a lot of gene editing programs or, you know, many programs other than gene editing, it's usually two to three months as you go from acceptance to ultimately getting the first patient enrolled. It might be a little different when you're thinking about a one-and-done therapy. But like anything, it's getting sites up and running, getting through all the IRB approvals. Depending on geography, different things might be needed. Some geographies go faster, some geographies go slower. The reason we like New Zealand and the U.S. is they tend to be geographies that can go a little bit quicker versus some of the European countries. So yeah, we are, I think everything is going according to plan and we hope to enroll a first patient in the not too distant future.

Arthur Herr, Analyst — H.C. Wainwright

So and for the study wise, so you guys highlight the the copper PET as a kind of functional readout from the program, plus additional multiple other biomarkers. So for that point of view, I guess, which one do you think is more critical to translate the clinical factor for the drug?

Alan Ryan, CEO

Yeah, well, if we think about radiolabeled copper PET that we'll be doing in this study. So let me explain a little bit about what that is. So what we do is we take patients, they'll be on standard of care when they come into the trial, which are typically your copper chelators, treatinine, et cetera, or zinc salts. So we'll take them off those therapies, those wash out in like a few days. We'll give them, challenge them with radio-labeled copper. We'll get a radio-labeled copper infusion, and then they'll get a full-body PET scan following that infusion. And what you'd expect to see in a Wilson disease patient is the liver really lighting up with copper. Because that copper is unable to be metabolized. It's all going to essentially stay in the liver when you do that measurement. You'll see it, and you can look at this on our website, in our investor presentation. You can see really exquisite mouse models that really demonstrate this. In a treated patient, if you're fully normalizing copper metabolism, you could see the liver essentially looks very similar to what you see in a wild-type animal with really no copper lighting up there. Another good organ to look at is you could actually just look at the gallbladder, right? So if you're looking at the gallbladder in a Wilson disease patient, you're not going to see copper mobilized to the gallbladder because it's all really going to the blood, it's not going to the feces, and if you're actually seeing that improvement in copper metabolism and we've done our work in correcting that enzyme, you're going to see a lot of that copper really being localized to that gallbladder at that time point as it gets ready to continue to go into the bile and into the feces. So we think that could be a really good, important measure. We'll be doing this in patients before they get dosed, so we'll have a baseline read. And then we'll be doing this in about six to eight weeks post-dose as well. And we think this could also be one of the tools we use to assess whether patients can come off standard care.

Arthur Herr, Analyst — H.C. Wainwright

Because if we can show via the radiolabeled copper PET scan that they have improved copper metabolism that could be one of the triggers to say we think these patients can come off standard of care oh that's great uh and uh i think you also touched a little bit earlier like for the same exact r d you can do multiple mutations right um so can you uh elaborate like what exactly for like for another for the well-synthesize for the like a predominant asia mutation what exactly you need to do to satisfy the requirement for the fda yes so for r778l we already have a very potent

Alan Ryan, CEO

editor in hand we're getting very high rates of editing efficiency very similar to what we're getting uh with our first program with our with the 1069q program um so for the fda as i said before we we'd likely do a abridged or awesome off-target package right because i think for all these editors you want to show that you have um you know a good off-target profile which thankfully for prime editing that's one of the advantages we very uh have very minimal if any off target for these for these for these editors and then it's really a function of do you want to do you know is there going to be any you know kind of small non-GLP stuff required but ultimately we think it could be a pretty minimal amount of work to get this into the IND.

Arthur Herr, Analyst — H.C. Wainwright

Awesome so let's switch gear to the other uh two programs actually so now the arbitration is behind you and congrats uh so and for the um can you tell us a little bit more how the alpha one program involved right now and um also i guess giving the competitive landscape for the alpha one what prime editing can be differentiated based on the technology-wise can translate to the clinical-wise?

Alan Ryan, CEO

Yeah, so where we are right now, so we've set a regulatory filing to go into the clinic during the third quarter, which we're still in, and still planning for data then in 2027 for next year. So data for both our two first-in-vivo programs. we expect to have next year. In terms of maybe the disease space, so it's obviously for Wilson, we really can own that disease or at least the addressable market within that disease, the mutations that we can target where there's very limited computation. There's some gene therapies, a couple other things, but we really think this will be the predominant therapy. In alpha-1, it's a little more crowded. There are a number of gene editing companies or RNA editing companies and the things that are going on within that disease. We think that, and the reason we went forward with a program, knowing that there was competition within the space, is we think taking a patient back to wild-type protein under endogenous control with a permanent change has the potential to really be a best-in-class therapy so we believe our approach or prime editing approach has that potential we think it's more than just efficacy it's going to be a combination of efficacy and safety at least pre-clinically we think we have a really safe LNP where we have a fairly wide or wider at least than some of the

Arthur Herr, Analyst — H.C. Wainwright

LNPs that have gone into the clinic that we've tested against therapeutic index so we think we've got a really good product as we go into the clinic obviously it's all data dependent but if things translate we think we have the real potential to have a best-in-class therapy there awesome so and for the cgd program um i know you guys still interact with the interaction with the fda regarding the the bla fighting um and target for which targeted for the second first half of next year um so could you give us a little bit background like how that uh composition involved and what exactly you need to uh prepare or get ready before the fighting yeah so i'm not going to go into full detail in

Alan Ryan, CEO

in terms of exactly what the FDA has asked for. But what I can say is the FDA has been, has, is definitely offering some flexibilities here to allow us to try and get this program, you know, to these patients in need. For one, it's a very small number of patients that we're gonna be filing with, right? We could file and get approval just based off of two patients. We're actually going to dose one more adolescent patient, but just being able to file for approval on two patients I think is a pretty incredible thing. I think it speaks to the strength of this data and what this drug can do in these patients. And then two, I think the FDA has come a long way in terms of this across not just for us but across the industry for these types of drugs as to the manufacturing requirements that are necessary pre-approval or for a BLA to get approved. And it's made it for us at least a much more cost effective way to get this drug there. So there's some additional flexibilities I'd say where they've helped us with some of that upfront cost and some of those costs could come after the BLA. So we think we're in a really good position there. Some of those CMC activities at least where we sit today, could be what is sort of gating, what gets us to that filing timeline next year. But again, we're just really excited to get this drug to patients. I know there's a couple stories online from the two patients that we treated, and it really is just an incredible benefit, and you're changing people's lives, and that's a great thing to be a part of. Sure.

Arthur Herr, Analyst — H.C. Wainwright

So getting to my favorite part, so could you remind us like what's the cadence of your catalyst in the next 12 months?

Alan Ryan, CEO

Sure. So I think obviously we're talking about, you know, we're talking about an Alpha-1 filing sometime this quarter. We've got FPIs for Wilson disease and ultimately at some point for Alpha-1. I think what's going to be really important is data from both of those programs in 2027, ultimately getting CGD, not just filing for the BLA, but actually getting to approval. With BMS, we continue to make good progress on our ex vivo CAR T cell therapy with them, getting to eventual milestones with BMS. And then as always, you know, there's conversations ongoing for additional business development, some that's sort of platform related, some that's product related, nothing that we kind of promise tomorrow. But I think, you know, we'd love to see more partnerships as we think about really broadening how much we can do with technology given the opportunity set. great so last question uh could you tell us your kind of cash position and more importantly what else is not including like those non-dilutive levers you guys have in hand yeah so our last report i think was just under 110 million um that does you know as we think about runway uh getting into you know somewhere into 2027 that does not include you know anything you would get in terms of potential PRV, does not include any milestones, BMS milestones, obviously does not include additional BD. So, you know, stay tuned. There's definitely ways that we'll make sure we're, you know, very funded with those things and others as we think about really, you know, bridging to data, but ultimately well beyond that data, those data sets.

Arthur Herr, Analyst — H.C. Wainwright

Awesome. Thanks, thank you appreciate it