Good morning, guys. Let's get started. Thanks for coming and joining the conversation with Allan, the Chief Executive Officer of Prime Medicine. My name is Arthur He, a Senior Biotech Analyst at H.C. Wainwright. Allan, welcome. Thank you, Arthur. Thank you for having us here. First of all, for the investors who are new to the story, could you give us a quick overview about Prime and especially, explain a little bit what Prime Editing can compare to the CRISPR and the base editing. What you guys have is special? Well, Prime Editing is a gene-editing technology that was founded out of David Liu's lab. This is a groundbreaking technology that really you can think about it as the most versatile and the safest way to edit the genome. To answer the second part of your question in terms of looking at other gene-editing technologies, we think there's obviously incredible advancements. 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. 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. If you're looking to knock out a gene or knock something out, it's very, very effective at that. 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, once 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. 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 four changes. It can change one base pair to another, and it can do that very effectively. Instead of a, uses more of a nickase, 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 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 base 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 repeat expansion, excise repeat expansions. And we can do large gene inserts that are very specific, with something we call a landing pad with our PASSIGE technology. So, it's incredibly versatile. It's incredibly safe, we think, compared to other approaches as well. 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. I recall you guys always kind of emphasize how the liver LNP platform can be universal. Your leading program with Wilson and Alpha-1, 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 leveragability as we go from program to program, and I'll give you a few different examples here. 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 R778L. We've got feedback from the FDA, we can do multiple mutations in the same IND. That's an incredible amount of leveraging we can do from one to the other. 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. It's sort of minimal changes that we don't think have any impact on safety or anything else. You might have to do a kind of small, off-target package for each editor, right? But that's a minimal amount of work. You'll probably want some 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 could be very cost-effective and very fast to go into additional indication. It really is a flywheel that we think is going to 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 new. It's the same LNP that we're using. At times, not always, it could be the same mRNA. Again, it's really just the guides that you're changing and that fill finish that you're doing at the end with the new guides that is going to be different. Awesome. Let's stick a little bit on the Wilson disease. Now you had the CTA and the IND in hand. What's the gating factor between the start of getting initiated and the first patient dosed for Wilson? Yeah, I think as you've seen with gene editing, a lot of gene editing programs or many programs other than gene editing, it's usually two, 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. 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. Yeah, I think everything is going according to plan. We hope to enroll the first patient in the not too distant future. For the study-wise, you guys highlight the copper PET as a kind of functional readout for the program, plus additional multiple other biomarkers. From that point of view, I guess which one you think is more critical to translate the clinical factor for the drug? Yeah. Well, if we think about radio-labeled copper PET that we'll be doing in this study, let me explain a little bit about what that is. We take patients, they'll be on standard of care when they come into the trial, which are typically your copper chelators, treatment, et cetera, or zinc salts. We'll take them off those therapies. Those wash out in a few days. We'll challenge them with radio-labeled copper. They'll get a radio-labeled copper infusion, and then they'll get a full body PET scan following that infusion. 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 will 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 are 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. If you are looking at the gallbladder in a Wilson disease patient, you are not going to see copper mobilized to the gallbladder because it is all really going to the blood. It is not going to the feces. If you are actually seeing that improvement in copper metabolism, and we have done our work in correcting that enzyme, you are 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. We think that could be a really good, important measure. We will be doing this in patients before they get dosed, so we will have a baseline read. Then we will be doing this about six to eight weeks post-dose as well. We think this could also be one of the tools we use to assess whether patients can come off standard of care. Because if we can show via the radio-labeled 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 is great. I think you also touched a little bit earlier, for the same exact R&D, you can do multiple mutations, right? Can you elaborate what exactly for the Wilson disease, for the predominant Asia mutation, what exactly you need to do to satisfy the requirement from the FDA? Yeah. For R778L, we already have a very potent editor in hand. We are getting very high rates of editing efficiency, very similar to what we are getting with our first program, with the H1069Q program. For the FDA, as I said before, we would likely do a bridged or some off-target package, right? Same thing for all these editors, you want to show that you have a good off-target profile, which thankfully for Prime Editing, that is one of the advantages. We have very minimal, if any, off-target for these editors. Then it is really a function of 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. Awesome. Let us switch gear to the other two program, actually. Now the arbitration is behind you, and congrats. Thank you. For the, can you tell us a little bit more how the Alpha-1 program evolved right now? Also, I guess, giving the competitive landscape for the Alpha-1, what Prime Editing can be differentiated based from the technology-wise can translate to the clinical-wise? Yeah. So where we are right now, 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, it's obviously for Wilson disease, 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 competition, there's 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, there are RNA editing companies, other 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, our 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 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 for the CGD program, I know you guys still interacting with the FDA regarding the BLA filing, which targeted for the first half of next year. Could you give us a little bit background, like how that conversation evolved and what exactly you need to prepare or get ready before the filing? Yeah. I am not going to go into full detail in terms of exactly what the FDA has asked for. What I can say is the FDA is definitely offering some flexibilities here, to allow us to try and get this program to these patients in need. For one, it is a very small number of patients that we are going to be filing with, right? We could file and get approval just based off of two patients. We are 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, and 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. It has made it, for us at least, a much more cost-effective way to get this drug there. There are some additional flexibilities, I would say, where they have helped us with some of that upfront cost, and some of those costs could come after the BLA. We think we are 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 are just really excited to get this drug to patients as I know there are a couple stories online from the two patients that we treated, and it really is just an incredible benefit and you are changing people's lives, and that is a great thing to be a part of. Sure. Getting to my favorite part. Could you remind us, what is the cadence of your catalyst in the next 12 months? Sure. I think, obviously, we are talking about an Alpha-1 filing sometime this quarter. We have got FPIs for Wilson disease and ultimately at some point for Alpha-1. I think what is 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. As always, there are conversations ongoing for additional business development. Some that is sort of platform related, then some that is product related. Nothing that we can promise tomorrow, but I think we would love to see more partnerships as we think about really broadening how much we can do with this technology given the opportunity set. Great. Last question. Could you tell us your current cash position and, more importantly, what else is not including, like, those non-dilutive levers you guys have in hand? Yeah. Our last report, I think, was just under $110 million. That is, as we think about runway, getting into somewhere into 2027. That does not include anything you would get in terms of potential PRV. It does not include any milestones, BMS milestones. Obviously, it does not include additional BD. Stay tuned. There are definitely ways that we will make sure we are very funded with those things and others as we think about really verging to data, but ultimately well beyond that data, those data sets. Awesome. Thanks, Allan, for coming in. All right. Thank you. Appreciate it.