Prime Medicine, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Thank you for having us here.

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 4 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.

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.

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 2-3 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.