All right. Welcome back, everyone, to HC Wainwright's Global Investment Conference. My name is Matthew Caulfield. I'm a Senior Biotech Analyst here at HC Wainwright. We're very excited to have our next guest, LENZ Therapeutics, and specifically President and CEO Evert Schimmelpennink. Evert, thank you very much for joining us. It's great to have you here. Thanks for having us, Matthew. Absolutely. There's been a lot of excitement for LENZ recently with the approval of your novel presbyopia eyedrop Viz, which is based on aceclidine. For those newer to the story, maybe you could just give us a high-level view of the LENZ platform and the recent progress that you've obviously had. Absolutely. Thanks, everyone, for joining us. At LENZ Therapeutics, we've developed a presbyopia eyedrop. Presbyopia is something that, and definitely if I look at this room, many people will be familiar with. It's the aging of your lens. It happens to all of us. Come 45 or around that age, you'll start to hold your phone further away from your face. That's because your lens hardens, so your near vision starts to become more blurry. You know the most used solution for that is reading glasses. That's up to about a month or so ago when we had our presbyopia eyedrop approved. I'm very pleased with that approval. I came in early. I'm glad to have worked with the FDA in a very collaborative manner. We're in the midst of our commercial launch now. You think of this as an eyedrop that you put in in the morning, and it restores your near vision for your full workday. For the full workday, you're back to what your vision was before presbyopia, back to what it was when you were 30, 35. Excellent. With the FDA approval of Viz, can you tell us more about your salesforce positioning and specifically plans for sampling availability as early as October and commercial product availability targeted to mid-fourth quarter of 2025? Absolutely. Indeed, like I mentioned earlier, we're obviously fully focused on the commercialization of Viz now. If we talk about our commercial strategy, you know three key pillars. First of it is doctors to recommend us. The second pillar is consumers to request us by name. The third one is making sure that we have seamless access for consumers to our product. If we double-click on those a little bit, the first one, doctors to recommend us, that's truly where the salesforce comes in. We have 88 salesforce people out in the market already. They've been out since July 1. Obviously, now that we have the label since a couple of weeks, they're really detailing on the label now, really making sure that doctors are in the first stage aware of this as a product. Driving confidence, that's where the samples come in, and samples which we will have available. We're very confident in that in October. Those samples are actually hand-delivered by our reps. Depending on the practice, they'll get samples. Think of these samples as a five-pack. Our product comes in these little low-fuel seal, single-use containers. These five packs are the samples that are then handed out to consumers so that they can try the product. We think that that's key because we know, if we look at our clinical data, that pretty much we can guarantee if you're a presbyope and you have trouble with seeing something up close, if you would drop a Viz in your eyes, you'll be able to see up close again. We had 93% of our patients in the study 20/40 or better at 30 minutes in the clinical trial on day one. That's why that sampling is so important. That's what the reps will ensure they drive. From that sampling, you drive confidence and get those doctors ready to prescribe. That's really what the salesforce is focused on. No, that's great. I'm also in the commercial category. Another key component is the position of Viz as a cash-pay product. Can you tell us more about the thinking behind this? Obviously, it's a possible therapeutic alternative to reading glasses. Absolutely. We like that a lot because it means that it's a very easy and a very clean revenue stream that we'll drive. We don't have to talk to insurance companies to get products on formulary. It's really the very first script that's going to be written. We'll hit our bottom line. We like that a lot. We get questions often from investors on, you know, you see the market in general, the pharmaceutical market moving there quite a bit. The TLP1s are obviously a prime example of this self-pay category that works well. We know it works well for an eyedrop like this because Vuity was launched by AbbVie about three years ago. Products had a very strong initial launch, showing that there's a large group of consumers waiting for an eyedrop. They got very quickly to about 150,000 patients or consumers that bought a script of Vuity. Unfortunately, Vuity didn't work. That fell off a cliff very rapidly. It very clearly showed that that market is there and that people are willing and looking to pay for something different than eyeglasses. They be highly motivated to use it if they're in that category to be pursued. Absolutely. Absolutely. Yeah. Appreciating that we're at the very earliest stages of initial commercialization, what early launch metrics do you expect to be focused on out of the gate? Yeah. Important to realize here is that the product will actually be available through two channels. Both e-pharmacy, and that's where we'll steer most of our consumers, but also retail pharmacy. We've been highlighting it, and I'll do it here again, that I'm sure everyone is going to try to very early get a read on what's the script data like. Don't look at IQVIA because IQVIA is not going to pick up the e-pharmacy side of the revenue. Therefore, they're going to be wrong. They're going to try to guess, and they'll be guessing wrong. What we'll do is over time start to share data, script data with all of you. Initially, we'll probably start focusing on what are the amount of ECPs, amount of doctors that have prescribed, amount of doctors that have prescribed more than once. Over time, we'll start to move into what's the total amount of scripts that we've sold. Importantly, what's the repeat use of patients as they're on the product? How often are they refilling those scripts? That's what we'll do. We have plenty of opportunity to keep everybody informed of those early metrics. That's very helpful. I also think key aspects of Viz's profile are that it's delivered as a once-daily topical eyedrop, and it's demonstrated efficacy to upwards of 10 hours in terms of durability. Can you discuss how this competitive profile is facilitated by acting as a pupil-selective miotic, targeting the iris with minimal ciliary muscle stimulation? Absolutely. This is a very important part of how Viz is different. You see it in all the data that it's a remarkably different profile from a product like Vuity. That is indeed because the MOA of aceclidine is different. Taking you back real briefly to what's important for a presbyopia eyedrop to truly work is to get your pupil to below 2 millimeters. There's a lot of peer-reviewed data. Frankly, you can see it in all the clinical data as well. Until you're below 2 millimeters, the product doesn't really drive a lot of near vision improvement. The aceclidine, uniquely, as you've mentioned, Matthew, is a pupil-selective miotic. It stimulates the ciliary body very minimally. That's actually something that the FDA recognized. We have that in the label, something that we're very pleased with because it very clearly shows that the aceclidine is different. Because we're so selective to the iris sphincter, we can actually develop, and we have developed, a product that gets 99% of the patients to below 2 millimeters. They actually get all of our patients almost in that therapeutic window, and we keep them there for 10 hours. That's the background. That's the MOA. That's the biomarker. What that then does, if you think about efficacy, three-line gains is what the FDA looks at. That's the FDA endpoint. At half an hour, 71% of our patients had at least a three-line gain. We saw four, five, six-line gains, and that very nicely stayed there the full 10 hours. What we've noticed now that we actually started to talk to doctors is that for them, that's all great. What they want to know is, does this product work? They use 20/40 or 20/happy, as they say, as the benchmark. If you're 20/40 or better, you can see up close without the use of reading glasses. This is where the numbers actually are extremely impressive. I think I mentioned earlier that at half an hour, 93% of our consumers, our patients in the study, hit at least 20/40 or better. At 10 hours, that's still 7 out of 10. 7 out of 10 patients actually truly have that 10-hour vision. If you compare that, you're asking about competitors, that's something that nobody comes even close to. Our 10-hour data is better than everyone's data and everyone's maximum efficacy at any given time point. It's just a completely different profile. With these products, it's important to realize that you can't market your way through this. This is a product that if you tell somebody you're going to be able to see up close for the full working day, that's something that after a day, they can judge whether that is true, yes, or no. That's what you saw with Vuity. They made that promise. 150,000 people believed in that promise, bought a product, but then were disappointed because it didn't deliver on it. That's why we feel we have a remarkably different profile. Considering Viz's achievement of the pinhole effect, inducing that sub-2-millimeter pupil without causing a myopic shift, can you further describe how the pinhole effect is conceptually similar or different from just using conventional reading glasses? Yeah, no, absolutely can. This will get a little bit technical, a little bit detailed. To keep it simple, if you use reading glasses, you're basically using them as a magnifying glass. It's not really changing how the light hits your retina, it's really magnifying. With that, you're able to see up close better. What you do with a small pinhole pupil, if you realize that, if you think through the fact that if you look at something up close, those light rays that come up from your phone, they need more reflection to actually hit your retina. What you do with a small pinhole pupil is you block the light rays that need the most reflection. The light that's coming into your eye, those light rays are more or less parallel to begin with to actually hit the back of your eye. For those in the room here that are photographers, you know this is why if you want a portrait photo, you want that nice blurry background, you use a large diaphragm. If you want a landscape photo with a lot of depth of field, you use a very small diaphragm. Same simple optic principle. Very helpful. I think we've kind of touched on this, but I think it's important to appreciate that there was a presbyopia eyedrop product that came before, namely AbbVie's Vuity product, which was based on pilocarpine. What were some of the limitations that arose from that product in your view? How has Viz and the aceclidine MOA been able to address those related issues? Fair question. You know, we really like to talk about our product more because the product works. It is a fair question and something that people obviously look at because the question was when Vuity launched, why did they fail? We've obviously looked at that a lot. I touched on some of it early on. Vuity failed if you sort of parade that out. First and foremost, the product only had about a 25% efficacy in the population, and that population was mostly emmetropes, actually, mostly people that had good distance vision. The first challenge that it had, it worked only in one in four patients. It was rolled out initially with samples, but then very quickly, the samples were withdrawn. One in four patients, or three in four patients, walked away disappointed, bought a bottle, and realized it doesn't really do anything. That was the first one. The second one was if you were in one of those four patients that actually did notice an effect, and I was frankly one of them, it only worked for about two, two and a half hours. It didn't hit on that desire of consumers, which is, I want an eyedrop that's once a day, and it works for the full workday. Thirdly, like I said, it was really focused on a relatively small group of emmetropic patients, so people that have good distance vision to begin with, which is only about a sixth of the 128 million people that are presbyopic. Those were the key reasons for Vuity to fail. Again, if you think about our profile, and it's all public data out there, if you compare it, we're at least three times more efficacious. Our 30-minute data or efficacy is about three times that of Vuity's, at least three times longer. Our last measured time point is at 10 hours. We have triple 0.01 P values at 10 hours still. At least three times longer in duration and about a six times larger population. That's where the difference comes in. That's where we actually feel that we very nicely hit the profile that consumers are looking for. Sure. I mean, along those lines, from our own team's conversations with optometrists and ophthalmologists, they have been overwhelmingly disappointed from Vuity's original limited durability and efficacy profile. Once prescribers understand that Viz has turned the page from pilocarpine as the mechanism, how would you characterize their early receptivity and interest in aceclidine? Are they excited? Is there any residual apprehension from their previous eyedrop experience? Yeah, we see very little of that. We have been talking to doctors for the last, whatever, 18 months or so now. Initially, obviously, with our MSL team, they've done thousands of doctor-to-doctor conversations. Frankly, the first question that we get is, this is not another pilocarpine, is it? When we say no, and show our data, they're very engaged and very interested. We see the same thing now with our salesforce. There is only a very, very small, you know, think about low single-digit% of doctors that say, no, I'm not interested in a presbyopia eyedrop. There is an enormous group, you know, 80, 85% of them that says this looks phenomenal. The data suggests that I can use this on pretty much every one of my presbyopic patients. Get me samples because I want to get a feel for this. We like that because, again, the sampling is going to be a key part of it. That is frankly already the group of doctors that's ready to write. They believe in it. They've seen the data. They've spoken to investigators that are in our study. They know the product works. They're ready to write. Great. When we think about the presbyopia marketplace overall, there's an additional pilocarpine-based eyedrop. There's a couple of other mechanisms that are in development. What do you believe will be the most important differentiators in the landscape that could have hypothetically different presbyopia options? Yeah. No, so there's three miotics. Miotics is the class of active ingredients. You've got pilocarpine, that's AbbVie, and there's another product approved. We know pilocarpine doesn't work. Vuity has shown that. It's hard to see how that's going to be successful. There's aceclidine, and then there's a clavicle product in development. Again, I'm not here to talk about the competition. You need to think about what a consumer wants, which is a once-a-day eyedrop that works rapidly and long. Long means at least 10 hours for a large population. If you look at the data, we're very confident that we hit all of those attributes. What we're focused on is getting this product launched, samples available in October, full product availability, wide availability by the middle of Q4. This is going to, in our mind, play out very quickly. We truly think about this category as a category of one, with Viz being the product that's going to dominate that. Very exciting. I think a key factor that affected former receptivity of the Vuity product was based on pilocarpine tolerability issues that could include headache or retinal risk, for instance. Can you describe how Viz has been able to improve upon such tolerability or safety concerns by being based on aceclidine? Yeah. So aceclidine, as I've mentioned earlier, is ciliary sparing. What that means is that it stimulates the ciliary body minimally or hardly at all. Now, the ciliary muscle is a muscle that actually ties your lens to the retina. If you overstimulate that, you increase the risk of more serious side effects like retinal detachments. If you look at, we've done large literature searches over the last 40 years, you don't see that correlation between aceclidine and retinal detachments. Also, we did a broad six-month safety study where we didn't see any of that. We feel that that serious side effect is something that we should not see with our product. If you look at the overall comfort profile of Viz, we've shown it's a very comfortable product. The ocular haze are mostly mild, very transient. Think of this as some people feel a little bit of a sting if you put a drop in their eye. One of them, you blink twice, that goes away. There's some mild dimness. You can imagine if you shrink a pupil from 5 or 5.5 down to 1.5, you feel you might see a little bit of dimness. It more feels like this room. It's not that you're stumbling around in the dark. Also, that goes away very, very quickly. Miotics, just as a class, for some people trigger a little bit of a headache, more like a pulling sensation. It doesn't happen to a lot of people. If it happens, it's mostly mild and very transient. That's actually something that we've shown in our study. It's not only transient in the day. Think of it, for most people, it's a 10, 15-minute pulling sensation. If you use the product over a couple of days, it doesn't occur to begin with anymore. Again, very benign, comfortable product profile. We've had a very low, less than 4% dropout rate across our three clinical studies. Very pleased with that profile. That's great. Thinking about the international landscape, there have additionally been licensing commercialization agreements for Viz, or formerly LNZ100, in Asia, including Greater China and recent NDA submission this July. We know you plan to launch Viz in the U.S., but can you talk about your overall ex-U.S. strategy? Absolutely. Now, that's clearly a huge market opportunity, ex-U.S. As focused as we are on launching a product in the U.S. ourselves, as clearly as we also stated that our strategy ex-U.S. is to find partners and license the product there. We did that early in Greater China. We signed that licensing agreement about three years ago now because they had to do their own clinical trial. That clinical trial read out about a year ago, carbon copy data, our outcomes to our U.S. trial. Again, a very clear proof point that the product works, different population, different partner driving it, same results. They've indeed recently submitted. You can think of them as like a 12, 18 months or so behind from a launch perspective. This year, we licensed Korea and Southeast Asia, huge market there as well. We also licensed out Canada to Thayer. We're in the process of submitting our NDA ourselves in Europe. You'll see us start to add markets to the total market opportunity over time. Excellent. I know we're kind of in our last minute here, but as we anticipate Viz's commercial availability in the near term, what are some high-level aspects of the launch that we can expect to see as investors, prospective patients, and prescribers, including prioritizing the product sampling, for instance? Yeah. I think it goes back a little bit to what I said earlier. If I think about the next months and quarters and how you can expect us to talk about that, we will press release product availability. Like I said, we're highly confident that samples will be available in October. That will be something that we will obviously share with everyone. We know how keen everyone is to see that product availability. In our Q3, our November earnings call, we may start to share some very initial feedback or numbers around doctor feedback, how many doctors have prescribed. As we think about Q1 of next year, we'll start to layer in what I mentioned earlier. What is the total amount of scripts? How is that divided over new scripts? Especially as we go into Q2, what's the refill rate? We'll do that as frequently as needed because, as I've mentioned earlier, it's going to be very hard for investors to actually get a good sense for script data because most of it, or at least a significant portion of it, we think will flow through e-pharmacy. Excellent. With that, Evert, a very exciting commercial opportunity. Thank you to LENZ Therapeutics. A really great story to keep following on our end. Thank you, Matthew. Thanks, everyone. Thanks, everyone.