Thank you very much. Thanks. Welcome back to our next session at the Leerink Partners Global Healthcare Conference. I'm Marc Goodman, one of the biopharma analysts, and we have LENZ Therapeutics. Eef, thank you very much. Eef Schimmelpenninck, who's the CEO of the company. What a ride we've had, right? I mean A lot of fun. a lot of fun. Absolutely. Let's talk about the product. Let's talk about what's been happening with the launch. Let's, you know, give people a sense of where we are. I think before we jump into that, just for background, just so everybody understands, you know, this is what's going on, this is the presbyopia market, this is how VIZZ works, just, you know, just a quick, you know, kind of level setting. Absolutely. Thanks, Mark. Thanks, Leerink, for having us here. We should have had this actually outside. It's gorgeous out there. Yeah. Um-. That would've been nice. Yeah, it would've been nice. If you think about the presbyopia market, what we have developed, and I know many of you here are very well aware, is an eye drop that treats presbyopia. Think of it as a drop that you put in your eyes in the morning. Within 10-15 minutes, it literally is gonna give you near vision improvement, and it's going to do that for the majority of all presbyopes out there. It's gonna give you that near vision improvement for the majority of the day. Our clinical trial, we studied it up to 10 hours. At 10 hours, still 71% of patients had you know a significant near vision improvement. The mechanism with which we do that is actually by giving people a small pinhole pupil. What happens if you have a smaller pupil, your depth of focus or your depth of field increases, and with that, you're able to actually look up close again. 'Cause the challenge with presbyopia is that this happens to everyone as you get older. Yet most people start noticing it when they're 45, 46. You start holding your phone a foot away from your eyes. You start to squint a little bit, which is actually the same effect you know, just to be able to see again. You can counter that by giving yourself a small pinhole pupil, which is what we do with aceclidine. Aceclidine, which is our active ingredient, is unique in that because it only stimulates the iris sphincter, which is the muscle that gets your pupil smaller. It avoids what's called the ciliary body. If you stimulate the ciliary body, and we're the only ones that are not doing that, if you do it, which is what you've seen with pilocarpine and some of the other miotics, you actually have a negative effect on both distance vision, so your distance vision now becomes blurry, but also can drive more significant AE's. Unique mechanism of action, unique API, and we've launched. We got our product approved in August, then we've launched that in October, so we're now, what, four, five months into our launch, which I said earlier is a ton of fun. You mentioned a couple of other products out there. Just let's make sure we understand the competitive landscape before-. Yep. We jump into your launch. Yeah. Very few companies out there. If you think about these miotics, the active ingredients, there's three of them. You know, obviously we have aceclidine, and we're the only ones with aceclidine, so aceclidine is fully ours. Then there's pilocarpine, which is the active ingredient of the product that AbbVie launched about three years ago, a little over three years ago now, VUITY. So that's a pilocarpine-based product. There's a second pilocarpine-based product called Qlosi. That's a low-dose pilocarpine. If we real quickly look at what VUITY did three years ago, they launched. They proved that there's a lot of interest in a presbyopia eye drop, but no surprise, you need to have a product that works. Unfortunately for them, VUITY was not that product. It works for very few people only. Only one in four patients actually noticed an effect. That effect was very short-lived. It was about three hours max. Launched well, but you know, quickly lost steam because nobody refilled that product. Again, Qlosi is a low-dose version of it, going through the same struggles. What we understand now is that they've actually let half of their sales force go. I think they have about 17 reps in the market left compared to the 117 that we will have in a couple of months. I think it's safe to say that pilocarpine is gone in the market. There's no other developers doing a pilocarpine for that reason. There's a third miotic, carbachol. Company called Tenpoint has that product approved. They're set to launch in second quarter. Clinically, if you look at the data, that's very similar to VUITY, so short-lived in its efficacy, but also a very narrow population that's only tested in what's called emmetropes, so people with good distance vision, which is only about 20% of the market. That would be the landscape. We truly think of this as a category of one. I-. A market for us to make. Yeah. I'm still a little confused why these other products are even trying to, I mean, like, your data is so much better. Like, what do you think their goal is? Like, what I think, like, people look at this, rightfully so, as it's a huge market. Yeah. Like, there's 128 million-. All we need is just a little sliver. Yeah. There's 120 million presbyopes out there. Yeah. If you know, if we make the market, which is what we're doing. Yep. Y ou take a sliver from it, you can still be, you know, profitable. I think to your point. Yeah. The clinical efficacy at 10-hour data is better than the peak efficacy for any of these products. You know, undoubtedly very different. Yeah. Clinical profile. Talk about the launch now. Yeah. You've been out for four or five months. What have you learned? You know, what are the positives? What are the negatives? What are things you've changed? What are things that are working really well? You know, just give us a sense of what's happening. Yeah. No, like I said, like, launching a product, that's just a ton of fun. You know, building a new category even more so. What we see if you step back a little bit, you know, and we talk about the product first, yes, we had all our clinical data. Great to see that translates into real world. When you talk to doctors, to patients, you know, many people in the room here are doing their own doctor checks, undoubtedly, because everybody comes back with the same thing. "Oh yeah, this works." Like, it clearly gives you that near vision effect very rapidly, works very long, works for the majority of patients. Great to see that again, what we've learned in the clinic actually translates into the real world. Very happy for that. Very early days, what we're starting to see as well is that the product is indeed sticky. What I mean with that is that, you know, the refill rates that we're starting to see are very encouraging. That's, again, very early. If we look at the people that bought their first script in Q4, we're seeing good refill rates on them. Our sampling strategy, which is always a key part and will continue to be a key part of our launch, is to have as many samples as needed out there in the field. Got a lot of doctor's offices, so people can come in if they're interested, get a five-pack. You get five days to try the product and then transition to a script if this is a product that works for you. We see a lot of people do that. From that script, like I said, it's sticky. You know, it's too early for percentages around that. You know, we've always said that's more a second half of the year thing. Even in the fourth quarter, you know, we're seeing people that start off maybe with a one-pack. You can actually get a three-pack with a little bit of a discount through UpScript ePharmacy. People are doing that. They're moving from a one to a three-pack. People are coming in and ordering immediately a three-pack. You know, they must have had a sample and liked it. Again, very encouraging on the patient side. On the doctor side, where we left everyone with Q4, when we flashed Q4, was that we had over 6,500 writing ECPs already. Optometrists and ophthalmologists are writing this product. The awareness is phenomenal. The willingness to prescribe is great. That number obviously continues to grow very significantly. We have built a very strong foundation of ECPs. 6,500, is that what-. 6,500 was the end of Q4. You know, that's growing very rapidly. If we compare ourselves with to where we are now to any other recent eye care launch, whether it's VEVYE, XDEMVY, MIEBO, we're significantly outpacing them from a doctor foundation. Very pleased with that. What we're seeing is that the refill rates again, are encouraging. The focus now is how do we make sure that we really start, you know, getting new patients in at a great rate. Push and pull. On the push side, continue to have the sales force out there talking to doctors. You know, the two biggest things that they're focusing on with the doctors are, one, how do you help them actually bring this up to patients in an adequate way? They all are focusing on chair time. They've done presbyopia in a certain way for decades. Now they need to start talking about an eye drop. It's truly a 7-second discussion. Getting them to understand how you bring it up and when you bring it up, sales tactics is a great thing. Then the other part is we do see a little bit of overhang. Like you asked what have you learned? I think there is a little bit of overhang in the market around, oh, VUITY is for, 'cause that's how it was marketed, young emerging presbyopes. What we see in the field, and when I'm out in the field, I see it all the time, a doctor will think about this when a patient comes in, and he or she goes, "Oh, Doctor, I'm 45. Something's terribly wrong with my eyes. I can't see up close anymore." That's when they go, "Oh, here's this new eye drop." We need to make that a much more, you know, frequent habit 'cause the product works for, like I said, everyone. We've tested it up to 75. Sorry, Jessica Parker, our DTC spokesperson, is 61, is actively using it. So those are the two things that we're focused on. So we're really leaning in now from an operational point of view on the sales force. I mentioned that earlier. We're expanding the sales force. Putting another 29, 30 reps. So we'll have 117 sales specialists in the field, 13 district managers, three RDs to really make sure that that sales tactic is in place. That's also because what we're seeing is that there's a lot of demand from doctors that are not in our current target panel. Mm-hmm. With the current sales force targeting 15,000 people, we're expanding that. You mentioned the sampling. Are you able to measure the sampling movement to a prescription? How is that going? Yeah, great question. Sampling for us is slightly different than what most of us, me included, are used to from a more traditional pharmacy dispense or pharmacy-driven products. Like that's where your sample would actually be dispensed by a pharmacist, and as a company you can track that. In our case, it's different. Our sales specialists, our reps leave samples with the doctor. They sign for them, and at that moment it's theirs, and we lose sight of where those samples are going. Now, we know when this rep comes back two to three weeks later, how many samples are gone, but we don't know where they went. Mm. We've always looked at samples. It's a very economic way to get people to use it, as it's less about, okay, we need to hit a certain conversion rate. It's much more around, like I said earlier, making sure that everyone that wants to try it has an opportunity to try it. We see patients and on the ePharmacy side, we have a lot of detail, as you would imagine. That's where we start picking them up again, and we can follow them on their journey from that moment onwards. 6,500 writers so far, you mentioned. Give us a sense of who they are. Are they optometrists? Are they ophthalmologists? Are they at big practices, small practices? Are they regionally based where someone's-. Yep. You know, like the Northeast is doing great and the South is struggling or, you know, just curious. Yeah. Okay. No, and again, those 6,500 doctors, that was the end of Q4. It's significantly more now. Yeah. If you look at them, it's panning out the way that we expected. You're asking earlier, any surprises on the launch, definitely not there. We see that 80% of writers are from optometry, ODs. Mm-hmm. 20% MDs, ophthalmologists. Exactly like we planned it, exactly how our sales force. Yep. I s set up. The regions where these scripts, where we see most of the revenue coming through, it's your usual suspects. It's Florida, California, New York, Texas. Those are the regions where you see a lot of people that are interested in a product like this. Doesn't mean that there's not, you know, great traction outside of those regions, but that's where the majority. How about Miami? Miami, here we are. Yeah. No, Florida is doing incredibly well. Miami, Fort Lauderdale, you name it, definitely a target audience. Yeah. Yeah. Interesting. When you talk to the optometrists, I guess it's 80%, so you, what are they saying? Like, what is their feedback from the patients that is from an efficacy standpoint, and what are they saying about any side effects or any issues with it, you know? Yeah, like I said earlier, doctors like the product. They've all had, you know, hands-on experience with it now. They've tried it themselves. They've tried it on their staff. They've definitely tried it in some patients. It pretty much works. Yeah. They're not saying. It's like-. They're not saying, "Oh, one of my patients complained it didn't work. No. You're not really getting any of that? None. Yeah. That's great, and if you think back, like how often do you get to launch a product that just very clearly is efficacious? The efficacy is there, and people know that. What they're now working through is, "Okay, who do I target with this product?" Like I mentioned earlier, they're sort of stuck in the moment at, "Okay, this is for my young emerging presbyopes-. Yeah. Never worn glasses. We help them understand that, no, this is much broader. You know, we tested in people with all sorts of refractive challenges, I guess. We tested it in pseudophakic people. People have had LASIK surgery. People are wearing contact lenses up to 75, so much broader group that this is applicable for. We help them to, just like with any drug, you know, set the right expectations. Tell your patient, "This is an eye drop. It's gonna make you see up close again. You'll notice the effect very rapidly. It's gonna last the full workday. This is how you use it. And by the way, on the first day, second day, you might notice a little bit of dimness, or you might notice a little bit of eye redness. That's why I'm gonna give you a five-day sample pack, 'cause those effects are very short-lived, if they happen at all even in a day. How long is that dimness? Dimness is short. Like, you neuro-adapt. For most people, it's five, six, seven minutes. Uh-huh. Good thing is that. What we see is that if you experience dimness because you have a smaller pupil, probably your near vision is great as well. Nobody goes, "My near vision is not good." The dimness is something that most people are very easily accommodated to. Mm-hmm. You neuro-adapt to that. Interestingly, you know, people don't notice it anymore after a couple of weeks of Right. of using it. Day one, they might say, "Oh, this is. There's like some dimming effect," or whatever, and then. Yeah. 10 minutes. They go, "But I can see my text message. Right. 10- minutes later, they're not complaining about the dimness as much anymore. Yeah. That's what you're hearing. That's what we're hearing. What about redness in the eye? Yeah. So redness is hyperemia. Yeah. Is something that may happen, just like if you Yeah Stop using contact lenses or any other eye drop. It's usually almost gone on the first day within 30- minutes. Second day, it happens even less. By the end of the five day pack, we have great materials for doctors in that they can see that, oh, you know, maybe it's something that I notice on day one. Yeah. or my patient notices. It's hardly there anymore on day five. It's also important to realize that hyperemia is not something that you feel and it like it doesn't burn, doesn't itch. It's not something that as a consumer you'll notice unless you look in the mirror. For most people, this is something that they use early in the morning. Yeah. brush your teeth, you hit the shower, and by the time that you're out of the door. Yeah. It's all gone. Is there any complaints on headache at all? I mean. No, that's an interesting one. Yeah. Thanks for bringing that up. That's one that we were focused on. These miotics sometimes, because they, you know, can have some side effects, cause a little bit of a headache. We have very little to none. Yeah. O f that. You know, it's a great, very positive surprise as we launched on that does not seem to be something that comes up. Yeah. Interesting. Now let's talk about yeah, I guess I'll just describe it as, you know, issues with the retina, whether it's a detachment or a tear or any type of, you know, issue, whatever. Talk about what is happening out there and also talk about what should be expected out there. Yeah. such that we can kinda understand. Yeah. put it in context a little, you know. Yeah. Retinal tears and retinal detachments are a focus for this group of products, for miotics, because it's something that with VUITY they saw a lot. VUITY stimulates the ciliary body, and we don't. The hypothesis was always, and the clinical data showed that we have a very safe product that doesn't cause that, and we saw it in our clinical trials. The background rate for retinal detachments and retinal tears is about 25 per 100,000. VUITY at this stage in their launch had 34 retinal detachments or retinal tears. Think of those numbers as, you know, what you could expect. I think it's safe to assume that between all our samples, VUITY never had samples, all the samples out there, all the patients on product, the fact that they're refilling, so using it a lot, you know, we're somewhat comparable to the 34 of VUITY. We've had one. Even though the background rate's 25 over 100,000, we've had one. Now, unfortunately, that one happened earlier in the launch. Yeah. It happened in December. When we looked at that patient, it's a patient with a long history of retinal issues. They had retinal tears, so not retinal detachments, but you know, the lighter one, if you will, of the two, before they had surgery for it. It's basically a patient that should have not been on any-. Yeah. products, frankly. It happened when the patient was actually not on drug. That stopped it for a couple of days. KOL's opinion is that this is non-causal. Yeah. I think the more important effect that we can say now is, look, VUITY at 34, background rate's 25 over 100,000. We've had the one in a patient with a long history. Yes, it's something that, you know, the street obviously looked at. I think where we are currently, people are getting very comfortable with the fact that, like, we know this is a very safe product. Right now, there's also the pointing out, like in the FAERS database or something like that, there's other ones and, like, what do we make of what's-. Yep. What we're seeing there? There's, like, hardly anything in there. What's different with the FAERS database, which goes for every product. FDA actually reports that on a daily basis. Yeah. What you see is that most of what's in there is very benign, 100% aligned with the label. You know, people will talk a little bit about maybe some instillation pain or dimness or eye redness. Again, you know, a very benign product. How much of a conversation is this with the optometrists out there that you're talking to? Like, are there patients asking about this? Are the optometrists asking about this? No. This is not something that. This is just Wall Street getting a little bit more nervous. Yeah. Trying to be forward-thinking, but they're. Yeah. getting ahead of themselves. We obviously kept looking at, you know, what's our script growth doing around this, you know, RT. We didn't see anything. Like, it just continued on a very nice clip, just like we wanted to see it. Optometrists are not focused on this. Don't forget, they will be focused on it if it becomes an issue because the KOLs will start talking about it. Yeah. From our perspective, this is something that we only talk about when we're at conferences like these, and people may ask about it less and less because people are also looking at the database and go, "Okay, the 34 VUITY compared to the one that you have, clearly there's no signal there. Yeah. Talk about Symphony data, talk about IQVIA data, and then give us a sense of how accurate, how much is it even remotely close? Like, you know, everybody's looking. Yep. Everyone's looking. Right? I can-. You know, you gotta give us a sense of like, don't look there, look here, extrapolate here. You know what I mean? Give us a sense of what the answer is. Yeah. Every Friday, as everyone knows, Symphony comes out with their data, and I can spell out the eight emails that I'm getting from the eight different-. Yeah. Investors on what does this mean. Like, we don't comment on data on a weekly basis. That's what our earnings calls are for. IQVIA only picks up retail and picks it up very inaccurately. You know, discount IQVIA. I don't think anybody's looking at IQVIA. It's not even worth it. It's not even. I think they're like 400 or 500 scripts a week, which is. Right. That's not even remotely close because. That's more close. You already said in the fourth quarter you had over 20. Correct. thousand. Yeah. If you look at IQVIA, it's like. Yeah. IQVIA's. Yeah. completely off. Yeah. If you think about how we're selling our product, it's both through ePharmacy and retail pharmacy. We always thought that Symphony was not gonna pick up anything in the ePharmacy, which is why we've always said, "Don't look at either. Yeah. What we saw when we just launched in October-ish was that they were actually picking up some, they call it mail order, but some ePharmacy. Now, it's off and, you know, the 20,000 scripts that we reported in Q4 corresponded to, like, 12,000 or 13,000 that Symphony picked up. They were underreporting by about 40%. Yeah. It's not gotten more accurate. It's not gotten more accurate. It's not gotten better. Right. That's the message. That's how we message it at the moment. It's not gotten more accurate. You know, we'll continue to update on a quarterly basis. Right. What we are seeing. I think the important thing is that we're seeing growth. We're happy with our foundation of doctors, very encouraged by the refill rates. Now the focus is on starting to fill that funnel with. Yeah. M ore patients, both through the ECPs, so that they start to mention more, and then obviously with the DTC campaign that we have going on. Yeah. I wanna come back to that, but I just wanna stay on the numbers for one second. Where's consensus right now for sales for this year? I think consensus is around $2 million or so for the quarter. Somewhere around $35 million -$40 million or so for-. For the full year. For the full year. Have you all commented that those numbers, you know, we're comfortable with it, we're not comfortable with it, we're not gonna comment at all about it? What have you been kind of talking about? I'll take the third option, Marc. Door number three. Yeah. No. Like, we're not commenting. At all. That's not surprising. Yeah. Like, we've always said that this year is all around building that market, proving that the refill rate's there. I think that's 1% in the second half of the year. That's a proof point. Obviously making sure that we can get new patients in. That's the focus again. Right. What we're focusing. The product's been out for how many months? Four or five months. Four or five months. Yeah. You kinda flipped a switch a little bit with Sarah Jessica Parker, and I guess the noise went to a different level maybe a month and a half ago. Yeah. Is that fair to say? Talk about what was that switch that was flipped, what was going on in the first couple months, and what really has now been going on in the past month and a half. Then secondly, have you noticed the noise go up? Have you, from the field, noticed sampling going up? Have you noticed prescriptions going up, you know? Yeah. As, because of it, you know? Any launch, and definitely ours, the first, let's call it, quarter or so, you focus on making sure that the ECPs, that one, there's awareness for the product. Awareness is in the high 90s for this, so we definitely achieved that. That they understand the product, so they... That's, we've achieved that, so that they're ready to prescribe. At the end of Q1, early Q1, sorry, our first quarter of launch, so Q4, we got to that point. Early in this quarter, our second quarter of launch, mid-January, second half of January, we turn on DTC. This is a self-pay product, so we don't have to wait for the product being on the different schedules or being reimbursed. That's why we can do it early. You know, what is it now? 5-6 weeks ago we started DTC. That's important to understand. DTC takes about two quarters at a minimum to really take full effect in scripts. What we're looking at is earlier signals. You know, DTC in our case means a lot of digital targeting. We target our patients very precisely. We're also doing one-offs. You know, we had a skit on the Kimmel show. We did Good Morning America. The first thing that we're looking at, besides click-through rate and how long people are spending on the different ads, is do you see our website traffic go up? We see that very clearly. The baseline, let's call it our normal day web traffic, is significantly higher than early in the launch. every time that we do something on top of that, like we bought all the ad space at The New York Times 10 -days or so ago, you can see the web, you know. Mm-hmm. The web traffic double, triple. So then it's all around, great, we've got people on the website. They're learning about the product. When and how are you gonna see that translates into script? I think we're starting to see the very first, you know, bit of that, but again, it truly takes a couple of quarters before you see that happen. You know, many people look at the Tarsus launch as a benchmark. Same thing there. I think it took them about three quarters to really see that effect. Mm-hmm. Will we see any noise, like if I watched a show on Netflix or something like that? Are you planning on moving there, or? Yeah. Is that just too expensive to kind of do, or too early for that? Yeah. We're doing a lot at the moment, and then what I mean with that, we're doing a lot in a good way. 'Cause you've got these big dashboards where you can truly see-. Yeah. If I run this ad in Dallas, how does that compare to another ad in New York or the same ad in New York? Of course. If we do billboards versus digital. We are going to test some, what's called linear TV ads, which is more what you're-. Right. Talking about, not quite Netflix, in select markets to see what that does. Everything comes at a price. Like, it's not cheap to buy-. Yeah. Out The New York Times. Yeah, yeah. Great, you know, we're seeing the impact. Is the ROI there? That's what this phase, and frankly a phase for any launch and building a category is really about. Making sure that you use, you know, these quarters this year to figure out what works best within a, you know, a very broad budget or a significant budget that we have on the marketing side. Sarah Jessica Parker is doing what, for instance, on a weekly basis or a monthly? Like monthly, is it? Like, just give a sense. Yeah. Of like what, yeah. No, she's the face of the campaigns. Right. You'll see her, and we got four or five different ads with her. You see them on your Instagram feed, your TikTok. You'll see her on, you know, different areas. We also have a whole set of campaigns that are branded, so around this. We're integrating those two at this moment. That's where you see her. If you think about what her role is, her role is to have people stop in the, you know, thousands of ads or impressions that you get as a consumer every day. You need to go, "Oh, what's she talking about?" And you stop for a little bit, and then you click and go, "I wanna learn more. Like, this eye issue, this presbyopia thing. Yep. T his blurry near vision, I've got that. I wanna learn more." That's her role. You pull people into the website. There's a whole host of influencers around it, you know, more people with 2, 3, 4 million followers. There's obviously the local influencers. It's a-. How many local influencers are there now? Yeah, there's a lot. I definitely don't know them by name. Like, is it, like, 10 or 50, 100? No. Well, I think we got maybe up to 10 or so of the main influencers. Right, right. The people who are at $3 million, $4 million, $5 million, sometimes. They're walking around in, like, main cities, for instance. Yeah. This is like if you're. Maybe a Miami, maybe a New York or. Yeah. If you're following this person in Miami-. Right. you know, that's somebody that you've-. Right. willingly are following, so you value what they say. Their opinion matters to you. Right. What part of the conversation do you think that we've just had is the biggest disconnect between how specifically the investment community is viewing the launch relative to how the launch is actually happening? Yeah. I think what I see is that, which is impressive, 'cause I'm very impatient, that the investor community is maybe even more impatient. Everybody's looking at script data, which I fully understand. Yeah. Like, we've always, I think we've laid it out quite well on, you know, the initial stage of any launch is building a category. This is a new thing for a large part. It's gonna take a little bit of time. It's making sure you've got the doctors that are willing to write it. It's making sure that you see that your product works. We've got those two. So the fact that we have a product that works incredibly well for almost everyone, and a market that's 128 million people is great. Like, that's unique. That's very powerful. It's up to us to now connect those dots. That's sales execution. I won't say it's easy, but that's blocking and tackling. Yeah. That's what many companies have done well before, and what we're doing, in my opinion. Right. In a great way. I think that's one part. Just in the very last, you know, minute here, the ex-U.S. piece is something that I think is not on anybody's radar yet. We actually this morning's press release that we've submitted a filing in Europe now as well. That's our fifth ex-U.S. submission. As focused as we are in the U.S., commercializing the product on our own, ex-U.S. is all partnering. We have great partnerships in place already, and we'll continue to add to that. Good. Thank you. Thanks very much for joining us. Thanks, Marc. Good luck with everything, and I think we'll try not to look at the IQVIA prescriptions and get confused on what's going on. Thank you. Thanks everyone. Good to see you. Good to see you, Marc.