Great. Well, thanks everybody for joining us here at Piper Sandler Annual Healthcare Conference. I'm Joe Catanzaro. I'm a biotech analyst here at Piper. It's my pleasure to welcome LENZ Therapeutics and their CEO, Eef Schimmelpennink. Eef, thanks so much for joining us. Maybe before we jump into questions, which there's a lot to get through, I'd sort of give you a minute or two. You could introduce LENZ, what you guys have been up to, and of course what we have to look forward to.
Absolutely. Thanks, Joe. Thank you to all Piper team for inviting us to the conference. Great day today. Great meetings. At LENZ, we've developed a pharmaceutical eye drop that restores your near vision for the full workday. That's very relevant because most of us, when we hit 45, 50, will start to notice that our near vision goes. We're carrying around these reading glasses that I definitely have. This eye drop reverses that. So think of this as you put your eye drops in in the morning, and for the full workday, your near vision is actually restored. You can look at your phone, read your notes, everything that you do with near vision.
Very late stage, we completed our phase III trial earlier in the year, submitted our NDA, and actually a couple of months ago, we were granted a PDUFA date for August 8th of next year, looking to launch the product in the U.S. in the fourth quarter of next year.
Perfect. So I want to try and tick through sort of areas of differentiation for LNZ100, sorry, versus other products in the space. And there's a lot to talk about there. But maybe first we could talk about LNZ100's mechanism of action relative to pilocarpine and why that really matters and how that maybe translates to other areas of differentiation.
Absolutely. So the MOA to restore near vision is actually pretty straightforward. What you want to do is create a small pinhole pupil. It's been known for decades, if not centuries, that if you look through a pinhole, your depth of focus or depth of field increases, and with that, your near vision gets restored. So you want to create a pinhole pupil. You do that by stimulating the iris sphincter. That's the muscle in your eye that gives you that small pinhole pupil. And you want to do that in a very selective way. So you want to stimulate the iris sphincter and avoid stimulating what's called the ciliary body. It's in the same region, and that distorts actually has a negative impact on your distance vision. So if you keep those two muscles in mind, the ideal presbyopia eye drop is aceclidine.
That's our active ingredient, and it's ideal because it's very pupil selective. So you can actually stimulate the iris sphincter without stimulating the ciliary body. That immediately brings us to that difference with pilocarpine. And pilocarpine was a product that was launched by Allergan in the same space, for presbyopia, a couple of years ago. That product is not pupil selective. So the moment that you stimulate the iris sphincter, you almost immediately also stimulate the ciliary body. And with that, you drive distance vision impacts, a negative distance vision impact, so you have blurry distance vision and actually also not that great near vision improvement. So that's the big difference between our product and VUITY, and I'm sure we're going to get into the clinical data in a moment.
Yeah, I think we'll sort of tick off a lot of those clinical data points that you've generated within the CLARITY data set. But maybe quickly on the sort of pupil selectivity, I know you guys have put a lot of effort into a non-branded marketing campaign and educating physicians. Maybe just speak a little bit to what you guys are doing and how physicians are receiving that message that you're trying to send.
Yeah, it's very well received. And we're indeed out there. We've been out there since the beginning of this year and even more intensely in the last couple of months now that we have our MSL team out there talking to doctors directly. And the focus of the message is really around pupil size matters. You need to be below two millimeters in pupil size to truly drive a significant near vision impact. That's known widely. There's a lot of peer-reviewed research that shows that. So that's the first part of the message. Then the second one is to be able to achieve that, you need to have a pupil selective, what's called miotic. So the active ingredient is this class that's called miotics. And then we start to transfer to, well, this is a huge market. You have 128 million presbyopes. Again, effectively everyone over 45, 50.
So in that large population, who would be the first groups to target? So that's the message. It resonates extremely well. The first question that we usually get when it's at conferences or elsewhere from doctors is, this is not another pilocarpine, is it? And we tell them, no, it's not. And then they immediately tell me more. This is truly Optometry 101. So it's something that's relatively easy to understand, and people immediately translate that into, yeah, this one's going to work.
Let's get into the CLARITY data sets and the package that's supporting the NDA filing. Maybe first, just from your view, you could sort of highlight the most important takeaways within those data sets and how they speak to the product's profile.
Yeah. The key things in any product is that it needs to be once a day. You don't want to have to redose during the day. It needs to work for the full workday, like I mentioned earlier. It needs to be comfortable. This is a self-pay product, so it needs to be something that people actually like putting into their eye. So if we touch on those different elements, let's start with efficacy first. So it needs to work for pretty much everyone. So if you look at our data, the FDA endpoint is three lines or more of near vision improvement. Those are the same three lines that you would look at your reading chart if you're at the optometrist. 71% of the population, and we had a very wide population going into the study, 71% of the population hit those three lines within 30 minutes.
So this product works very rapidly. This is day one, naive patients that on day one put a drop in, and after 30 minutes, have at least three lines of near vision improvement. The two lines of near vision improvement, which is what's actually clinically meaningful already, we had over 90%, 95% of patients receiving that benefit. So it works rapidly. Within half an hour, you can read your phone again. So secondly, like I mentioned, you need to actually maintain that effect throughout the workday. The last time point that we measured was at 10 hours. That makes over a 12 or 13-hour day in clinic. So it's more practical than anything else. At 10 hours, we still had 40%, four-zero, of the population hitting at least 40, at least three lines or more of near vision improvement. 69% hit two lines or more.
So very long duration of that effect. And it's not that it ends there. That was just the last time that we've measured. So you see just very gradually it diminishes then over time. Then on the safety side of it, or the comfort side of it, this is a very comfortable drop. So on the ocular AEs, 100% was noted as mild, so a very mild drop to put in. And then a very low rate of headaches that sort of comes with the class. Those headaches were only 7.6% of people noticed them. They're very short-lived. There's like a 10-20-minute headache. That's very transient, but also it's tachyphylactic. So after a couple of days of use, most people don't get those headaches anymore. Again, very small percentage.
And I think all of that translated into the fact that we only had about a 4% dropout rate over a six-month study. So again, very well tolerated product that people liked using.
When we think about the efficacy profile and patient receptivity, what do you think is going to resonate most? Is it the depth of effect, the rapidity of effect, or the duration of effect? What do you think matters most to patients?
Yeah. So I could give you all of the above, but I won't do that necessarily. But what we see, especially as we're now talking to doctors a lot more, is that that duration is the one that they gravitate to most. That's the one where they go, wow, if I can truly promise my patients that you're going to put this in, you're going to notice the effect immediately, but it's going to stay there for the full workday. That's the one that seems to resonate the most.
And then maybe on the flip side of sort of safety, general patient experience. I know you said really well tolerated, mild, very low rate of AEs. I know you surveyed patients, right, after they completed the study. For those who maybe said they wouldn't continue using, which was a very small sort of fraction, maybe on the tolerability, convenience side of things, is there anything there that's notable that matters to patients that maybe is going to be particularly important to keep an eye on in the launch?
Yeah. So if you look at that data that you referenced, so we asked patients coming out of the phase III study that were on product. First question was, do you want to continue to use the product? And we had a very high percentage of 75% of the patients said, yes, I want to continue to use the product. Now the question that you ask is, okay, what about that 25% that apparently didn't want to use it? What you see is that that's mostly the elderly segment of the study. You mostly find patients in there that are a little bit more advanced in their presbyopia and have found different solutions. Maybe they're on two bifocals and they like that. Maybe they're actually not that active in life anymore and they don't mind wearing reading glasses for prolonged periods of time. So that's mostly that group.
The group that wants to continue to use it, again, that very large three-quarters of the population, if you ask them how often, you actually see that they want to use it, they claim, pretty much every day of the week. That's how much they liked it.
So you mentioned PDUFA date August 8th of next year. I know we're still early in the review cycle, but any updates you could provide there on sort of the current status, feedback interactions with the FDA, and I guess particularly any expectations around label and wording and risk and warnings relative to pilocarpine-based products?
Yep. No, so the discussions with the FDA have been very productive, very few actually. We've had a great working relationship with them over the last three, three and a half years. We feel very confident that throughout all the discussions, we've been able to put an NDA together, a package together that satisfies their needs. This, we feel, is not an overly complicated submission. There's obviously a precedent with VUITY getting approved that we could look at. So all the questions that we've had so far were relatively benign. It seems the FDA is working very well through it. The next time point, if you will, is their day 150 meeting, which is an internal meeting, which will happen in Q1. From there, we'll go into label discussions. I think there's a relatively high conviction that this product will get approved around the August time frame.
Perfect. So I want to talk about another data set, but it's your ECP survey that you recently did, 400+ eye care professionals. And maybe there too, I'll sort of leave it to you. And when you look at that data set, what were some of the most important takeaways there and what they might mean about the potential LNZ100 launch?
Yeah. No, we're very pleased with the outcomes of that study. So just to frame it, indeed, 430 or so ECPs, 80% of them were optometrists, 20% ophthalmologists by design, because that's where we see the scripts break out. That's where if you look at VUITY, we actually had a great launch where the scripts came from. So that's how we designed the group that we surveyed. So on average, each one of those doctors sees about 350 patients a month, so large groups of patients that they see. And 61% of them are presbyopic. So each doctor sees about 215 presbyopes every month. There are a couple of questions that we asked them. First one was when we showed them our profile. So we basically gave them a version, a short version of our clinical data, efficacy, and the safety tables.
The first question was, do you feel it is a safe and tolerable product? 78% said yes, 18% was neutral, only about 4% said no. So clearly, people look at this as, yeah, this is a drug that I feel is safe and tolerable. And the second question was around, do you feel it is a good addition to your, if you will, presbyopia toolkit? Very similar responses. Close to 80% said yes, absolutely. Again, about 16%, 18% said, I think so, but I'm neutral. And 2% or so said no. So doctors are looking for something that they can add to it. And then we switched to, well, are you likely to sample? Is this a product that obviously lends itself extremely well for sampling?
We'll come out with a five-pack in sampling, and we can pretty much guarantee on the basis of the fact that 95% of people hit at least two lines of near vision improvement, and if somebody that's a presbyope puts a drop in their eye, they'll be able to see their phone. And again, in the low 80% there, 82%, 83% of doctors said, yes, I'll be willing to sample this, and this is before it's approved. Again, about 16%, 70% of memory serves of people that were neutral. Very few said no, and we saw the same thing when we asked the question around, are you willing to prescribe?
So it seems that we have a large doctor group that sees a lot of patients that feels on the basis of the data that we've shared with them, this is a safe product that they're willing to prescribe and sample. So it all sets us up, we feel, very well for a successful launch.
So I want to jump to VUITY. I think the most frequent question I get is, what are the main reasons why LNZ100's commercial outcome can be different from VUITY's outcome? So maybe you could sort of speak to why VUITY had some of its challenges and why LNZ100 couldn't probably overcome those.
Yeah. So the main reason is that VUITY didn't work and LNZ100 does. And I say that a little bit tongue in cheek, but that's really the difference. So if you look at how the data is different, we sometimes talk about it is our product is at least three times more efficacious. So if you look at efficacy early on, we had about placebo-corrected about 70% compared to 25% for VUITY. So VUITY only worked in one of four patients, but work was very relative. So it only worked for about two to three hours. That was the outcome. Again, we had 10 hours. We had triple zero one p- values at 10 hours. But also VUITY was focused mostly on early presbyopes that are also emmetropes. So emmetropes, people that have good distance vision because there was that distance vision impact.
So our product works three times more efficacious, works at least three times longer for a six times larger population. So that's truly that efficacy component that's very different. And it's not something that you can fake. You cannot tell a patient that you just use this for three months, and maybe after that you'll notice something. You'll notice within half an hour it works, yes or no. So that's the core of what's different. And if you then overlay the VUITY launch, VUITY actually had a very successful launch if you look at it. So they went out with the promise of what actually our product delivers. And what you saw was that initially when they were out there with their sales force, they generated very quickly up to about 3,000 new scripts a week.
Then after about a quarter or so, they turned on their version of DTC, which was Hallmark Channel commercials, which we don't feel is the right way to go. We'll do DTC for short, but in a different way. But you'll see that that number doubled. So they went to about 3,000 new scripts a week. Now the problem was that those people went out. They paid on average about $80 for a bottle of VUITY, used it, and I was one of them, and went, well, this doesn't really work, so I'm not refilling. So that trajectory that they were on could have been a blockbuster product had they have had a half-decent refill rate, which unfortunately for them, they didn't.
So that's where we feel the big difference will be that even though patients say that they're going to use it five, six, seven days a week, if you pare that down and you go very conservatively to, let's say it's three days a week, that's five refills a year on a fewer NRXs and RXs, you come out very quickly to very attractive numbers. And I think that's what's currently being reflected in other companies being valued.
So you mentioned DTC, so maybe I'll loop this into another question. So you mentioned the Hallmark Channel. I presume that's not where med spa patients are found, and that seems like that's maybe one pool of your initial targets. So maybe speak to what you see as the initial target patient population and where you think you could really see the most receptivity and strong initial uptake.
Yeah. So what you see is that in general, you got 128 million people, and if you survey them around, are you interested in a presbyopia eye drop? How likely are you to sample? There's a 60%, 70% likelihood in general. That's the top box on a five-point scale. In there, there's groups that are over-indexing. There's three that we currently focus on. One is contact lens wearers. So people that wear contact lenses do that because they don't want to wear reading glasses, and they're used to paying out of pocket for their vision solution. So that's the first group. There's 47 million people in contact lenses in the US. That drops off dramatically at 50 because people become presbyopic and there's not a good contact lens solution for them.
With this eye drop, they can actually stay in contact lenses, and incidentally, that's also a very valuable group for optometry. So sort of a win-win there. So that's that first group. That's over 10 million people right there. And second group, again, over 10 million people are people that have had LASIK surgery. So these are people that have spent $3,000-$5,000 per eye back in the day to get that distance vision corrected, not wearing glasses. And as they age, they actually become presbyopic, and now they're back to having to wear reading glasses. Again, not looking to do that, this eye drop can be a perfect solution for them. And then the third group is the group that you've mentioned, people that are going to med spa. So think of this as the people that are using Botox and other cosmetic enhancements, if you will.
Clearly, they don't want to put reading glasses on. So those are all groups that over-index at 90%, 95% of, are you interested in an eye drop? So those are the group that we would go first. And tying it into your DTC question, we can target those very precisely through DTC, but not through the Hallmark Channel indeed.
Yeah. Maybe sort of the flip side of that equation, going back to the ECP survey in terms of those most likely to be prescribers and maybe those least likely, maybe how you go about sort of targeting those most likely to prescribe LNZ100.
So this is again where VUITY is helpful. So we have the data of where VUITY or who prescribed VUITY. What you see is about 15,000 healthcare professionals split 80/20 optometry to ophthalmology prescribe about 85% of the VUITY scripts. So we know exactly who to target first. We're going to target them through obviously a sales force. So we're building that sales force as we speak. There'll be about 100 reps that we will have ready by mid-year ahead of PDUFA date to really start to go out and meet those ECPs or those eye care professionals and really educate them on the product. That will then be followed by DTC a couple of quarters or so later.
So yeah, so back to the DTC, I guess. How important is that for you, and what sort of are the gating steps to triggering fully committing to that effort?
Yeah. No, starting with the last bit, you do not want to start your DTC prior to having your doctors really well educated. It's very frustrating for them if they see patients coming in asking about a product that they've not been trained on that they don't know about. So you want to have enough time between training the doctors and turning your DTC on. Usually, that's about a quarter, maybe a little bit longer. So you could expect that to be the case for us as well. So we'll go out with that sales force as soon as we have the PDUFA date or the product approved. They'll go out then a couple of months after, a quarter or so after, we expect to have products in the market, and that's around the time that we'll turn DTC on.
There's no other gating factor than making sure that doctors are ready to receive the patients. We know that it's a very DTC-sensitive market because we saw with VUITY that, again, they did about 3,000 scripts solely through the sales force. They turned on DTC, and they doubled that. So those are patients that maybe normally don't go to an optometrist and now are triggered to go in. And again, you want to have the doctors ready to receive.
So there's been another recent topical launch in XDEMVY that's had some good success. Any learnings there? Anything you could sort of take from what they've done and incorporate into how you think about materializing this launch in the early days?
Yeah, no, they've done great. So you're talking about Tarsus. And very similar, their core point is optometry. So what we've learned there and what they've showed is that you can actually, with a targeted sales force, activate an optometry channel. So they did that really well. What we like and what we see and what we have implemented, for example, is their MSL, so their medical science liaison team, was fully made up of optometry. So that match of having an optometry MSL talking to an optometrist works really well. So if you look at our sales force now, again, currently 100% optometry. So those are definitely some of the learnings. And I think some of the clear indications for investors as well that you can actually be successful, and they are very successful in selling a product into optometry.
So maybe looking out into the future as it relates to the competitive landscape within presbyopia, I mean, what do you see in the maybe near term and maybe what does it look like in five years from your standpoint?
Yeah, we truly feel this is going to be a category of one. And we can say that on the basis of just the overall clinical data. So there's three miotics, and I'll keep it brief because we're running up on time here. But obviously, aceclidine would be the only company that has aceclidine. You have pilocarpine. That's been tried by VUITY in the highest concentration. There's a lower dose pilocarpine that exactly mimics the VUITY efficacy, which we know doesn't cut it. So people don't want pilocarpine. Also, doctors don't want pilocarpine. So we feel that that's not going to go anywhere. And then there's a third miotic, carbachol. But again, very similar efficacy and what we understand an even less comfortable profile compared to VUITY.
So just on the basis of actual data, you could see that there's only one product, and I think that, again, is what we're hearing that probably is going to be successful in the market.
I want to squeeze one last one in on U.S. opportunities. You saw positive phase III data in China just a couple of months back. Maybe more broadly, how you're thinking about ex-U.S. opportunities and when you start to sort of push forward. I guess I'm specifically thinking about the EU.
Yep. So we will license the product ex-U.S. We've started to do that with China. We did that early because they needed to do their own clinical trial. And to your point, they released that data a couple of months ago, which was a carbon copy of what we had, which was great to see. There's ongoing discussions with other territories, European being one. We're not overly urgent in signing. We don't feel that we need to be leading in too much in signing that. I could see how the value of those territories actually increases with the U.S. launch. But those discussions are ongoing. Again, that will all be out licensed.
Perfect. Well, with that, we're out of time. So Eef, thanks so much for your time and thoughts.
You're welcome.
Enjoyed the discussion. Thanks, everybody, for joining us. And take care.