Greetings. Welcome to the LENZ CLARITY Phase III Top-Line Results Conference Call. At this time, all participants are in listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during today's call, please press star zero from your telephone keypad. As a reminder, this conference is being recorded. At this time, I would now like to turn the conference over to Eef Schimmelpennink, Chief Executive Officer. Mr. Schimmelpennink, you may now begin your presentation.
Thank you, Rob, and good morning, everyone. Thank you for joining us. Before we begin, I encourage everyone to go to the investor section of the LENZ Therapeutics investor website to view the CLARITY phase III data readout release and the related material, materials that we will be discussing today. I'd also like to draw your attention to slide two, which contains our forward-looking statements. During this call, the company will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. The company encourages you to consult the risk factors contained in our SEC filings for additional detail. On the call today, joining me from LENZ for Q&A are Dr. Marc Odrich, Chief Medical Officer, Dan Chevallard, Chief Financial Officer, and Shawn Olsson, Chief Commercial Officer.
As many of you are aware, we recently successfully became a publicly traded company, representing a landmark event for our organization. Today marks yet another important milestone for LENZ, as I'm excited to be able to share our positive phase III data with you. Before I go into detail into the data, I want to acknowledge the investigators that led our CLARITY study, the close to 1,100 participants in the study, and the phenomenal team here at LENZ. Without them, we would not be where we are today. On this call, we will be reviewing certain top-line results from our CLARITY phase III study, a group of three trials evaluating the efficacy and safety of LNZ100 and LNZ101 for the treatment of presbyopia.
As a reminder, presbyopia is the inevitable loss of near vision that impacts the daily lives of nearly all people over the age of 45. As the crystalline lens in our eyes hardens with age, the eye is less able to accommodate and focus the incoming light for near vision on the retina. This results in blurry near vision. Although the progression of presbyopia is gradual, presbyopes often experience an abrupt change in their daily life as the symptoms become more pronounced, starting in their mid-40s, when reading glasses or other corrective aids are suddenly necessary to read text or conduct close-up work. To address the daily challenges faced by presbyopes, LENZ Therapeutics is developing a once-daily pharmaceutical eye drop that has the potential to improve near vision throughout the full workday without the need for reading glasses.
On that note, and moving to slide three, I am very proud to begin to review the CLARITY phase III study results. Building on our previously reported data from the INSIGHT phase II study and looking at the top-line data of all three CLARITY trials, we are very pleased to report that LNZ100, a single agent, once daily, a cyclodextrin product candidate, continued to show potential best-in-class performance. Based on LNZ100's very strong efficacy and safety profile in the trials thus far, and the fact that LNZ101 did not show superiority, we have, with great confidence in its potential, selected LNZ100 to become our future commercial candidate, for which we intend to submit a new drug application to the FDA by mid-2024.
Consistent with previous trials, and for the moment focusing on day 1 results for CLARITY 2, as this is the direct vehicle control trial, LNZ100 showed a rapid onset effect, with 71% of participants achieving three lines or more of near vision improvement without losing one line or more of distance vision at 30 minutes. At the primary endpoint of three hours, we also observed three lines or more responder rates of 71%. LNZ100 also maintained high levels of near vision improvement, with 40% of participants achieving three lines or more of near vision at 10 hours, the last time point measured in our efficacy trials. All results were highly statistically significant, with P values at each time point of less than 0.001.
We also saw a very impressive near universal response to LNZ100, with 95% of participants achieving at least two lines of near vision improvement. This is an important measure because it is seen as clinically meaningful and significant for most presbyopes. Notably, 69% of the participants still reported this improvement at the end of the day, 10 hours after dosing. Importantly, we tested our product candidates in a broad population, representing the majority of the 128 million presbyopes in the U.S. We had a mean age of 55, within a range of 45-75 year olds. The inclusion criteria incorporated participants who previously had LASIK surgery or are pseudophakes. In our CLARITY 1 and 2 trials, the participants used their assigned treatment agent every day, once daily, for 42 days.
We saw similar high response rates for LNZ100 across both trials at the various days we brought participants in for measurements. In terms of safety, LNZ100 was seen to be well tolerated, with no treatment-related serious adverse events observed in the over 30,000 treatment days across all three CLARITY trials. All of the reported adverse events, of all reported adverse events, 95% were classified as mild, believed to be transient, and consistent with those observed in previous trials. LNZ101, a combination of aceclidine and brimonidine, showed similar response rates, but was not superior in performance compared to LNZ100. As mentioned earlier, we therefore selected LNZ100 as our commercial candidate, which, if approved, could launch as early as the second half of 2025. Let us now walk through key data points in more detail.
Slide four outlines the design of our six-week randomized, double-masked, controlled CLARITY 1 and 2 safety and efficacy trials, as well as the key parameters of the study population, which include the participants within age ranges of 45-75 years and a refractive index range of -4 to +1 diopter spherical equivalent, who previously had LASIK surgery or pseudophakes and had a baseline near visual acuity of 20/50 or worse. In both trials, participants were randomized to either LNZ100, LNZ101, or depending on the trial, brimonidine or vehicle as control. In total, 234 participants were administered LNZ100. Now turning to slide five, you will see the percentage of participants that achieved three lines or more of near vision improvement without losing five letters or more of distance vision in day one of our vehicle-controlled CLARITY trial.
I would like to highlight that because CLARITY 2 is the vehicle control trial, which allows comparison to future or other presbyopia trials, we will focus on that trial first. But you will find, and we will discuss an overview of all three and two-line data across both CLARITY 1 and 2 for both LNZ100 and LNZ101, a few slides further in the back. As you can imagine, we are very pleased to see confirmation of the high response rates, rapid onset, and long duration that we had seen in our phase II INSIGHT trial. All three are elements that we believe are key for the commercial success of a presbyopia eye drop. Already 30 minutes after treatment, 71% of responders had improved their near vision with at least three lines.
At three hours, our primary endpoint, this was again 71%, and at ten hours, LNZ100 still had 40% of three-line responders. Additionally, we achieved statistically significant P values below 0.001 and low vehicle responder rates for all time points measured. On slide six, we see confirmed that LNZ100 is a product candidate that generates a near universal response. Impressively, we observed that 95% of participants achieved at least two lines of near vision improvement, with that percentage being 69% at ten hours. This is important as two lines of near vision improvement is often referred to as being clinically meaningful for presbyopes. And yet again, we saw P values below 0.001 across all time points measured. On this slide, slide seven, we show the impact of LNZ100 on distance vision in both normal and low light conditions compared to vehicle.
From these data, it is clear that using LNZ100 does not have any negative impact on distance vision in any of these conditions. In fact, LNZ100 treatment actually showed a statistically significant improvement of 2-4 letters in distance vision in normal light. We were especially interested, impressed by the P values of less than 0.001 for this study parameter. Importantly, the data also shows that there's no negative impact on distance vision in low light. Moving to slide 8. Here we are comparing the results of three lines of near vision improvement at the different days measurements were taken, day one, 15, and 28. As a reminder, the participants come in for the first day of treatment at day 1 and undergo a full day of testing. They then go home with the assigned eye drops and use them every day for the next six weeks.
On day 15, they come back in for a short visit, and we measure efficacy over the course of three hours. Then on day 28, they come in again, this time for a full 10 hours of testing. At day 42, we only measure safety parameters. As you can see, participants experience a similar near vision improvement profile across the 4-week study period. Based on the results, we believe it is evident that the clinical benefit of LNZ100 is reproducible and robust. Going to slide nine to review the safety profile of LNZ100 further. Looking at the AE profile of LNZ100 across both CLARITY 1 and CLARITY 2 trials, zero serious treatment-related adverse events were reported, and the product candidate was very well tolerated.
The only ocular AEs observed at or over 5% are shown on the slide here, including a mild and brief stinging feeling upon instillation, often seen with the use of eye drops, mild dimness of vision, which, if it occurs, is believed to be mostly immediately after instillation, and some mild hyperemia. Importantly, 100% of these ocular AEs were reported as mild by investigators and participants. The only non-ocular AE observed over 5% was headaches at a vehicle-corrected 7.6%, with the vast majority classified again as mild. We believe these adverse events were transient, consistent with those observed in previous trials. Turning to slide 10. The impressive responder rates of LNZ-100 in combination with favorable tolerability profile contributes to what we believe to be very encouraging patient-reported outcomes, as also seen with the statistics reported on this slide.
To elaborate on these statistics, on day 28 of the CLARITY 1 and 2 trials, we provided all participants with detailed questionnaires asking them to report on their treatment experience. The results obtained from the participants who received LNZ100 showed that 90% of them noted an improvement in their near vision. 75% said that they would like to continue to use eye drops after the study, of which 81% indicated that they would expect to use the eye drops 4-7 times a week. We believe that extrapolation of these percentages across the 128 million presbyopes in the U.S. alone provides a interesting indication of the significant commercial opportunity that we hope to unlock. Moving to slide 11.
As a reminder, we generated safety data from the two six-week CLARITY 1 and CLARITY 2 studies, as well as from the CLARITY 3 trial, which is designed to confirm the long-term safety profile of our development candidates over a six-month period. We conducted this long-term safety study with a cohort of 144 participants who were using LNZ-100 eye drops daily for six months and were followed for any potential safety concerns. It is worth noting that, to our knowledge, this is the first time that any presbyopia eye drop in development has undergone a long-term safety study. Against this backdrop, we are extremely pleased to report that across the three separate CLARITY trials, we had a total of 378 participants using LNZ-100 for a combined over 30,000 patient treatment days, and not one treatment-related serious adverse event was reported.
On slide 12, and as promised, we see the percentage of three and two-line responders for both LNZ100 and LNZ101 against their control, being a brimonidine vehicle, and for both CLARITY 1 and 2. For each time point in either trial and each time point, endpoint, we achieved p-values below 0.001. We believe LNZ100's transformative potential in presbyopia is evidenced by these strong efficacy and safety data results. And while LNZ100 performance was also impressive, you can see that it was not superior to LNZ100. Based on the study findings across multiple parameters and endpoints, and with great confidence in its potential, we have selected LNZ100 as our lead candidate, for which we intend to submit an NDA to the FDA by mid-2024. Furthermore, we look forward to sharing any additional CLARITY data at an upcoming medical meeting.
Finally, I would like to close by once again expressing my sincere gratitude to patients, physicians, and site staff participating in the CLARITY trials. It is thanks to all of you that this milestone was made possible. And thanks to our highly committed and fantastic team at LENZ, we are so grateful for your utmost dedication to developing a better treatment alternative for presbyopia patients. With that, operator, please open the call for questions.
Thank you. We'll now be conducting a question and answer session. If you'd like to ask a question, please press star one from your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to withdraw your question from the queue. For participants that are using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please while we poll for questions. Thank you. Thank you. Our first question is from the line of Joe Catanzaro with Piper Sandler. Please proceed with your questions.
Hey, everybody. Appreciate you taking my question and congrats on these results. Maybe a couple from me. I guess I'm most interested in the tolerability data you're reporting here. I guess for both the ocular AEs and headache, is there some period of tolerization, meaning, you know, you see these for the first few doses, but then not thereafter? Any details there, I guess, would be super helpful, and I have a couple follow-ups.
Great. No, great question, Joe. Thanks for joining. So we do not, in this top-line data at this moment, have insight in the frequency or occurrence of the AEs. So it's worth noting that these patients are asked over and over how they're feeling. So if you think about the CLARITY 1 and 2 trial, there's five days in which we ask them how they're doing. If they report an AE in just one of those five days, they're reported 100% as having that AE. So, you know, we're, we're really looking into the maximum, if you will, of AEs that you can find. We will start to see data on how that develops over time and if indeed, you know, these AEs, as we, you know, sometimes have heard, are tachyphylactic and basically stop occurring over time. So we look forward to sharing that data, later on.
Okay, thanks. That's helpful, that's helpful. And then I guess a follow-up. I know historically with miotics, right, there's been a concern that you could impact distance vision negatively. So maybe, you know, help us understand what's happening here that's allowing patients on LNZ100 to, you know, actually have distance vision improvements. And then, is this something you think could actually be included in a future label?
Yeah, let me take the first part, and then I'll actually hand over to Marc Odrich, who can go into more detail. But to your point, you know, you often see that with miotics that actually stimulate the ciliary body, there's an impact on distance vision. As you know, it's like it does not impact the ciliary body. And we've historically, and again in this trial, seen that therefore, there's no impact on distance vision. We were, you know, very impressed by the fact that it's actually now shown to be statistically significant, a 2-4-letter improvement in normal light, and a slight but no improvement, if you will, in low light. So let me hand over to Marc Odrich to give some more background on why that is.
Yes, thank you. That, that's a great question. The smaller pupil improves the quality of the image, and it does so by blocking some of the higher order aberrations from the peripheral parts of the optical system, specifically the cornea and the lens. As we avoid the ciliary muscle, we're not inducing myopia, and so what we have really is a better quality of vision being presented to the retina through the optics, the improved optics of this particular small aperture. That, that's the mechanism by which this distance vision improves.
Okay, great. And then maybe if I could squeeze one last one in, maybe one actually, for Shawn here. When you query patients on their experience, you know, what are they citing with regards to efficacy? Is it the depth of efficacy they're observing early on, or is it more the duration effect they're observing? And, you know, what do you guys see as mattering most from a commercial perspective? Thanks again.
Yeah. Yeah, thank you. So the results that we saw from the patient-reported outcomes is extremely encouraging, right? So to see the interest that was so high from the participants in the study is great. The questions we asked and have shared today from the top-line data were truly binary with just the outcomes that we shared. We did not have additional details on those patient-reported outcomes.
Okay, got it. Thanks, again for taking my question, and congrats again on the data.
Thanks, Joe.
Our next question is from the line of Tim Lugo with William Blair. Please proceed with your question.
Congratulations on the data, and thank you for taking the question. The data looks so consistent between CLARITY 1 and 2 and even INSIGHT. I know you give a bit of background on the patients. Can you maybe talk... Were the background data or profiles between CLARITY 1 and 2 also relatively consistent, you know, in terms of patient background, age, the acuity range, all of that? It looks like you provide background, but only in a pooled manner.
Yeah, no, thanks, Tim. Great question. So yes, the background or the populations are very similar across all trials, and most notably, we have the broadest patient population that we test. So we have the widest age range, 45-75, and we have truly all ages in our trial, with a mean of 55. We have a refractive range, as you can see there, -4 to +1, and again, all patients in that group. Importantly, we let in LASIK patients or previous LASIK patients, pseudophakics, and we do that consistently across all our trials because we believe that, and I think the data shows this, that we have a product that actually is beneficial for pretty much every presbyopia out there. It is truly the vast majority of the 128 million presbyopia population in the US that we intend to service with this potential drop.
Understood. And what kind of sub analyses do you plan to do? I assume maybe the pseudophakic, but also post LASIK. Maybe those would be an interesting subgroup to dig into. Can you, you know, maybe talk about what you would like to see for sub analyses?
Yeah. No, there'll be no shortage of data cuts that we'll be looking at. You know, as we've shared, we have close to 250 patients on LNZ100 over CLARITY 1 and 2. So there's a lot of opportunity to start to look at these subpopulations. How do people perform over time? You know, is there - how do they perform if you cut them by starting refraction, refractive error, sorry, age? All those cuts we will, at some point, start to make.
Okay. And I noticed the day 15 10-hour time point data wasn't available on slide 8. Is there, you know, anything there? Do you think that that's much of an issue? Will it-
No.
-be available?
That's, that's per protocol, Tim. So on day 15, we only bring patients in for a three-hour day. So we truly only measure those first couple of hours, which is why, logically, we don't have a 10-hour time point.
Oh, understood. Well, congratulations.
Thank you.
Thank you. That concludes our questions from the conference call line. I'll now pass it to the LENZ speakers to take questions that came through the Q&A chat box.
Yep, and there are no questions in the chat box. Thank you.
Thank you. At this time, I'll turn the call back to Mr. Schimmelpennink for closing remarks.
Thanks, everyone. Thanks for dialing in. We appreciate it. Have a great day. Bye-bye.
Thank you. This will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.