Eef Schimmelpennink is the president and CEO of LENZ Therapeutics, a late clinical-stage biopharmaceutical company focused on developing the first and only aceclidine-based eyedrop (LNZ100) to improve vision in patients diagnosed with presbyopia. Mr. Schimmelpennink previously held executive positions with Pfenex Inc. (acquired by Ligand Pharmaceuticals), Alvotech, Pfizer Inc., Hospira Inc. and Synthon BV. He currently serves on the board of directors of LENZ, iBio Inc. and Continuem Therapeutics.
Ophthalmology Management: How does LENZ’s lead product candidate LNZ100 (1.75% aceclidine) for the treatment of presbyopia work?
Eef Schimmelpennink: Aceclidine is a unique, pupil selective miotic that creates a pinhole pupil to restore near vision. Because of its high selectivity to the iris sphincter, LNZ100 has been shown across various clinical studies to be able to achieve an ideal pupil size for depth of focus, below 2 mm, without overstimulating the ciliary muscle (which is known to cause significant side effects). Aceclidine’s pupil selective mechanism of action, in which miosis is decoupled from myopic shift, is expected to provide near vision improvement for the full workday. With LNZ100, LENZ hopes to deliver an “all eyes, all day” presbyopia solution.
OM: In April 2024, LENZ reported positive data from its Phase 3 CLARITY study of LNZ100. Can you give us an overview?
ES: We are very pleased with our CLARITY Phase 3 trials, which met all primary endpoints and showed a strong safety profile. In our vehicle-controlled CLARITY 2 trial, our lead LNZ100 demonstrated that 71%, 71% and 40% of participants achieved a ≥3-line improvement at 0.5, 3 and 10 hours respectively.
We tested the product in a broad population of participants aged 45-75, a refractive range of -4.0 D to +1.20 D SE and up to 2 D of cylinder. We also included participants who previously had refractive surgery such as LASIK or were pseudophakes.
In terms of safety, LNZ100 was perceived to be well-tolerated with no treatment-related serious adverse events observed in the over 30,000 treatment days across all three clinical trials. Of all reported non-serious adverse events, 95% were classified as mild, believed to be transient and consistent with those observed in previous trials.
With this data the company is targeting a mid-year 2024 new drug application submission. We have heard great excitement from physicians to address near vision needs in a new, unique and effective manner, with a pupil-selective miotic in development.
In our study of aceclidine, 90% of the participants stated they noticed an improvement in near vision and 75% indicated they would continue to use LNZ100 after the study. Of those, 81% said they expected to use the product 4-7 days a week. It is quite exciting to see participants confirming the interest and desire for a pharmacological treatment for presbyopia.
OM: In February 2024, your company initiated its “Eye Am…” campaign to educate physicians about future presbyopia solutions. Can you tell us more?
ES: Our desire with this campaign is to generate a discussion among physicians of what the ideal solution to treat presbyopia with an eyedrop looks like. What we heard from physicians is that it really comes down to targeting the right muscle in the eye (pupil selective and ciliary sparing), achieving the needed pupil for depth of focus (below 2 mm) and focusing on the early adopters in the sea of 128 million presbyopes (contact lens wearers, post refractive surgery patients and those who have been to a medical spa in the past 12 months).
The campaign is going great, and the request from physicians to share their voice and be a part of the campaign has been outstanding. We can’t wait to see it continue to grow over the next year.
OM: In March 2024, LENZ announced the completion of its merger with Graphite Bio. Can you discuss the significance of this transaction?
ES: The natural growth and next step for LENZ was to become a public company, and this transaction enabled a pathway for LENZ to become a publicly traded company (NASDAQ: LENZ) while increasing our cash on hand to $213 million as of the end of the first quarter of 2024. This is very significant because this provides LENZ to be well-positioned to bring aceclidine to market with the potential to provide a once-daily pharmacological eyedrop treatment to improve near vision throughout the workday for millions of presbyopes in the United States. OM
