LENZ Therapeutics, Inc. · NASDAQ:LENZ
LENZ Therapeutics — Investor Presentation (December 2021)
24 slides from LENZ Therapeutics's investor presentation, December 2021
Slide 1: LENZ Therapeutics, December 2021
LENZ THERA PEUT I December 2021
Slide 2: LENZ Therapeutics: Focused on innovative science to improve vision
LENZ THERAPEUTICS Focused on innovative science to improve vision Aceclidine - best-in-class Q2 2022 Phase 3 candidate to target presbyopia • Exclusive and novel active ingredient • Successful Phase 2 • Quickly improves near vision with a long duration • Strong IP • No impact on distance vision and
Slide 3: Presbyopia, the inevitable loss of near vision
Problem Presbyopia, the inevitable loss of near vision Research shows adults over 45 lose on average 1.5 lines of near vision per 6 years1 Most of us first start noticing this as… • We hold our phones farther from our eyes • We have difficulty reading a menu in a dimly lit restaurant 3
Slide 4: Imperfect treatment options
Imperfect treatment options Struggle Impacts over 120M people in the US 1.4M New presbyopes Aesthetic compromises Invasive and limited and inconvenience surgical solutions with every year2,3 inherent risk 4
Slide 5: An eye drop to improve near vision while preserving distance vision
Solution An eye drop to improve near vision while preserving distance vision 5
Slide 6: Meet Aceclidine: Best-in-class potential
Meet Aceclidine Best-in-class potential The first and only aceclidine-based eye drop with potential of providing all day seamless vision for the vast majority of presbyopes, with no preservatives 6
Slide 7: How the eye focuses light for near and far vision
How the eye focuses light for near and far vision Distance vision: Near vision: The lens is in its native shape which The lens changes shape, known as enables far vision accommodation, to allow focus on close objects Contracted Relaxed ciliary muscles ciliary muscles Thick lens Thin lens 7
Slide 8: Presbyopia is the age-related loss of near vision
Presbyopia is the age-related loss of near vision Problem: Solution: The lens hardens with age, limiting A pinhole pupil only allows light that will accommodation and shifting near vision focus on the retina as a surrogate for focus accommodation Contracted Contracted ciliary muscles iris muscles Pi
Slide 9: Reducing pupil diameter below 2mm increases depth-of-focus
Research shows reducing the pupil diameter below 2mm dramatically increases depth-of-focus8,9 Total Depth-of-Focus vs Pupil Diameter 2 Rapid DOF Increase Charman & Whitefoot Total Depth-of-Focus (D) Rayleigh limit “Although differences 1.5 between studies, DOF increases rapidly as the pupil diameter
Slide 10: Key side effect to avoid is the myopic shift
Key side effect to avoid is the myopic shift Risk: Problem: Triggering the iris for pinhole effect while Resulting in improved near vision overstimulating the ciliary muscle causing at the expense of impaired unwanted refractive change distance vision Contracted iris muscle Distance vision focus shi
Slide 11: Aceclidine targets iris sphincter without overstimulating the ciliary muscle
Research shows aceclidine targets iris sphincter without overstimulating the ciliary muscle7 Iris sphincter muscle Ciliary muscle Independence ratio EC50 (nmol/l) EC50 (nmol/l) iris to ciliary EC50 20,000 Longitudinal 22 Aceclidine 900 25,000 Circular 28 1,800 3,360 Longitudinal 1.9 Pilocarpine 2,84
Slide 12: Which allows it to uniquely avoid the myopic shift
Which allows it to uniquely avoid the myopic shift4 Miotic pinhole effect achieved Corresponding myopic shift (iris sphincter muscle) (ciliary muscle) -0.13 Diopters myopia 2% Aceclidine 1.40 mm 0.078 mm lens shift 0.07 mm increase lens thickness -1.3 Diopters myopia 2% Pilocarpine 1.35 mm 0.234 mm
Slide 13: One diopter of myopic shift is meaningful
One diopter of myopic shift is meaningful 20/20 20/50 Perfect vision 1 Diopter myopic shift 20/40 20/40 Drivers test line 13
Slide 14: Addressable market is largest when pinhole effect is decoupled from myopic shift
Addressable market is largest when pinhole effect is decoupled from myopic shift Presbyopia market segments 40 – 54 yrs 55 – 64 yrs Over 65 yrs Population 31% 30% 39% - Optimal concentration for pinhole effect Aceclidine Broad addressable market - Minimal concern of induced myopia 14
Slide 15: Phase 2: Met endpoints for near vision improvement
Phase 2 Met endpoints for near vision improvement 3 lines or more near vision improvement 53% 47% Rapid Onset / On Demand 39% 22% 22% 17% 81% gained at least 2 lines within 30 minutes 2% 2% 0% 0% 0% 0% 53% gained at least 3 lines within 30 minutes 0.5 Hour 1 Hour 3 Hours 4 Hours 5 Hours 7 Hours P Va
Slide 16: Phase 2: No impact to distance vision
Phase 2 Met endpoint for no impact to distance vision with trend towards net gain Photopic best-corrected distance visual acuity No change in best corrected normal light distance visual acuity (P≥0.99 placebo vs -0.1 Aceclidine at all time points) -0.08 4 Letter Improvement BETTER VISION No change i
Slide 17: Phase 2: Maintained pupil size in target sweet spot for 7 hours
Phase 2 Maintained pupil size in target sweet spot for 7 hours 5.1 mm Pupil size over time Average pupil size reduced from 5.1 mm to 1.5 mm at 30 minutes Pupil size in mm Average pupil size maintained in 2 mm 1.8 mm sweet spot of 1.5mm to 2 mm for 7 1.6 mm 1.7 mm 1.5 mm 1.5 mm hours Pupil size corre
Slide 18: LENZ is preparing for a Q2 2022 pivotal Phase 3
LENZ is preparing for a Q2 2022 pivotal phase 3 LNZ100 1.75% Aceclidine - Optimal concentration for pinhole effect • Both use LENZ’s proprietary, - Minimal concern of induced myopia preservative free vehicle matrix to maximize comfort, efficacy and bioavailability LNZ101 • Type C meeting completed 1
Slide 19: Aceclidine safety history
Aceclidine Safety history History of use in Europe for Glaucoma • Approved for Glaucoma in Europe in 1970’s6 • Approved at higher concentration and QID dosing6 • Rapid anterior chamber penetration • Well tolerated with no tachyphylaxis • No US DMF submission and therefore a US NCE 19
Slide 20: Aceclidine broad exclusivity protection
Aceclidine Broad exclusivity protection US • 15 granted method of use and formulation patents • 7 patent applications under review Ex-US • 13 granted method of use and formulation patents • 33 patent applications under review FDA exclusivity provided by NCE status upon approval 20
Slide 21: LNZ100 & LNZ101 positioned to be best-in-class presbyopia eye drop
LNZ100 & LNZ101 positioned to be best-in-class presbyopia eye drop Only miotic shown to achieve pupil diameter <2mm for Unique true depth of field expansion without overstimulating MOA Profile the ciliary muscle Aceclidine Highest placebo adjusted responder rates, suggesting a Best-in-class Propriet
Slide 22: Experienced leadership
Experienced leadership Management: Eef Schimmelpennink Shawn Olsson Marc Odrich, MD Gerald Horn, MD President and CEO Chief Commercial Officer Chief Medical Officer Senior Scientific Advisor & Founder Board: Clare Ozawa, PhD Zach Scheiner, PhD Frederic Guerard Eef Schimmelpennink Jim McCollum Managi
Slide 23: About LENZ Therapeutics
About LENZ THERAPEUTICS LENZ Therapeutics is a late-stage clinical company developing innovative ophthalmic pharmaceutical products that improve vision. Our lead program is an aceclidine based eye drop designed to restore the loss of near vision associated with presbyopia. Presbyopia impacts almost
Slide 24: References
References 1. Progression of Near Vision Loss and Incidence of Near Vision Impairment in an Adult Chinese Population, PMCID: PMC6053595 2. Global Prevalence of Presbyopia and Vision Impairment from Uncorrected Presbyopia - Ophthalmology (aaojournal.org) 3. Population of the United States by sex and
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