Abstract
Purpose :
Development of novel eyedrops to treat presbyopia is a predominating trend in the evolving standard-of-care for the ubiquitous disorder of the aging lens. Lento Bio seeks to improve upon a field dominated by short-acting miotics through reducing lens stiffness directly, which could durably restore accommodation. Thus, we tested the effects of N-(2-fluoro-2-methyl-1-oxopropyl)-cysteine (termed LB-01) on lens flexibility in 8-month-old mice and compared it to Lipoic Acid Choline Ester (LACE), an asset previously being developed clinically.
Methods :
In Vivo Assay: 7-month-old C57BL/6 mice were treated 2x/daily with 3μl eyedrops of 200mM LB-01, 1.5% W/V LACE, or vehicle (artificial tears) in each eye. After 4 weeks dosing (at approximately 8 months of age), mice were euthanized, the lens removed, and stiffness measured via the coverslip method (Cheng et al. 2016). In this procedure, a 588mg coverslip was placed atop the lens and axial compression is measured. Measurement was performed blinded to group IDs. Results were aggregated across several separate studies following the same protocol.
Materials: LB-01 was synthesized at Florida State University by Dr. James Frederich's lab.
Results :
Lens stiffness was significantly reduced in LB-01 treated mice compared to both LACE and vehicle treated mice. Vehicle (n=73) averaged 199.34 μm total compression (stdev 32.16). LB-01 (n=19) had an average of 281.05 μm total compression (stdev 40.70). LACE (n=19) averaged 209.68 μm total compression (stdev 28.16). Two-month-old young comparators (n=7) had an average of 319.71 μm total compression (stdev 40.05). LB-01 was superior to both 8-month-old vehicle (p<.0001) and LACE (P<.0001) and is able to restore 67.9% of lens stiffness lost to aging from 2-8 months.
Conclusions :
Our data shows that LB-01 is an effective lens stiffness reducing agent. Notably, Lipoic Acid Choline Ester (which was being developed under the name UNR844) proved insufficiently efficacious in the Phase 2B READER trial for presbyopia conducted by Novartis and development was discontinued. Superior efficacy to this molecule in direct comparison, as well as strong overall results over just 1 month of treatment, suggest that LB-01 has significant potential in the treatment of presbyopia.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.