Ocular and systemic distribution of MRZ‐99030 in pigmented mouse, rat, rabbit and non‐human primate by quantitative tissue analysis

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AbstractPurpose The ocular tissue distribution and systemic pharmacokinetics of MRZ‐99030 was determined after single or repeated topical ocular dose regimens of MRZ‐99030 to pigmented mice, rats, rabbits, and non‐human primates. MRZ‐99030, an amyloid‐β aggregation modulator, is currently under development for the treatment of glaucoma and AMD, which are the leading causes of blindness and represent diseases with high unmet medical need.Methods Dutch Belted rabbits, Cynomolgus monkeys, Dark Agouti rats, and C57/BL6 mice received single or repeated bilateral topical ocular doses of MRZ‐99030. Ocular tissues and plasma were collected up to 24h after dosing and analyzed for MRZ‐99030 by liquid chromatography‐mass spectrometry (LC‐MS).Results MRZ‐99030 was readily absorbed into ocular tissues for all species with highest concentrations observed in the cornea and conjunctiva. MRZ‐99030 was also found in the ocular tissues of the posterior segment (choroid with RPE and retina) at all time points. Pharmacokinetics show MRZ‐99030 in all tissues and systemically, with elimination half‐lives that indicate somewhat sustained concentrations in melanin containing tissues. Concentrations in ocular tissues, in particular for the retina, increase with an increase in dose level (mouse and rat) and dose frequency (all species).Conclusion The results show that MRZ‐99030 is absorbed into the ocular tissues in all species following topical administration and is readily distributed to the posterior segment of the eye, including the retina. Therefore, this finding strongly supports that MRZ‐99030 is able to modulate the Aß aggregation in the target tissue of glaucoma and AMD.