Assessment of the pharmacological and safety profile of the small molecule MP-004 after topical eye drops administration

MP-004 is a novel small molecule under development as a non-invasive therapeutic for inherited retinal dystrophies (IRDs), including retinitis pigmentosa. Here, we evaluated its ocular concentration and safety profile following topical administration in three animal species —mouse, rabbit, and pig—. MP-004 formulation with 0.3% hyaluronic acid significantly enhanced retinal concentration in mice compared to non-formulated compound (6.67 vs 1.27 µg/g at 4 h). MP-004 reached therapeutically relevant retinal concentrations in all species tested, with minimal systemic exposure: in mice, levels detected in serum were lower than 5 ng/mL while in rabbits, the compound was undetectable in blood and peripheral tissues 12 h post-dose.

Seven-day repeated-dose toxicity studies in mice and rabbits showed no systemic or ocular toxicity. In rabbits, only transient ocular redness was observed post-administration, with no evidence of corneal damage or systemic adverse effects. Hematological and biochemical parameters in both species remained within normal limits. Importantly, retinal and optic nerve concentrations remained detectable in rabbits 7 days after final dosing, while the compound was eliminated systemically, supporting prolonged target tissue retention.

These findings demonstrate that MP-004 is well tolerated and achieves effective retinal concentrations via topical delivery, overcoming a major barrier in retinal drug development. The favorable pharmacokinetic and safety profile across species, including anatomically relevant models, supports MP-004’s advancement toward regulatory preclinical studies and clinical translation as a non-invasive therapy for IRDs.