This is a multicenter, double-blind, randomized, vehicle-controlled, parallel-group proof-of-concept study designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of topically applied ESR-114 following twice daily (BID) application for 42 days (6 weeks).

Inclusion Criteria:

• Subject has a history of plaque psoriasis for at least 6 months.
• Subject has PGA of mild (2) or moderate (3) at Day 1.
• Subject has total LSS of ≥6 at Day 1.
• Subjects with plaque psoriasis-affected BSA to be treated of 1% to 15% at Screening and Day 1.

Exclusion Criteria:

• Subject has non-plaque psoriasis at Screening and Day 1.
• Subject has a history of skin disease or presence of skin condition that, in the opinion of the Investigator, would interfere with the study assessments at Screening and Day 1.
• Subject has used any topical therapy to treat psoriasis within 2 weeks prior to Day 1.