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To assess the safety, tolerability, preliminary efficacy and skin penetration of a topical 1% ZL\u20101102 hydrogel in patients with mild\u2010to\u2010moderate CPP, a two\u2010part, Phase Ib study was conducted. Open\u2010label Part A: six patients received a single topical application of ZL\u20101102 onto a psoriatic plaque; double\u2010blind Part B: 53 patients were randomised 1:1 to twice\u2010daily ZL\u20101102 or vehicle for 4\u2009weeks. Key primary endpoints included treatment\u2010emergent adverse events (TEAEs), tolerability and changes in local psoriasis area and severity index (PASI). TEAEs occurred in two (33.3%) patients in Part A and in 16 (59.3%) and 13 (50.0%) patients in the ZL\u20101102 and vehicle arms, respectively, in Part B. No grade \u22653 TEAEs were seen with ZL\u20101102. ZL\u20101102 led to numerically greater changes in local PASI versus vehicle (\u221228.8% vs. \u221217.2%), with good local tolerability. The trend towards local PASI improvement was accompanied by biomarker changes based on RNA sequencing, indicative of ZL\u20101102 penetration into psoriatic plaques. Topical ZL\u20101102 showed good safety, local tolerability and a trend towards improved local PASI; skin penetration was observed without measurable systemic exposure. 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