Safety and efficacy of the selective TYK2/JAK1 inhibitor TLL-018 in moderate-to-severe plaque psoriasis: A phase 1b, randomized, double-blind, placebo-controlled study.

Background: Psoriasis treatments that provide rapid and extensive itch relief, lesion clearance are inadequate.

Objective: To evaluate the efficacy and safety of the tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in patients with moderate-to-severe psoriasis.

Methods: This phase 1b, double-blind, placebo-controlled study randomized participants to receive TLL-018 (2:2:2:1) 10:20:30 mg:placebo (12 weeks) twice daily (BID) orally (NCT05342428). The study included 73 patients with moderate-to-severe psoriasis. Eligible patients were aged 18-75 years and were diagnosed with moderate-to-severe psoriasis at least 6 months prior to screening, as defined by a psoriasis area and severity index (PASI) of ≥12, a body surface area (BSA) ≥10%, and a physician's global assessment (PGA) of ≥3. The primary endpoint was safety of TLL-018. The efficacy endpoints were proportions of patients achieving a PASI 75, PGA of 0 or 1, and DLQI 0/1 at week 12.

Results: A total of 73 participants were treated. TLL-018 was well tolerated, and most treatment-emergent adverse events were mild/moderate. At week 12, 40.0% (8 of 20 patients) of the patients achieved PASI 75 with TLL-018 10 mg BID; 47.6% (10 of 21 patients), with 20 mg BID; 61.9% (13 of 21 patients), with 30 mg BID; and 9.1% (1 of 11 patients), with placebo. The PGA 0/1 were 35%, 42.9%, 71.4% and 0%, respectively. 10 of 21 patients (47.6%) in TLL-018 30 mg BID group achieved PASI 90.

Conclusions: TLL-018 was well tolerated and showed promising efficacy at week 12 comparing placebo in patients with moderate-to-severe plaque psoriasis.