Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: efficacy by baseline body surface area (BSA) involvement and baseline Psoriasis Area and Severity Index (PASI) April W Armstrong,1 Mark Lebwohl,2 Jerry Bagel,3 Todd Schlesinger,4 Subhashis Banerjee,5 Renata M Kisa,5 Thomas Scharnitz,5 Kim Hoyt,5 Bruce Strober6 1University of Southern California, Los Angeles, CA, USA; 2Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Psoriasis Treatment Center of New Jersey, East Windsor, NJ, USA; 4Clinical Research Center of the Carolinas, Charleston, SC, USA; 5Bristol Myers Squibb, Princeton, NJ, USA; 6Yale University School of Medicine, New Haven, and Central Connecticut Dermatology Research, Cromwell, CT, USA Presented at the Winter Clinical Dermatology Conference - Hawaii®, January 13-18, 2023, Kohala Coast, HI, and Winter Clinical - MiamiTM, February 17-20, 2023, Miami, FL Email: aprilarmstrong@post.harvard.edu Copies of this poster are for personal use only and may not be reproduced without written permission from the authors. Introduction • Tyrosine kinase 2 (TYK2) is an intracellular enzyme that mediates signaling of cytokines (interleukin-23 and Type I interferons) involved in psoriasis pathogenesis (Figure 1)1,2 • Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy3 Figure 1. Mechanism of action of deucravacitinib TYK2 Deucravacitinib (allosteric inhibitor class) Unique regulatory domain Catalytic domain (highly conserved across JAK family) ATP-binding active site (approved JAK inhibitor class) •  ≥100-fold greater selectivity for TYK2 vs JAK 1/3 • ≥2000-fold greater selectivity for TYK2 vs JAK 2 Selectivity in cells1,2: ATP, adenosine triphosphate; JAK, Janus kinase; TYK2, tyrosine kinase 2. • In 2 pivotal, multinational phase 3 trials, POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751), in patients with moderate to severe plaque psoriasis, deucravacitinib treatment was associated with: — Significantly greater response rates for ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician’s Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (sPGA 0/1) at Week 16 vs placebo and apremilast4,5 — Maintenance of clinical efficacy was seen through Week 52 with continuous deucravacitinib treatment6 Objective • To examine the efficacy of deucravacitinib in patients with moderate to severe plaque psoriasis based on baseline body surface area (BSA) involvement and PASI score Methods • Adult patients with moderate to severe plaque psoriasis (PASI ≥12, sPGA ≥3, BSA involvement ≥10%) were randomized 1:2:1 to placebo, oral deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily (Figure 2) • Blinded treatment switches occurred at Week 16 and Week 24 — Patients randomized to placebo crossed over to deucravacitinib at Week 16 — Patients randomized to apremilast who failed to meet trial-specific efficacy thresholds (≥50% reduction from baseline in PASI [PASI 50] in POETYK PSO-1; PASI 75 in POETYK PSO-2) switched to deucravacitinib at Week 24 Figure 2. POETYK PSO-1 and PSO-2 study designs Coprimary endpoints: PASI 75 and sPGA 0/1 for deucravacitinib vs placebo at Week 16 POETYK PSO-1 (N = 666) Deucravacitinib 6 mg QDPlacebo (n = 166) Deucravacitinib 6 mg QD