Expert: Allosteric TYK2 inhibitor binding JH2 pseudokinase domain, locking TYK2 in inactive conformation. 100-2000x selectivity over JAK1/2/3. Inhibits IL-23, IL-12, Type I IFN signaling. Incomplete pathway blockade from fluctuating oral PK; never achieves 100% TYK2 occupancy. PASI 75 53-58% Wk16, PASI 90 27-36% Wk16 (well below injectable biologics). POETYK PSO-1/2: beat apremilast but inferior to all injectable biologics. No boxed warning (unlike JAK class). 5yr data clean (POETYK extension: PASI 75 71.7%, PASI 90 47.5% Wk208). ICONIC-ADVANCE: lost to icotrokinra H2H. Revenue $246M (2024) vs BMS $4B peak target — significant commercial disappointment. US generic entry estimated ~2033.

Everyday: Blocks TYK2, an enzyme INSIDE immune cells that relays the IL-23 signal. An oral pill that partially dampens the same pathway that Skyrizi fully blocks. WHERE TYK2 FITS: The signaling cascade works like a relay race: IL-23 (the baton) passes to the IL-23 receptor (first runner, on the cell surface) → the receptor hands it to TYK2 (second runner, just inside the cell) → TYK2 hands it to STAT3 (third runner) → STAT3 runs into the nucleus and tells the cell to make IL-17. Skyrizi intercepts the baton (IL-23) before the race even starts — complete blockade. Sotyktu tackles the second runner (TYK2) but only partially slows him down. WHY LESS EFFICACIOUS: Oral pills have fluctuating blood levels throughout the day — Sotyktu never achieves 100% TYK2 inhibition. It is a dimmer switch vs cutting the power line. PASI 90 ~27-36% Wk16 (vs ~75% for Skyrizi). TYK2 also mediates IL-12 and Type I interferon signaling, causing some pathway crosstalk. KEY ADVANTAGE: Oral convenience, no injections, no lab monitoring needed (unlike broader JAK inhibitors which cause heart/clot/cancer risks). No boxed warning. Clean safety profile. For patients who absolutely refuse injections and cannot wait for icotrokinra. COMMERCIAL REALITY: Revenue has disappointed ($246M in 2024 vs $4B peak target). Once icotrokinra is approved (oral with IL-23-class efficacy), Sotyktu will likely be displaced.

Targets: ["TYK2"]

Primary EP: [{"id":"pasi75-w16","name":"PASI 75 at Week 16","type":"PRIMARY","unit":"%","results":[{"value":58.4,"arm_id":"deuc-arm","p_value":0.001},{"value":35.1,"arm_id":"apr-arm"},{"value":12.7,"arm_id":"pbo-

First oral TYK2 inhibitor for PsO. PASI 90 ~28-36% Wk16 — well below injectable biologics. For injection-averse patients only. Beat Otezla H2H (POETYK). No boxed warning (unlike JAK inhibitors — TYK2-selective). 5yr safety clean. Lost H2H to icotrokinra in ICONIC-ADVANCE (PASI 90: 41-43% vs 55-57%). BMS guided $4B peak but Wall Street consensus ~$1.9B. Revenue disappointing: $246M (2024). Will likely be displaced when icotrokinra launches (oral with IL-23-class efficacy vs TYK2-class). Only advantage: already approved.