Oruka Therapeutics (ORKA) Study result summary

Study design

• EVERLAST-B was a randomized, double-blind, placebo-controlled global Phase 2b trial in moderate-to-severe plaque psoriasis; 187 participants enrolled at 36 sites, with less than 30% of sites overlapping with EVERLAST-A.

• Participants received placebo or ORKA-001 37.5 mg, 300 mg, or 600 mg; the primary endpoint was PASI 100 at Week 16.

• The study continues through Week 100 to assess durability, maintenance dosing and long-term safety; Week 28 PASI 100 responders are re-randomized to annual 600 mg or no further dose until recurrence, while others receive 300 mg every 6 months.

Efficacy

• Week 16 PASI 100 rates were 61% with 600 mg, 44% with 300 mg, 43% with 37.5 mg and 0% with placebo; all doses beat placebo (p<0.0001).

• PASI 90 rates were 86% with 600 mg, 85% with 300 mg, 70% with 37.5 mg and 0% with placebo; high-dose IGA 0 was 61% and IGA 0/1 was 86%.

• High-dose results were consistent with EVERLAST-A: Week 16 PASI 100 was 61% vs. 63%, PASI 90 was 86% vs. 83%, IGA 0/1 was 86% vs. 84%, and PASI 75 was 95% vs. 94%.

• Across EVERLAST-A and B, pooled 600 mg Week 16 results were 63% PASI 100 and 84% PASI 90; cross-trial comparisons suggested ~20pp and ~10pp gains vs. leading IL-23s, respectively.

Safety and tolerability

• Across doses, 49% reported at least one TEAE; serious and severe TEAEs each occurred in 2%, and 1% discontinued due to a TEAE. In the high-dose group, TEAEs occurred in 39% vs. 43% with placebo.

• Safety was consistent with the IL-23p19 class; no serious or severe TEAEs were considered treatment-related, and no serious TEAEs occurred in the high-dose group.

• Upper respiratory tract infections and headaches were the most frequent TEAEs; no injection-site reactions occurred across ORKA-001 recipients or more than 500 injections.

• More than 250 subjects have been dosed, with over 100 patient-years of experience; no apparent anti-drug antibody impact on PK, efficacy or safety was reported.