Oruka Therapeutics has shared interim Phase 1 data for ORKA-001, a long-acting IL-23p19 antibody, at the EADV Congress in Paris. The candidate could reshape plaque psoriasis (PsO) care by enabling once-yearly dosing and higher skin clearance rates than current treatments.
Why This Matters
- Psoriasis burden: Current IL-23p19 therapies are injected 4–6 times per year.
- Clearance gap: Less than half of patients reach fully clear skin (PASI 100) at four months.
- Big promise: ORKA-001 aims for annual dosing, higher efficacy, and even off-treatment remissions.
Key Phase 1 Findings
- Pharmacokinetics: Half-life of ~100 days—over 3x longer than risankizumab.
- Pharmacodynamics: Complete inhibition of STAT3 signaling for 24 weeks.
- Safety: Favorable profile; most common issues were headache, mild infections, and transient injection-site reactions. No severe events reported.
EVERLAST-A: The Phase 2a Trial
- Design: 80 patients, randomized 3:1 (ORKA-001 vs placebo).
- Dose: 600 mg at Weeks 0 and 4.
- Primary endpoint: PASI 100 at Week 16.
- Durability test: Patients with full clearance at Week 28 will either stop dosing until relapse or shift to twice-yearly dosing.
- Placebo arm: Switches to ORKA-001 at Week 16, then tested for yearly dosing.
- Timeline: Initial readout expected 2H 2026.
Next Steps
- EVERLAST-B (Phase 2b): Starts 1H 2026. Will test three dosing regimens:
- 37.5 mg at Week 0
- 300 mg at Weeks 0 + 4
- 600 mg at Weeks 0 + 4 - Primary endpoint: PASI 100 at Week 16.
The Bigger Picture
- ORKA-001 could extend dosing intervals from every 2–3 months to just once per year.
- Higher exposures than marketed IL-23p19s may unlock best-in-class clearance rates.
- Oruka’s mission: give patients freedom from chronic skin disease with long-lasting, simplified therapy.
