Oruka Therapeutics announces interim data from ORKA-001 trial at EADV

Oruka Therapeutics (ORKA) announced interim data from its Phase 1 trial of ORKA-001, the company’s long-acting IL-23p19 antibody, in a late-breaking abstract at the European Academy of Dermatology and Venerology Congress in Paris, France. These results, as well as additional details on the EVERLAST-A trial design, will be presented in two oral presentations at the conference. Interim results from the Phase 1 trial support the potential for ORKA-001 to change the PsO treatment paradigm. The ongoing EVERLAST-A Phase 2a trial is designed to test whether ORKA-001 can enable annual dosing, higher rates of skin clearance than standard of care, and long-term off-treatment remissions. Oruka expects to present initial data from EVERLAST-A in 2H 2026. The Phase 1 trial is a first-in-human, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and pharmacokinetics of ORKA-001 in healthy volunteers. The study enrolled 24 healthy adult participants into three single ascending subcutaneous dose cohorts of 300 mg, 600 mg, and 1200 mg. Interim results from the Phase 1 trial include: ORKA-001 showed a half-life of approximately 100 days, greater than three times that of risankizumab, and a Cmax that exceeded risankizumab at an equivalent dose, based on previously reported risankizumab data. These properties increase the likelihood of achieving once-yearly maintenance dosing and demonstrate comparable exposures to the KNOCKOUT study, which could lead to best-in-class rates of skin clearance and extended off-treatment remissions. Single doses of ORKA-001 demonstrated complete and sustained inhibition of STAT3 signaling, a downstream marker of IL-23 activity, in an ex vivo assay through 24 weeks. ORKA-001 was well tolerated at all dose levels, with a favorable safety profile consistent with the anti-IL-23 class. There were no severe treatment-emergent adverse events or serious adverse events. The only TEAEs to occur in more than two subjects were headache, upper respiratory tract infections, and transient erythema at the injection site. The study remains blinded, and all subjects remain on study. The ongoing EVERLAST-A trial is a randomized, double-blind, placebo-controlled Phase 2a trial designed to evaluate the safety and efficacy of a single dose level of ORKA-001 in moderate-to-severe PsO patients. Enrollment and dosing at sites across the U.S. and Canada are currently progressing well, and the company expects to share initial data from EVERLAST-A in 2H 2026. Data presented at that time is expected to include PASI 100 at Week 16 for all patients and preliminary durability data that could show the potential for yearly dosing and off-treatment remissions. EVERLAST-A will enroll approximately 80 patients randomized 3:1 to receive 600 mg ORKA-001 at Week 0 and 4 or matching placebo. The primary endpoint is PASI 100 at Week 16. ORKA-001 exposures are expected to match or exceed exposures in the KNOCKOUT study, testing whether higher antibody exposures can lead to greater efficacy. At Week 28, patients who have achieved PASI 100, or completely clear skin, will be randomized 2:1 to an arm where either they do not receive another dose until disease recurrence or they receive 300 mg ORKA-001 every six months. The “no-dose” arm will evaluate the possibility of both yearly dosing and extended off-treatment remissions. Patients who have not achieved PASI 100 at Week 28 will receive 300 mg ORKA-001 every six months. At Week 16, patients receiving placebo will cross over to 600 mg ORKA-001 at Week 16 and 20, followed by once-yearly dosing of ORKA-001, providing additional data on the efficacy of yearly dosing. In addition, Oruka expects to initiate a dose-ranging Phase 2b trial of ORKA-001 in moderate-to-severe PsO patients, EVERLAST-B, in 1H 2026. EVERLAST-B will evaluate three dose levels of ORKA-001: 37.5 mg at Week 0, 300 mg at Weeks 0 and 4, and 600 mg at Weeks 0 and 4, versus placebo. The primary endpoint is PASI 100 at Week 16. To expedite development, EVERLAST-B dosing is projected to begin enrolling before the completion of EVERLAST-A.