Oruka’s ORKA-001 Delivers 61% Complete Skin Clearance in Phase IIb Psoriasis Study

Key Points

• ORKA-001’s 600-milligram regimen achieved a 61% PASI 100 complete-clearance rate and an 86% PASI 90 response rate at week 16 in the Phase IIb EVERLAST-B psoriasis study. Lower-dose regimens produced PASI 100 rates of 44% and 43%, while no placebo patients achieved complete clearance.
• The treatment was reportedly well tolerated, with adverse-event rates comparable to placebo, no treatment-related serious adverse events, and no injection-site reactions. Oruka plans to advance the 600-milligram dose into Phase III, targeted to begin in the first half of 2027 pending regulatory discussions.
• Oruka expects week 52 durability data from the EVERLAST-A study in December to assess the potential for annual maintenance dosing. The company also reported more than $1 billion in cash at the end of the second quarter, with funding expected through an ORKA-001 biologics license application filing.

Oruka Therapeutics NASDAQ: ORKA reported interim week 16 results from EVERLAST-B, a Phase IIb dose-ranging study of ORKA-001 in adults with moderate-to-severe plaque psoriasis. The company said its 600-milligram regimen achieved complete skin clearance, measured by PASI 100, in 61% of participants at week 16, while 86% achieved PASI 90.

The randomized, placebo-controlled trial enrolled 187 participants at 36 sites in the U.S., Canada, Germany and Spain. Patients were assigned equally among three ORKA-001 dose regimens or placebo. The high-dose group received 600 milligrams subcutaneously at weeks zero and four; the mid-dose group received 300 milligrams on the same schedule; and the low-dose group received 37.5 milligrams at week zero only.

“Today, we're very pleased to share that our candidate showed highly similar results in a second independent study while also generating the dose-ranging data needed to support moving this program forward into Phase III studies,” Chief Executive Officer Lawrence Klein said.

High-Dose Regimen Produced Highest Clearance Rate

The 600-milligram group produced the highest PASI 100 response rate at week 16, at 61%. The 300-milligram and 37.5-milligram groups recorded PASI 100 rates of 44% and 43%, respectively, while no placebo-treated participants achieved PASI 100.

Joana Goncalves, Oruka’s chief medical officer, said IGA 0 results, another measure of completely clear skin, matched the PASI 100 findings across treatment groups. Both the 600-milligram and 300-milligram regimens generated PASI 90 response rates in the mid-to-high 80% range, while the low-dose group reached 70%. No placebo recipients reached PASI 90.

Oruka said the 600-milligram results were consistent with those from its earlier EVERLAST-A trial despite limited overlap in study sites and differences in patient characteristics. The company noted that the 600-milligram cohort in EVERLAST-B was, on average, about 9 kilograms heavier than the comparable EVERLAST-A group and included a higher incidence of prior biologic use.

Across the two studies, more than 100 participants have received the 600-milligram induction regimen. Klein said pooled results showed approximately 63% PASI 100 and 84% PASI 90 at week 16.

Safety and Phase III Plans

ORKA-001 was well tolerated, according to the company. In pooled ORKA-treated participants, rates of treatment-emergent adverse events, severe treatment-emergent adverse events and serious adverse events were comparable with placebo. None of the serious adverse events were considered treatment-related, and Oruka reported no dose-dependent safety trends.

The most frequently reported events among ORKA-001 recipients were upper respiratory tract infections and headaches. The company said there were no injection-site reactions in any ORKA-001 treatment group, consistent with its prior EVERLAST-A findings.

Oruka has now dosed more than 250 subjects with ORKA-001 and accumulated more than 100 patient-years of experience, Klein said. The company plans to advance the 600-milligram dose into Phase III, pending regulatory discussions, with Phase III initiation targeted for the first half of 2027.

Management said it expects to include an active comparator in Phase III but has not finalized the trial design or comparator choice. Klein said the company is weighing a head-to-head study against a leading IL-23p19 inhibitor against other options that could affect study size, cost, risk and potential market access.

Durability Data Expected in December

The next major ORKA-001 update is expected to be week 52 data from EVERLAST-A in December. The company views those results as an initial clinical test of whether ORKA-001 could support annual maintenance dosing.

In EVERLAST-B, patients achieving PASI 100 at week 28 will be re-randomized to either annual 600-milligram maintenance dosing or no additional dosing until disease recurrence. Participants not reaching PASI 100 at week 28 will receive 300 milligrams every six months. Oruka expects additional EVERLAST-B results in the second half of 2027 after participants complete week 52 of the ongoing two-year study.

Klein said the company sees a potential annual regimen with a six-month dosing option. He said that maintaining PASI 100 in roughly 80% of patients in the no-dose arm could support use of once-yearly dosing broadly, while a lower maintenance range could still support an annual product with a six-month option for patients needing more frequent treatment.

Other Pipeline Milestones

Oruka also plans to report initial Phase II psoriasis results for ORKA-002, its extended-half-life IL-17AF antibody, in the first quarter of 2027. ORKA-002 is also in Phase II development for hidradenitis suppurativa. The company said it is assessing psoriasis, psoriatic arthritis and hidradenitis suppurativa as key potential indications for the program.

ORKA-004, an extended-half-life TL1A antibody, is expected to enter Phase I around year-end, with combination studies planned to begin in 2027. Oruka said its cash balance exceeded $1 billion at the end of the second quarter and is expected to provide runway through an ORKA-001 biologics license application filing.

About Oruka Therapeutics (NASDAQ:ORKA)

Oruka Therapeutics, Inc NASDAQ: ORKA is a clinical-stage biopharmaceutical company developing long-acting antibody therapies for immune-mediated diseases. The company is focused on creating treatments that may provide durable disease control while reducing the frequency of administration compared with conventional biologic therapies.

Oruka's pipeline is centered on engineered monoclonal antibodies that target the interleukin-17 (IL-17) pathway, an important driver of inflammation in conditions such as psoriasis and other autoimmune diseases.

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