Oruka Therapeutics Touts “Category-Winning” ORKA-001 Data, Targets Once-Yearly Psoriasis Dosing

Key Points

• ORKA‑001 delivered strong 16‑week efficacy in EVERLAST‑A, with 63.5% of treated patients achieving PASI 100 versus 1 of 21 on placebo (p<0.0001) and high PASI 90 and other endpoint responses.
• Safety was comparable to placebo—ORKA‑001 was well tolerated with no serious adverse events, no discontinuations, mostly mild TEAEs, and no injection‑site reactions reported across >200 injections.
• Phase I pharmacokinetics (≈100‑day half‑life) and biomarker data show serum exposure above approved IL‑23 troughs through one year, supporting a potential once‑yearly maintenance dosing strategy; additional week‑28 and partial week‑52 data and a parallel EVERLAST‑B dose‑ranging study are forthcoming.

Oruka Therapeutics NASDAQ: ORKA reported 16-week interim results from EVERLAST-A, a double-blind, placebo-controlled phase II study evaluating ORKA-001, the company’s extended half-life IL-23/p19 monoclonal antibody for moderate-to-severe plaque psoriasis. Management highlighted what it described as a potentially “category-winning” efficacy profile alongside a safety profile consistent with the IL-23 inhibitor class, and pointed to pharmacokinetic data supporting the goal of once-yearly maintenance dosing.

Study design and dosing strategy

CEO Lawrence Klein said the company’s mission is to “advance the standard of care in psoriatic disease,” with two co-lead programs: ORKA-001 (IL-23/p19) and ORKA-002 (IL-17A/F). Klein positioned ORKA-001 as a potential annually dosed option for patients with predominantly skin psoriasis, while ORKA-002 is being developed for patients with concurrent joint disease and for additional indications such as hidradenitis suppurativa (HS).

Chief Medical Officer Joana Goncalves said EVERLAST-A enrolled 84 participants across 26 sites in the U.S. and Canada. Participants were randomized 3:1 to ORKA-001 or placebo. The active arm used a 600 mg subcutaneous induction regimen at week 0 and week 4, which Goncalves said was “at least 4x higher than the induction dosing of market-leading IL-23 inhibitors,” selected based on literature suggesting higher exposure may yield higher efficacy at week 16 and beyond.

Goncalves noted that all participants reached the week 16 primary endpoint “with no discontinuations.” She also emphasized that the trial used PASI 100 as the primary endpoint—“the first time that PASI 100 is being used as a primary endpoint in a phase II psoriasis study”—reflecting a focus on complete skin clearance.

Week 16 efficacy highlights

At week 16, 40 of 63 participants treated with ORKA-001 achieved PASI 100 (63.5%) using non-responder imputation, compared with 1 of 21 participants on placebo. Goncalves said the p-value for the primary endpoint was “less than 0.0001.” She added that investigator global assessment (IGA) 0 was “identical to PASI 100 for all participants,” which she said supported consistency in investigator assessment.

Additional efficacy measures also favored ORKA-001. Goncalves reported that 53 of 63 participants (83%) achieved PASI 90 at week 16, compared with one participant on placebo. She said the study also showed high response rates on other endpoints including absolute PASI ≤1, IGA 0/1, and PASI 75.

Management discussed subgroup observations while cautioning that baseline characteristics have historically shown limited correlation with outcomes in plaque psoriasis. Goncalves said efficacy was similar across subgroups by baseline PASI and IGA, and that higher body-weight patients showed “slightly higher rates of PASI 100,” suggesting exposure may have reached a level where weight is less influential. She also noted participants with prior biologic use showed slightly higher efficacy, which she attributed to the limited size of that subgroup.

Safety and tolerability

Goncalves said ORKA-001 was “well-tolerated with a profile comparable to placebo.” Treatment-emergent adverse events were reported by 50.8% of participants on ORKA-001 and 57.1% on placebo, with most events described as mild and none leading to discontinuation. There were no serious adverse events, and the only severe adverse event—a bone fracture and dislocation—occurred in the placebo group.

Upper respiratory tract infection was the only adverse event occurring in 5% or more of participants in either group and was described as balanced between arms; Goncalves noted the study was conducted during peak respiratory virus season. She also said there were no injection-site reactions reported “for over 200 injections” and “no evidence of an ADA effect on safety, efficacy, or PK.” In the Q&A, Klein characterized ADA positivity as “a very low rate,” without providing a specific percentage.

Durability, annual dosing, and next data updates

While the week 16 dataset does not directly demonstrate one-year durability, Klein emphasized updated phase I healthy volunteer pharmacokinetic data showing an approximately 100-day half-life and serum levels for the 600 mg dose remaining above the trough levels of approved IL-23 antibodies through one year. He also said pharmacodynamic biomarker data from the same study showed suppression of IL-23 signaling out to a full year at 600 mg.

EVERLAST-A includes a longer-term design intended to explore durability and dosing intervals. Goncalves said that at week 28, participants who achieve PASI 100 will be re-randomized 2:1 to either a treatment-free arm (no dosing until disease recurrence) or a twice-yearly maintenance dosing arm. She said the no-dose arm is intended to inform the potential for once-yearly dosing and evaluate whether induction may lead to “long-lasting duration of skin clearance” and possible off-treatment remission. Placebo participants crossed over to active drug at week 16 and will enter a 24-month regimen in an open-label extension to gather additional data on once-yearly maintenance dosing.

The company expects to provide a second update from EVERLAST-A in the second half of the year, including all participants through week 28 and data from a portion of the cohort out to week 52, according to Goncalves. In the Q&A, Klein said seeing “a dozen or so people out to a year” with maintained response would add confidence in the once-yearly dosing concept.

Development timeline and broader pipeline context

Oruka said ORKA-001 is being studied in two parallel phase II trials: EVERLAST-A and the dose-ranging EVERLAST-B, which Klein said began enrolling in December and is “enrolling rapidly,” with a 16-week readout anticipated next year. Klein indicated EVERLAST-B’s data will be “gating” for an end-of-phase discussion with regulators and said the company is preparing other elements such as CMC and clinical operations to avoid delays.

On phase III planning, Klein said Oruka is evaluating options including the possibility of both once-yearly and twice-yearly dosing on the label. He also said the company would “probably include an active comparator” in phase III, while noting that head-to-head studies have not historically been required for approval or uptake in psoriasis.

Klein reiterated that ORKA-002 is now in phase II in psoriasis and is anticipated to enter the clinic for HS in the second half of the year. He said Oruka expects “meaningful data updates” across programs approximately every six months and described the company as “well funded with runway over one year beyond” at least some upcoming readouts.

About Oruka Therapeutics NASDAQ: ORKA

Oruka Therapeutics, Inc is a clinical‐stage biopharmaceutical company focused on the development of novel peptide‐based therapies for oncology. The company's proprietary stapled peptide platform is designed to selectively disrupt intracellular protein–protein interactions that drive tumor growth and immune evasion. By combining the specificity of biologics with the cell‐permeability of small molecules, Oruka aims to target cancer pathways that have been historically considered “undruggable.”

The company's lead candidate, ONCT-01, is currently in Phase 1 clinical trials for patients with advanced solid tumors, assessing safety, tolerability and preliminary efficacy.

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