ORKA-001 / Oruka Therapeutics - LARVOL DELTA

EVERLAST-A: A Phase 2a Study Design of ORKA-001, a Novel Half-Life Extended IL-23p19 Monoclonal Antibody for Plaque Psoriasis (ISDS 2025) - "ORKA-001 is a novel half-life extended monoclonal antibody targeting IL-23p19 with similar potency and epitope binding to risankizumab... EVERLAST-A is a Phase 2 proof-of-concept study evaluating efficacy and safety of ORKA-001 in adults with moderate-to-severe psoriasis. The study aims to investigate whether high induction doses of ORKA- 001 can lead to increased rates of skin clearance and prolonged durability of responses."

P2a data • Dermatology • Immunology • Psoriasis • IL23A

Additional…updates (GlobeNewswire) - "The Company completed a $180M PIPE financing, extending runway over one year past three Phase 2 catalysts: the ORKA-001 Phase 2a and 2b studies (EVERLAST-A and -B), and the ORKA-002 Phase 2 study in PsO."

Financing • Psoriasis

Additional programs… (GlobeNewswire) - "(i) ORKA-021 (ORKA-002 → ORKA-001): Oruka continues to advance a sequential combination regimen of ORKA-002 and ORKA-001, which could deliver rapid and deep responses with an ideal maintenance profile. ORKA-021 could create another opportunity for the Company to define the best possible regimen for the treatment of psoriatic disease; (ii) ORKA-003: The Company continues to progress ORKA-003 through preclinical development."

Pipeline update • Psoriasis

Oruka plans to initiate a dose-ranging Phase 2b trial of ORKA-001, EVERLAST-B, in 1H 2026 (GlobeNewswire) - "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."

New P2b trial • Psoriasis

Enrollment is progressing well in EVERLAST-A, a randomized, double-blind, placebo-controlled Phase 2a trial of ORKA-001 in moderate to severe PsO (GlobeNewswire) - "The Company expects to share PASI 100 data at Week 16 for all patients, as well as response duration data out to approximately one year for some patients, in 2H 2026."

Enrollment status • P2a data • Psoriasis

Phase 1 clinical data of ORKA-001, a novel half-life extended IL-23p19 monoclonal antibody with potential for once-yearly dosing in plaque psoriasis (EADV 2025) - "Conclusion PK and PD results in this Phase 1 study of ORKA-001 support the potential for once-yearly dosing while maintaining trough antibody concentrations above approved IL-23 targeting antibodies like risankizumab...ORKA-001 was well-tolerated across all dose levels, with a favorable safety profile consistent with the IL-23p19 inhibitor class. These attributes are being further explored in an ongoing Phase 2a study, EVERLAST- A, which is evaluating efficacy and safety of ORKA-001 in adults with moderate-to-severe psoriasis."

Clinical data • Late-breaking abstract • P1 data • Dermatology • Immunology • Infectious Disease • Psoriasis • Respiratory Diseases • IL23A

EVERLAST-A: A phase 2a study design of ORKA-001, a novel half-life extended IL-23p19 monoclonal antibody for plaque psoriasis (EADV 2025) - "ORKA-001 is a novel half-life extended monoclonal antibody targeting IL-23p19 with similar potency and epitope binding to risankizumab... EVERLAST-A is a Phase 2 proof-of-concept study evaluating efficacy and safety of ORKA-001 in adults with moderate-to-severe psoriasis. The study aims to investigate whether high induction doses of ORKA-001, a novel IL-23p19 inhibitor with an extended half-life, can lead to increased rates of skin clearance and prolonged durability of responses. This dosing strategy could support infrequent individualized dosing and potentially lead to disease remission in some individuals."

P2a data • Dermatology • Immunology • Psoriasis • IL23A

…Oruka expects to initiate a dose-ranging Phase 2b trial of ORKA-001 in moderate-to-severe PsO patients, EVERLAST-B, in 1H 2026. (GlobeNewswire)

New P2b trial • Psoriasis

Oruka Therapeutics Announces Positive Interim Phase 1 Results for ORKA-001 (GlobeNewswire) - "PK: 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....Pharmacodynamics (PD): 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 (the longest follow-up available)."

P1 data • PK/PD data • Psoriasis

EVERLAST Phase 2 Trials of ORKA-001 in Plaque Psoriasis (GlobeNewswire) - "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....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."

Clinical protocol • P2a data • Psoriasis

EVERLAST-A: ORKA-001 Versus Placebo in Patients With Moderate-to-Severe Plaque Psoriasis (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Oruka Therapeutics, Inc.

New P2 trial • Dermatology • Immunology • Psoriasis

ORKA-001: a novel half-life extended IL-23p19 monoclonal antibody (GlobeNewswire) - "Enrollment is ongoing in EVERLAST-A following clearance from both the U.S. FDA and Health Canada in July, and the first patients have been dosed in the study...Additional details on the EVERLAST-A design will be presented at the European Academy of Dermatology and Venereology (EADV) Congress in September. The Company expects to share efficacy and response duration data from EVERLAST-A in 2H 2026....Oruka’s Phase 1 trial of ORKA-001 is ongoing, with dosing completed for all 24 subjects across three dose levels."

P2a data • Trial status • Immunology • Psoriasis

Oruka Therapeutics Announces IND Clearance for EVERLAST-A Phase 2a Trial of ORKA-001 in Psoriasis with Phase 1 Data to be Presented at EADV in September (GlobeNewswire) - "Oruka Therapeutics...announced that the U.S. FDA cleared its investigational new drug (IND) application for its Phase 2a trial of ORKA-001 (the Company’s long-acting anti-IL-23p19 antibody) in moderate-to-severe psoriasis, called EVERLAST-A...EVERLAST-A 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 psoriasis patients. EVERLAST-A will enroll approximately 80 patients, randomized 3:1 to receive ORKA-001 or matching placebo...Additional details on the EVERLAST-A design, as well as interim data from the ORKA-001 Phase 1 study, will be presented at the European Academy of Dermatology and Venereology (EADV) Congress in September. The Company expects to share efficacy and response duration data from EVERLAST-A in 2H 2026."

IND • New P2a trial • P2a data • Psoriasis

FDA clears Oruka’s IND for psoriasis drug ORKA-001 phase 2a trial (Investing.com) - "Oruka Therapeutics, Inc...announced Monday that the U.S. Food and Drug Administration has cleared its investigational new drug application for ORKA-001, allowing the company to proceed with its Phase 2a EVERLAST-A trial in moderate-to-severe psoriasis...The EVERLAST-A study will evaluate the safety and efficacy of ORKA-001, the company’s long-acting anti-IL-23p19 antibody. The randomized, double-blind, placebo-controlled trial will enroll approximately 80 patients, with participants randomized 3:1 to receive either ORKA-001 or placebo...The company expects to share efficacy and response duration data from EVERLAST-A in the second half of 2026."

IND • New P2a trial • Psoriasis

ORKA-001-111: ORKA-001 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Oruka Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Oruka Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Oruka initiated a Phase 1 trial of ORKA-001 in December 2024, ahead of schedule. The trial is a double-blind, placebo-controlled, single ascending dose study evaluating the safety, tolerability, and pharmacokinetics (PK) of ORKA-001 in approximately 24 healthy volunteers. The Company expects to share interim data from this trial, including initial PK data, in the second half of 2025. Oruka plans to initiate a Phase 2a proof-of-concept study of ORKA-001 in the second half of 2025 that will enroll approximately 80 patients with moderate-to-severe psoriasis. The planned study design is innovative, with a primary endpoint of PASI 100 at week 16 (versus PASI 90 for prior biologics studies) and maintenance arms evaluating a six-month dosing interval alongside a cohort of patients who are not re-dosed until disease recurrence to test the potential for ultra-long responses. The Company expects to share efficacy and response duration data from this study in the second half of 2026."

New P2a trial • P1 data • Trial status • Psoriasis

ORKA-001-111: ORKA-001 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Oruka Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

ORKA-001: a novel extended half-life monoclonal antibody targeting IL-23 with the potential to improve upon currently available therapies for psoriasis (PsoriasisG2C 2024) - "Materials & ORKA-001 was evaluated in multiple in vitro and ex vivo assays in comparison to two benchmark antibodies that target IL-23p19: risankizumab (RIS) and guselkumab (GUS)... ORKA-001 exhibits high selectivity and affinity for IL-23 in vitro, potent inhibition of downstream cellular signalling ex vivo, and an extended half-life in non-human primates compared with RIS and GUS. Both affinity and antibody exposure have been shown to have a positive correlation with efficacy in psoriasis, and ORKA-001 has the potential to exceed RIS and GUS on both metrics while requiring significantly fewer doses per year. In total, these data provide preclinical evidence of ORKA-001’s clinical potential to improve upon currently available therapies for psoriasis."

Dermatology • Immunology • Psoriasis • IL17A • IL23A • STAT3

Oruka Therapeutics Announces First Participants Dosed in Phase 1 Trial of ORKA-001, its Novel Half-life Extended Anti-IL-23p19 Antibody (GlobeNewswire) - "Oruka Therapeutics...announced that it has initiated dosing of healthy volunteers in its first clinical trial of ORKA-001....The ORKA-001 Phase 1 trial is a double-blind, placebo-controlled, single ascending dose study evaluating the safety, tolerability, and pharmacokinetics (PK) of ORKA-001 in healthy volunteers. The study is expected to enroll approximately 24 healthy volunteers across three subcutaneous dose cohorts. Oruka expects to share interim data from this study in the second half of 2025. Pending data from the Phase 1 trial, Oruka plans to initiate a proof-of-concept study of ORKA-001 in moderate-to-severe psoriasis in the second half of 2025....This study is anticipated to evaluate the safety and efficacy of a single dose level of ORKA-001 versus placebo in approximately 80 subjects, followed by randomization to one of two maintenance dosing arms. The company expects to share initial data from the proof-of concept study in the second half of 2026."

New trial • P1 data • Trial status • Psoriasis

ORKA-001-111: ORKA-001 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Oruka Therapeutics, Inc.

New P1 trial

Oruka Therapeutics Announces Preclinical Data for ORKA-001 at the European Academy of Dermatology and Venereology Congress (GlobeNewswire) - "Oruka Therapeutics, Inc...announced new preclinical data on ORKA-001, a novel extended half-life monoclonal antibody targeting IL-23p19, from its presentation at the European Academy of Dermatology and Venereology Congress (EADV)....ORKA-001 has an NHP half-life of 30.3 days following SQ administration and 33.8 days following IV administration, over three times longer than risankizumab and one of the longest NHP half-lives observed for an extended half-life antibody....ORKA-001 binds to a similar epitope with similar affinity to risankizumab and shows equivalent potency across a variety of in vitro assays. ORKA-001 binds IL-23p19 with an affinity below five picomolar. Based on cryo-EM structural analysis, ORKA-001 binds to a nearly identical epitope to risankizumab."

PK/PD data • Preclinical • Immunology

Characterization of ORKA-001, a Novel Extended Half-life Monoclonal Antibody Targeting IL-23 for the Treatment of Psoriasis (EADV 2024) - "Materials & ORKA-001 was evaluated in multiple in vitro and ex vivo assays in comparison to two benchmark antibodies that target IL-23p19: risankizumab (RIS) and guselkumab (GUS)... ORKA-001 exhibits high selectivity and affinity for IL-23 in vitro , potent inhibition of downstream cellular signaling ex vivo , and an extended half-life in non-human primates compared to RIS and GUS. Both affinity and antibody exposure have been shown to have a positive correlation with efficacy in psoriasis, and ORKA-001 has the potential to exceed RIS and GUS on both metrics while requiring significantly fewer doses per year. In total, these data provide preclinical evidence of ORKA-001 ’ s clinical potential to improve upon currently available therapies for psoriasis."

Dermatology • Immunology • Psoriasis • IL17A • IL23A • STAT3