Oruka Therapeutics, Inc. · NASDAQ:ORKA

Oruka Therapeutics — Investor Presentation (January 2026)

38 slides from Oruka Therapeutics's investor presentation, January 2026

  1. Slide 1: Corporate Overview

    Corporate Overview NASDAQ: ORKA January 2026 ©2026 ORUKA THERAPEUTICS

  2. Slide 2: Disclaimers

    Disclaimers The information contained in this presentation has been prepared by Oruka Therapeutics, Inc. (the “Company”) and contains information pertaining to the business and operations of the Company. The information contained in this presentation: (a) is provided as at the date hereof, is subjec

  3. Slide 3: On a mission to enable freedom from chronic skin disease

    On a mission to enable freedom from chronic skin disease Our goal Our pipeline Help patients with chronic PROGRAM PRECLINICAL PHASE 1 PHASE 2 INDICATIONS skin conditions experience the greatest possible freedom from disease ORKA-001 IL-23p19 Interim data 2H26 PsO PsO initiation 1H26 PsO, PsA, ORKA-0

  4. Slide 4: Bimzelx launch shows that better biologics will win in psoriasis

    Bimzelx launch shows that better biologics will win in psoriasis Bimzelx versus Sotyktu performance validates our thesis Script volume from recent U.S. launches in psoriasis1 • UCB’s Bimzelx launch has exceeded expectations, 1,800 driven by strong demand – ~$2B annualized 2025 Bimzelx (approved Oct

  5. Slide 5: The psoriasis market will continue to reward biologic innovation

    The psoriasis market will continue to reward biologic innovation 0 0 0 Massive Continued pharma Better biologics market size investment continue to win $30B+ $5B+ peak sales forecast Growing moderate-to-severe Pharma has bet big on orals, Bimzelx launch shows psoriasis market, with further sacrifici

  6. Slide 6: ORKA-001 & -002 complement each other to address all PsO/PsA

    ORKA-001 & -002 complement each other to address all PsO/PsA ORKA-001 ORKA-002 For patients with joint involvement, For patients with purely skin disease including PsA, or recalcitrant skin disease Majority of dermatologists Anti-IL-17 preferred, and IL-17A/F prefer an anti-IL-23p19 emerging as the

  7. Slide 7: 1-2 doses per year is enough to win, but we are aiming far higher

    1-2 doses per year is enough to win, but we are aiming far higher Greater efficacy KNOCKOUT demonstrates potential for highest ever efficacy from higher IL-23 antibody exposure Off-treatment remission Maximizes odds of having a strong value Ultra-long dosing High anti-IL-23 exposures could lead to p

  8. Slide 8: Advancing co-leads rapidly towards multiple clinical data catalysts

    Advancing co-leads rapidly towards multiple clinical data catalysts 2025 2026 ORKA-001 Interim PK in HVs EVERLAST-A: FIH Ph1 EVERLAST-B PASI 100 rates & Q4 2024 EVERLAST-A initiation initiation response duration ORKA-002 Ph2 initiation FIH Ph1 Interim PK Ph2 initiation in PsO Ahead of schedule in HV

  9. Slide 9: ORKA-001: potentially best-in-class anti-IL-23p19

    ORKA-001: potentially best-in-class anti-IL-23p19

  10. Slide 10: Biologics have raised the bar on standard of care in PsO

    Biologics have raised the bar on standard of care in PsO, but there is ample room for improvement 80 60 ORKA-001 target range PASI 100 (Week 16) (%) 40 20 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Time Between Doses (Weeks) Anti-IL-23 Anti-IL-17A/F Anti-TNF Highly safe; no AEs / SAEs of note Black bo

  11. Slide 11: ORKA-001 targets validated biology with significantly extended PK

    ORKA-001 targets validated biology with significantly extended PK ORKA-001 could be the last word Binds a nearly identical epitope Comparable potency to risankizumab in IL-23p19 inhibitors to risankizumab across a variety of assays ORKA-001 Risankizumab Specific for 120 IL-23p19 IL23p40 100 % Inhibi

  12. Slide 12: ORKA-001 Phase 1 results set the stage for a step-change in PsO

    ORKA-001 Phase 1 results set the stage for a step-change in PsO Phase 1 results Three major “ways to win” • Half-life of ~100 days Once per year dosing, with a Q6M option if needed Annual dosing for hard-to-treat patients • Cmax and AUC that enable “KNOCKOUT” exposures Best-in-class “KNOCKOUT” antib

  13. Slide 13: ORKA-001's 100-day half-life and high AUC derisks upside case

    ORKA-001’s 100-day half-life and high AUC derisks upside case Pharmacokinetic profile of a single subcutaneous dose of ORKA-001 1000 • ~100-day half-life in humans, >3x longer than risankizumab 100 • Cmax exceeds risankizumab’s ORKA-001 (1200 mg) [Ab] (μg/mL) at an equivalent dose1, ORKA-001 (600 mg

  14. Slide 14: ORKA-001 demonstrated deep and sustained inhibition of STAT3 signaling

    ORKA-001 demonstrated deep and sustained inhibition of STAT3 signaling, a downstream marker of IL-23 activity, through 24 weeks ORKA-001 from serum inhibits STAT3 phosphorylation following ex vivo IL-23 stimulation 3000 2500 Mean pSTAT3 (RLU) Placebo 2000 ORKA-001 (300 mg) 1500 ORKA-001 (600 mg) 100

  15. Slide 15: EVERLAST-A Phase 2a – a potential game changer in PsO

    EVERLAST-A Phase 2a – a potential game changer in PsO EVERLAST-A Phase 2a proof-of-concept trial in moderate-to-severe psoriasis (NCT07090330) Induction period Maintenance period OLE Initial data in 2H 2026 has Primary endpoint: potential to deliver on all PASI 100 at W16 No dose until disease recur

  16. Slide 16: EVERLAST-B Phase 2b – initiated in December 2025

    EVERLAST-B Phase 2b – initiated in December 2025 EVERLAST-B Phase 2b dose-ranging trial in moderate-to-severe psoriasis (NCT07290569) Induction period Maintenance period OLE Primary endpoint: PASI 100 at W16 • Dose-ranging trial to ORKA-001: 37.5 mg W01 enable Phase 3 No dose until disease recurrenc

  17. Slide 17: Phase 2 psoriasis data is robust and predictive of Phase 3

    Phase 2 psoriasis data is robust and predictive of Phase 3 Consistent Phase 2 to 3 translation Low placebo rates Phase 2 PASI 100 rates strongly correlate with Phase 3 at both Week 16 and 28 0-2% PASI 100 placebo rate 100 Week 16 100 Week 28 50 Phase 3: PASI 100 (%) Phase 3: PASI 100 (%) 80 80 40 PA

  18. Slide 18: EVERLAST-A provides multiple "ways to win"

    EVERLAST-A provides multiple “ways to win” Provide definitive test of higher Establish evidence for annual Show compelling signs of efficacy at higher exposures dosing and lock in Q6M off-treatment remissions1 PASI 100 data at Week 16, Open-ended cohort will validate Kaplan-Meier curve of PASI 100 W

  19. Slide 19: ORKA-001 PK profile could enable higher efficacy in PsO

    ORKA-001 PK profile could enable higher efficacy in PsO KNOCKOUT study testing 2-4x the approved Skyrizi dose Skyrizi exposure-response model indicates potential showed the highest anti-IL-23 efficacy to date to increase efficacy with higher exposure Projected 5-95th percentile ORKA-001 Cavg W0-16 1

  20. Slide 20: 100-day half-life brings once annual dosing within reach

    100-day half-life brings once annual dosing within reach ORKA-001 projected steady-state exposures significantly exceed Skyrizi and make annual dosing likely 600 Skyrizi Cmax in UC (median ± 5th and 95th percentiles) 400 supports safety of high anti-IL-23 exposures 200 80 Steady-state [Ab] (μg/mL) 6

  21. Slide 21: "KNOCKOUT" IL-23 inhibition could generate off-treatment remissions

    “KNOCKOUT” IL-23 inhibition could generate off-treatment remissions by depleting pathogenic TRMs Robust inhibition of IL-23 could create High anti-IL-23 exposures deplete an “immune reset” in PsO pathogenic TRMs in the skin P=0.04 80 P=0.10 Number of CD8+ TRM17 60 40 20 0 Lesional Nonlesional 300 mg

  22. Slide 22: EVERLAST could enable compelling rates of off-treatment remission

    EVERLAST could enable compelling rates of “off-treatment remission” for the first time in psoriasis ORKA-001 could affect the disease biology in a …potentially resulting in longer-term responses that unique way due to optimized exposure and PK… exceed those seen with prior IL-23 inhibitors Maintenan

  23. Slide 23: Looking forward to a potential label

    Looking forward to a potential label – illustrating the paradigm- changing potential of ORKA-001 Induction Maintenance Treatment upon recurrence Induction with ORKA-001 at Evaluate at 6 and 12 months Administer ORKA-001 as a a dose level selected based after induction dosing to inform subcutaneous i

  24. Slide 24: Dermatologists value both extended dosing and higher efficacy

    Dermatologists value both extended dosing and higher efficacy Dermatologists say that annual dosing and higher efficacy would drive similar 50%+ share for ORKA-001, even when accounting for entry of icotrokinra 70 65 % of moderate-to-severe psoriasis patients on 58 56 ORKA-001 53 48 New starts 44 Pa

  25. Slide 25: ORKA-002: potentially best-in-class anti-IL-17A/F

    ORKA-002: potentially best-in-class anti-IL-17A/F

  26. Slide 26: ORKA-002 targets IL-17A/F, a new mega-blockbuster class

    ORKA-002 targets IL-17A/F, a new mega-blockbuster class with an ideal setup for a longer-acting entrant Bimzelx launch validates both the IL-17A/F class and ability to differentiate in PsO • Brand new class – superior efficacy vs. IL-17A1 across multiple indications and high levels of skin 6,000 Bim

  27. Slide 27: ORKA-002 matches Bimzelx's IL-17A/F potency with extended PK

    ORKA-002 matches Bimzelx’s IL-17A/F potency with extended PK ORKA-002 binds a nearly identical epitope ORKA-002 has comparable potency to bimekizumab to bimekizumab across a variety of assays ORKA-002 Bimekizumab IL-17A IL-17F 100 100 IL-17A1 % Inhibition of NFκB surface 75 75 ORKA-002 50 50 epitope

  28. Slide 28: ORKA-002 Phase 1 trial design

    ORKA-002 Phase 1 trial design Phase 1 trial to evaluate the safety, tolerability, and PK of ORKA-002 in healthy participants (NCT06944379) Design Dose levels and length of follow-up to date • Double-blind and placebo-controlled • Single ascending dose 160 mg SC ~6 months Population • Healthy adult v

  29. Slide 29: ORKA-002 safety profile was consistent with the IL-17 class

    ORKA-002 safety profile was consistent with the IL-17 class ORKA-001 and placebo 160 mg 320 mg 640 mg All cohorts (blinded) N 8 8 8 24 ≥1 TEAE 8 (100%) 8 (100%) 7 (87.5%) 23 (95.8%) ≥1 SAE 0% 0% 0% 0% ≥1 severe TEAE 0% 0% 0% 0% Discontinued due to TEAE 0% 0% 0% 0% Only AEs occurring in >2 subjects w

  30. Slide 30: Half-life of 75-80 days enables potential for twice-yearly dosing

    Half-life of 75-80 days enables potential for twice-yearly dosing Pharmacokinetic profile of a single subcutaneous dose of ORKA-002 1000 • t1/2 of 75-80 days in humans, >3x longer than bimekizumab 100 ORKA-002 (640 mg) • Cmax comparable to [Ab] (μg/mL) bimekizumab at an ORKA-002 (320 mg) 10 equivale

  31. Slide 31: ORKA-002 demonstrated deep and sustained inhibition of IL-17 signaling

    ORKA-002 demonstrated deep and sustained inhibition of IL-17 signaling in an ex vivo IL-17 stimulation assay through 24 weeks ORKA-002 from serum inhibits IL-17 signaling following ex vivo IL-17 stimulation 2.0 Mean expression (OD) 1.5 Placebo ORKA-002 (160 mg) 1.0 ORKA-002 (320 mg) 0.5 ORKA-002 (64

  32. Slide 32: Potential for Q6M dosing in PsO and Q3M dosing in HS

    Potential for Q6M dosing in PsO and Q3M dosing in HS Projected Ctrough of ORKA-002 exceeds approved bimekizumab regimens in PsO and HS PsO HS 100 100 80 80 [Ab] (μg/mL) [Ab] (μg/mL) 60 60 Steady-state Cmax of Steady-state Cmax of bimekizumab 320 mg Q2W bimekizumab 320 mg Q4W 40 40 20 20 0 0 0 8 16 2

  33. Slide 33: ORCA-SURGE – initiation expected 1H 2026

    ORCA-SURGE – initiation expected 1H 2026 ORCA-SURGE Phase 2 dose-ranging trial of ORKA-002 in moderate-to-severe psoriasis Induction period Maintenance period Primary endpoint: PASI 100 at W16 ORKA-002: 40 mg at W0, W41 • ORCA-SURGE data expected in 2027 ORKA-002: 160 mg W0, W4 R • Phase 2 trial in

  34. Slide 34: ORKA-021: Potential to combine the best of IL-17s and IL-23s

    ORKA-021: Potential to combine the best of IL-17s and IL-23s IL-17s: fastest onset and highest peak response IL-23s: less frequent dosing and best durability and safety Combining the two mechanisms sequentially could provide the “best of both worlds” Feedback from U.S. 100 dermatologists: Possible w

  35. Slide 35: Four ways to deliver a best-in-class regimen for psoriatic disease

    Four ways to deliver a best-in-class regimen for psoriatic disease • Once yearly dosing and off-treatment remissions go beyond ORKA-001 convenience to change the treatment paradigm • Clinical precedent supports potential for best efficacy in the IL-23 class ORKA-001 • Only long-acting IL-17A/F in a

  36. Slide 36: Multiple Phase 2 readouts coming over the next two years

    Multiple Phase 2 readouts coming over the next two years 2H 2026: PASI 100 rates and Phase 2a (PsO) response duration ORKA-001 Strong cash position provides runway >1 year beyond three Phase 2b (PsO) 2027: Week 16 and durability major readouts: EVERLAST-A, EVERLAST-B, and ORCA-SURGE 1H 2026: Initiat

  37. Slide 37: Slide 37

  38. Slide 38: Shares outstanding

    Shares outstanding As of September 30, 2025 Number of shares1 Common stock • Shares outstanding 48.4M • Preferred stock 11.4M Common stock (as-converted to common stock) equivalents • Pre-funded warrants 7.3M Common stock and common stock • Total outstanding2 67.1M equivalents Notes: Please refer to

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