Oruka Therapeutics, Inc. · NASDAQ:ORKA

Oruka Therapeutics — Investor Presentation (January 2025)

35 slides from Oruka Therapeutics's investor presentation, January 2025

  1. Slide 1: Corporate Overview

    Corporate Overview NASDAQ: ORKA January 2025 ©2025 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 approach Help patients with chronic Advance potentially best-in-class, half-life extended monoclonal antibodies skin conditions experience the targeting mechanisms with proven efficacy and safety greatest possible freedom POTENTIA

  4. Slide 4: Psoriasis is the ideal indication space for our strategy

    Psoriasis is the ideal indication space for our strategy Large, well-validated market with proven ability for differentiated new entrants to gain share Physicians want new and better biologics – the field has focused on orals, but they have consistently fallen short of biologic efficacy Best targets

  5. Slide 5: ORKA-001 and ORKA-002 complement each other

    ORKA-001 and ORKA-002 complement each other 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 best approach ORK

  6. Slide 6: Our programs target a $50B+ total market opportunity

    Our programs target a $50B+ total market opportunity ORKA-001/002 target the dominant mechanisms in the largest I&I market 140 Global I&I market 2028 PsO sales estimate ($B) Share increasing, decreasing, or equal 127 Skyrizi $50B+ addressable 120 for ORKA-001/002 IL-23 class forecast to 32 PsO Tremf

  7. Slide 7: ORKA-001: potentially best-in-class anti-IL-23p19

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

  8. Slide 8: Biologics have raised the bar on standard of care in PsO, but there is ample room for improvement

    Biologics have raised the bar on standard of care in PsO, but there is ample room for improvement 80 60 PASI 100 (Week 16) (%) ORKA-001 target range 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

  9. Slide 9: Base case is best-in-class, upside could be paradigm changing

    Base case is best-in-class, upside could be paradigm changing Base case scenario Upside scenario Once per year and/or Dosing interval Once per six months patient-specific Comparable PASI 100 Better PASI 100 Efficacy to Skyrizi than Skyrizi Best-in-class profile Paradigm-changing ©2025 Oruka Therapeu

  10. Slide 10: ORKA-001 could be the last word in IL-23p19 inhibitors

    ORKA-001 could be the last word in IL-23p19 inhibitors Binds similar epitope to Skyrizi (risankizumab) with similar potency • Validated mechanism of action • Specific for IL-23p19 (not IL-12/23 p40) • KD < 5 pM • Predicted equivalent safety • Predicted to meet or beat efficacy Novel IP for compositi

  11. Slide 11: ORKA-001 binds a similar epitope as risa with similar potency

    ORKA-001 binds a similar epitope as risa with similar potency ORKA-001 binds a nearly identical epitope to risankizumab ORKA-001 shows comparable potency to risankizumab Inhibition of IL-17 release in human PBMCs 120 ORKA-001 100 Risankizumab IL23p40 80 % Inhibition 60 40 20 0 10 -2 10 -1 10 0 10 1

  12. Slide 12: Clinical experience with YTE predicts significant t1/2 extension

    Clinical experience with YTE predicts significant t1/2 extension ORKA-001 has a >3x longer half-life Implies ORKA-001 could have a than risankizumab in NHPs significantly longer half-life in humans ORKA-001 (IV) Risa (IV) For YTE mAbs, human t1/2 ≈ 2-4x NHP t1/2 based 1000 ORKA-001 (SC) Risa (SC) on

  13. Slide 13: Base case is achievable even at lower end of predicted half-life

    Base Base case is achievable even at lower end of predicted half-life ORKA-001 exposure could exceed SKYRIZI under a variety of half-life scenarios ORKA-001 (~50d half-life): 300 mg W0, 4, Q6M Skyrizi: 150 mg W0, 4, Q12W (approved regimen) ORKA-001 (~75d half-life): 300 mg W0, 4, Q6M 50 50 Even at a

  14. Slide 14: ORKA-001 benefits from a large body of clinical evidence with IL-23 inhibition

    Base ORKA-001 benefits from a large body of clinical evidence with IL-23 inhibition Skyrizi regimen in UC establishes the safety of very high exposures Very uncommon to have clinical precedent in large numbers of patients for the safety of higher exposures 400 Skyrizi: 1200 mg W0, 4, 8 (IV) then 360

  15. Slide 15: Dermatologists view the "base case" as highly attractive

    Base Dermatologists view the “base case” as highly attractive In the “base case,” dermatologists would put half of new patients on Multiple examples support dosing as a ORKA-001 even when accounting for entry of new oral medicines major commercial differentiator: PsO vs. 75% Q12W Q8W % of patients t

  16. Slide 16: Three potential upside scenarios for ORKA-001

    Upside Three potential upside scenarios for ORKA-001 Superior efficacy 1-year dosing interval Disease modification Higher exposure could Enabled by half-life Patient-specific dosing to allow drive higher PASI 100 extension for treatment-free remissions ©2025 Oruka Therapeutics 16

  17. Slide 17: Higher exposures drove higher efficacy in KNOCKOUT study

    Upside Higher exposures drove higher efficacy in KNOCKOUT study KNOCKOUT evaluated 2-4x the approved Skyrizi dose… …and resulted in the highest PASI 100 rates observed to date 100 Double-blind Double-blind follow-up KNOCKOUT (pooled across dose levels) Screening dosing (W0-16) (W16-52) UltIMMa-1/2 (

  18. Slide 18: ORKA-001 could drive higher efficacy based on KNOCKOUT and exposure-response trend

    Upside ORKA-001 could drive higher efficacy based on KNOCKOUT and a consistent exposure-response trend across trials Induction phase (0-16 weeks) Steady-state phase (40-52 weeks) 100 100 80 80 Exposure KNOCKOUT deciles PASI 100 (%) PASI 100 (%) Exposure 60 deciles 60 Projected Phase 3 ORKA-001 avera

  19. Slide 19: KNOCKOUT-like exposures are possible with one dose per year

    Upside KNOCKOUT-like exposures are possible with one dose per year 60 ORKA-001 (~75d half-life): 600 mg Q12M Skyrizi: projected KNOCKOUT exposure (pooled) Skyrizi: steady-state (W52) Ctrough in Phase 3 trials 40 With a ~75-day half-life, [Ab] (μg/mL) ORKA-001 at one dose per year could match or exce

  20. Slide 20: Potential for disease modification or cure by depleting TRMs

    Upside Potential for disease modification or cure by depleting TRMs Anti-IL-23 acts upstream of disease-causing TRMs, Leading to long-lasting remissions after treatment and has a unique ability to deplete them from tissue withdrawal – pointing to possibility of disease modification 15% Loss of PASI

  21. Slide 21: ORKA-001 development path sets up a catalyst-rich next 2 years

    ORKA-001 development path sets up a catalyst-rich next 2 years 2025 2026 Phase 1 study to evaluate the safety, tolerability, and PK of ORKA-001 in Phase 1 in HVs healthy participants • Placebo-controlled, single ascending Phase 2a/b in PsO dose study (NCT06698939) 1200 mg SC Interim PK Final PK Phas

  22. Slide 22: Phase 2a to test KNOCKOUT-like exposures of ORKA-001

    Phase 2a to test KNOCKOUT-like exposures of ORKA-001 Phase 2a proof-of-concept study of ORKA-001 in moderate-to-severe psoriasis Induction Maintenance ORKA-001 ORKA-001 Q6M • Phase 2a expected to N ~80 OLE start in 2H 2025 Placebo ORKA-001 No dose until disease recurrence • Initial efficacy data exp

  23. Slide 23: ORKA-002: potentially best-in-class anti-IL-17A/F

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

  24. Slide 24: IL-17A/F dual blockade has emerged as the superior strategy

    IL-17A/F dual blockade has emerged as the superior strategy Bimzelx has had a very strong launch, validating both IL-17A/F shows superior efficacy to IL-17A in PsO IL-17A/F and the ability to differentiate in PsO 70 1,800 Bimzelx (approved Oct ’23) 60 1,600 Additional 20-30% of Cosentyx PASI 100 (We

  25. Slide 25: ORKA-002 could be the best-in-class IL-17A/F inhibitor

    ORKA-002 could be the best-in-class IL-17A/F inhibitor Similar epitope to Bimzelx (bimekizumab) with equal or better potency • Validated mechanism of action • Binds IL-17A and IL-17F to prevent homodimer and heterodimer signaling • Equal or greater affinity vs. bimekizumab • Predicted equivalent saf

  26. Slide 26: Potential for 2-3 doses per year in PsO/PsA via half-life extension

    Potential for 2-3 doses per year in PsO/PsA via half-life extension ~2x longer half-life than bimekizumab Implies ORKA-002 could have a with precursor mAb in NHPs significantly longer half-life in humans Dosing interval Plasma Concentration (ng/mL) NHP t1/2 (d) Human t1/2 (d) PsO PsA 10 5 ORKA-002 2

  27. Slide 27: ORKA-002 could be best-in-class in a $15B market

    ORKA-002 could be best-in-class in a $15B market Best • Dual IL-17A/F inhibition has shown superior efficacy vs. IL-17A target • $15B+ in future market potential Best • Potential for Q16W dosing interval or longer profile • Reduced biological risk by pursuing Bimzelx MoA Limited • Few other IL-17A/F

  28. Slide 28: ORKA-021

    ORKA-021

  29. Slide 29: 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: 80 Possibl

  30. Slide 30: Multiple orthogonal paths to differentiate beyond dose interval

    Multiple orthogonal paths to differentiate beyond dose interval Greater efficacy Potential demonstrated by KNOCKOUT and anti-IL-23 mAb exposure-response Long-term “remissions” Maximizes our odds of having the Improved dosing High exposures of anti-IL-23 could lead to best biologics in a intervals wi

  31. Slide 31: Corporate

    Corporate

  32. Slide 32: Multiple inflection points across the pipeline over the next 2+ years

    Multiple inflection points across the pipeline over the next 2+ years 2025 2026 ORKA-001 FIH Ph1 Interim PK Final PK Phase 2a: in HVs in HVs Initial PsO data ORKA-002 FIH Ph1 Interim PK (3Q25) in HVs ORKA-003 Target disclosure Funded through 2027, at least one year past ORKA-001 efficacy data in PsO

  33. Slide 33: Building rapidly with backing from Paragon

    Building rapidly with backing from Paragon Lawrence Klein Joana Goncalves Paul Quinlan Laura Sandler Arjun Agarwal CEO CMO General Counsel SVP, Operations SVP, Finance Christopher Finch Alan Lada Rajiv Panwar Joe Senn Andrew Blauvelt VP, Corp Dev & Strategy VP, Investor Relations VP, Head of CMC SVP

  34. Slide 34: Shares outstanding

    Shares outstanding As of September 30, 2024 Number of shares1 Common stock • Shares outstanding 35.0M • Preferred stock 13.9M Common stock (as-converted to common stock) equivalents • Pre-funded warrants 6.2M Common stock and common stock • Total outstanding2 55.1M equivalents Notes: Please refer to

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