Oruka Therapeutics Presentation of Interim EVERLAST-B Data - ORUKA THERAPEUTICS INC

Explicit Guidance:

• ORCA-001 Phase 3 Initiation: Planned to begin in the first half of 2027 using the 600-milligram dose.
• Everlast A 52-Week Data Readout: Expected in December (following the call date) to assess durability and support annual maintenance dosing potential.
• ORCA-002 Psoriasis Phase II Results: Expected in the first quarter of 2027.
• ORCA-001 Phase IIb (Everlast B) 52-Week Data: Expected in the second half of 2027.
• ORCA-004 Phase I Initiation: Planned to begin around year-end.
• ORCA-004 Combination Studies: Expected to commence in 2027.
• Financial Runway: Cash balance of >$1 billion (as of Q2) is expected to provide sufficient runway through the ORCA-001 BLA filing.

Business-Segment Outlook:

• ORCA-001 (IL-23p19):
  • Dosing Strategy: Aiming for a maintenance regimen with once- to twice-per-year dosing; the 600-milligram dose is the candidate for Phase 3.
  • Target Population: Envisioned for patients across the spectrum, with flexibility for a six-month option for those requiring more frequent dosing.
  • Efficacy Ceiling: Belief that ORCA-001 efficacy is "at the ceiling" for moderate to severe plaque psoriasis (~61% PASI-100 at week 16), potentially rivaling or exceeding the benchmark set by Benzelex (IL-17).
  • Commercial Vision: Aiming for a "category-winning profile" with the potential for a franchise value of $5–$10 billion+ annually, driven by superior disease clearance and reduced dosing frequency.
• ORCA-002 (IL-17AF):
  • Indication Expansion: Phase II ongoing in psoriasis and hidradenitis suppurativa (HS); expects quarterly dosing potential in HS and twice-yearly in psoriasis/psoriatic arthritis (PsA).
  • PsA Data Strategy: Baseline PsA assessments in current Phase II are not for follow-up; dedicated PsA exploration planned for Phase III.
  • Label Strategy: Top three target indications for label expansion are psoriasis, PsA, and HS.
• ORCA-004 (TL1A):
  • Combination Therapy: Planned to initiate first combination studies with ORCA-001 and ORCA-002 in 2027 to explore synergistic opportunities.
• Geographic Footprint: Everlast B study conducted across the US, Canada, Germany, and Spain to ensure reproducibility across diverse sites.

Market and Competitive Outlook:

• Efficacy Positioning: Anticipates separating from current IL-23 inhibitors (Skyrizi, Tremfya) by ~20 percentage points on PASI-100; expects ~2x higher complete clearance rates compared to daily oral options (Upadacitinib/Ixekizumab context).
• Convenience Advantage: Seeks to disrupt the market by offering the first once-annually dosed biologic for a chronic immune disease, contrasting with current monthly or quarterly schedules.
• Competitive Landscape: Views the IL-17 space (led by Benzelex) as the ceiling for efficacy; ORCA-002 aims to capture value through extended half-life and quarterly dosing in HS and dual coverage in PsA.
• Market Dynamics: Anticipates physician demand for maximizing disease control while reducing treatment burden; expects high patient adoption for a "trifecta" of efficacy, safety, and convenience.

Macro / Industry Outlook:

• Standard of Care: Believes IL-23p19 and IL-17AF mechanisms will remain the "gold standard" for psoriasis treatment.
• Regulatory Path: Engaging with regulators to finalize Phase 3 design, including the potential use of an active comparator (likely an IL-23p19 inhibitor) vs. placebo/biosimilar; seeking alignment on annual vs. semi-annual dosing labels.
• Indication Rights: Secured license amendments with Paragon and Spire to access all indication rights for ORCA-001 (including IBD) and ORCA-002; restricted from starting IBD studies until mid-2028.

Strategic Initiatives:

• Phase 3 Design Optimization: Actively working with regulators to design a Phase 3 study that supports both 12-month and 6-month maintenance dosing regimens on the label.
• Commercial Channel Strategy: Exploring both in-clinic and at-home administration options to maximize market access and convenience.
• Key Personnel: Chief Commercial Officer Todd Edwards is leading commercial planning for dual-channel distribution and market positioning.
• Pipeline Synergy: Leveraging the "co-lead" strategy of ORCA-001 and ORCA-002 to offer complementary treatments for distinct patient segments (e.g., PsA vs. skin-dominant).

Risks and Headwinds to Outlook:

• Regulatory Approval: Final data may differ from interim results; regulatory feedback on Phase 3 trial design and comparator selection remains a variable.
• Durability Uncertainty: While PK suggests annual dosing is feasible, the actual proportion of patients maintainable without dosing until week 52 (Everlast A no-dose arm) is unconfirmed until December.
• Head-to-Head Competition: Launching against biosimilars or new entrants in the IL-17/IL-23 space could impact adoption; Phase 3 comparators introduce execution risk.
• Safety Profile: No dose-dependent trends observed to date, but long-term safety in the Phase 3 population remains to be established.
• Timeline Constraints: IBD development for ORCA-001 is contractually restricted until mid-2028, limiting immediate expansion in that high-value indication.

Management Tone on the Future:

• High Confidence: Management expresses strong confidence in the reproducibility of efficacy across Everlast A and B, describing the results as "unprecedented" for an IL-23 inhibitor.
• Aggressive Timeline: "Move quickly" into Phase 3; no delays expected given the robust dose-ranging data.
• Optimism on Differentiation: Views the potential for once-annual dosing as a "huge opportunity" and a "substantial further advance" over current categories.
• Caveats: Acknowledges the "high bar" of PASI-100 and notes that while the 52-week "perfect maintenance" is a target, a flexible label with both annual and semi-annual options is preferred to accommodate patient variability.

Miscellaneous:

• Safety Data: Over 250 subjects dosed with ORCA-001, accumulating >100 patient-years of exposure; no injection-site reactions observed; AE profile consistent with the IL-23p19 class (upper respiratory infections, headaches).
• Weight/Baseline Impact: Efficacy in Everlast B was consistent despite the 600mg group being ~9kg heavier and having higher prior biologic exposure compared to Everlast A.
• Anti-Drug Antibodies: No apparent impact on PK, efficacy, or safety.
• Dosing History: 600mg regimen involves Week 0 and Week 4 doses; single-dose maintenance is not currently planned for induction.