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

Financial Performance:

• No specific revenue, earnings, or profit margin figures disclosed as the company is in clinical development.
• Cash balance stands at over $1 billion as of Q2, providing a runway sufficient to reach an ORCA-001 Biologics License Application (BLA) filing.
• Over $1 billion in cash supports the planned Phase 3 initiation in early 2027 and subsequent operations.

Guidance and Future Outlook:

• Plan to advance the 600 mg dose of ORCA-001 into Phase 3 studies in the first half of 2027.
• Week 52 "Everlast A" data (dosing durability) expected in December 2027 to inform annual vs. biannual maintenance regimens.
• Additional Week 52 data from "Everlast B" anticipated in the second half of 2027.
• ORCA-002 Phase 2 psoriasis results expected in Q1 2027; Phase 2 results for hidradenitis suppurativa (HS) are ongoing.
• ORCA-004 expected to enter Phase 1 around year-end, with first combination studies planned for 2027.
• Long-term goal is a once-annual dosing regimen for ORCA-001, with a six-month option for flexibility.
• IBD indication for ORCA-001 is restricted until mid-2028 due to licensing agreement with Paragon/Spire.

Business Segments and Product Lines:

• ORCA-001 (IL-23p19 inhibitor): Everlast B (Phase 2b) showed 61% PASI-100 and 86% PASI-90 at Week 16 for the 600 mg dose, consistent with Everlast A. The 600 mg dose demonstrated superior efficacy over 300 mg and 37.5 mg doses.
• ORCA-002 (IL-17AF inhibitor): Extended half-life antibody with potential for twice-yearly dosing in psoriasis/psoriatic arthritis and quarterly in HS; currently in Phase 2.
• ORCA-004 (TL1A inhibitor): Extended half-life antibody intended for future combination studies with ORCA-001 and ORCA-002.
• Pipeline anchored on two co-lead programs targeting IL-23p19 and IL-17AF, viewed as gold standards in psoriasis treatment.

Market and Competitive Landscape:

• ORCA-001 efficacy appears to exceed historical IL-23 inhibitors (e.g., Skyrizi, Trumfya) by roughly 20 percentage points for complete skin clearance (PASI-100) at Week 16.
• Differentiation potential lies in a "trifecta" of high efficacy, favorable safety, and ultra-rare dosing (once/twice yearly).
• Competitors include established biologics and daily oral agents; ORCA-001 aims to be the first once-annual maintenance biologic for a chronic immune disease.
• IL-17AF class (ORCA-002) is growing, with Bimzelx setting a high bar for efficacy; ORCA-002 seeks to compete via extended dosing intervals.

Risks and Challenges:

• Forward-looking statements are subject to risks regarding regulatory feedback, final clinical results differing from interim data, and potential delays in Phase 3 initiation.
• Uncertainty remains regarding the exact durability of the annual dosing regimen until Week 52 data is released in December.
• Head-to-head Phase 3 trial design against competitors (e.g., Trumfya) is under consideration but not finalized, introducing strategic risk regarding trial size, cost, and unpredictability.
• No near-term plans for IBD due to licensing restrictions until 2028.

Management Commentary and Tone:

• Tone is highly confident and optimistic, emphasizing the "reproducibility" of high efficacy across two independent studies (Everlast A and B).
• Management views the 600 mg PASI-100 rate as "unprecedented" for an IL-23 mechanism and comparable to the "ceiling" of current biologic efficacy.
• CEO Lawrence Klein and CMO Joe Goncalves stressed the safety profile is consistent with the IL-23p19 class, with zero injection-site reactions across >250 subjects.
• Strategic focus is on maximizing disease control while minimizing dosing frequency to improve patient experience.

Analyst Questions and Answers:

• 52-Week Data: Management expects data to clarify if 80% of patients can maintain PASI-100 on a once-annual regimen, with a six-month option for those requiring it.
• Phase 3 Comparator: Regulators are being engaged to decide on an active comparator; head-to-head trials against leading IL-23s are being considered but not confirmed.
• Dose Selection: The 600 mg dose at Weeks 0 and 4 is the selected regimen; no plans to test single-dose arms for Phase 3.
• Subgroup Analysis: No impact of patient weight or prior biologic experience on efficacy was observed; results were consistent across demographics.
• ORCA-002 Expectations: Expected to match Bimzelx-like efficacy (low 60s PASI-100) given the saturation of the IL-17 pathway; tolerability expected to mirror current class standards.
• Commercialization: Exploring both in-clinic and at-home administration options; Chief Commercial Officer Todd Edwards is evaluating channel strategies.

Other Key Points:

• Study design for Everlast B included 187 participants across 36 sites in the US, Canada, Germany, and Spain, with <30% site overlap with Everlast A.
• Safety data pooled over 100 patient-years of experience shows no dose-dependent adverse events and no treatment-related serious adverse events.
• The 37.5 mg low-dose arm showed significant efficacy, validating exposure-response modeling and confirming the need for the higher 600 mg dose for optimal clearance.
• Pipeline expansion includes potential indication diversification for ORCA-002 into Hidradenitis Suppurativa (HS) and Psoriatic Arthritis (PsA).