Core Insights - Oruka Therapeutics announced positive interim data from its Phase 1 trial of ORKA-002, indicating a half-life of 75-80 days, which supports potential dosing of twice a year for psoriasis and quarterly for hidradenitis suppurativa [1][6] - Phase 2 studies for ORKA-002 are expected to begin in the first half of 2026 for psoriasis and the second half of 2026 for hidradenitis suppurativa [1][4] - The first patients were dosed in the EVERLAST-B Phase 2b trial of ORKA-001 in December 2025, with data anticipated in 2027 [1][5] ORKA-002 Phase 1 Trial Findings - The Phase 1 trial was a randomized, double-blind, placebo-controlled study involving 24 healthy adult participants across three dosing cohorts: 160 mg, 320 mg, and 640 mg [3] - ORKA-002 demonstrated a half-life greater than three times that of bimekizumab, with a comparable Cmax at equivalent doses [6] - The safety profile of ORKA-002 was favorable, with no severe treatment-emergent adverse events reported [6] ORKA-002 Phase 2 Trials - ORCA-SURGE, a Phase 2 trial for ORKA-002 in moderate-to-severe psoriasis patients, is expected to start in the first half of 2026, aiming to enroll approximately 160 patients [6] - The primary endpoint for ORCA-SURGE will be PASI 100 at Week 16, with maintenance dosing evaluating the potential for twice-yearly administration [6] ORKA-001 Updates - The EVERLAST-B trial is evaluating three induction dose levels of ORKA-001, with data expected in 2027 [5][7] - The study design includes re-randomization for patients achieving PASI 100 at Week 28, testing the potential for yearly dosing and extended off-treatment remissions [7] Company Overview - Oruka Therapeutics is focused on developing novel biologics aimed at setting a new standard for chronic skin disease treatment, particularly plaque psoriasis [8] - The company's mission is to provide high rates of complete disease clearance with infrequent dosing, potentially as little as once or twice a year [8]

Summary of Avalo Therapeutics FY Conference Call Company Overview - **Company**: Avalo Therapeutics (NasdaqCM:AVTX) - **Location**: Near Philadelphia - **New Asset**: AVTX-009, a high affinity human anti-IL-1 beta monoclonal antibody targeting hidradenitis suppurativa (HS) [2][3] Key Points Product Development - **Background**: AVTX-009 was originally developed by Lilly for type 2 diabetes, showing a moderate effect size of 0.25-0.3 grams reduction in hemoglobin A1C, but was not pursued further [2][3] - **Acquisition**: Avalo acquired the asset after it was not advanced by previous owners [3] - **Funding**: The company raised $185 million in 2024 to support its operations and trials [3] - **Lotus Trial**: A phase 2b proof of concept study for AVTX-009 is fully enrolled, with data expected in mid-2026 [4] Mechanism of Action - **IL-1 Beta Role**: IL-1 beta is a master regulator of the immune system, crucial in the inflammatory response in HS lesions [5][6] - **Cytokine Levels**: IL-1 beta is the most abundant cytokine in HS lesions, making it a prime target for treatment [7] Comparison with Competitors - **AbbVie’s Lutikizumab**: A bispecific anti-IL-1 beta and anti-IL-1 alpha drug with a shorter half-life and lower affinity for IL-1 beta compared to AVTX-009 [11][12] - **Efficacy Data**: AbbVie reported a drug effect size of approximately 46% in a severe HS population, which Avalo aims to exceed with its higher affinity drug [13][15] Trial Design and Expectations - **Placebo Response**: The Lotus trial is designed to mitigate placebo responses, with a conservative estimate of a 20% placebo rate based on historical data [19][20] - **Patient Demographics**: The trial includes a mix of biologically experienced patients, with a higher proportion of TNF and IL-17 failures compared to competitors [25][26] Future Indications - **Exploration Beyond HS**: Avalo is interested in expanding indications to include crystal arthropathies, such as gout, in addition to other inflammatory conditions [30][31] Financial Health - **Balance Sheet**: Avalo has $115 million available, sufficient to fund operations through data release and into 2028, with plans to raise funds for phase three trials [33] Additional Insights - **Trial Management**: The company emphasizes rigorous training for investigators to ensure objective assessments and accurate data collection [27][28] - **Statistical Approach**: Avalo plans to handle non-responder imputation scientifically, contrasting with other companies' methods that may artificially lower efficacy results [29]