Summary of Avalo Therapeutics Conference Call Company Overview - **Company**: Avalo Therapeutics (NasdaqCM:AVTX) - **Focus**: Development of AVTX-009, a potent anti-IL-1 inhibitor for hidradenitis suppurativa (HS) [3][5] Key Points and Arguments Product Development - **AVTX-009 Background**: Originally developed by Eli Lilly for type 2 diabetes, showing a reduction in A1C by 0.25 to 0.3 grams but not pursued further due to insufficient effect size [4] - **Acquisition**: Acquired from AlmataBio in 2024, with rapid progression to phase 2B trials [5] Mechanistic Insights - **IL-1 Role**: IL-1 beta is a central regulator of the immune system, driving chronic inflammation in HS lesions [7][8] - **Clinical Evidence**: AbbVie's data supports the efficacy of targeting IL-1, while Johnson & Johnson's anti-IL-1 trial showed no treatment effect in HS, reinforcing the focus on IL-1 as a target [10] Clinical Trial Design - **Phase 2 Trial**: Designed to mirror successful elements from other trials, allowing for both bio-naive and bio-experienced patients [15][16] - **Enrollment Success**: Exceeded initial enrollment timelines, with over 250 patients enrolled, indicating strong interest from both patients and investigators [19][26] Efficacy and Safety Expectations - **Efficacy Goals**: Aiming for a treatment effect size comparable to or better than AbbVie’s results, with a favorable dosing regimen of every four weeks [28][29] - **Safety Profile**: IL-1 inhibitors are well-tolerated, with a lower risk of opportunistic infections compared to IL-17 inhibitors [33] Market Opportunity - **HS Market Growth**: Increasing awareness and earlier diagnosis are expected to expand the patient population significantly [36] - **Market Size Estimates**: Projected to exceed $10 billion by 2035, with a conservative estimate of a $1 billion opportunity from a 5% patient penetration of a target market of 200,000 patients [37][38] Additional Important Insights - **Competitive Landscape**: The HS treatment market is competitive, with multiple companies developing various drugs, but there is optimism about the unique mechanism of AVTX-009 [26][36] - **KOL Enthusiasm**: Key opinion leaders express high enthusiasm for IL-1 targeting in HS, suggesting a robust market for multiple agents [38]

Summary of Oruka Therapeutics Conference Call Company Overview - **Company**: Oruka Therapeutics (NasdaqGM: ORKA) - **Focus**: Advancing the standard of care in psoriatic disease with a pipeline centered around two co-lead assets, ORCA-001 and ORCA-002, both extended half-life monoclonal antibodies targeting plaque psoriasis, psoriatic arthritis, and related conditions [2][3] Key Products and Pipeline - **ORCA-001**: Modeled after Risankizumab (Skyrizi), targeting IL-23p19, with a 100-day half-life, aiming for once-a-year dosing [2][6][7] - **ORCA-002**: Modeled after Bimekizumab (Bimzelx), targeting IL-17A/F, with expected half-life around 75 days, aiming for twice-yearly dosing [2][17] - **Clinical Development**: - ORCA-001 is in phase 2 development, with readouts expected in the second half of next year [3][10] - ORCA-002 is in phase 1, with data anticipated around year-end [16][17] Market Opportunity - **Psoriasis Pipeline**: The current pipeline for psoriasis is relatively empty, presenting a significant opportunity for Oruka to introduce new biologics [4][5] - **Patient Preference**: The company believes that patients and physicians would prefer less frequent dosing with biologics over oral options, which are currently being explored by competitors [5] Clinical Data and Efficacy - **Efficacy Expectations**: - ORCA-001 aims for PASI 100 (fully clear skin) rates potentially in the 50s or 60s, compared to Skyrizi's 43% and Bimekizumab's 62% [11][12] - The innovative design of the phase 2A study includes a primary endpoint of PASI 100 at week 16, which is a novel approach in psoriasis trials [9][10] - **Durability of Response**: The study will also assess how long patients can maintain clear skin without additional doses, with expectations of 20-30% of patients remaining clear for two years or more after initial doses [10][14] Financial Position - **Cash Reserves**: The company is well-capitalized with over $500 million in cash, providing a runway through multiple significant inflection points, including phase 2 readouts for both programs [3][27] Future Directions - **Expansion into Hidradenitis Suppurativa (HS)**: The company plans to pursue HS after establishing its psoriasis programs, leveraging the success of Bimekizumab in psoriasis and psoriatic arthritis [21][22] - **Combination Therapy Concept**: ORCA-021 aims to explore the potential of using IL-17 for induction followed by IL-23 for maintenance, which has received positive feedback from experts [25][26] Conclusion - Oruka Therapeutics is positioned to capitalize on a significant market opportunity in psoriatic disease with its innovative pipeline of extended half-life monoclonal antibodies, backed by strong clinical data and a solid financial foundation. The company is strategically planning to expand its indications and explore combination therapies to enhance treatment outcomes for patients.

Core Insights - Oruka Therapeutics is developing ORKA-002, a novel monoclonal antibody with an extended half-life targeting IL-17A/F, which is expected to set a new standard for treating chronic skin diseases like plaque psoriasis [1][2][3] Group 1: Product Development - ORKA-002 has a half-life in non-human primates (NHP) of more than 30 days, over three times longer than bimekizumab, allowing for potential dosing intervals of two to three times per year [1][6] - The first subject for ORKA-002 is expected to be dosed in Q3 2025 [1] - ORKA-002 demonstrates equivalent potency to bimekizumab with similar binding affinity and epitope in various preclinical assays [1][6] Group 2: Competitive Advantage - ORKA-002's dual inhibition of IL-17A and IL-17F has shown superior efficacy compared to IL-17A inhibition alone, as evidenced by the performance of bimekizumab in Phase 3 trials [3] - Unlike existing therapies that require monthly maintenance dosing, ORKA-002 could potentially be administered just two to three times a year, positioning it as a leading therapy in the IL-17 class [3][6] Group 3: Company Overview - Oruka Therapeutics aims to provide patients with chronic skin diseases the highest possible freedom from their condition, targeting complete disease clearance with infrequent dosing [4] - The company is advancing a proprietary portfolio of potentially best-in-class antibodies engineered to target the core mechanisms underlying plaque psoriasis and other dermatologic diseases [4]