Core Insights - Alumis Inc. announced new data from Phase 3 ONWARD1 and ONWARD2 clinical trials for envudeucitinib, a selective oral TYK2 inhibitor for moderate-to-severe plaque psoriasis, presented at the 2026 AAD Annual Meeting [1] Group 1: Clinical Efficacy - Envudeucitinib showed significant skin clearance, with PASI 90 responses at Week 16 being 59.9% and 53.1% for the treatment groups, compared to 4.8% and 4.3% for placebo, increasing to 68.0% and 62.1% at Week 24 [2] - Complete skin clearance (PASI 100) was achieved by 29.4% and 27.7% of envudeucitinib patients at Week 16, rising to 41.0% and 39.5% at Week 24 [2] - Approximately 75% of envudeucitinib patients achieved clear or almost clear scalp psoriasis by Week 24, with over 30% responding as early as Week 4 [3] Group 2: Quality of Life Improvements - Quality-of-life improvements and itch relief were observed before PASI 90 responses, with significant enhancements noted by Week 12, where about 50% of patients achieved DLQI 0/1 [4][7] - Patients experienced an average improvement of over 4 points on the Worst Pruritus Numeric Rating Scale by Week 16, with meaningful itch relief as early as Week 2 [7] Group 3: Safety Profile - Treatment with envudeucitinib was generally well tolerated, with a safety profile consistent with Phase 2 studies, showing no significant laboratory abnormalities or tuberculosis reactivation [5] - Most treatment-emergent adverse events were mild and transient, with common issues including headache, nasopharyngitis, upper respiratory tract infection, and acne [5] Group 4: Future Developments - Alumis plans to submit a New Drug Application to the U.S. FDA in the second half of 2026 and is continuing to evaluate long-term efficacy and safety in the ONWARD3 trial [8] - The ONWARD clinical program involved over 1,700 patients in two parallel trials, assessing the efficacy and safety of envudeucitinib compared to placebo and apremilast [11]

Core Insights - Alumis Inc. announced the acceptance of results from its Phase 3 ONWARD program for envudeucitinib, a TYK2 inhibitor for moderate-to-severe plaque psoriasis, for a late-breaking oral presentation at the 2026 AAD Annual Meeting [1][2] - A new biomarker analysis from the Phase 2 STRIDE trial of envudeucitinib will also be presented as an e-poster at the same event [1][2] Presentation Details - The late-breaking oral presentation will cover the 24-week results from the randomized, double-blind, active comparator- and placebo-controlled Phase 3 ONWARD 1 and 2 studies, scheduled for March 28, 2026, at 11:12 am MDT [2] - The e-poster will focus on how envudeucitinib attenuates inflammatory biomarkers in plaque psoriasis, based on a subgroup analysis from the STRIDE Phase 2 clinical trial [2] Investor Engagement - Alumis will host a webcast for investors on March 29, 2026, at 5:00 pm MDT to review the Phase 3 ONWARD data presented at AAD, with a replay available on the company's website [3] Product Overview - Envudeucitinib is a next-generation, highly selective oral allosteric inhibitor of TYK2, designed to address immune dysregulation in diseases driven by proinflammatory mediators [4] - The drug has shown sustained, maximal 24-hour inhibition in psoriasis patients while minimizing off-target effects [4] - Alumis is also evaluating envudeucitinib in the Phase 3 ONWARD3 program and in a Phase 2b trial for systemic lupus erythematosus, with topline data expected in Q3 2026 [4] Company Background - Alumis is a late-stage biopharmaceutical company focused on developing targeted therapies for immune-mediated diseases, leveraging a proprietary data analytics platform [5] - The company's pipeline includes envudeucitinib for moderate-to-severe plaque psoriasis and systemic lupus erythematosus, as well as A-005 for neuroinflammatory diseases and lonigutamab for thyroid eye disease [5]

Core Viewpoint - Alumis (ALMS.US) shares surged over 154% to a record high of $20.60 following the announcement of positive topline results from its phase III clinical trials ONWARD1 and ONWARD2 for envudeucitinib, a next-generation highly selective oral TYK2 inhibitor targeting moderate to severe plaque psoriasis [1] Group 1: Clinical Trial Results - Envudeucitinib achieved high statistical significance in meeting all primary and secondary endpoints in the ONWARD1 and ONWARD2 trials [1] - At week 16, envudeucitinib demonstrated superior skin clearance effects compared to placebo, with a p-value of less than 0.0001 for the primary endpoint of PASI 75 and static Physician's Global Assessment (sPGA) 0/1 [1] - On average, 74% of patients reached PASI 75 and 59% achieved sPGA 0/1, with responses deepening over time [1] Group 2: Consistency of Results - The placebo-corrected response rates for the primary endpoints remained consistent between the two trials [1]

Core Viewpoint - Alumis (ALMS.US) shares surged over 154% to a record high of $20.60 following positive topline results from its phase III clinical trials for envudeucitinib, a next-generation selective oral TYK2 inhibitor targeting moderate to severe plaque psoriasis [1] Group 1: Clinical Trial Results - Envudeucitinib achieved statistically significant results for all primary and secondary endpoints in the ONWARD1 and ONWARD2 trials [1] - At week 16, envudeucitinib demonstrated superior skin clearance compared to placebo, with a p-value of less than 0.0001 for the primary endpoints of PASI 75 and sPGA 0/1 [1] - On average, 74% of patients reached PASI 75 and 59% achieved sPGA 0/1, with responses deepening over time [1]

Core Insights - Alumis Inc. is advancing its pipeline with key milestones expected in early 2026, including topline Phase 3 ONWARD data for envudeucitinib in moderate-to-severe plaque psoriasis and Phase 2b LUMUS data in systemic lupus erythematosus [2][4] Financial Results - For the quarter ended September 30, 2025, Alumis reported total revenue of $2.1 million, primarily from collaboration revenue, compared to no revenue in the same quarter of 2024 [10][12] - Research and development expenses increased to $97.8 million from $87.8 million year-over-year, driven by higher clinical trial costs and severance expenses related to the merger with ACELYRIN [10][12] - General and administrative expenses rose to $19.5 million from $10.6 million year-over-year, attributed to severance costs and increased personnel-related expenses [10][12] - The net loss for the quarter was $110.8 million, compared to a net loss of $93.1 million in the same quarter of 2024 [10][12] Cash Position - As of September 30, 2025, Alumis had cash, cash equivalents, and marketable securities totaling $377.7 million, which is expected to support its pipeline advancement through 2027 [7][10] Pipeline Developments - Envudeucitinib is a next-generation oral TYK2 inhibitor showing promise in treating immune-mediated diseases, with positive results from Phase 2 trials published in the Journal of the American Academy of Dermatology [5][8] - A-005, another TYK2 inhibitor, is set to enter a Phase 2 clinical trial for multiple sclerosis in the first half of 2026 [5][4] - Lonigutamab, an anti-IGF-1R therapy for thyroid eye disease, is also progressing with positive early results [5][4]

Summary of Alumis Conference Call Company Overview - **Company**: Alumis (NasdaqGS:ALMS) - **Focus**: Development of TYK2 inhibitors for autoimmune diseases, specifically psoriasis and lupus [2][4] Key Points Product Pipeline - **Envudeucitinib**: - Phase 3 trial for psoriasis nearing completion, with data readout expected in Q1 2026 [4] - Phase 2b trial for systemic lupus erythematosus (SLE) planned for Q3 2026 [4] - **Second TYK2 Inhibitor**: - A brain-penetrant TYK2 inhibitor entering Phase 2 for multiple sclerosis (MS) in H1 2026 [3] - **Lonigutamab**: - Acquired through merger with Acelyrin, currently in Phase 2 [3] Market Opportunity - **Psoriasis**: - Significant unmet need for high-efficacy oral drugs; over 75% of patients prefer oral medications over injectables [5][6] - Current leading drugs are Otesla and methotrexate, indicating a gap for better-tolerated options [6] - **Lupus**: - No approved oral therapies currently available; potential for Envudeucitinib to fill this gap [14] - Anifrolumab, a competitor, is projected to reach $1 billion in sales, highlighting market potential [14] Clinical Data and Efficacy - **Psoriasis Data**: - Phase 2 results show PASI 75 efficacy between 80-90%, PASI 90 between 60-70%, and PASI 100 between 35-45% [11] - Strong impact on itch reduction, with over 70% of patients experiencing significant improvement [12] - **Safety Profile**: - Data from over 2,000 patients shows no significant safety signals, critical for market acceptance [7] Competitive Landscape - **TYK2 Inhibitors**: - Conviction that TYK2 can be effective across various immune indications based on early data [4][20] - Comparison with other TYK2 inhibitors indicates a more favorable PK/PD profile for Envudeucitinib [21][23] - **Market Positioning**: - Emphasis on the simplicity of oral administration as a competitive advantage [9][30] Strategic Considerations - **Partnership Strategy**: - Plans to partner Envudeucitinib to maximize asset value, with flexibility to wait for additional data before finalizing partnerships [32][33] - **Cash Position**: - Over $480 million in cash, providing runway into 2027 to support ongoing trials [37] Future Outlook - **2026 Expectations**: - Anticipation of multiple transformational events, including data readouts for psoriasis and lupus [4][18] - **Long-term Vision**: - Continued development of A-005 and Lonigutamab as part of Alumis's future pipeline [34] Additional Insights - **Genomic Data**: - Strong correlation between TYK2 inhibition and autoimmune disease prevention, suggesting a robust scientific foundation for the drug's efficacy [10][20] - **Enrollment Success**: - Rapid enrollment in lupus trials, indicating strong investigator interest and confidence in the drug's profile [30][31]

Financial Status and Pipeline - Alumis had $486.3 million in cash, cash equivalents, and marketable securities as of June 30, 2025, expected to fund operations into 2027[12] - The company has a portfolio of three clinical molecules against validated targets, including Envudeucitinib, A-005, and Lonigutamab, plus multiple pipeline assets in late-stage research[12] Envudeucitinib (TYK2 Inhibitor) - Phase 3 topline data for Envudeucitinib in Psoriasis is expected in early Q1 2026, and Phase 2b topline data for SLE is expected in Q3 2026[12] - Envudeucitinib targets a market opportunity greater than $4 billion in SLE[27, 75] - In a Phase 2 trial, Envudeucitinib demonstrated high statistical significance at Week 12 (PASI 75: p < 0001)[45] - Approximately 75% of psoriasis patients prefer an oral therapy[25, 33, 40] A-005 (CNS Penetrant TYK2 Inhibitor) - A-005 is a first-in-class brain-penetrant TYK2 inhibitor for neuroinflammation and neurodegeneration, with Phase 2 initiation in MS expected in 1H 2026[14, 16] - A-005 demonstrated full CNS penetration in Phase 1, with doses established to provide high peripheral and CSF exposure[29, 86] Lonigutamab (Anti-IGF-1R Therapy) - Lonigutamab is an anti-IGF-1R therapy with a unique MOA for Thyroid Eye Disease (TED), with development program evaluation ongoing[12, 16] Market Opportunities - Near-term results could unlock interferon and IL-23 pathway-driven diseases with global market opportunities greater than $150 billion[15] - Approximately 16 million people worldwide have moderate-to-severe psoriasis, representing a global market of over $25 billion[40] Kaken Collaboration - Alumis is receiving $40 million near-term for Japan, which is less than 5% of the worldwide psoriasis market (estimated at $600 million in 2024), highlighting significant opportunity for Alumis in ROW[72]