Summary of AC Immune Conference Call - December 11, 2025 Company Overview - **Company**: AC Immune (NasdaqGM: ACIU) - **Focus**: Development of active immunotherapies for neurodegenerative diseases, particularly targeting alpha-synuclein in Parkinson's disease and tau/amyloid-beta in Alzheimer's disease [4][27] Key Industry Insights - **Parkinson's Disease**: Second most common neurodegenerative disorder, fastest growing neurological disease, affecting approximately 1% of the population over 65 years [9] - **Market Need**: Significant unmet need for disease-modifying therapies in Parkinson's disease, with current treatments primarily symptomatic [28] Core Points from the Call 1. **Vaccine Phase Two Trial Results**: - Positive interim results from the phase two trial of ACI-7104, an anti-alpha-synuclein active immunotherapy for early Parkinson's disease patients [2][24] - The trial included 34 subjects aged 40-75 with early-stage Parkinson's disease [13] 2. **Safety and Tolerability**: - ACI-7104 demonstrated a favorable safety profile with no serious adverse events related to the study drug [24] - Common adverse events included injection site reactions (56%), headache (14%), and fatigue (12%) [15] 3. **Immunogenicity**: - ACI-7104 achieved a 100% responder rate, with significant increases in antibody titers observed after each immunization [16][24] - Antibodies generated were shown to cross the blood-brain barrier, indicating potential efficacy in targeting alpha-synuclein in the brain [17] 4. **Biomarker Analysis**: - Interim analysis showed stabilization of total alpha-synuclein levels in cerebrospinal fluid (CSF) in the treatment group, suggesting target engagement [25] - Neurofilament light chain (NFL) levels remained stable in the treatment group, indicating a potential slowing of neurodegeneration [20] - DaT-SPECT imaging indicated no progression in dopamine transporter levels in the treatment group, contrasting with expected declines in the placebo group [21][32] 5. **Clinical Measures**: - MDS-UPDRS Part III scores, which assess motor symptoms, showed minimal changes in the treatment group over 74 weeks, suggesting stabilization of motor function [23][30] 6. **Future Development Plans**: - AC Immune is considering an accelerated development pathway towards registration, potentially skipping part two of the trial [46] - Plans to include U.S. sites in future studies and explore the inclusion of tracer molecules in the next study [47] Additional Insights - **Market Potential**: Partner programs have generated over CHF 450 million in payments, with potential for an additional CHF 4 billion in milestone payments and royalties [5] - **Long-term Vision**: AC Immune aims to pioneer precision prevention strategies for neurodegenerative diseases, leveraging their active immunotherapy platform [27] Conclusion - The interim results from the ACI-7104 trial indicate promising safety, immunogenicity, and potential disease-modifying effects in early Parkinson's disease, positioning AC Immune favorably in the neurodegenerative disease market [26][50]

Summary of AC Immune Conference Call Company Overview - **Company**: AC Immune (NasdaqGM: ACIU) - **Focus**: Development of precision medicine for neurodegenerative diseases, particularly through active immunotherapy and small molecules [3][4] Key Points Pipeline and Financials - AC Immune has a focused pipeline with several phase two products and wholly owned assets [3] - The company has generated over $430 million from partnerships, with potential for an additional $4 billion in milestones and royalties [3] - Cash reserves are projected to last until Q3 2027, allowing for investment in precision medicine [3] Active Immunotherapy Programs - Lead programs ACI-35.030 and ACI-24 are partnered with Johnson & Johnson and Takeda, both receiving fast-track designation from the FDA [4] - ACI-7104, an active immunotherapy against alpha-synuclein, is in phase two development, with data expected by the end of the year [4][15] Precision Medicine Approach - The company emphasizes the importance of precision medicine in neurodegenerative diseases, particularly in Alzheimer’s, where there are approximately 100 million patients and 300 million at risk [5] - Active immunotherapies and small molecules target various proteins involved in neurodegenerative diseases, including tau and alpha-synuclein [6] Small Molecule Development - Small molecules derived from the Morphomer platform can penetrate the brain and target misfolded proteins, showing potential for preventing neurotoxicity [6][7] - The Tau morphomer (664) demonstrated over 50% reduction in Tau pathology in aggressive mouse models [9] - NLRP3 inhibitors are in development for CNS applications and show promise in treating diseases like Parkinson's and Alzheimer's [10][11] Upcoming Milestones - Data from the ABATE trial in phase two, partnered with Takeda, is expected in December [14] - Results on immunogenicity and pharmacodynamics for ACI-7104 are anticipated, with a focus on alpha-synuclein reduction in the brain [15][18] - The company plans to submit IND CTA for several small molecules by December, with clinical trials starting early next year [15] Market Position and Strategy - AC Immune positions itself as a leader in active immunotherapy, which is seen as a safer and more effective long-term treatment option compared to monoclonal antibodies [21] - The company aims to transition into phase three development based on encouraging data from ongoing trials [19][20] Collaboration and Future Directions - The small molecule Tau program is partnered with Eli Lilly, with decisions on clinical lead molecules expected soon [25] - The company is exploring both CNS and non-CNS applications for its NLRP3 inhibitors, with a focus on neuroinflammation and metabolic diseases [26][27] Additional Insights - The company is optimistic about the potential of its therapies to modify disease progression in Alzheimer’s and other neurodegenerative conditions [13][24] - There is a growing interest in the role of inflammation in neurodegenerative diseases, which AC Immune aims to address through its innovative therapies [26][27]