Summary of Annexon (ANNX) FY Conference - August 13, 2025 Company Overview - **Company**: Annexon Biosciences - **Industry**: Ophthalmology and Neuroinflammatory Diseases - **Key Focus**: Development of therapies targeting complement-mediated diseases, particularly in ophthalmology Core Points and Arguments 1. **Leadership and Experience**: Lloyd Clark, a retina specialist with 25 years of experience, has joined Annexon to advance their lead candidate for dry Age-related Macular Degeneration (AMD) through Phase 3 trials, aiming for a potential blockbuster treatment option [5][6][34] 2. **Product Pipeline**: - **Lead Candidate**: Vonapruvment (formerly known as ANX007) for geographic atrophy associated with dry AMD, which has shown vision preservation in clinical trials [12][13][29] - **Other Candidates**: - Tanrupebar, a systemic C1Q inhibitor for Guillain-Barré syndrome, has completed Phase 3 trials with positive results [7][11] - An oral complement inhibitor in earlier phases targeting multiple indications [8] 3. **Scientific Approach**: The company utilizes a pioneering scientific approach to inhibit the classical complement pathway, specifically targeting C1Q to mitigate neuroinflammation across various diseases [9][10][30] 4. **Clinical Data**: - Positive Phase 2 results for vonapruvment indicate significant visual acuity preservation and anatomical benefits, with a 73% risk reduction in 15-letter loss compared to sham treatment [23][31] - The ARCHER II Phase 3 trial has completed enrollment with over 630 patients, focusing on those with potential for vision preservation [26][33] 5. **Regulatory Progress**: - Vonapruvment has received PRIME designation in the EU, marking it as the first dry AMD drug to achieve this status [16][28] - The company is in discussions with global regulators to bring therapies to market [8][11] Important but Overlooked Content 1. **Market Need**: There are currently no approved therapies for geographic atrophy outside the US, highlighting a significant unmet medical need for patients suffering from severe blinding eye diseases [14][16] 2. **Safety Profile**: The ARCHER study indicated a favorable safety profile for vonapruvment, with minimal adverse events reported, including only one case of endophthalmitis [25][32] 3. **Future Outlook**: The company anticipates reporting top-line data from the ARCHER II trial in 2026, with a strong cash runway to support ongoing development [34] This summary encapsulates the key insights from the conference, focusing on Annexon's strategic direction, product pipeline, and the significant clinical advancements in treating neuroinflammatory diseases and ophthalmological conditions.

Core Insights - The completion of enrollment in the Phase 3 ARCHER II trial for vonaprument indicates strong demand for a therapy aimed at preserving vision in patients with dry age-related macular degeneration (AMD) with geographic atrophy (GA) [1][4] - Topline pivotal data from the trial is expected to be reported in the second half of 2026, with the potential for vonaprument to be the first approved treatment for dry AMD with GA in Europe and the U.S. [1][10] Company Overview - Annexon, Inc. is a biopharmaceutical company focused on developing novel therapies for neuroinflammatory diseases, including those affecting the eye [1][13] - The company aims to deliver first-in-kind medicines that address significant unmet needs in various therapeutic areas, including autoimmune, neurodegenerative, and ophthalmic diseases [13] Product Details - Vonaprument is a first-in-kind, non-pegylated antigen-binding fragment designed to inhibit C1q locally in the eye, demonstrating significant vision preservation in previous trials [2][9] - The Phase 2 trial showed that vonaprument provided statistically significant protection against vision loss, measured by best corrected visual acuity (BCVA) [11] Trial Design and Objectives - The ARCHER II trial is a global, randomized, double-masked, sham-controlled study that has enrolled over 630 patients, with a primary endpoint focused on preventing a ≥15-letter loss in BCVA [3][6] - Secondary endpoints include safety, low-luminance visual acuity (LLVA), and photoreceptor integrity [8] Regulatory Designations - Vonaprument has received Priority Medicine (PRIME) designation in Europe and Fast Track designation in the U.S., indicating its potential therapeutic advantages [3][10] Market Need - There is an urgent need for effective treatments for GA, as current options are limited and no approved therapies have demonstrated significant prevention of vision loss [5][12]