Annexon (ANNX) Study update summary

Program rationale and unmet need

• Vonaprument’s anti-C1q approach targets C1q in the retina to protect synapses, neurons and photoreceptors and preserve BCVA, based on a neuroprotective mechanism.

• GA affects more than 8 million people worldwide, with more than 80% untreated; approved therapies have not established functional vision benefit.

• In a patient and caregiver survey, 91% of patients worried most about loss of independence; 64% cited losing the ability to read or watch TV.

Phase II evidence

• At month 12, confirmed ≥15-letter BCVA loss occurred in 16.9% of sham patients, 8.7% with EOM and 4.5% with EM; EM HR was 0.272 (95% CI 0.090–0.819; nominal p=0.0119), and EOM HR was 0.504 (nominal p=0.1098).

• EZ loss decreased dose-dependently versus sham: 27% across the pan-macula, 48% in the central 2.0 mm and 59% in the central 1.5 mm.

• In foveal disease, confirmed 15-letter loss occurred in 25% of sham patients versus 5.9% with monthly treatment; vision-protection effects were also observed in non-foveal disease and across healthier and less healthy eyes.

• In ARCHER’s final six months off treatment, vision loss resumed across groups at the same rate, without treated eyes catching up; the presentation characterized the dose-dependent effects as consistent with disease modification.

ARCHER II design and readout

• ARCHER II enrolled 659 patients, randomized 2:1 to monthly vonaprument 5.0 mg per eye or sham; confirmed ≥15-letter BCVA loss at months 15 and 24 are dual primary endpoints, with most alpha allocated to month 15.

• The trial was over-enrolled by 30 patients and finished enrollment two months early; 12-month discontinuation was in the mid-single digits versus ~15% in Phase II.

• The cohort excludes patients with BCVA below 20/100 and otherwise mirrors Phase II, including similar enrollment in foveal and LLVD <30 subgroups.

• A single-study analysis is targeted for Q4 2026, followed by powered sub-study analyses in Q1 2027 and 24-month analyses in Q3 2027; if any analysis is not positive, the study remains masked through month 24.

• The FDA-aligned plan includes two site-level sub-analyses balanced by patient count, events and stratification factors, each powered at 90% or better; FDA Fast Track and EMA PRIME designations support US and EU filing strategies.