Annexon (ANNX) KOL event summary

Scientific and clinical rationale for C1q inhibition in GA

• C1q is implicated as an upstream driver of neurodegeneration in geographic atrophy (GA), leading to early photoreceptor synapse loss before RPE atrophy occurs.

• Inhibition of C1q offers a differentiated mechanism from downstream complement inhibitors (C3, C5), aiming to preserve photoreceptors and visual function.

• Preclinical and clinical data show that C1q inhibition protects synapses and reduces neuroinflammation, with animal and human evidence supporting this approach.

• Current approved therapies slow RPE lesion growth but do not prevent vision loss; C1q inhibition targets the root cause of neurodegeneration.

• The approach preserves the alternative complement pathway, potentially reducing side effects like increased CNV risk seen with C3/C5 inhibitors.

Introduction, agenda, and KOL background

• Event focused on vonaprument for GA in dry AMD, outlining company mission, clinical perspectives, disease mechanism, trial data, and strategic outlook.

• Presenters included executive leadership, clinical experts, and key opinion leaders in ophthalmology.

• Panel included SVP of Ophthalmology Strategy & Innovation, Vice Chair of Ophthalmology Clinical Research at Duke, Chair of Clinical Trials at Retina Consultants of America, and executive leadership.

Market insights and analysis

• GA affects over 8 million globally, with incidence rising due to aging populations.

• Current GA treatments focus on lesion-sparing, with combined sales of ~$1.5B, but lack vision preservation; vision-preserving therapies could exceed $7B in global peak sales.

• No approved vision-preserving treatments for GA, representing a significant unmet need.