Annexon (ANNX) Study Update summary

Study overview and design

• Pivotal, randomized, double-blind, placebo-controlled phase III trial evaluated ANX005 in 241 GBS patients in Bangladesh and the Philippines, with patients randomized to 30 mg/kg, 75 mg/kg, or placebo.

• The trial excluded standard-of-care IVIG or plasma exchange to isolate ANX005's effect.

• Primary endpoint was GBS Disability Scale (GBS-DS) at week 8; secondary endpoints included muscle strength (MRC Sum Score), motor disability (ONLS), ventilation duration, and nerve damage biomarkers.

• Patients had moderate to severe GBS, with rapid time to treatment and well-balanced baseline characteristics; stratification by muscle strength and time from onset.

• FDA Fast Track and Orphan Drug Designations granted; study design aligned with regulatory expectations.

Efficacy results

• ANX005 30 mg/kg met the primary endpoint, with a 2.4-fold higher likelihood of better health at week 8 vs. placebo (p=0.0058).

• 28% of ANX005-treated patients had a clinically meaningful three-point or higher improvement in GBS-DS, compared to 13.6% with placebo.

• Early and sustained improvements in muscle strength (MRC sum score), daily function (ONLS), and reduced time on ventilation (median 28 days earlier) and walking (31 days earlier).

• Early reduction in serum neurofilament light chain (NFL) by 11.2% vs. placebo, indicating reduced neuronal damage.

• Durable benefits maintained through 26 weeks, with consistent efficacy across subgroups, including those with Western characteristics.

Safety and tolerability

• ANX005 was generally well-tolerated at both doses, with adverse event rates similar to placebo and no new safety signals.

• Most adverse events were mild or moderate infusion reactions and transient rashes (30.4%).

• No increase in infection rates, no autoimmune-related adverse events, and no drug-related deaths or serious infections observed.

• All-cause mortality was similar to placebo; deaths were consistent with expected rates in severe GBS.

• No new safety signals or increased risk of serious adverse events.