Abstract Details

Title Inhibition of C1q, Initiator of the Classical Complement Cascade, by ANX005 for the Treatment of Guillain-Barré Syndrome: Results from a Phase 1b Study

Topic Autoimmune Neurology

Presentation(s) S34 - Clinical Trials and Therapeutics in Autoimmune Neurology (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Objective

To assess anti-C1q antibody ANX005 in patients with Guillain-Barré Syndrome (GBS).

Background GBS is a serious, life-threatening autoimmune disorder causing acute neuronal injury and progressive paralysis, sometimes leading to permanent disability or death. Symptoms peak within 4 weeks and recovery ranges from months to years. Although not FDA-approved, IVIg and plasma exchange are the standard of care in the US. Onset is associated with autoantibody-induced activation of the classical complement cascade. Inhibition of C1q, the initiating molecule of the cascade, early in the course of GBS may minimize disease severity and accelerate recovery.

Design/Methods A phase 1b double-blind, placebo-controlled, single ascending dose study assessed safety, pharmacokinetics, and pharmacodynamics of ANX005 (n=23) vs placebo (n=8) in patients with GBS in Bangladesh. Neurofilament light chain (NfL), a nerve damage biomarker, and functional efficacy measures were assessed.

Results In 23 patients aged 18-58 years, ANX005 infusions up to 75 mg/kg were well tolerated with no drug-related serious adverse events (AEs) or discontinuations. The most common AE was infusion-related reactions, manifesting as transient low-grade rashes. Doses ≥18 mg/kg fully inhibited C1q in serum and CSF; inhibition was sustained for up to 3 weeks with 75 mg/kg (n=6). ANX005 resulted in early decline in serum NfL vs placebo from week 2 to 4 post-dose (P=.012) and a dose-dependent improvement in Medical Research Council sum score at week 1. Early improvement correlated with GBS-Disability Score reduction (r²=0.48; P<.0001). At week 8, 28% of patients treated with ANX005 18-75 mg/kg improved by ≥3 points on GBS-Disability Score vs 0% with placebo. Trends for improvement were observed in length of ICU stay and duration of mechanical ventilation.

Conclusions The classical complement inhibitor ANX005 was well tolerated and demonstrated robust target engagement, impact on biomarkers of neuronal damage, and preliminary evidence of efficacy. A phase 2 trial is planned.

Authors/Disclosures
Sanjay C. Keswani, MBBS (Annexon BioSciences) PRESENTER	Dr. Keswani has received personal compensation for serving as an employee of Annexon Biosciences. Dr. Keswani has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Nura Bio. Dr. Keswani has received stock or an ownership interest from Annexon Biosciences. Dr. Keswani has received stock or an ownership interest from Nura Bio.
Zhahirul Islam	Zhahirul Islam has nothing to disclose.
Nowshin Papri	No disclosure on file
Israt Jahan, MD (Parkinson's &Neurology Clinic, LLC)	No disclosure on file
	No disclosure on file
Henk-Andre A. Kroon, MD, MBA (Annexon Biosciences)	Dr. Kroon has received personal compensation for serving as an employee of Annexon Biosciences. Dr. Kroon has stock in Annexon Biosciences.
Eric Humphriss	Eric Humphriss has received personal compensation for serving as an employee of Annexon Biosciences. Eric Humphriss has stock in Annexon Biosciences.
	No disclosure on file
Ted Yednock, PhD (Annexon Biosciences)	Ted Yednock, PhD has received personal compensation for serving as an employee of Annexon Inc. Ted Yednock, PhD has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Annexon Inc. Ted Yednock, PhD has stock in Annexon Inc. Ted Yednock, PhD has received intellectual property interests from a discovery or technology relating to health care.
Quazi Deen Mohammad, MD (National Institute of Neuroscience (NINS).)	Dr. Deen Mohammad has nothing to disclose.

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