Abstract Details

Title A Phase 2 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous ANX005 in Patients with, or at Risk of, Manifest Huntington’s Disease (HD)

Topic Movement Disorders

Presentation(s) S32 - Movement Disorders: Trials (5:06 PM-5:18 PM)

Poster/Presentation
Number 009

Background ANX005 is a humanized monoclonal antibody designed to inhibit C1q.

Objective Report final results of ANX005-HD-01, a phase 2 study of patients with or at risk of manifest HD.

Design/Methods Eligible patients (CAP>400) received intravenous ANX005 every 2 weeks through week 22 (NCT04514367). Endpoints were assessed on-treatment through week 24, with off-treatment follow-up through week 36. Primary objectives included safety/tolerability, pharmacokinetics (PK), and C1q, C4a, and NfL levels (CSF and plasma). Exploratory objectives of clinical efficacy included cUHDRS and total functional capacity (TFC).

Results All safety population (n=28) patients experienced transient infusion-related reactions during the first dose, mainly transient maculopapular rash. Two serious adverse events occurred, lupus-like presentation and idiopathic pneumonitis, which reversed or improved upon treatment discontinuation. Steady-state PK were achieved by week 6 in the blood and CSF. ANX005 demonstrated complete and durable C1q inhibition in CSF and serum, consistent with drug levels. Mean plasma and CSF NfL levels for 24-week completers (n=23) tracked with NfL natural history. Clinical disease progression was stable in the overall patient population throughout the entire 9-month study as measured by mean change in cUHDRS and TFC relative to baseline. Subgroup analysis indicated that patients with high baseline C4a/C4 (n=12) exhibited clinical improvement in cUHDRS at all timepoints, with a significant difference from patients with low baseline C4a/C4 (n=11) at week 24 (p=0.037). Consistent separation in TFC between the two subgroups was observed throughout the study. Rapid and sustained reduction in downstream complement activation and neuroinflammation, as measured by CSF C3a and C3 levels, respectively, was also observed through the 9-month study. A trend of decreased CSF YKL40 suggested a positive impact of ANX005 on microglial activity in patients exhibiting improved clinical response.

Conclusions ANX005 was generally well-tolerated, maintained full target engagement, and showed clinical improvement in a subgroup of HD patients.

Authors/Disclosures
Rajeev Kumar, MD, FRCPC (Rocky Mountain Movement Disorders Center) PRESENTER	The institution of Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Teva Pharmaceuticals. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Annexon. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cerevel Therapeutics. Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel Pharma. Dr. Kumar has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda Therapeutics. The institution of Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Research Catalyst, LLC. Dr. Kumar 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 CenExel RMCR. Dr. Kumar has stock in Research Catalyst, LLC. Dr. Kumar has stock in CenExel. The institution of Dr. Kumar has received research support from Supernus. The institution of Dr. Kumar has received research support from Sage Therapeutics. The institution of Dr. Kumar has received research support from Prilenia Therapeutics. The institution of Dr. Kumar has received research support from Roche. The institution of Dr. Kumar has received research support from Triplet Therapeutics. The institution of Dr. Kumar has received research support from CHDI Foundation. The institution of Dr. Kumar has received research support from Neurocrine Biosciences. The institution of Dr. Kumar has received research support from Biovie. The institution of Dr. Kumar has received research support from Neuroderm. The institution of Dr. Kumar has received research support from Sanofi. The institution of Dr. Kumar has received research support from Addex Pharma. The institution of Dr. Kumar has received research support from Integrative Research Laboratories. The institution of Dr. Kumar has received research support from Takeda Pharmaceuticals. The institution of Dr. Kumar has received research support from Neuraly. The institution of Dr. Kumar has received research support from Abbvie. The institution of Dr. Kumar has received research support from Cerevel Therapeutics. The institution of Dr. Kumar has received research support from Transposon Therapeutics. The institution of Dr. Kumar has received research support from Lundbeck. The institution of Dr. Kumar has received research support from Biohaven. The institution of Dr. Kumar has received research support from Revance Therapeutics. The institution of Dr. Kumar has received research support from Impax Laboratories. The institution of Dr. Kumar has received research support from Pharma Two B. The institution of Dr. Kumar has received research support from Enterin. The institution of Dr. Kumar has received research support from CND Life Sciences. The institution of Dr. Kumar has received research support from Neuron23. The institution of Dr. Kumar has received research support from Annexon Biosciences. The institution of Dr. Kumar has received research support from Annovis. The institution of Dr. Kumar has received research support from PTC Therapeutics. The institution of Dr. Kumar has received research support from Uniqure. The institution of Dr. Kumar has received research support from Alexza. The institution of Dr. Kumar has received research support from SparkNeuro. The institution of Dr. Kumar has received research support from Praxis. The institution of Dr. Kumar has received research support from Scion Neurostim. The institution of Dr. Kumar has received research support from Cognition Therapeutics. The institution of Dr. Kumar has received research support from Eli Lilly. Dr. Kumar has received personal compensation in the range of $100,000-$499,999 for serving as a Medical Director with CenExel RMCR. Dr. Kumar has received personal compensation in the range of $1,000,000+ for serving as a Managing Member with Research Catalyst, LLC.
Daniel O. Claassen, MD, FAAN (Vanderbilt University Medical Center)	Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Neuroscience. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark . The institution of Dr. Claassen has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Alterity. Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Neuroscience. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for HD Insights. The institution of Dr. Claassen has received research support from NIH. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from HDSA. The institution of Dr. Claassen has received research support from Department of Defense. The institution of Dr. Claassen has received research support from Griffin Family Foundation. The institution of Dr. Claassen has received research support from Neurocrine. The institution of Dr. Claassen has received research support from Vaccinex. The institution of Dr. Claassen has received research support from AbbVie. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from Genentech/ Roche. The institution of Dr. Claassen has received research support from Prilenia. The institution of Dr. Claassen has received research support from Neurocrine/ HSG.
Ann Mongan, PhD (Annexon Biosciences)	Dr. Mongan has received personal compensation for serving as an employee of Annexon Biosciences.
Benjamin Hoehn (annexon biosciences)	No disclosure on file
	No disclosure on file
	No disclosure on file
Chenying Guo, PhD (Annexon Biosciences)	Dr. Guo has received personal compensation for serving as an employee of Annexon Biosciences. Dr. Guo has received personal compensation for serving as an employee of Novartis. Dr. Guo has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Lori K. Taylor	Lori Kell Taylor has received personal compensation for serving as an employee of Annexon Biosciences. Lori Kell Taylor 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 received stock or an ownership interest from Annexon Inc. Ted Yednock, PhD has received intellectual property interests from a discovery or technology relating to health care.
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.