Abstract Details

Title Safety and Pharmacokinetics of GNbAC1, a Humanised Monoclonal Antibody Against the Multiple Sclerosis Retrovirus Envelope Protein in Patients with Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) S31 - (-)

Poster/Presentation
Number 003

Objective

Background Human endogenous retrovirus (HERV) genes represent about 8% of the human genome. A member of the HERV family W, the Multiple Sclerosis Retrovirus (MSRV), codes for an envelope protein (Env), which can activate a pro-inflammatory and autoimmune cascade through the interaction with Toll-Like receptor 4 (TLR4) on antigen-presenting cells and which inhibits the oligodendrocyte precursor cell differentiation. In several independent studies, the MSRV-Env protein was shown to be expressed in patients with MS and in particular in MS lesions. Due to these properties, the MSRV-Env protein could play a critical role in the MS pathology and appears as a valid therapeutic target. GNbAC1 is a humanised monoclonal antibody of the IgG4 isotype, which is directed against the MSRV-Env protein. It showed a favorable safety profile and linear pharmacokinetic in a Phase I trial.

Design/Methods We report a Phase IIa clinical study of GNbAC1. This single-blind placebo controlled dose-escalation study evaluated the safety, pharmacokinetics and pharmacodynamics of GNbAC1 in 10 MS patients. Each subject received a single intravenous infusion of GNbAC1 at doses of 2 mg/kg or 6 mg/kg body weight or placebo, infused over 1 hour. Safety parameters were observed and blood samplings were performed to study the monoclonal antibody pharmacokinetics.

Results The first safety findings and pharmacokinetics results in MS patients will be presented and compared to the results obtained in healthy subjects.

Conclusions Based on the safety and pharmacokinetics data of this small phase IIa study, a larger phase II program with monthly administrations of the monoclonal antibody will be launched to evaluate the efficacy and safety of this anti-HERV monoclonal antibody in MS.

Authors/Disclosures
Tobias Derfuss, MD PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Patrice LaLive, MD	Dr. LaLive has nothing to disclose.
	No disclosure on file
	No disclosure on file
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Genzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. The institution of Dr. Kappos has received research support from Shionogi. The institution of Dr. Kappos has received research support from Japan Tobacco. The institution of Dr. Kappos has received research support from Auriga Vision AG. The institution of Dr. Kappos has received research support from EMD Serono. The institution of Dr. Kappos has received research support from Glaxo Smith Kline. The institution of Dr. Kappos has received research support from Wellmera AG. The institution of Dr. Kappos has received research support from Eli Lilly (Suisse) SA. The institution of Dr. Kappos has received research support from Bristol Myers Squibb. The institution of Dr. Kappos has received research support from Celltrion Inc. Dr. Kappos has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Herve Perron, PhD	Mr. Perron has received personal compensation for serving as an employee of Geneuro-Innovation. Mr. Perron has stock in GeNeuro. The institution of Mr. Perron has received research support from European Union (EU) HORIZON HEALTH Program.
Francois Curtin	No disclosure on file

��ɫ��

��ɫ��