Abstract Details

Title First-in-Human Dose Selection and Pharmacokinetics, Safety, Tolerability, and Immunogenicity of ARGX-119, an Agonist Antibody for Human Muscle-Specific Kinase

Topic General Neurology

Presentation(s) P10 - Poster Session 10 (5:00 PM-6:00 PM)

Poster/Presentation
Number 2-007

Objective To present the approach for selection of first-in-human (FIH) doses and the results of a phase 1, FIH, double-blinded, placebo-controlled study (NCT05670704) of single ascending doses (SAD) and multiple ascending doses (MAD) of ARGX-119 in healthy participants.

Background ARGX-119 is the first agonist antibody for human muscle-specific kinase (MuSK). Upon activation of MuSK, ARGX-119 may stabilize the neuromuscular junction (NMJ) in patients with neuromuscular diseases such as congenital myasthenic syndrome (CMS) and amyotrophic lateral sclerosis (ALS). Nonclinical, proof-of-concept (PoC) studies of ARGX-119 showed restoration of NMJ signaling in mouse models of Docking Protein 7 (DOK7)-CMS and MuSK-myasthenia gravis. Results from nonclinical, repeated dose toxicity studies supported initiation of this FIH study with ARGX-119.

Design/Methods Dose selection was based on the determination of the (minimally) active dose in nonclinical PoC studies and human pharmacokinetic (PK) predictions based on a non-human primate PK model. This FIH study evaluated the safety, tolerability, PK, and immunogenicity of ARGX-119 versus placebo, administered as intravenous SAD (9 cohorts), subcutaneous SAD, and intravenous MAD (4 once-weekly intravenous doses in 4 cohorts) in healthy participants.

Results Preliminary results from the FIH study suggest that ARGX-119 has a favorable safety profile in healthy participants at the doses investigated. There were no changes in the original design of single and multiple doses as decided by the Data Review Team evaluating accumulating PK and safety data. PK data in humans showed nonlinear elimination, suggesting target-mediated elimination as the relevant elimination pathway at low ARGX-119 concentrations, as observed in nonclinical studies.

Conclusions ARGX-119 was well tolerated and has a favorable safety profile in healthy participants at the doses investigated in single- and multiple-dose cohorts in this FIH study. ARGX-119 is currently being evaluated in a phase 1b study in adult participants with DOK7-CMS (NCT06436742) and a phase 2a study in adult participants with ALS (NCT06441682).

Authors/Disclosures
Rebecca Shilling (Alnylam Pharmaceuticals) PRESENTER	Rebecca Shilling has received personal compensation for serving as an employee of argenx pharmaceuticals. Rebecca Shilling has stock in argenx pharmaceuticals. Rebecca Shilling has received intellectual property interests from a discovery or technology relating to health care.
Tonke van Bragt, MSc	The institution of Mrs. van Bragt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for argenx. Mrs. van Bragt has stock in argenx.
Christa Kneip, PhD	Dr. Kneip has received personal compensation for serving as an employee of argenx.
Sofie Priem (argenx)	No disclosure on file
Xinghong Leng	Dr. Leng has received personal compensation for serving as an employee of argenx. Dr. Leng has stock in argenx.
Rachelle D. Mutch, MD	Dr. Mutch has nothing to disclose.
Sonya Patel, MD	Dr. Patel has nothing to disclose.
Peter Vanhoenacker, PhD	Dr. Vanhoenacker has received personal compensation for serving as an employee of argenx. Dr. Vanhoenacker has stock in argenx.
Cristina Vaghi, PhD	Dr. Vaghi has received personal compensation for serving as an employee of argenx.
Roeland Vanhauwaert, PhD	Mr. Vanhauwaert has stock in argenx.

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