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Tyrosine

Cohort A: Infusion of MuSK-CAART at various dose levels with or without pre-treatment (6 groups planned).

Cohort B: Infusion of MuSK-CAART at the dose regimen selected from Part A.

Intravenous infusion of MuSK-CAART at different doses. Subjects may also receive MuSK-CAART following pre-treatment with CY, or CY plus FLU.

MuSK-CAART

Cabaletta Bio

Mani Nistor

Ali Habib, MD

Joshua Valdez

David Richman, MD

Andrew J Heim

Mazen Dimachkie, MD

Katie Lewis

Nizar Chahin, MD

Medical Director

Muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG) is a rare but potentially severe disease, in which patients develop pathogenic autoantibodies that specifically target the MuSK protein in the neuromuscular junction. This phase 1 study is being conducted to evaluate the safety of various dosing regimens of an investigational cell therapy, MuSK-CAART, that can be given to patients with anti-MuSK antibody positive Myasthenia Gravis (MuSK MG), who have active disease. Various dosing regimens of MuSK-CAART alone, in combination with cyclophosphamide (CY), and in combination with CY and fludarabine (FLU) will be evaluated. Treatment with MuSK-CAART may potentially lead to complete and durable remission of disease.

Open-label Study to Evaluate the Safety of Various Dosing Regimens of MuSK-CAART for MuSK Myasthenia Gravis

A Phase 1, Open-label, Safety and Dose-finding Study of Autologous Muscle-specific Tyrosine Kinase Chimeric Autoantibody Receptor T Cells (MuSK-CAART) in Subjects With Anti-MuSK-antibody-positive Myasthenia Gravis

Frequency and dose of concomitant therapies.

Measurement of clinical symptoms using the Myasthenia Gravis Activities of Daily Living (MG-ADL) assessment.

Measurement of clinical symptoms using the Quantitative Myasthenia Gravis (QMG) assessment.

Measurement of clinical symptoms using the Myasthenia Gravis Composite (MGC) assessment.

Measurement of Quality of Life using the MG-QOL-15r (Myasthenia Gravis Qualify of Life 15-item scale, revised) questionnaire.

Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART.

Total MuSK-CAART positive cells for each manufacturing run.

Percent of total cells for infusion that are CAAR (Chimeric Autoantibody Receptor)-transduced cells.

Cellular kinetics profile of MuSK-CAART after infusion.

Change in MuSK autoantibody titer compared to pre-infusion visit by clinically validated assay.

Gulsen Oztosun, MD

The MuSK myasthenia gravis 1000 study seeks to collect saliva samples from 1000 subjects with laboratory confirmed diagnosis of MuSK myasthenia to identify genetic variations associated with MuSK MG. The data collected may be used by researchers to gain a better understanding of the cause of MuSK MG and to identify biomarkers and targeted therapy for MuSK MG.

Myasthenia gravis is a rare, neuromuscular (disease of the muscle and nerves) autoimmune disease characterized by weakness of the muscles. MG has a prevalence of approximately 14-40 per 100,000 people in the United States. There is no cure for MG, however understanding the disease is crucial to pave the way for development of new therapies. Important to note, the most common subtype of MG associated with Acetylcholine receptor antibodies (AChR) are found in more than 80% of patients with generalized myasthenia gravis, whereas muscle-specific kinase (MuSK) antibodies are found in only 8% of MG patients. These are found in patients with the AChR antibodies. Since the discovery of MuSK antibodies in patients, much has been learned. It has become clear that MuSK antibody MG differs in many ways from AChR antibody MG. There is some information that specific genetic factors play a role in development of MuSK MG.

Our objective is to collect saliva samples from 1000 subjects with laboratory confirmed diagnosis of MuSK myasthenia. These saliva samples will be then sent to the laboratory of Bryan Traynor who directs the Neurogenetics Laboratory at NIH. Dr. Traynor will conduct a genome-wide association study (GWAS). This study will provide important information of genetic factors leading to MuSK MG.

GWAS, also known as genome-wide association study, is a study performed to identify genetic characteristics associated with a particular disease. GWAS is currently used across various disciplines in medicine to better understand complex conditions where genetic risk factors contribute to the development of diseases.

Presently, this study has not been done in patients with MuSK MG. Researchers can use information from this study to develop quality treatment and ultimately, move toward targeted therapy approach for patients. We hope to find unique results and further enhance myasthenia research.

MuSK Myasthenia 1000 Study

Genome Wide Association Study of Patients With Muscle Specific Kinase Myasthenia Gravis

identify genetic characteristics associated with musk myasthenia gravis

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Open-label Study to Evaluate the Safety of Various Dosing Regimens of MuSK-CAART for MuSK Myasthenia Gravis	NCT05451212	MuSK Myasthenia...	MuSK-CAART	18 Years -	Cabaletta Bio
MuSK Myasthenia 1000 Study	NCT06259071	Myasthenia Grav... MuSK MG MuSK Myasthenia...		7 Years - 99 Years	Myasthenia Gravis Rare Disease Network

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