KYSA-6: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, in Subjects With Refractory Generalized Myasthenia Gravis

A Study of the Anti-CD 19 Chimeric Antigen Receptor T Cell Therapy for Subjects with Myasthenia Gravis

Myasthenia gravis (MG) is a chronic autoimmune disease that affects the neuromuscular junction and is characterized by muscle weakness. B cells play a role in MG, and the disease is characterized by the presence of autoantibodies such as anti-AChR and anti-MuSK antibodies. CD-19 target chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete both normal and autoreactive B cells in the circulation as well as impacted lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with myasthenia gravis (MG).

Eligibility Criteria:
Key Inclusion Criteria

1. Diagnosis of MG with presence of autoantibodies to AChR and MuSK
2. Myasthenia Gravis Foundation of America (MGFA) Class IIB-IV\*
3. MG-Activities of Daily Living (MG-ADL) total score of ≥6 at screening and at pre-dose baseline
4. Failed treatment over 1 year or more with 2 or more immunosuppressive/immunomodulatory therapies or; failed at least 1 immunosuppressive therapy and required chronic plasmapheresis, or IVIG to control symptoms\*\*
5. On a stable dose of glucocorticoids and/or other immunotherapies for ≥1 month prior to screening. For azathioprine, being on a stable dose for ≥2 months prior to screening is require
6. No change in dose of acetylcholinesterase inhibitors for ≥2 weeks prior to screening
7. No use of IV Igor plasma exchange (PLEX) within 4 weeks of pre-dose baseline

(\*) For Germany Sites: Myasthenia Gravis Foundation of America (MGFA) Class III-IV. Patients with disease classified as MGFA Class IIB may be included if the patient requires continuous treatment with IVIG or PLEX to be maintained at MGFA class IIB.

(\*\*) For Germany Sites: In the preceding 2 years failed two monoclonal antibodies with different mechanisms of action - or - failed at least 1 monoclonal antibody and required chronic plasmapheresis, or IVIg to control symptoms. Patients are required to have failed two different monoclonal antibodies as treatment for the preceding 1 to 2 years.

Key Exclusion Criteria

1. Impaired cardiac function or clinically significant cardiac disease including:

   1. Unstable angina or myocardial infarction or coronary artery bypass graft within 6 months prior to apheresis
   2. New York Heart Association stage III or IV congestive heart failure
   3. History of clinically significant cardiac arrhythmia (e.g., ventricular tachycardia, QTc prolongation, and/or torsades de pointes), complete left bundle branch block, high-grade atrioventricular block
   4. History of severe nonischaemic cardiomyopathy
   5. Left ventricular ejection fraction (LVEF) \<45% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
2. Serious and/or uncontrolled medical condition and severity of the underlying MG disease activity that, in the investigator's judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol, such as:

   1. Active, uncontrolled, viral, bacterial, or systemic fungal infection (including human T -cell lymphotropic virus \[HTLV\], human polyomavirus 2 \[JC virus\], or syphilis); or recent history of repeated infections
   2. Clinical evidence of dementia or altered mental status
   3. Recent thromboembolic event
   4. On anti-coagulation agents that would be unsafe to transiently hold for medical procedures