Investigating an mRNA CAR T-cell Therapy, Known as Descartes-08, as a Potential Approach to Treat Myasthenia Gravis

Inclusion Criteria:

• Patient must be at least 18 years of age.

• Patient must have generalized myasthenia gravis (gMG), Myasthenia Gravis Foundationof America (MGFA) clinical classification grades 2-4 at the time of Sscreening.

• MG-Activities of Daily Living (MG ADL) total score ≥ 6.

• Concomitant immunosuppressive drugs must be deemed necessary by the investigator.The dose must be stable for a minimum of 8 weeks prior to Baseline visit.

• If a patient is using corticosteroids, the daily dose should not exceed 40 mg/day ofprednisone equivalent. The dose must have been stable for a minimum of 8 weeks priorto Baseline visit.

• Acetylcholine receptor autoantibody (anti-nAChR) titer or anti-AChR cluster antibodymust be above the reference laboratory upper normal limit (UNL) and documentedwithin the past 10 years of screening.

• Patient must be willing to return for all study visits.

• Patient must be able to give written informed consent.

• Women of childbearing potential must agree to use highly effective birth controlfrom Screening until 14 days post last dose of Descartes-08,

Exclusion Criteria:

• Major chronic illness that is not well managed at the time of study entry and in theopinion of the investigator may increase the risk to the patient.

• Diagnosis of gMG within 12 months of screening.

• No history of systemic treatment for gMG other than acetylcholine esteraseinhibitors.

• Diagnosis of a neuromuscular disease other than gMG.

• Patient is pregnant or lactating.

• Treatment with intravenous immunoglobulin (IVIG) or plasma exchange within 4 weeksprior to the Baseline visit.

• Treatment with rituximab or ocrelizumab within 12 months prior to Baseline visit;treatment with calcineurin inhibitors (e.g. tacrolimus, cyclosporine,cyclophosphamide), Neonatal Fc receptor antagonists, and/or other biologics within 3weeks prior to planned leukapheresis and within 8 weeks prior to Baseline visit.

• The patient has started treatment with a complement 5a (C5a) inhibitor, such aseculizumab, within 8 weeks of Baseline visit. (NOTE: patients who have beenreceiving a C5a inhibitor for more than 8 weeks and meet other criteria forenrollment are eligible for treatment).

• Prior treatment with B-cell maturation antigen (BCMA)-directed therapy (e.g.monoclonal antibody, T-cell engager, or chimeric antigen receptor T-cell [CAR-T]).

• Abnormal prothrombin (PT)/international normalized ratio (INR) or partialthromboplastin time (PTT) increased > 1.5-fold above the normal range at Screeningor patient is on anticoagulation therapy (except in cases of elevated PTT withdocumented lupus anticoagulant; or in patients who have been on stable doses ofanticoagulation therapy for more than 6 months of venous thromboembolism (VTE)diagnosis; or in patients on stable doses of anticoagulation therapy for at least 8weeks of atrial fibrillation diagnosis; these conditions will not be exclusionaryunless, in the investigator's opinion, they make participation in the study unsafe).

• Absolute neutrophil count (ANC) < 1000 cells/microliter.

• Hemoglobin < 8.0 g/dL.

• Platelets < 50,000/mm3.

• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3x abovenormal.

• Creatine clearance less than 30 mL/min.

• History of primary immunodeficiency, organ, or allogeneic bone marrow transplant.

• Patients must be seronegative for hepatitis B surface antigen.

• Patients must be seronegative for hepatitis C antibody. If hepatitis C antibody testis positive, then patients must be tested for the presence of viremia by reversetranscriptase polymerase chain reaction (RT-PCR) and must be hepatitis C virus (HCV)ribonucleic acid (RNA) negative.

• History of positive human immunodeficiency virus (HIV) or positive HIV at screening.

• Active tuberculosis or positive QuantiFERON test at screening.

• Any other clinical or laboratory abnormality that, in the opinion of theinvestigator, may jeopardize the subject's ability to participate in the study orcould affect study outcome.

• Any active significant cardiac or pulmonary disease that, in the opinion of thePrincipal Investigator, is significant and/or uncontrolled.

Note: Patients with asthma and chronic obstructive pulmonary disease (COPD) controlled with inhaled medications are allowed.

• History of malignancy that required treatment in the past 3 years, except forsquamous cell carcinoma, basal cell carcinoma of the skin, or breast or early-stagecolon cancer that is surgically removed and did not require adjuvant chemotherapy orradiotherapy.

• Treatment with any investigational agent 4 weeks prior to screening or 5 half-livesof the investigational drug (whichever is longer).

• Receipt of a live vaccination within 4 weeks prior to Baseline visit or intent toreceive live vaccination during the study (Note: messenger RNA [mRNA]-based vaccinessuch as those against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)are not considered live; likewise, the Janssen Covid-19 vaccine is not live).

• History of significant recurrent infections or any active infection that in theopinion of the Investigator may interfere with the patient's participation in theopinion of the investigator.

• Any known psychiatric illness that in the opinion of the Investigator, may interferewith the patient's participation in the study in the opinion of the investigator.