Myasthenia Gravis (MG)
MG is a rare, chronic autoimmune neuromuscular disorder marked by weakness and fatigue. It affects approximately 125,000 to 150,000 people in the U.S. and 1.4 million globally. The condition arises when the immune system produces autoantibodies that attack the communication between nerves and muscles, primarily targeting acetylcholine receptors at the neuromuscular junction. In some cases, antibodies may also target other proteins, such as muscle-specific kinase (MuSK). This disruption impairs the transmission of nerve impulses, leading to muscle weakness. MG symptoms can be transient and may spontaneously remit in the early stages, they typically become more persistent as the disease progresses, with symptom-free intervals becoming less frequent.
Treatment includes steroids, immunosuppressants, complement inhibitors, and FcRn inhibitors, which are experiencing significant commercial adoption. However, patients become refractory to treatment and these treatments rarely lead to disease remission..
B-cell depletion targeting CD20 with rituximab has shown clinical benefit. TCEs targeting BCMA or CD20 offer a novel mechanism with the potential for deeper clinical responses and disease remission.
Rheumatoid Arthritis (RA)
RA is a chronic systemic autoimmune disease that affects approximately 1.3 million people in the U.S. and 18 million worldwide. It causes persistent inflammation in the joints, leading to cartilage destruction, bone erosion, and disability—most commonly impacting the hands and wrists. Symptoms can develop at any age, with peak onset between 30 and 50 years.
The treatment and management of RA is based on the guidelines from the American College of Rheumatology and the European Alliance of Associations for Rheumatology. Both guidelines highlight the importance of initiating disease-modifying antirheumatic drug (DMARD) therapy, with first line being the conventional synthetic DMARD, methotrexate. For patients who don’t respond adequately, additional DMARDs or biologics such as TNF inhibitors (e.g., Humira) are added. Nearly 50% of patients discontinue newly started DMARDs within 12–18 months due to side effects or lack of efficacy, and 20–30% are refractory to all available options, representing a large unmet medical need.
Emerging clinical data support the potential of T-cell engagers (TCEs) targeting BCMA or CD20 to provide meaningful responses in RA patients who have failed multiple prior therapies.
Systemic Lupus Erythematosus (SLE)
SLE is a complex autoimmune disease that causes widespread inflammation across multiple organ systems. Some patients with SLE also have lupus nephritis which is a disease affecting the kidneys. Over 200,000 people in the U.S. and 3 million globally are living with SLE.
Current treatments are focused on symptom control and flare prevention, including NSAIDs, corticosteroids, immunosuppressants, and hydroxychloroquine. While these options help manage the disease, there is still no cure, and many patients continue to experience significant disease burden.
CD20-targeting therapies such as obinutuzumab (Gazyva) have shown promise in SLE, and new modalities like CD20 TCEs (e.g., Lunsumio) and B-cell depleting approaches including CAR-T and bispecific TCEs have demonstrated clinical activity in highly refractory patients.
Systemic Autoimmune Rheumatic Disease-Associated Interstitial Lung Disease (SARD-ILD)
SARD-ILD encompasses progressive pulmonary complications that occur in patients with systemic autoimmune rheumatic diseases, including systemic sclerosis (SSc), rheumatoid arthritis (RA), idiopathic inflammatory myopathies, Sjögren’s syndrome, and systemic lupus erythematosus. Interstitial lung disease represents one of the most serious and life-threatening manifestations of these autoimmune conditions, characterized by inflammation and progressive fibrosis of the lung interstitium, leading to impaired gas exchange, declining lung function, and respiratory failure.
B cells and plasma cells are believed to play a central role in disease pathogenesis through production of autoantibodies, secretion of pro-inflammatory and pro-fibrotic cytokines, and aberrant immune cell activation. The progressive nature of SARD-ILD significantly impacts quality of life and carries substantial mortality risk in several patient populations