Immunovant’s primary product candidate, IMVT-1401, is a human recombinant anti-neonatal Fc receptor (FcRn) monoclonal antibody for the treatment of IgG mediated diseases. The antibody facilitates the degradation of IgG by targeting FcRn and preventing endogenous IgG—including auto-antibodies—from binding. The increased catabolism curtails the harmful immune response exhibited by auto-antibodies.1
Immunovant is currently conducting a single and multiple ascending dose Phase 1 clinical trial in healthy volunteers with plans to initiate a number of patient-based studies in early 2019. IMVT-1401 is being developed as a subcutaneous injection, providing a convenient and minimally invasive treatment option for patients.
Mechanism of Action
FcRn prolongs the half-life of IgG and albumin by actively binding these proteins and recycling them to the cell surface. Anti-FcRn antibodies disrupt this process by selectively binding FcRn. The IMVT-1401 antibody binds FcRn with high affinity at a region that prevents IgG recycling. The engineered receptor sites, in conjunction with two natural FcRn ligand sites, enable favorable binding kinetics with the FcRn receptor compared to IgG.1
Indication: Myasthenia Gravis
Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease characterized by weakness and fatigue of voluntary muscles. The disease is caused by pathogenic antibodies that target the neuromuscular junction, including the acetylcholine receptor (AChR) and the muscle specific tyrosine kinase receptor (MuSK), disrupting normal function.2 MG is a rare disease that affects approximately 46,000 to 66,000 people in the United States.3 MG is more prevalent in women and tends to affect younger women. In men, MG tends to affect an older population.4,5
The clinical course of MG is variable but usually progressive.6 Symptoms typically emerge in the eyes (e.g., drooping eyes, double-vision, blurred vision) and progress into the face, throat, and limbs.7 The chronic nature of MG requires patients to cope with fluctuating symptoms and multiple treatment regimens for management. Overall, the persistent muscle weakness associated with MG often negatively interferes with patients’ ability to engage in daily and physical activities, including demands of work, family, and social functions.
Indication: Graves’ Ophthalmopathy
Graves’ ophthalmopathy (GO), also known as thyroid eye disease, is an autoimmune disorder that affects the muscles and other tissues around the eyes. GO is most commonly caused by IgG autoantibodies that form against the thyroid-stimulating hormone receptor (TSHR). These antibodies, which also cause Graves’ disease, activate certain cell types, such as fibroblasts and adipocytes, that are present in the extraocular space, promoting inflammation and cellular expansion that result in the clinical manifestations of the disease. GO has an estimated annual incidence of 16 per 100,000 women and 2.9 per 100,000 men in North America and Europe.
Approximately one in twenty patients with Graves’ disease will present with moderate-to-severe GO that is characterized by swelling and redness of the eyelids, proptosis (protrusion of the eyeball), double vision, and, in severe cases, corneal ulceration and decreased visual acuity. There are no therapies approved by the Food and Drug Administration (FDA) for GO.