Evaluate IgG reducing effects of BHV-1300.

Approximately 3-10% of the population is affected by autoimmune diseases, many of which are associated with pathogenic autoantibodies. IgG targeting approaches (Fc receptor antagonists, plasmapheresis, IVIG) are now approved or used in various neurological disorders including myasthenia gravis (MG). Importantly, available IgG reducing therapeutics have suboptimal pharmacology and pharmacodynamic effects, cannot be co-administered with monoclonal antibodies, and have mechanism-based safety and tolerability issues.

BHV-1300 is a first-in-class extracellular IgG degrader engineered to rapidly and efficiently deplete IgG after intravenous or subcutaneous injection. BHV-1300 is a bispecific molecule that specifically targets intravascular IgG for rapid lysosomal degradation in the liver. 

Pharmacodynamic effects of BHV-1300 on circulating immunoglobulin isotypes were evaluated after administration of single/multiple doses up to 500 mg/kg in cynomolgus macaques and rabbits.

Deep, dose-dependent reductions in IgG concentrations occurred. Concentration profiles showed rapid onset of IgG reduction within 6 hours, with deep reductions in IgG after single doses of approximately 75-80% in monkeys and rabbits. Deeper, 92% reductions were observed after multiple doses of BHV-1300. IgA or IgM were not impacted. No significant changes occurred in clinical chemistry parameters.

BHV-1300 demonstrated rapid, robust, safe, and selective IgG reductions in monkeys and rabbits. This compares favorably to published data for FcRn inhibitor IgG reducing therapies; BHV-1300 has important differentiating properties: speed of onset, shortened time to maximal effect, depth of IgG lowering, ability to be co-administered with biologics and target-related safety. Coupled with other potential mechanistic advantages (brief period of exposure; lack of effects on albumin, cholesterol, or triglycerides; potential for reduced immunosuppression; and compatibility with Fc-containing biologics), BHV-1300 represents the first member of a new drug class with potentially significantly improved benefit-risk for neuroinflammatory and autoimmune disorders including acute manifestations (MG crises/flares) or chronic disease (MG, rheumatoid arthritis, etc).