New Haven-based Biohaven Ltd. has enrolled the first patient in a pivotal Phase 3 trial of BHV-1300, a first-in-class extracellular protein degrader targeting the autoimmune root cause of Graves' disease, a condition for which no new therapy has been approved in more than 70 years.

Graves' disease is the most common cause of hyperthyroidism, driven by a thyroid-stimulating hormone receptor immunoglobulin G1 (TSHR-IgG1) autoantibody that overstimulates the TSH receptor. Standard treatments, including antithyroid drugs, radioactive iodine, and thyroidectomy, address downstream effects rather than the autoimmune mechanism itself. Among patients on antithyroid drugs, 93% report ongoing symptoms and 72% report five or more.

BHV-1300, exclusively licensed from Yale University, uses Biohaven's Molecular Degrader of Extracellular proteins (MoDE) platform to direct the TSHR-IgG1 autoantibody to the body's natural hepatic clearance pathways for selective elimination. Phase 1b data demonstrated greater than 80% reduction of pathogenic TSHR autoantibodies, rapid normalization of free T4 and free T3, and preservation of protective immunoglobulin subclasses IgG3, IgA, IgM, and IgE.

Beth Emerson, MD, MBA, Executive Medical Director of Biohaven and Lead for the Graves' disease clinical trial, said, "The enrollment of the first patient in this pivotal trial marks an important moment for the Graves' disease community. For decades, physicians have relied on treatments that either suppress thyroid function or destroy the gland. BHV-1300 represents an opportunity to bring forward a disease modifying therapy, targeting the underlying cause of Graves' disease, thyroid eye disease, and pretibial myxedema rather than addressing the downstream complications."

The pivotal trial (NCT07661056) is a randomized, double-blind, placebo-controlled study enrolling approximately 300 adults, with a primary objective of assessing restoration of normal thyroid function at 26 weeks without an antithyroid drug. BHV-1300 is delivered via a self-administered subcutaneous autoinjector.

"Enrollment of the first patient in our pivotal Graves' disease trial is a landmark moment for patients and for the future treatment of Graves' disease," said Tova Gardin, MD, MPP, Chief Translational Officer of Biohaven. "With a precision therapeutic designed to be self-administered at home in a patient-friendly autoinjector, BHV-1300 integrates groundbreaking high-science with life-centric solutions."

Gardin added, "We look forward to investigating BHV-1300 for the treatment of Graves' disease and follow-on IgG-mediated indications. This is more than a single trial or a single molecule; it potentially represents a new paradigm of precision immunology, one in which we move beyond managing disease toward precisely eliminating the proteins that drive it, unlocking this potentially groundbreaking platform."

Beyond Graves' disease, BHV-1300 targets the TSHR autoantibody implicated in thyroid eye disease, thyroid dermopathy, and Graves' embryopathy, positioning the MoDE platform as a potential treatment backbone for a range of immunoglobulin-driven autoimmune conditions.