Biohaven’s Potential First-in-Class Autoimmune Therapy BHV-1300 Cuts Total IgG by Over 80%

Biohaven Ltd. (NASDAQ: BHVN) announced promising results from its ongoing Phase 1 study of BHV-1300, a potential first-in-class extracellular IgG degrader for autoimmune diseases. The study showed that weekly subcutaneous doses of 1000 mg led to rapid, deep, and sustained reductions in total immunoglobulin G (IgG) levels. Participants experienced reductions of up to 84%, with an average drop of 80% over four weeks. The treatment was well-tolerated, with no serious adverse events reported. Biohaven, a biopharmaceutical company with a market cap of $3.76 billion, remains financially strong, holding more cash than debt. 

BHV-1300 Selectively Targets IgG1, IgG2, and IgG4 While Preserving IgG3 for Immune Defense

In the recently reported findings, the experimental extracellular IgG degrader, BHV-1300 indicated that weekly subcutaneous doses of 1000 mg led to reductions in total IgG levels, a key driver of autoimmune disorders. The reductions in IgG levels occurred within hours of each dose and were sustained throughout the study period, with some participants experiencing up to an 84% decrease and a median reduction of 80% over four weeks.

IgG, or Immunoglobulin G, is an antibody that plays a key role in defending the body against infections. However, in autoimmune disorders, elevated IgG levels can lead to the immune system mistakenly attacking the body’s own healthy cells. BHV-1300 selectively targeted IgG1, IgG2, and IgG4 while sparing IgG3, which plays a role in immune defense against infections. Other immunoglobulin levels, including IgA, IgE, and IgM, showed no clinically significant changes compared to baseline. These findings suggest that BHV-1300 may provide targeted IgG reduction without broadly suppressing the immune system.

Unlike monoclonal antibodies that inhibit FcRn, BHV-1300 provides deep, tunable IgG degradation, with dosage and frequency adjustments allowing for customizable treatment. It is designed for self-administration via an easy-to-use autoinjector, developed in partnership with Ypsomed AG.

BHV-1300’s Safety and Tolerability Confirmed at Higher Doses

Biohaven’s MoDE technology, which powers BHV-1300, offers a distinct advantage over FcRn-targeting monoclonal antibodies by enabling customizable control over both the speed and depth of IgG reduction through adjustments in dose level and frequency. The company is continuing dose escalation in the study to assess whether deeper reductions can be achieved while maintaining safety and tolerability. 

The treatment was generally well-tolerated, with no serious adverse events observed. HV-1300 was well tolerated at doses up to 2000 mg, with most adverse events reported as mild and self-resolving. No participants discontinued treatment due to adverse events, and there were no serious or severe reactions. Additionally, no clinically significant changes were observed in liver enzymes (ALT, AST), bilirubin, albumin, or cholesterol levels over the four-week period compared to placebo.

Biohaven Confirms Plans to Launch Phase 2 Study of BHV-1300 for Graves’ Disease in Mid-2025

Biohaven has reaffirmed plans to launch a Phase 2 study of BHV-1300 for Graves’ disease in mid-2025, following the observed rapid and significant reductions in total IgG levels with subcutaneous administration. The company also intends to explore additional studies in other autoimmune diseases.

Graves’ disease, a common autoimmune disorder, affects approximately 3 million individuals in the US and 80 million globally. It is caused by IgG1 autoantibodies that over-activate the thyroid-stimulating hormone (TSH) receptor. BHV-1300 is designed to target and degrade these IgG1 autoantibodies, while preserving the body’s immune defense.

Tova Gardin, MD, MPP, Chief Translational Officer at Biohaven, commented on the data from the ongoing Phase 1 study, saying, “This data released today supports advancing BHV-1300 as a potential first-in-class, small molecule approach to treating Graves’ disease, a common autoimmune disease that is currently treated with surgery, ablation, or anti-thyroid drugs. Our innovative approach unifies cutting-edge science with a renewed understanding of disease pathology, to advance a potential first and best-in-class therapeutic for the treatment of Graves’ disease. Based on the PK/PD and safety profiles exhibited in the ongoing Phase 1 study, we are thrilled to advance BHV-1300 forward as we aim to disrupt the current treatment paradigm in Graves’ disease and potentially revolutionize the treatment of this disease, which impacts millions of patients across the world.”

Advancing Clinical Development Across Immunology, Neuroscience, Oncology, and Rare Diseases

In addition to BHV-1300, Biohaven is advancing its next-generation TRAP degraders from the MoDE platform. These include BHV-1400, a selective degrader targeting Gd-IgA1 for IgA nephropathy, and BHV-1600, a β1AR autoantibody degrader being developed for cardiomyopathy, both in Phase 1. Biohaven will present further details and data on these TRAP degraders at an upcoming conference. Other degraders in development include an IgG4 degrader, PLA2R autoantibody degrader, insulin autoantibody degrader, and TSH receptor autoantibody degrader.

Biohaven is also preparing for the commercial launch of troriluzole for spinocerebellar ataxia (SCA) in 2025, pending FDA approval. The company is progressing with several other assets, including:

• BHV-7000, a selective Kv7.2/7.3 potassium channel activator, advancing in Phase 2/3 trials for major depressive disorder and epilepsy.
• BHV-2100, a TRPM3 antagonist for migraine and neuropathic pain, with topline data expected in 1H 2025.
• Taldefgrobep alfa, a myostatin inhibitor, with a Phase 2 study in obesity and discussions with the FDA regarding its SMA registrational path.
• BHV-8000, a TYK2/JAK1 inhibitor, advancing in Phase 2/3 trials for Parkinson’s disease and neurodegenerative disorders.
• An expanding oncology portfolio, including BHV-1510, a next-generation ADC, and BHV-1530, an FGFR3-directed ADC, with Phase 1 data expected in 2025.

Biohaven, with a market cap of $3.76 billion, reported a financial position with more cash than debt. The company is advancing clinical development across its broad pipeline, targeting various disease indications in immunology, neuroscience, oncology, and rare diseases.

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Author

Bernice Lottering