Biohaven Ltd. provided an overview of its development and regulatory advances across multiple therapeutic areas, and highlights the progress of its innovative degrader pipeline at the Company's 2024 Investor R&D Day, held concurrently with the Yale Innovation Summit in New Haven, Connecticut. The clinical progress, regulatory updates and pipeline developments at Biohaven's R&D Day include: Molecular Degrader of Extracellular Proteins (MoDE) Platform: Harnessing a New Modality with Transformational Potential for the Treatment of Immunological and Inflammatory Disorders The Company unveiled new positive data from its ongoing Phase 1 single ascending dose (SAD) study with BHV-1300, a first-in-human IgG degrader that uses an ASGPR-bispecific from its MoDE platform. Emerging results in healthy subjects confirm that BHV-1300 rapidly and selectively lowers IgG in a dose-dependent manner in the first 4 cohorts completed to date.

Preliminary IgG lowering data is consistent with modeling, with dose- and time-dependent IgG lowering observed even in initial low-dose cohorts. Some subjects experienced IgG reductions as low as 50 to 70% of baseline. BHV-1300 demonstrated reduction of IgG without significantly impacting LFTs, albumin, LDL cholesterol or other serum labs.

BHV-1300 has been safe and well tolerated to date, with no serious or severe adverse events. Most AEs were mild, deemed unrelated to study drug and resolved spontaneously. As expected from the selectivity of the molecule for IgG, when compared to placebo, there were no meaningful reductions in average IgA, IgM or IgE levels during the week after dosing.

No adverse trends have been observed in vital signs or ECGs. Given the levels of IgG lowering observed to date, the company plans to evaluate approximately 6 cohorts of BHV-1300. Modeling suggests additional cohorts in the Phase 1 study will achieve > 70% lowering of IgG utilizing doses compatible with subcutaneous administration.

Given the promising results of the SAD study thus far, the MAD study will proceed in patients with rheumatoid arthritis. Advancing 3 additional novel MoDE degrader INDs on timelines for 2024. Differentiated IgG degrader, BHV-1310, for myasthenia gravis.

Galactose-deficient IgA1 degrader, BHV-1400, for IgA nephropathy. ß1-AR autoantibody degrader for dilated cardiomyopathy. Disclosing Additional Emerging Degrader Programs. Biohaven disclosed additional novel MoDE degraders advancing to INDs including potential treatments for: Type 1 diabetes with its degrader targeting anti-insulin and anti-proinsulin autoantibodies; kidney disease with its degrader targeting phospholipase A2 receptor (PLA2R) antibodies for idiopathic membranous nephropathy; IgG4 specific degrader to target IgG4-mediated rare diseases; and gene therapy administration optimization with its degrader to target AAV9.

Multiple other degrader targets in development remain undisclosed. Ion Channel Platform: Forging Much-Needed Novel Treatments for Patients with Neurological and Neuropsychiatric Disorders. Selective Kv7 Activator, BHV-7000, for Epilepsy, Bipolar Disorder, Major Depressive Disorder and Pain.

Initiated 5 pivotal clinical trials with BHV-7000, targeting focal epilepsy, generalized epilepsy, bipolar disorder and major depressive disorder. BHV-7000 offers the potential of a highly differentiated profile, having potent efficacy without burdensome central nervous system side effects. This furthers Biohaven's goal of elevating the standard of care for these large indications with significant treatment gaps.

Presented new data showing BHV-7000 attenuates action potential firing in inherited erythromelalgia (IEM) patient-derived sensory neuron induced pluripotent stem cells, suggesting potential to modify disease phenotype in patients with IEM and other pain disorders. Novel TRPM3 Antagonist, BHV-2100, for Migraine and Pain. Reported positive pharmacokinetic and safety data from the completed Phase 1 study with BHV-2100.

The results demonstrate rapid absorption with therapeutic concentrations achieved by 20 minutes. The favorable tolerability profile at single doses up to 500 mg exceeds the anticipated therapeutic dose and is well above the EC90 concentration. These findings provide a compelling rationale for the advancement of BHV-2100 into clinical trials for both acute treatment of migraine and pain as a non-opiate therapy with minimal CNS side effects.

Plans to initiate a Phase 2 study in acute treatment of migraine and a proof-of-concept study in pain in second half of 2024. Myostatin Program: Advancing an Innovative Approach for Improving Muscle Health. Myostatin Inhibitor, Taldefgrobep alfa, for Disrupting the Public Health Crisis of Obesity · New preclinical data showing that administration of taldefgrobep alfa directly reduced the increased adipose fat storage caused by myostatin.

New preclinical data from a diet induced obesity mouse model, showed treatment with taldefgrobep alfa together with a GLP-1 agonists produced greater reductions in body weight and fat mass, and a larger increase in lean muscle mass, compared to treatment with GLP-1 alone. These data highlight the potential for taldefgrobep alfa to offer additional benefits, including enhancing muscle growth, when used in combination with a GLP-1. The Company plans to initiate a Phase 2 study in obesity in second half of 2024. Myostatin Inhibitor, Taldefgrobep alfa, for Spinal Muscular Atrophy (SMA).

Baseline characteristics of the population enrolled in the ongoing Phase 3 study in SMA were reported and confirmed to be well matched to the target clinical population. The primary endpoint of the study, the 32 Item Motor Function Measurement (MFM-32), is a reliable and validated endpoint for measuring clinically meaningful benefit in SMA. The MFM-32 lacks floor and ceiling effects, and has been used successfully in previous, registrational trials.

Expect Phase 3 study top-line results in SMA in second half of 2024. Neuroinflammation Platform: Selectively Targeting the Immune System to Treat Neurodegenerative Diseases · Brain-Penetrant TYK2/JAK1 Inhibitor, BHV-8000, for Prevention of Amyloid-Related Imaging Abnormalities (ARIA), Parkinson's disease, Multiple Sclerosis and Alzheimer's disease · Reported positive results from the Phase 1 single and multiple ascending dose study with BHV-8000 in healthy subjects, including evidence of target engagement (i.e., biomarker reductions in high-sensitivity C-reactive protein and interferon beta) along with a safe and well tolerated profile. Announced key regulatory updates, including the successful completion of two FDA meetings with favorable feedback enabling registrational programs for Parkinson's disease and for the prevention of ARIA, a novel indication.