FULFILLING OUR COMMITMENT TO PATIENTS

Biohaven has earned its reputation as a leader in scientific innovation. Our portfolio includes treatments for a range of diseases with unmet medical needs including focal epilepsy, obsessive-compulsive disorder (OCD), spinocerebellar ataxia (SCA), spinal muscular atrophy (SMA) and more. We are proud of our pioneering science and a growing pipeline built by our own discoveries and collaborations with others. We continue to apply scientific breakthroughs to make a difference in the lives of people living with debilitating diseases around the world.

RESEARCH PIPELINE

Our broad and growing R&D pipeline includes an array of novel therapies for people suffering from neurological and neuropsychiatric diseases, rare disorders and other strategic therapeutic adjacencies. Our diverse portfolio includes numerous product candidates across all stages of development.

ION CHANNEL Kv7 ACTIVATOR

INDICATION

PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

FILED

MORE INFO

Epilepsy, Bipolar Disorder

BHV-7000

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INDICATION:

The lead indication for BHV-7000 is refractory focal epilepsy. Epilepsy affects approximately 3.5 million Americans and more than 50 million people worldwide. Sixty percent of people with epilepsy have focal epilepsy, and of those, approximately one in three are refractory to available anti-seizure medications. Epilepsy can also be lethal. SUDEP is the sudden, unexpected death of someone with epilepsy, who was otherwise healthy. Each year, more than one in 1,000 people with epilepsy die from SUDEP.

RATIONALE:

BHV-7000 is a potent activator of voltage-gated Kv7.2/7.3 potassium channels, key subunits involved in neuronal signaling and in regulating the hyperexcitable state in focal epilepsy. BHV-7000 is highly selective for Kv7.2/7.3 channels, avoiding activation of the GABAA receptor in vitro, thereby reducing the potential for off-target effects. BHV-7000 is structurally distinct from other Kv7 activators, demonstrates potent anti-seizure effects and is well-tolerated in preclinical seizure models, and has shown potential to be a best-in-class Kv7 activator.

STATUS:

Biohaven expects to initiate an EEG study in the first half of 2023 and expects to initiate Phase 2/3 studies in focal epilepsy patients and bipolar disorder patients in the second half of 2023.

Epilepsy, Mood Disorders

BHV-7010

PC
P 1
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FILE

INDICATION:

The lead indication for BHV-7010 is refractory focal epilepsy. Epilepsy affects approximately 3.5 million Americans and more than 50 million people worldwide. Sixty percent of people with epilepsy have focal epilepsy, and of those, approximately one in three are refractory to available anti-seizure medications. Epilepsy can also be lethal. SUDEP is the sudden, unexpected death of someone with epilepsy, who was otherwise healthy. Each year, more than one in 1,000 people with epilepsy die from SUDEP.

RATIONALE:

BHV-7010 is being developed as a next generation Kv7.2/7.3 activator with improved selectivity over Kv7.4 and differentiated absorption, distribution, metabolism, and excretion ("ADME") properties that provide flexibility for the treatment of different neurological diseases.

STATUS:

Biohaven expects to submit an IND application in the second half of 2023.

ION CHANNEL TRPM3

INDICATION

PRECLINICAL

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PHASE 3

FILED

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Chronic Pain Disorders

BHV-2100

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Biohaven’s first-in-class molecule directed against TRPM3, a novel druggable calcium channel in the transient receptor potential (TRP) cation channel family.

RATIONALE:

TRPM3 is expressed in the relevant human tissue types for neuropathic pain, and both preclinical models and human genetics implicate TRPM3 in pain signaling. BHV-2100 is our lead orally-bioavailable small molecule TRPM3 antagonist which we are developing as a potential non-opioid treatment for neuropathic pain.

STATUS:

Biohaven expects to submit an IND application in the second half of 2023.

INFLAMMATORY: TYK2/JAK1 INHIBITOR

INDICATION

PRECLINICAL

PHASE 1

PHASE 2

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Immune-Mediated Brain Disorders

BHV-8000

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INDICATION:

Immune-Mediated Brain Disorders

RATIONALE:

Dysregulation of the immune system has been implicated in several neurodegenerative and neuroinflammatory disorders including Parkinson's Disease, Multiple Sclerosis, Alzheimer's Disease, Amyotrophic Lateral Sclerosis and Autoimmune Encephalitis. Over-active immune cells and microglia driving chronic neuroinflammation results in release of cytokines with activation of leukocytes and is thought to contribute to neuronal injury, death, gliosis, and demyelination. The tyrosine kinase 2 (TYK2) and janus kinase 1 (JAK1) signal transduction pathways mediate highly complementary immune and inflammatory signaling events. Targeted, small-molecule therapies that inhibit TYK2 or JAK kinases have separately demonstrated robust efficacy in autoimmune, dermatologic and gastrointestinal disorders. TYK2 is a validated immune target as evidenced by a recent peripheral program that gained FDA approval, and there are multiple additional peripheral non-CNS programs in clinical development. Brain penetrant inhibitors of TYK2/JAK1 have the potential to bring this validated immune target to brain disorders.

STATUS:

Biohaven expects to advance BHV-8000 into a Phase 1 study in 2023.

GLUTAMATE PLATFORM

INDICATION

PRECLINICAL

PHASE 1

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FILED

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Spinocerebellar Ataxia (SCA)

BHV-4157

PC
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INDICATION:

Spinocerebellar ataxias (SCA) are a group of rare and ultra-rare progressively debilitating and fatal genetic conditions with no treatments available. SCA are characterized by progressive ataxia affecting coordination of hands, arms and legs as well as balance and speech. Patients experience significant morbidity, including progression to a wheelchair, impaired gait leading to falls, inability to communicate due to speech impairment, difficulty swallowing, and premature death. The range of symptoms and rate of progression of disease depend on the type of SCA, age of onset, and other factors. More than 40 different types of SCA are now recognized. SCA3 (Machado-Joseph Disease) is the most prevalent form of SCA worldwide, representing 30 to 50% of patients.

RATIONALE:

Troriluzole is a new chemical entity (“NCE”) and tripeptide prodrug of the active metabolite, riluzole. Troriluzole is optimized for improved bioavailability, pharmacokinetics, tolerability, and dosing compared to its active metabolite. Based on its mechanism of action, preclinical data and clinical studies, troriluzole has potential for therapeutic benefit in a range of neurological and neuropsychiatric illnesses. Initial development focused on SCA, based on two prior randomized controlled trials conducted by third parties that demonstrated preliminary efficacy of riluzole in the treatment of patients with ataxia.

Troriluzole has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of SCA.

STATUS:
Top-line results from a Phase 3 clinical trial evaluating the efficacy and safety of troriluzole in SCA were announced in May 2022.

Obsessive-Compulsive Disorder (OCD)

BHV-4157

PC
P 1
P 2
P 3
FILE

INDICATION:

Obsessive-Compulsive Disorder (OCD) is a chronic neuropsychiatric disorder characterized by symptoms of obsessions (intrusive thoughts) and compulsions (repetitive behaviors) that can interfere with patients’ functional abilities. According to the National Institute of Mental Health, the 12-month prevalence of OCD is 1% of the U.S. adult population, and approximately half of these cases are characterized as severe. Despite the significant public health burden, no novel mechanisms of action have been approved by the FDA for OCD in over two decades. First-line treatment for OCD includes cognitive behavioral therapy, selective serotonin reuptake inhibitors and adjunctive use of atypical antipsychotics. Nonetheless, up to 60% of patients have an inadequate response to conventional intervention strategies and some seek invasive neurosurgical procedures to ameliorate symptoms.

RATIONALE:

Troriluzole is a new chemical entity (“NCE”) and tripeptide prodrug of the active metabolite, riluzole. Troriluzole is optimized for improved bioavailability, pharmacokinetics, tolerability, and dosing compared to its active metabolite. Based on its mechanism of action, preclinical data and clinical studies, troriluzole has potential for therapeutic benefit in a range of neurological and neuropsychiatric illnesses. The rationale for use of troriluzole in OCD is supported by clinical data with its active metabolite, riluzole, in populations with OCD in open-label and placebo-controlled clinical trials as well as in preclinical, genetic and neuroimaging studies implicating the glutamatergic hyperactivity in the pathogenesis of OCD.

Phase 2/3 study results demonstrated that troriluzole administered once daily as adjunctive therapy in OCD patients with inadequate response to standard of care showed consistent numerical improvement over placebo on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at all study timepoints (weeks 4 to 12). While the primary outcome measure at week 12 (p = 0.22 at week 12) was not met, it was significant at week 8 (p = 0.05). Given the strong signal in the Phase 2/3 proof of concept study, a Phase 3 program was initiated.

STATUS:
Two Phase 3 studies evaluating the efficacy and safety of troriluzole as adjunctive therapy in OCD are currently ongoing.

MYOSTATIN PLATFORM

INDICATION

PRECLINICAL

PHASE 1

PHASE 2

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FILED

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Spinal Muscular Atrophy (SMA)

BHV-2000

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INDICATION:

Spinal muscular atrophy (SMA) is a rare genetic neurodegenerative disorder characterized by the loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk, and progressive muscle weakness that is often fatal and typically diagnosed in young children. The underlying pathology of SMA is caused by insufficient production of the SMN (survival of motor neuron) protein, essential for the survival of motor neurons, and is encoded by two genes, SMN1 and SMN2. In the U.S., SMA affects approximately 1 in 11,000 births, and about 1 in every 50 Americans is a genetic carrier.

RATIONALE:

Taldefgrobep is an investigational, muscle-targeted recombinant protein with the potential to enhance muscle mass and strength in people living with SMA when used in combination with other approved treatments. Taldefgrobep targets myostatin, a natural protein that limits skeletal muscle growth, through two mechanisms: lowering myostatin directly and blocking key downstream signaling mechanisms. Myostatin inhibition is a potential therapeutic strategy for children and adults with a range of neuromuscular conditions for whom active myostatin can limit the skeletal muscle growth needed to achieve developmental and functional milestones.

STATUS

A Phase 3 trial to evaluate the efficacy and safety of taldefgrobep in SMA is currently ongoing.

BISPECIFIC TARGETED CELL THERAPY

INDICATION

PRECLINICAL

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PHASE 2

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Multiple Myeloma

BHV-1100

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INDICATION:

BHV-1100 is being studied to provide antigen target specificity to natural killer (NK) cell therapies with the goal of enhancing efficacy and safety in the combination treatment of multiple myeloma.

RATIONALE:

Antibody Recruiting Molecules (ARM™) are bispecific molecules that recruit endogenous antibodies to target cancer, virally infected cells, and disease-causing microorganisms for immune-mediated clearance. Similar to biologics, ARM™s directly engage the immune system to destroy disease cells by connecting target disease cells with components of the immune system. ARM™s are engineered as modular components that are readily interchangeable, giving the platform tremendous flexibility for a variety of indications and therapeutic areas.

STATUS

A Phase 1 trial to evaluate the safety and tolerability as well as exploratory efficacy endpoints in newly diagnosed multiple myeloma patients is currently ongoing.

DISCOVERY RESEARCH

PLATFORM / PROGRAM

PRECLINICAL

PHASE 1

PHASE 2

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FILED

MORE INFO

IgG Degrader

PC
P 1
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P 3
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INDICATION:

Our MoDE™ platform is being explored for use in a wide range of therapeutic areas, including indications in autoimmune diseases, cancer and infectious disease.

RATIONALE:

Molecular Degraders of Extracellular Proteins (“MoDE™”) are bispecific molecules that target pathologic circulating proteins and direct them to the liver (or other organ systems) for degradation by the endosomal/lysosomal pathway. Hepatic asialoglycoprotein receptor (ASGPR) ligand degraders able to recognize all potentially pathogenic isoforms of IgG represent a novel, competitive platform with a differentiated profile relative to FcRN inhibitors. Specifically, high circulating levels of antibodies (monoclonal or polyclonal gammopathy) drive conditions such as myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus, pemphigus vulgaris and many other diseases. It is hypothesized that rapid and sustained lowering of pathogenic antibody titers in blood will significantly reduce disease symptoms. Therapeutic pan-IgG depletion using Biohaven’s proprietary MoDE™ platform technology is expected to have significant potential benefit for multiple diseases.

STATUS:

BHV-1300 demonstrated robust reduction of IgG levels in preclinical studies, with 75% depletion from baseline. This effect was rapid, occurring by 3 days. Biohaven expects to submit an IND application for BHV-1300 with the FDA in the second half of 2023.

IgA Degrader

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INDICATION:

IgA nephropathy (“IgAN”) is the most common primary glomerulonephritis that can progress to renal failure and is characterized by immunoglobulin deposits in the renal mesangium comprised exclusively of the IgA1 subclass. Currently, no IgAN-specific therapies are available. Patients are managed with the aim of controlling blood pressure and maintaining renal function.

RATIONALE:

Molecular Degraders of Extracellular Proteins (“MoDE™”) are bispecific molecules that target pathologic circulating proteins and direct them to the liver (or other organ systems) for degradation by the endosomal/lysosomal pathway. We are leveraging our MoDE™ platform to develop novel bispecific molecules for the treatment of IgA nephropathy (“IgAN”) that remove potentially disease-causing Gd-IgA or total IgA in patients and prevent harmful kidney deposits. We have taken a published rodent format IgG antibody that recognizes Gd-IgA and converted it into a partially-humanized, liver-targeted degrader MoDE™ using Multimodal Antibody Therapy Enhancer ("MATE™") conjugation that potently binds Gd-IgA and causes its endocytosis in human liver cells.

STATUS:

Further work is ongoing to progress this as a potential IgAN treatment.

Next-Gen ADC Platform

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We are using Multimodal Antibody Therapy Enhancer (“MATE™”) conjugation technology to generate site-specific antibody drug conjugates (ADCs) from native IgG1 proteins that we believe will show superior stability in comparison with those using current industry-standard cysteine maleimide conjugation. Our expectation is that the enhanced in vivo stability and expected superior physicochemical properties of these ADCs will lead to increased therapeutic indices (more cytotoxic payload reaching cancer cells and less reaching normal tissues). Over 15 site-specific ADCs using the well validated valine-citrulline monomethyl auristatin E payload linker system have been prepared and are undergoing biological testing in comparison with industry standard maleimide conjugated ADCs.

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