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. At Biohaven, we believe that “DAYS MATTER™” and are committed to pursuing innovative treatments for patients suffering with neurologic diseases.

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

Kv7

Epilepsy

BHV-7000

PC
P 1
P 2
P 3
FILE

INDICATION:

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 1/3 are refractory to available anti-seizure medications (ASMs). After starting an ASM, 80% of patients will experience burdensome adverse events, which can include somnolence, dizziness, cognitive dysfunction, and mood disturbances. Epilepsy can also be lethal; each year, more than one in 1,000 people with epilepsy die from SUDEP (sudden, unexpected death of someone with epilepsy).

RATIONALE:

BHV-7000 is a potent, selective activator of Kv7.2/7.3 potassium channels, a clinically validated target to regulate the hyperexcitable state in epilepsy. BHV-7000 is structurally and pharmacologically distinct from other potassium channel activators and demonstrates minimal GABAA receptor activation, potentially providing better tolerability. BHV-7000 was potent in the maximal electroshock (MES) preclinical epilepsy model without adverse effects on neurobehavior and was well-tolerated in a Phase 1 SAD/MAD clinical study without CNS adverse events typical of anti-seizure medications.

STATUS:

Biohaven reported positive, interim data from an EEG study in July 2023 and expects to initiate a Phase 2/3 study in focal epilepsy in the second half of 2023.

Bipolar Disorder

BHV-7000

PC
P 1
P 2
P 3
FILE

INDICATION:

Bipolar disorder affects 11 million adults in the US and requires lifelong treatment. Approximately 50% of patients with bipolar disorder are medication nonadherent, with discontinuations most commonly due to poor tolerability. While bipolar disorder is characterized by mania, most of the time spent sick is with depression, yet there are few effective options for bipolar depression and maintenance treatment. In the last 20 years, no new mood stabilizer has been approved for the treatment of bipolar disorder, with the only new agents being antipsychotics.

RATIONALE:

BHV-7000 is a potent, selective activator of Kv7.2/7.3 potassium channels, a compelling target for bipolar disorder based on molecular, cellular, and preclinical evidence as well as mechanistic overlap with existing bipolar treatments. BHV-7000 has the potential for best-in category tolerability and safety with no expected long-term metabolic adverse events, titration, or laboratory monitoring. The novel mechanism of BHV-7000 also has potential for antidepressant effects without the risk of mood switching.

STATUS:

Biohaven reported positive, interim data from an EEG study in July 2023 and expects to initiate a Phase 2/3 study in bipolar disorder in the second half of 2023.

Epilepsy, Mood Disorders

BHV-7010

PC
P 1
P 2
P 3
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 or first half of 2024.

ION CHANNEL: TRPM3 ANTAGONIST

INDICATION

PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

FILED

MORE INFO

TRPM3

Chronic Pain Disorders

BHV-2100

PC
P 1
P 2
P 3
FILE

INDICATION:

Chronic Pain Disorders

RATIONALE:

BHV-2100 is a first-in class, selective, potent, and peripherally-restricted TRPM3 antagonist. TRPM3 is a novel druggable calcium channel in the transient receptor potential (TRP) cation channel family. TRPM3 channels are expressed in relevant human tissue types for neuropathic pain, and both preclinical models and human genetics implicate TRPM3 in pain signaling. BHV-2100 is our lead oral small molecule TRPM3 antagonist which we are developing as a potential non-opioid treatment for neuropathic pain. BHV-2100 preclinical data shows reversal of pain in various models, without sedative effects. Selectivity within the TRP family avoids potential class liabilities such as hyperthermia and may provide a novel option for the >50% of neuropathic pain patients who still have inadequately controlled 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

PHASE 3

FILED

MORE INFO

TYK2/JAK1

Neuroinflammatory Disorders

BHV-8000

PC
P 1
P 2
P 3
FILE

INDICATION:

Neuroinflammatory Disorders

RATIONALE:

Dysregulation of the immune system has been implicated in several neurodegenerative and neuroinflammatory disorders including Parkinson's disease, Alzheimer's disease, multiple sclerosis, 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 advanced BHV-8000 into a Phase 1 study in the first half of 2023 and expects to initiate a Phase 2 study in Parkinson's disease in 2024.

GLUTAMATE PLATFORM

INDICATION

PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

FILED

MORE INFO

Troriluzole

Spinocerebellar Ataxia (SCA)

BHV-4157

PC
P 1
P 2
P 3
FILE

INDICATION:

Spinocerebellar ataxia (SCA) is an ultra-rare, genetically-defined, progressive neurodegenerative disease associated with chronic disability, frequent falls, loss of ambulation, speech and swallowing impairment and premature death. 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. SCA3 (Machado-Joseph Disease) is the most prevalent form of SCA worldwide, representing 30 to 50% of patients.

RATIONALE:

Troriluzole is a novel, rationally designed, third-generation tripeptide prodrug of the glutamate modulating agent riluzole. Troriluzole was designed to increase oral bioavailability, deliver consistent drug exposures, bypass first-pass metabolism, allow for QD dosing, and avoid the negative food effect associated with riluzole. The synaptic glutamate modulating activity of troriluzole is hypothesized to address the widely documented glutamatergic dysregulation that underlies neurodegeneration and Purkinje cell dysfunction in patients with SCA.

Troriluzole has received Fast-Track and Orphan Drug Designation (ODD) from the FDA, and ODD from the European Medicines Agency, for the treatment of SCA.

STATUS:
Regulatory interactions ongoing.

Clinical Trial

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 US 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:

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:
Biohaven expects to complete enrollment by the end of 2023.

Clinical Trial

MYOSTATIN PLATFORM

INDICATION

PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

FILED

MORE INFO

Taldefgrobep alfa

Spinal Muscular Atrophy (SMA)

BHV-2000

PC
P 1
P 2
P 3
FILE

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 US, 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

Enrollment complete.

Clinical Trial

Metabolic Disorders

BHV-2000

PC
P 1
P 2
P 3
FILE

INDICATION:

Obesity is a disease of excess and/or abnormal deposits of adipose tissue and a current global public health crisis. By 2030, it is expected that nearly one billion people will be living with obesity, including 50% of the adult and 25% of the adolescent US population. The primary driver of obesity-related morbidity and mortality is metabolically active visceral adipose tissues and associated deposits in and around organs such as the heart, liver, kidneys, and muscle.

RATIONALE:

Taldefgrobep is an investigational fusion protein with the potential to induce physical and metabolic changes that are highly relevant to individuals living with overweight and obesity. Taldefgrobep targets myostatin, a natural protein that limits skeletal muscle growth. Taldefgrobep’s binding of myostatin prevents activin receptor signaling, resulting in muscle hypertrophy. Current anti-obesity therapies achieve weight loss through the reduction in both fat mass and lean muscle mass. Taldefgrobep offers a potential novel approach to addressing the primary pathology of obesity. Through its unique mechanism of action, taldefgrobep may be able to meaningfully reduce total body and visceral adipose tissue volumes and improve insulin sensitivity, while increasing lean muscle mass.

STATUS

Biohaven expects to initiate a Phase 2 trial in 2024.

BISPECIFIC TARGETED CELL THERAPY

INDICATION

PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

FILED

MORE INFO

CD-38

Multiple Myeloma

BHV-1100

PC
P 1
P 2
P 3
FILE

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, ARMs directly engage the immune system to destroy disease cells by connecting target disease cells with components of the immune system. ARMs 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, tolerability and exploratory efficacy endpoints in newly diagnosed multiple myeloma patients who have minimal residual disease (MRD+) in first remission is currently ongoing.

Clinical Trial

DISCOVERY RESEARCH

PLATFORM / PROGRAM

PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

FILED

MORE INFO

Discovery Research

IgG Degrader

BHV-1300 | Immune-Mediated Diseases

PC
P 1
P 2
P 3
FILE

INDICATION:

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

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:

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

IgA Degrader

IgA Nephropathy

PC
P 1
P 2
P 3
FILE

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:

Biohaven expects to submit an IND application in first half of 2024.

Next-Gen ADC Platform

Oncology

PC
P 1
P 2
P 3
FILE

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.

EXPLORE OUR PROGRAMS

Kv7
TRPM3
GLUTAMATE
MYOSTATIN
CD-38