Pipeline

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 patients with epilepsy have focal epilepsy, and of those, approximately one in three are refractory to available antiseizure 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 GABA_A 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.

INDICATION:

KCNQ2 Developmental and Epileptic Encephalopathy (DEE) is a rare, serious, and debilitating disease that manifests in infants and children as early-onset seizures and encephalopathy due to a defect in the function of the Kv7.2 channel caused by pathogenic mutations in the KCNQ2 gene.  KCNQ2-DEE has a characteristic newborn presentation including hypotonia, treatment-resistant tonic seizures, a profoundly abnormal EEG, and most often with moderate-to-profound developmental impairment, with limited or no achievement of normal language, motor, or cognition milestones.

RATIONALE:

In addition to being a potent activator of normal Kv7.2/Kv7.3 channels, BHV-7000 has been shown to normalize the impaired channel function resulting from the KCNQ2 mutations that cause KCNQ2-DEE in neonates and infants. In in vitro studies of Kv7.2/7.3 channels poisoned by KCNQ2-DEE mutations, BHV-7000 was able to restore pathologically reduced channel currents to normal levels, providing evidence of the drug’s potential as a precision treatment directed at the root cause of the disease.

BHV-7000 has received rare pediatric disease designation from the U.S. Food and Drug Administration for the treatment of KCNQ2-DEE.

Approximately 1 in 5 adults in the U.S. are living with neuropsychiatric illnesses that are, in turn, associated with inadequate treatment, poor quality of life, disability, and considerable direct and indirect costs. There is significant unmet need for novel and effective therapeutic options that are not limited by long latency periods to clinical effects, low response rates, and significant risks and side effects. Increasing evidence from animal models and clinical trials now suggests that Kv7.2/7.3 targeting drugs offer the potential to treat a spectrum of these neuropsychiatric diseases including, but not limited to, mood disorders such as major depressive disorder, bipolar disorder, and anxiety.

In the United States, over 30 million adults are estimated to be living with chronic pain. Pharmacological treatments for pain vary according to patient needs. Initial or first line treatment often includes agents that reduce neuronal hyperexcitability, such as antiseizure medicines. Second line treatment of persistent, severe pain may require escalation to opioids. Thus, an urgent need exists for effective, non-addictive pain therapies. Selective Kv7 potassium channel activators represent a new approach in the development of non-opioid therapeutic options for pain.

In addition to reduced abuse and addiction risk potential, our Kv7 potassium channel platform addresses the complexities of channel subtype physiology through targeted pharmacology to overcome the limitations inherent in unbiased Kv7 activators and is intended to deliver a well-tolerated, highly effective, non-opioid treatment for pain.

Our Kv7 program research was supported in part with funding from the National Institutes of Health (“NIH”) through the NIH Helping to End Addiction Long-term Initiative (“NIH HEAL Initiative”).