About The Science

CNS/Epilepsy Program

Epilepsy—a common and poorly treated condition

Epilepsy is a chronic disorder characterized by recurrent, unprovoked seizures that affects about three million people in the US and over 50 million people worldwide. In more than half of patients, the cause is unknown. Many patients with epilepsy have more than one type of seizure and patients often display other neurological symptoms, such as cognitive dysfunction. Current anti-seizure medications fail to help many epilepsy patients, and some can cause disabling side effects.  It is estimated that up to one in 3 patients with epilepsy is unable to control their seizures with current therapies, whether taken alone or in combination.

Overview of Biscayne’s unique platform

Biscayne’s platform for developing new central nervous system therapies is based on huperzine A, a highly potent acetylcholinesterase inhibitor (AChE) that drives important inhibitory circuits in the brain critical for controlling epilepsy and managing pain. Its efficacy has been demonstrated in multiple CNS disease models, including highly predictive preclinical models of refractory epilepsy such as refractory complex partial seizures and the catastrophic childhood epilepsy known as Dravet syndrome. Huperzine A has also demonstrated efficacy in models of pain and dementia. Biscayne’s BIS-001 is a synthetic form of a natural extract of huperzine A produced by a proprietary process that ensures a consistent pharmaceutical grade supply. Biscayne has also developed an extended release formulation of BIS-001 (BIS-001 ER) designed to enhance tolerability across a range of doses and ensure patient convenience and medication adherence.

In a Phase 1a trial in patients with drug-resistant epilepsy, BIS-001 appeared safe at exposures planned for future studies.  A Phase 1b trial with BIS-001 ER in adult healthy subjects is planned for 2017.


BIS-001, is a synthetic version of huperzine A – a single agent traditional Chinese medicine that has been widely used to treat CNS ailments such as pain, inflammation and cognitive disorders for hundreds of years, with a long history of safety. Huperzine A is differentiated from other acetylcholinesterase inhibitors by its high brain penetration and very high affinity for the binding site in the brain. Biscayne has developed a totally synthetic method of manufacture for BIS-001 that ensures a plentiful supply of pharmaceutical grade product and is consistent with pharmaceutical good manufacturing practice standards.

Biscayne has licensed intellectual property protecting various elements of its huperzine A program from Harvard University, Yale University, and the University of South Florida, and has also generated intellectual property internally. The discoveries licensed from Harvard are based on the work of internationally known epilepsy expert Dr. Steven Schachter, who is a neurology professor and researcher at Harvard Medical School and a senior advisor to Biscayne.

Biscayne’s first target for BIS-001 is for the treatment of refractory forms of focal epilepsy. These debilitating disorders affect millions of people in the US and worldwide. Nearly one-third of patients with epilepsy continue to have uncontrolled seizures despite being on multiple medications and another one-third have only partial control of seizures. In addition, the side effects associated with current anti-seizure medications seriously compromise patients’ ability to work and their overall quality of life.

BIS-001 offers a new mechanism of action to treat epilepsy, as illustrated in the graphic below.

In epilepsy, increases in acetylcholinesterase (AChE) activity causes a reduction in extracellular acetylcholine (ACh). Treatment with BIS-001 reduces AChE activity, thereby increasing ACh and restoring cholinergic input to the inhibitory interneurons. As a result, GABA production increases and inhibits pyramidal cell hyper-excitability, thereby restoring normal hippocampal signaling and suppressing seizures.

Complex partial seizures are the most commonly-occurring form of adult epilepsy, but in controlled clinical trials, even the best available treatments typically provide only 50% improvement in seizures in half of the subjects. BIS-001 was 30–500 times more potent than current anti-epileptic drugs in an animal model of refractory complex partial seizures, and it demonstrated promising efficacy in highly predictive preclinical models of refractory epilepsy, providing 100% elimination of seizures in many of the animal subjects. In genetic preclinical models of Dravet syndrome, the severe seizure condition affecting young children, BIS-001 achieved complete suppression of seizures. There are no approved products for Dravet syndrome and therapies used off-label have limited therapeutic effects and may worsen symptoms such as cognitive dysfunction.

In fact, many anti-epileptic drugs hinder cognitive function. In contrast, BIS-001 may actually improve cognition in patients due to its known cognition improvement qualities as an acetylcholinesterase inhibitor. BIS-001 has exhibited the cognition-enhancing properties seen with other AChE drugs, but with much better central nervous system and systemic tolerability and safety than currently available agents. Biscayne’s clinical program will assess both anti-seizure efficacy and whether BIS-001 supports improved cognition in epilepsy patients. At a minimum, Biscayne researchers are optimistic BIS-001 will be devoid of the detrimental effects on cognition seen with many existing antiepileptic drugs.

BIS-001 ER is expected to enter a Phase1b trial in healthy subjects in 2017. Going forward, Biscayne intends to assess BIS-001 in a variety of conditions, given the high unmet therapeutic need that exists across the spectrum of seizure disorders.