BIS-001 is a synthetic version of huperzine A, an acetylcholinesterase inhibitor that naturally found in a plant called Huperzia serrata, colloquially known as toothed clubmoss. Huperzine A has been used in traditional Chinese medicine for hundreds of years to treat pain, inflammation, and cognitive disorders.

It is being looked at as a potential treatment for Alzheimer’s disease.

BIS-001, under development at Biscayne Neurotherapeutics, is being investigated as an antiepileptic agent to treat complex partial seizures, also known as focal impaired-awareness seizures (FIAS).

The U.S. Food and Drug Administration (FDA) designated BIS-001 as an orphan drug for the treatment of Dravet syndrome in 2017. Current Dravet syndrome medications are not sufficiently effective in patients.

How BIS-001 works

Huperzine A is a molecule that inhibits, or blocks, an enzyme called acetylcholinesterase. Acetylcholinesterase works to break down acetylcholine, a signaling molecule in the brain.

Inhibiting the activity of this enzyme should lead to a rise in acetylcholine levels, which in turn can trigger the release of gamma-aminobutyric acid (GABA) in specific brain cells (by a mechanism not entirely understood). GABA is another signaling molecule and one that has an inhibitory effect on nerve cells. Because seizures are the result of poorly regulated or overactive neuronal activity — resulting in the constant firing of electric signals among brain cells — the stimulating effect of huperzine A on GABA release may work to suppress seizures.

Compared to other acetylcholinesterase inhibitors, huperzine A has the advantage of easily crossing the blood-brain-barrier and reaching the brain.

BIS-001 in clinical trials

A Phase 1b clinical trial (NCT03156439) assessed the safety and tolerability of BIS-001 treatment in eight healthy volunteers. Participants received BIS-001 twice a day, and the dose was increased every two to three days until a maximum daily dose of 2.5 mg was reached. The treatment was well-tolerated with mild to moderate, transient, and non-dose limiting adverse events.

A Phase 1/2 clinical trial (NCT03474770) is currently enrolling patients with focal impaired-awareness seizures at the Alfred Hospital and the Royal Melbourne Hospital in Australia. Participants will receive a dose of 0.25 mg BIS-001 twice a day, and the dose will be escalated every four days until a maximum tolerated dose, or the target dose of 1.75 mg twice a day, is reached. This dose will be maintained for one month.

Additional information

BIS-001 is an oral therapy that is intended for twice-daily dosing. Through its long-time use in Chinese medicine, it is known to be safe to use. A dose of 2.5 mg per day is well-tolerated and leads to blood levels of BIS-001 that are almost twice as high as the anticipated level thought necessary for efficient seizure treatment.


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