Serotonin agonist BMB-101 found safe, well-tolerated in healthy adults

Oral medication for epilepsies, other indications set to move to Phase 2 testing

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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BMB-101, an oral serotonin agonist being developed by Bright Minds Biosciences for the treatment of Dravet syndrome and other forms of epilepsy, was found to be safe and well-tolerated in healthy individuals, even at the highest dose tested.

These are data from a now-complete Phase 1 study (NCT05397041) suggesting that BMB-101 may be taken in moderate doses without causing side effects. Earlier serotonin agonists had side effects that limited the dose that could be used.

The company is now ready to move the experimental medication on to Phase 2 testing.

“BMB-101 is now a Phase 2 ready asset, and we look forward to sharing our further progress,” Ian McDonald, CEO of Bright Minds, said in a company press release.

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“Learnings from the study will inform our path forward as we seek to develop effective therapeutic options with convenient dosing regimens for patients,” said Mark A. Smith, MD, PhD, chief medical officer of Bright Minds.

Dravet syndrome causes long-lasting seizures that usually start in the first year of life and are often refractory, or difficult to control with available medications.

Seizures are sudden bursts of unusual electrical activity in the brain that can lead to changes in behavior, movement, and awareness. It is thought that low levels of serotonin, a chemical that relays messages between nerve cells, may trigger seizures.

Serotonin, also known as 5-hydroxytryptamine (5-HT), plays a role in regulating various functions such as mood, appetite, and sleep. It acts by activating (turning on) specific receptors found in cells throughout the body.

BMB-101 designed to imitate effects of serotonin

BMB-101 is designed to imitate the effects of serotonin on 5-HT2C, a receptor that is found in the brain and spinal cord. By activating this receptor, BMB-101 is expected to control seizures in people with Dravet syndrome.

According to Bright Minds, it may be more specific (and thus carry fewer side effects) than lorcaserin, a similar serotonin agonist that Eisai is testing in a Phase 3 study (NCT04572243) as an add-on medication for Dravet syndrome.

In preclinical studies, BMB-101 reduced the duration of seizures in a zebrafish model of Dravet syndrome and protected against seizures in mouse and rat models. Repeated dosing of BMB-101, twice daily for nearly one month, was found to be safe and well-tolerated in mice and dogs.

The three-part Phase 1 study, which began dosing in August 2022, took place at CMAX Clinical Research in Adelaide, Australia. It involved in 76 healthy individuals and evaluated how safe and well-tolerated BMB-101 may be, how it moves through the body, and if it is affected by food.

In the first part, 32 participants were randomly assigned to receive a single dose of BMB-101 at either of four dose levels or a placebo. The medication had predictable pharmacokinetics, meaning it moved into, through, and out of the body as expected.

There is a great opportunity and an unmet need to develop improved treatments for these and potentially numerous other indications, including psychosis and addiction disorders.

BMB-101 found to be well-tolerated at higher doses

The most common side effect was paresthesia (tingling feeling) in the mouth from the liquid formulation of BMB-101. The medication was escalated to the highest planned dose of 180 mg/70 kg, indicating that it was well-tolerated at higher levels.

The second part tested how BMB-101 was affected by food in 12 healthy individuals who took a single dose of 120 mg/70 kg while fasting and then, at another moment, after a high-fat breakfast. Food did not change the levels of BMB-101 much, indicating that it does not need to be taken while fasting.

In the third part, 32 participants were randomly assigned to receive BMB-101 twice daily after a meal for seven days (one week) at one of four dose levels or a placebo. The medication was escalated to the top dose of 150 mg/70 kg.

Transient, dose-dependent increases in prolactin, a hormone that is released upon activation of 5-HT2C, suggested that BMB-101 fully engaged with its target and that higher doses resulted in better activation, or higher levels of prolactin.

The company is now waiting for more detailed data on a quantitative electroencephalogram, a test that measures brain activity.

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BMB-101 has potential for psychosis, addiction, impulse control disorders

“We are highly encouraged by the Phase 1 study observations and results, which give us confidence in selecting doses of BMB-101 for testing in refractory epilepsies and other disorders where serotonin 2C agonists are indicated,” Smith said.

Other indications for BMB-101 may include psychosis, addiction, and impulse control disorders such as binge eating.

“There is a great opportunity and an unmet need to develop improved treatments for these and potentially numerous other indications, including psychosis and addiction disorders,” McDonald said.

“The successful and on-time completion of the study is an important achievement for us, as we continue to evolve from a drug discovery to a drug development stage company,” he added.