Bright Minds Biosciences Reports Phase 2 BMB-101 Data: 73% Median Drop in Absence Seizures on EEG

Bright Minds Biosciences (NASDAQ:DRUG) reported top-line results from an open-label Phase 2 “breakthrough” study evaluating BMB-101 in adults with highly refractory absence seizures and developmental and epileptic encephalopathies (DEE), emphasizing both the treatment-resistant nature of participants and the use of objective EEG endpoints in the absence cohort.

Study overview and patient population

Chief Executive Officer Ian McDonald said the readout should be interpreted in the context of “highly refractory” adult patients with substantial treatment histories. The trial was conducted in Australia across five epilepsy centers and included two separate adult cohorts: refractory absence seizures and refractory DEE.

Chief Medical Officer Dr. Stephen Collins described a standard anti-seizure medication study structure: a one-month baseline period, four weeks of weekly titration using weight-based dosing, and a maintenance phase. The maintenance phase differed by cohort: two weeks for absence seizure subjects (due to high seizure frequency) and four weeks for DEE subjects.

BMB-101 was administered as a liquid formulation starting at 0.67 mg/kg twice daily, increased by 0.33 mg/kg up to a maximum of 2 mg/kg twice daily, with investigators, subjects, and caregivers able to stop titration early based on efficacy or tolerability. Participants maintained seizure calendars, and all subjects underwent 24-hour ambulatory EEG monitoring during baseline and maintenance. Absence subjects had two 24-hour EEGs at baseline and two at the end of maintenance; DEE subjects had one baseline EEG and one at the end of maintenance. EEG interpretation and seizure counting were conducted by independent blinded readers.

Enrollment totaled 15 absence subjects and nine DEE subjects. Collins said participants were heavily pretreated and on substantial background polytherapy. Absence subjects had failed up to seven treatments to control seizures, while DEE subjects had histories of more failed medications and devices, including use of fenfluramine and vagus nerve stimulation. The DEE cohort included seven Lennox-Gastaut syndrome (LGS) subjects, along with two categorized as other DEE, including one Dravet syndrome subject and one Rett syndrome subject.

Top-line efficacy: absence seizures measured by 24-hour EEG

In the absence cohort, the primary efficacy assessment was based on seizure frequency captured by 24-hour EEG. Bright Minds reported a median reduction of 73.1% in absence seizure events lasting at least three seconds, along with a median reduction of 74.4% in seizure burden (total time spent in seizures over 24 hours). The reduction in seizure frequency was reported as statistically significant with a p-value of 0.0117 (Wilcoxon signed-rank test).

Collins said the reduction in seizure number closely tracked the reduction in seizure burden, and that reductions were seen across a range of seizure durations. In a Q&A exchange, he also said the absence cohort showed “homogeneous reductions,” with no super-responders or non-responders, and argued that EEG metrics are not susceptible to placebo effects.

The company also highlighted sleep-related findings from the 24-hour EEG recordings. Collins said REM sleep increased substantially and significantly in the absence cohort, “nearly doubling from baseline,” and suggested that improved REM sleep could support memory consolidation, emotional regulation, and cognition. He stated there was no reason to believe commonly used absence therapies would increase REM to a similar extent and said sleep endpoints could potentially be explored as secondary endpoints in future studies.

Top-line efficacy: DEE major motor seizures by seizure diary

In the DEE cohort, efficacy was assessed primarily by change in major motor seizures using a 28-day seizure diary. Bright Minds reported a median reduction of 60.3% in major motor seizures in the LGS subgroup and 76.1% in the “DEE other” subgroup. Collins said that on a per-patient review, one subject experienced a small worsening while others showed reductions ranging from 47.3% to 100%.

As examples, Collins cited a 50.3% reduction in major motor seizures for an adult Dravet subject who had failed multiple medications including fenfluramine, and a Rett subject who achieved a 100% reduction in seizures that had lasted 43 days as of the update, including during a pneumonia episode that would typically increase seizure risk.

In closing comments, McDonald summarized the DEE result as approximately a 63% median reduction in major motor seizures across the DEE cohort and emphasized the adult-only, heavily pretreated, polytherapy background of participants. During Q&A, Collins said the company saw a trend toward better seizure reduction among those with higher baseline seizure frequency.

Safety, tolerability, and discontinuations

Bright Minds said BMB-101 was generally safe and well tolerated across both cohorts. Collins reported no drug-related serious adverse events and no significant adverse effects on vital signs, laboratory values, or electrocardiograms. Adverse events occurring at greater than 10% were described as either not related to drug (including respiratory infections) or possibly related (including fatigue, constipation, headache, and drowsiness). The only severe adverse event considered related to drug was dry mouth, which resolved without dose adjustment.

Discontinuations occurred in both cohorts. In the absence cohort, one subject discontinued due to inability to tolerate the taste of the original formulation, prompting a reformulation with less sweetening agent while maintaining the same active-drug concentration. Two other absence subjects discontinued due to fatigue (flu-like symptoms) and dizziness, both rated as possibly related. In the DEE cohort, three subjects discontinued due to behavioral fluctuations (possibly related), lethargy (possibly related), and a seizure-related fall resulting in shoulder fracture (not related to drug).

In Q&A on fatigue, Collins compared the rate to placebo arms in recent Lennox-Gastaut studies, saying it was in a similar range.

Development plans and additional pipeline items

Management said the Phase 2 readout supports moving into global registrational development. McDonald stated the company plans to initiate global Phase 2–3 regulatory studies in both DEE and absence seizures, with work underway to engage sites, and said Bright Minds expects to provide additional analyses from the breakthrough study during 2026.

The company also said it plans to initiate the NOVA study in Prader-Willi syndrome in Q1. In response to a question, Collins said two participants with obesity (including one with binge eating disorder) showed notable improvements in their relationship with food and “fairly substantial” weight loss over the short study duration, while the company did not observe a material reduction in weight among normal-weight participants.

Beyond BMB-101, Bright Minds outlined additional preclinical assets, including BMB-201 (a serotonin 2A/2C program) and BMB-202 (a serotonin 2A agonist program), and said it expects to have five clinical studies underway across the portfolio during the year.

About Bright Minds Biosciences (NASDAQ:DRUG)

Bright Minds Biosciences Inc, trading on the NASDAQ under the symbol DRUG, is a clinical-stage biotechnology company focused on developing novel small-molecule therapeutics for mental health and neurodegenerative disorders. The company’s research leverages proprietary chemistry platforms to create serotonin-modulating and neuroprotective compounds derived from psychedelic-inspired structures. Bright Minds aims to address unmet needs in conditions such as major depressive disorder, post-traumatic stress disorder and Alzheimer’s disease through orally administered treatments.

The company’s lead candidate, BMB-101, is an oral 5-HT2A receptor-modulating compound in clinical development for mood and anxiety disorders.