Mr. Alex Vasilkevich reports

BRIGHT MINDS BIOSCIENCES ANNOUNCES POSITIVE TOPLINE RESULTS FROM PHASE 2 CLINICAL TRIAL OF BMB-101 IN PATIENTS WITH Absence seizURES AND DEVELOPMENTAL AND ENCEPHALOPATHIC EPILEPSIES (DEE)

Bright Minds Biosciences Inc. has released positive and significant top-line results from its phase 2 breakthrough clinical trial evaluating BMB-101, a selective 5-HT2C biased agonist, in adult patients with drug-resistant Absence seizures and developmental and encephalopathic epilepsies. The study met its primary efficacy end points in both cohorts, demonstrating robust seizure reduction with a favorable safety and tolerability profile.

• BMB-101 demonstrated significant anti-seizure benefit in both cohorts with favourable safety and tolerability:
  • Absence: 73.1-per-cent median reduction in the number of Absence seizure greater than or equal to three seconds, p equal 0.012;
  • DEE: 63.3-per-cent median reduction in major motor seizures.
• REM sleep improvement in patients with Absence seizures: mean 90-per-cent increase in REM sleep with no change in total sleep duration;
• Company has initiated preparations for global registrational trials in both DEE and Absence seizure patients;
• Bright Minds to hold conference call and live webcast at 8 a.m. ET today.

Phase 2 breakthrough study overview

The phase 2 open-label, multicentre study evaluated safety, tolerability and efficacy of BMB-101 in adults with drug-resistant Absence seizures and DEE. A total of 24 patients were enrolled, exceeding the original target of 20. The study included a four-week baseline, four-week titration and maintenance period (two weeks for Absence cohort, four weeks for DEE cohort).

Primary end points:

• Absence cohort: change from baseline in the number of Absence seizures (lasting greater than or equal to three seconds) on 24-hour EEG, conducted by independent and blinded reviewers;
• DEE cohort: change from baseline in major motor seizure frequency (seizure diary).

Patient profile

The study enrolled 24 patients (15 with Absence seizures and nine with DEE), with a mean age of 30 years. Participants were receiving a median of three concomitant anti-seizure treatments in the Absence cohort and five in the DEE cohort, having previously failed up to 16 treatments (with a failed mean of 3.7 antiseizure treatments for the Absence cohort, and a failed mean of 9.8 for antiseizure treatments for the DEE cohort). The population also included patients treated with neuromodulation: two with Vagus Nerve Stimulators (VNS) in the Absence cohort and five in the DEE cohort. At baseline, the median number of Absence seizures greater than or equal to three seconds was 22, and similarly, the median number of countable motor seizures for the DEE cohort was 22.

Patient disposition

A total of 24 patients were enrolled (Absence cohort: n equals 15; DEE cohort: n equals nine).

Absence cohort: Twelve/15 patients completed the maintenance period. Three patients discontinued during titration/early treatment. Reasons reported across discontinuations included taste intolerance (related; drug product formulation subsequently updated), flu-like symptoms with muscle ache/fatigue (possibly related), dizziness (possibly related) and with insufficient baseline seizure counts.

The prespecified efficacy-evaluable population comprising 11 patients (including one DEE patient with atypical Absence seizures) with analyzable paired baseline and maintenance 24-hour ambulatory EEG recordings. One enrolled patient was excluded from the efficacy analysis because the baseline EEG did not meet entry criteria, and one maintenance EEG was of insufficient quality for reliable analysis.

DEE cohort: Six/nine patients completed the maintenance period. Three patients discontinued during titration/early treatment. Reasons reported across discontinuations included fluctuation in a pre-existing behavioural condition, lethargy (possibly related) and an intercurrent shoulder fracture with associated drowsiness/opiate use (not drug related). The prespecified efficacy-evaluable population comprising six patients. The DEE cohort included four Lennox-Gastaut Syndrome (LGS) patients, one Dravet syndrome and one Rett syndrome patient.

Efficacy results

Absence seizure cohort (n equals 11):

• 73.1-per-cent median reduction in the number of Absence seizure greater than or equal to three seconds. P equal 0.012 (Wilcoxon Signed Rank Test);
• 74.4-per-cent median reduction in total time in seizures lasting greater than or equal to three seconds during 24 hours (seizure burden). P equal 0.012 (Wilcoxon Signed Rank Test);
• Patients achieved robust reduction of Absence seizures regardless of seizure duration.

DEE cohort (n equals six):

• Cohort included four LGS patients, one Dravet Syndrome (who previously failed fenfluramine for efficacy) and one Rett Syndrome patient.
• 63.3-per-cent median reduction in major motor seizures;
• 60.3-per-cent median reduction in LGS patients and 76.1 per cent in other DEE patients;
• Last observation carried forward applied to two patients.

Safety and tolerability

BMB-101 was generally well tolerated. Most treatment-emergent adverse events were mild (79.6 per cent) or moderate (17.2 per cent), with no treatment-related serious adverse events. Most common AEs (greater than or equal to 10 per cent): respiratory infections (20.8 per cent), fatigue (16.7 per cent), constipation (16.7 per cent), headache (12.5 per cent), drowsiness (12.5 per cent). There were three severe adverse events, including dry mouth (transient, no dose change, no discontinuation), and one patient who had fractured shoulder and opiate-related drowsiness (not related).

Additional effects beyond seizure control

The study explored the effects of BMB-101 on sleep. There was a 90-per-cent increase in REM sleep (56.2 minutes at baseline to 106.7 minutes on BMB-101) in patients, while overall sleep duration remained unchanged (9.1 hours at baseline versus 8.9 hours on BMB-101). This is crucial since REM sleep increase was not due to increased sleep duration. REM sleep is important for memory consolidation, emotional-behaviour regulation and cognitive function.

Next steps

Bright Minds Biosciences has initiated preparations for global registrational trials in Absence seizures and DEE. Additional data including long-term outcomes will be presented throughout the year. Bright Minds Biosciences will also be initiating a study in Prader Willi Syndrome, currently anticipated to begin in Q1 2026 (PWS program).

Conference call/webcast information

The Bright Minds virtual event will be webcast live by visiting the investors section of the company's website and selecting events and presentations.

A replay of the webcast will not be available after the event.

Date and time:  Jan. 6, 2026, 8 a.m. ET

The call will include a discussion of the data followed by a Q&A (question-and-answer) session. Individuals who wish to ask questions should use the questions tab available during the live webcast.

About BMB-101

BMB-101 is a novel scaffold 5-HT2C Gq-protein biased agonist developed using structure-based drug design. It was explicitly designed for chronic treatment of neurological disorders where tolerance and drug resistance are common issues. Biased agonism at the 5-HT2C receptor is one of its key features and adds another layer of functional selectivity within a well-validated target. BMB-101 works exclusively via the Gq-protein signaling pathway and avoids beta-arrestin activation, which is crucial to minimize the risk of receptor desensitization and tolerance development.

In preclinical studies, BMB-101 has demonstrated efficacy in animal models of epilepsy, binge eating, aggression, substance use disorder and cognitive decline which highlights its potential for the use in multiple neurological and neuropsychiatric disorders, including drug-resistant epilepsy, Prader-Willi Syndrome (PWS) and others.

In phase 1 clinical studies, BMB-101 was given to 64 healthy volunteers in a single ascending dose (SAD), multiple ascending dose (MAD) and food-effects study. BMB-101 was demonstrated to be safe and well tolerated at all doses. No serious adverse events (SAEs) were observed, and adverse events (AEs) were mild in nature and in line with on-target effects for serotonergic drugs.

An extensive target-engagement study was conducted using both fluid biomarkers (transient prolactin release) and physical biomarkers (quantitative electroencephalogram, qEEG). Both methods confirmed robust central target engagement. A qEEG signature typical for anti-epileptic drugs was observed, with a selective depression of EEG power at frequencies observed during epileptic seizures. Furthermore, a potentiation of frontal gamma-power was observed in this study which could indicate the potential for improved cognition.

About Bright Minds Biosciences Inc.

Bright Minds is a biotechnology company developing innovative treatments for patients with neurological and psychiatric disorders. The company's pipeline includes novel compounds targeting key receptors in the brain to address conditions with high unmet medical need, including epilepsy, PWS, depression and other CNS disorders. Bright Minds is focused on delivering breakthrough therapies that can transform patients' lives.

Bright Minds has developed a unique platform of highly selective serotonergic agonists exhibiting selectivity at different serotonergic receptors. This has provided a rich portfolio of NCE programs within neurology and psychiatry.

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