Firefly Neuroscience is thrilled to share the publication of the Bright Minds Biosciences Inc., a biotechnology company, first in-human Phase 1 study of its lead component, BMB-101, focused on developing novel drugs for the targeted treatment of neuropsychiatric disorders and refractory epilepsy, announcing positive results of the qEEG (Quantitative Electroencephalogram).

The results shared in the below study are a great example of how Firefly Neuroscience’s advanced EEG analysis platform can make CNS drug development process much more accurate and efficient from the early phases. Through our reliable and validated EEG analysis platform, pharmaceutical companies can objectively show drug-target engagement, make data-driven decisions about selected doses, and continue to the next phases with much more certainty.

Leveraging the BNA™ platform and EEG-based biomarkers for informed patient selection in the next steps would make the drug development process even more cost-effective and successful.

There is incredible potential ahead in our pursuit of leveraging AI with our proprietary EEG database to bring valuable clinical insights into brain health.

Firefly Neuroscience is paving the way forward by employing sophisticated and updated machine-learning methods to discover EEG-based biomarkers that will bring unprecedented clinical value to psychiatrists, neurologists, and pharmaceutical companies. Our biomarker discovery is driven by our proprietary AI platform that harnesses our unique EEG database. At Firefly Neuroscience, we are committed to continuously adapting and improving our methods to stay at the forefront of innovation.

You can learn more about our AI platform and the unique properties of our database in this article.

Details of the study are included below and and the full media release can be read here

On July 20, 2023, Bright Minds Bioscience announced the completion of the study, along with positive top-line data that demonstrated BMB-101’s excellent safety and tolerability profile in the single ascending dose, multiple ascending doses, and food effects. BMB-101 also demonstrated central target engagement and predictable plasma pharmacokinetics.

Using Firefly Neurosciences’ BNA™ technology in the qEEG study, BMB-101 demonstrated:

• Central target engagement, as the treatment group was easily identified in blinded data using qEEG power signature.
• A robust increase in central delta power and robust reduction in central alpha and beta power in the active group, as previously reported for Anti-Epileptic Drugs (AEDs) in healthy individuals.
• Power and connectivity changes were concentration dependent.

“The positive top-line findings from our recently completed Phase 1 study of BMB-101, together with the observations from the qEEG portion of the study, validate our approach as we continue to evaluate this important product candidate. BMB-101 is clearly [getting into the brain/achieving brain penetration] and activating the target receptors as we had predicted, setting us up for potential success in a number of indications that have been validated with the 5-HT_2C mechanism. With this study complete, BMB-101 is now a Phase 2 ready asset, and we intend to move forward with an investigative new drug submission immediately,” stated Ian McDonald, CEO of Bright Minds.

“We are especially pleased that BMB-101 has demonstrated central target engagement by transient prolactin increase and qEEG changes. The treatment group was readily identified in blinded data using the qEEG power signature. In addition, increased frontal gamma power represents an improved AED principle over [existing] benzodiazepine (GABA receptor) AED drugs. We believe that BMB-101 has the potential to be a best-in-class, novel pharmacophore 5-HT_2C agonist for the treatment of seizure disorders, and our team is committed to advancing this product candidate for application where serotonin 2C agonists would be said useful,” said Jan Torleif Pedersen, Ph.D., MSc, Chief Science Officer of Bright Minds.

During the EEG recording, subjects were seated with a U.S. Food and Drug Administration (FDA)- approved 19 electrode EEG headset provided by Zeto™ Inc. Channels were sampled at 250 or 500 Hz and referenced to A1/A2 channels (linked-ears reference) during recording. The EEG recording time was 10 minutes (~5 minutes resting with eyes closed and ~5 minutes resting with eyes open). There were four EEG recording time points: day 1 pre-dose (immediately before dosing) and post-dose (1h after dosing), and day 7 pre-dose and post-dose. Data were analyzed using Firefly Neuroscience’s advanced EEG analysis platform.

BMB-101 is a highly selective and potent 5-HT_2C agonist being developed to treat refractory epilepsies and other indications, such as psychosis, addiction, and impulse control disorders. BMB-101 demonstrated an excellent safety and tolerability profile. 5-HT_2C target engagement was demonstrated by transient, dose-dependent increases in prolactin. BMB-101 exhibited predictable plasma pharmacokinetics with relatively small inter-individual variability. The current formulation allows for twice-a-day oral dosing, and with further development, there may be potential for once-a-day dosing. Based on these observations, the Company believes that moderate doses of BMB-101 will fully engage 5-HT_2C receptors and, therefore, not be dose-limited by side effects, which will help to achieve maximal efficacy in future Phase 2 studies. Dose limited side effects exhibited by first-generation 5-HT_2C agonists have prevented exploiting the full potential of this pharmacological mechanism.

The Phase 1 study was conducted in Adelaide, Australia, by CMAX Clinical Research, a clinical trial center specializing in a range of early-phase trials and first in-human studies. The study evaluated the safety, tolerability, pharmacokinetic (PK) and food effect of BMB-101 in healthy volunteers.

About the Phase 1 Study

Part 1: Single Ascending Dose

• 4 cohorts (6 drug and 2 placebo) – single dose (oral solution)
• Reached the planned top dose of 180 mg/70 kg, which approached preclinical exposure limits
• Well tolerated with predictable PK
• The most common adverse event was oral paresthesias from liquid formulation

Part 2: Food Effect

• 12 subjects – crossover with and without breakfast, 120 mg/70kg
• The effect of food on BMB-101 levels was relatively small, and therefore BMB-101 can be administered without the need for fasting

Part 3: Multiple Ascending Dose

• 4 cohorts (6 drug and 2 placebo) – twice a day dosing for seven days after meals
• Reached a top dose of 150 mg/70 kg twice a day
• Biomarkers for central target engagement: Prolactin release and qEEG

Good Manufacturing Practices (GMP) production completed for BMB-101 drug substance and drug product.