Summary of Bright Minds Biosciences FY Conference Call Company Overview - **Company**: Bright Minds Biosciences (NasdaqCM:DRUG) - **Focus**: Development of therapies targeting serotonin receptors, specifically the 5-HT2 family - **Current Clinical Assets**: - BMB-101 in Phase 2 for two types of epilepsy: developmental and epileptic encephalopathies (DEEs) and absence epilepsy - New program targeting Prader-Willi syndrome (PWS) with a 5-HT2C molecule - Several preclinical assets focusing on the 5-HT2A receptor for potential use in pain and neuropsychiatric disorders [2][60] Key Points and Arguments Clinical Development - **BMB-101**: - A G protein-based agonist at the 5-HT2C receptor, differentiating it from other compounds like fenfluramine and BMB-101 by avoiding beta-arrestin pathway activation, which can lead to tolerance [3][4] - Better pharmacokinetics (PK) with a proposed once-daily formulation compared to BMB-101, which requires refrigeration and is taken three times a day [4][7] - Phase 1 data indicates better tolerability and a linear dosing response, reducing side effects compared to BMB-101 [8][9] Epilepsy Indications - **Absence Epilepsy**: - The FDA is interested in absence seizures due to the lack of effective treatments; EEG is a reliable measurement tool for these seizures [16][17] - The benchmark for approval is a 50% reduction in seizures in 50% of patients, adjusted for placebo effects [17][18] - Enrollment target for the study is about 10 patients, with doses ranging from 0.67 to 2 mg/kg [28][31] - **Developmental and Epileptic Encephalopathies (DEEs)**: - Majority of patients will likely be from the Lennox-Gastaut syndrome (LGS) population, with a similar benchmark for efficacy as absence epilepsy [36][38] - Multi-center trial being conducted in Australia, with plans for a global Phase 2/3 trial [37][44] Market Opportunity - **DEEs**: Potential peak sales for treatments in this area are estimated at $1.5 billion to $2 billion [49] - **Absence Epilepsy**: Bright Minds aims to be the first branded agent in this indication, with a patient population estimated at around 275,000 to 500,000 annually [49][51] Prader-Willi Syndrome (PWS) - **Mechanistic Rationale**: Genetic link to 5-HT2C receptors in PWS patients; targeting these receptors may alleviate symptoms including hyperphagia and neuropsychiatric issues [60] - **Clinical Evidence**: Previous studies with fenfluramine showed improvements in weight and neuropsychiatric symptoms, supporting the rationale for 5-HT2C agonism in PWS [60] Financials and Capitalization - The company is operating with a focus on capital efficiency, with current funding covering ongoing and upcoming studies [69] Additional Important Information - Future studies planned for both DEE and absence epilepsy, with a need for regulatory alignment on seizure counting methods [46][48] - The company is also advancing a second asset, BMB-105, to potentially save time in development [62][63] - The upcoming data release is expected in early January, strategically timed to capture investor attention [42]

Financial Data and Key Metrics Changes - As of March 31, 2025, the company had cash, cash equivalents, and short-term investments of approximately $27.1 million, down from $44.9 million as of December 31, 2024 [20] - Cash used in operations for the first quarter of 2025 was $18.1 million, compared to $13 million for the same period in 2024 [21] - The net loss for the first quarter of 2025 was $17.6 million, or $0.58 per basic and diluted share, compared to a net loss of $21.8 million, or $0.72 per basic and diluted share for the first quarter of 2024 [22] Business Line Data and Key Metrics Changes - Research and development expenses for the first quarter of 2025 totaled $12 million, down from $13.3 million in the first quarter of 2024, primarily due to lower study costs [21] - General and administrative expenses for the first quarter of 2025 were $6.3 million, compared to $9.7 million in the first quarter of 2024, driven by a decrease in stock-based compensation expense [22] Market Data and Key Metrics Changes - The market opportunity for NDV-one includes approximately 75,000 new cases of bladder cancer diagnosed each year in the US, with about 50% having high-grade disease at high risk of recurrence [8] - The potential market for sopranolone includes Prader Willi syndrome, which affects approximately 350,000 people worldwide, including about 20,000 in the US [17] Company Strategy and Development Direction - The company aims to advance its pipeline to important clinical milestones with a disciplined development plan and a clean balance sheet [6][20] - The strategic focus includes bringing NDV-one for bladder cancer and sopranolone for Prader Willi syndrome and Tourette syndrome to patients as soon as possible [5][24] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of NDV-one to improve care for bladder cancer patients, citing positive Phase two data presented at the AUA meeting [7][14] - The company plans to secure U.S. IND clearance for NDV-one in the second half of 2025 and is preparing for the next set of studies [15][24] Other Important Information - NDV-one is a novel sustained release formulation of gemcitabine and docetaxel, designed to maximize local dosage concentration while minimizing systemic toxicity [9] - The initial Phase two data for NDV-one showed an overall response rate of 85% at three months and 90% at any time point, with a 100% complete response rate in carcinoma in situ patients [12][13] Q&A Session Summary Question: What gives confidence that the current data from the Phase two study would be sufficient for the FDA to agree for NDV-one to move into registrational study? - Management highlighted the well-known efficacy and safety of the drug combination and the advantages of the new formulation that allows for easier administration [29][30] Question: Could you elaborate on scaling up supply? - The company is looking to secure manufacturing capacity for commercial needs and plans to have at least two manufacturers for risk management [47] Question: When should updates on the complete response rate for the entire population be expected? - The next data point will be the six-month results, expected around June or July, with further updates planned for nine and twelve months [52][53] Question: What would the Phase three trial design look like? - Management discussed potential routes for approval, including a single-arm trial or a randomized trial against placebo, depending on FDA feedback [62][64]