New BREAKTHROUGH Study of BMB-101, Positive Phase 1 Data on Orexin Agonist ORX750, Dosing Commenced for QRL-101

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to an announcement from Bright Minds Biosciences, the company has initiated a new phase 2 study, dubbed BREAKTHROUGH, that will assess the safety and efficacy of its investigational agent BMB-101 in adults with classic absence epilepsy and development epileptic encephalopathy (DEE). The therapy, a 5-HT2C receptor agonist, has previously demonstrated efficacy in animal models of Dravet syndrome and numerous models of generalized seizures.The study, designed as a basket clinical trial, features a 4-week baseline period, 8-to-12-week treatment period, and a 4-week follow-up phase for additional safety monitoring. BREAKTHROUGH is expected to include 20 adults aged 18-65 years old with absence epilepsy or a DEE. These comprise a range of rare epilepsy disorders, including epilepsy with eyelid myoclonia, also known as Jeavons (Jayvons) Syndrome. Following the conclusion of the follow-up period, patients may be eligible to receive BMB-101 in an open-label extension that will last 12 months.

Centessa Pharmaceutical recently announced positive interim results from a phase 1 trial of ORX750, an orexin receptor 2 (OX2R) agonist, aimed at treating sleep disorders. In a cohort of healthy volunteers, treatment with the agent resulted in significant improvements in wakefulness at doses of 1.0 mg and 2.5 mg, as measured by the Maintenance of Wakefulness Test (MWT).All told, the data revealed that the 2.5 mg dose of ORX750 was particularly effective, restoring normal wakefulness with a sleep latency of 32 minutes. In addition, ORX750 was considered safe and well tolerated, with no common adverse events (AEs), liver toxicity, or visual issues. Encouraged by these findings, the company plans to advance the investigational agent to phase 2 trials targeting narcolepsy types 1 and 2, and idiopathic hypersomnia, starting in late 2024.

According to a recent announcement, dosing has commenced for a phase 1 multiple-ascending dose (MAD) clinical trial (NCT06532396) assessing QRL-101 (QurAlis), a first-in-class selective Kv7.2/7.3 ion channel opener for the treatment of hyperexcitability-induced disease progression in amyotrophic lateral sclerosis (ALS). Known as QRL-101-03, the phase 1 study is expected to include 60 healthy participants, with topline results expected in the first half of 2025. QRL-101-03 is a follow-on study to QRL-101-01, an ongoing phase 1, single-ascending dose study (NCT05667779) to determine the safety, tolerability, and pharmacokinetic profile of QRL-101 after a single dose. The newly initiated phase 1 MAD portion includes up to 5 cohorts of 8 participants each, who are randomly assigned in a 9:3 ratio to either QRL-101 or placebo. In total, the approximate duration of study participation for each participant may be up to 39 days.

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