GRIN Therapeutics, a leader in targeted therapies for serious neurodevelopmental disorders, has dosed the first patient in its global Phase 3 Beeline trial of investigational radiprodil for individuals with GRIN-related neurodevelopmental disorder (GRIN-NDD) carrying gain-of-function variants.
Radiprodil, a selective negative allosteric modulator of the NMDA receptor GluN2B subunit, is designed to target the underlying biology of GRIN-NDD—not just its symptoms. By directly addressing receptor overactivation, the therapy has the potential to impact the full spectrum of manifestations of the disorder, offering advantages over traditional non-targeted anticonvulsants.
“This study reflects a truly collaborative effort between investigators, patient communities, and industry partners,” said Kristen Park, pediatric epileptologist and Principal Investigator for the Beeline trial at Children’s Hospital Colorado.
“GRIN-NDD is one of the most complex neurodevelopmental disorders with limited treatment options today. The Beeline trial gives us the opportunity to further evaluate whether radiprodil can address not only seizures but also the cognitive and behavioral aspects of the disease and provide the kind of treatment option that patients and families have been hoping for. We are proud to be a part of this important trial at Children’s Hospital Colorado.”
“With the first patient dosed, the Beeline trial marks a pivotal moment for GRIN Therapeutics and the community,” said Michael Panzara, Chief Medical Officer.
“For the first time, through the Phase 3 Beeline trial, patients have the opportunity to receive a drug that specifically targets the abnormal receptor leading to their condition – a drug that aims to address the underlying biology of GRIN-NDD, potentially modifying the course of disease.
"In four years, we have advanced from company inception to a global Phase 3 program built around deep scientific understanding of the disease and engagement with key stakeholders, including families and global regulatory authorities. This milestone represents what can be achieved when the right team with the right background and experience, the right resources, and the right collaborators align to drive clinical development.”
The Beeline trial is designed to evaluate the efficacy and safety of radiprodil in patients with confirmed gain-of-function GRIN-NDD variants. It incorporates a disease-specific endpoint—the GRIN-specific Clinical Global Impression (GRIN-CGI) scale, developed with caregivers—alongside traditional outcome measures and seizure reduction assessments.
The trial builds on promising results from the Phase 1b/2a Honeycomb trial, in which patients experienced a median 86% reduction in countable motor seizures. During the eight-week maintenance period, 71% of patients achieved more than 50% seizure reduction, and six of seven were seizure-free on at least 80% of days.
Clinicians and caregivers also reported overall clinical improvements, regardless of seizures, with the most common adverse events linked to infections or underlying disease rather than radiprodil itself.
