Gilgamesh Pharmaceuticals, a clinical-stage neuroscience biotech developing best-in-class medicines to redefine mental healthcare, announces the successful completion of its Phase 1 Single Ascending Dose (SAD) trial of GM-2505, a novel 5-HT2A receptor agonist. While initially in development for treatment-resistant depression (TRD) and major depressive disorder (MDD), GM-2505 has the potential to enhance patient care and outcomes as a rapid-acting, durable, safe, and intermittent therapeutic option across a broad range of other severe mental health disorders, such as alcohol use disorder, anxiety disorders, and obsessive-compulsive disorder (OCD).
In the Phase 1 study, GM-2505 exhibited dose-proportional PK and dose-dependent effects on multiple pharmacodynamic measures, including subjective effects, electroencephalogram (EEG), and neuroendocrine markers. Subjective effects reached a peak intensity consistent with a full psychedelic experience, while the duration of those effects was limited to 60-90 minutes. “We were thrilled to obtain clinical confirmation of the short half-life and strong psychedelic effects of GM-2505 that were suggested by preclinical data and look forward to advancing this promising therapeutic candidate into patients,” says Andrew Kruegel, PhD, CSO and Co-Founder of Gilgamesh. Gilgamesh believes that GM-2505’s short duration of action will harness the impressive clinical efficacy of other 5-HT2A receptor agonists while better aligning with existing healthcare infrastructure and clinical workflow, which will broaden patient access on contrast to longer-acting agents such as psilocybin. Additional details will be presented at the American College of Neuropsychopharmacology (ACNP) meeting in December.
“In the Gilgamesh Phase 1 study, a full range of GM-2505 doses have been tested with the highest doses of 15 and 20 mg manifesting a full psychedelic effect with minimal effects below 10 mg. This provides a basis to move confidently into initial Phase 2a testing in patients with GM-2505,” says Matthias E Liechti, MD. Dr. Liechti is Professor at the University Hospital of Basel in Switzerland, Head Division of Clinical Pharmacology, University Hospital Basel, where the clinical pharmacology of psilocybin, DMT, and other psychedelics has been extensively investigated.
Following the successful completion of the Phase 1 SAD trial, Gilgamesh will initiate a Phase 2a study in major depressive disorder (MDD) patients during the 1st quarter of 2024. The aim of the Phase 2a study will be to refine the dosing regimen, confirm safety, and demonstrate an early efficacy signal of GM-2505.
“The successful completion of our GM-2505 Phase 1 SAD trial marks another significant milestone for Gilgamesh Pharmaceuticals,” says Jonathan Sporn, MD, the CEO and Founder of Gilgamesh. “The progress across our pipeline shows that we are entering a new era of accessible, rapid-acting, intermittent, and effective treatment options for mental healthcare.”
Gilgamesh’s team of seasoned biotech veterans and innovative entrepreneurs boasts a wealth of expertise spanning medicinal chemistry, neurobiology, translational science, clinical research, and commercial development. With their collective experience, the team is well-equipped to usher GM-2505 through the development pipeline and ultimately bring this life-changing therapy to millions of patients in need.