Gilgamesh Advances Pipeline Of Novel Psychoactive Drugs Aimed At Revolutionizing Psychiatric Disorders Treatment

Private psychedelics biotech company Gilgamesh Pharmaceuticals is currently developing a diverse portfolio of novel, potentially first-in-class compounds targeting mechanisms with demonstrated clinical efficacy, onset duration or prolonged treatment duration, for the treatment of psychiatric conditions.

Gilgamesh’s work focuses on the central nervous system (CNS). As such, the company is developing a pipeline of novel agents that retain or improve on the therapeutic effects of prototypical psychoactive substances—like psilocybin, LSD, ketamine and MDMA—while enhancing their safety and efficacy profile.

The company’s preclinical technology platform characterizes existing molecules and integrates the findings into the development of novel therapies, creating a drug discovery cycle through high-resolution electrophysiology, disease-relevant models and behavioral assessment of proprietary entities.

The Pipeline

The current portfolio includes four programs with composition of matter IP coverage. The first, GM-1020, is an antagonist of the NMDA receptor being developed for depression and other indications. Preclinical studies have demonstrated GM-1020 retains the rapid and robust efficacy of ketamine while avoiding first-pass metabolism, which allows for oral administration and attenuated dissociative side effects and therefore making it potentially suitable for at-home use. The new compound is set to enter clinical trials before the end of 2022.

Two advanced programs target the 5-HT2A receptor, the primary target of classic psychedelics. GM-2505 is a short-acting 5-HT2A receptor agonist/5-HT releaser being developed for the treatment of depression and anxiety and for strengthening the psychotherapy work. It produces noticeable changes in perception, emotion and cognition yet, since its effects are shorter compared to those of psilocybin, patients would need to spend less time in therapist-supervised office visits. GM-2505 will enter clinical trials in late 2022.

The other, GM-200X, is assessing non-hallucinogenic 5-HT2A receptor agonists for depression and anxiety treatments. Preclinical evidence suggests these compounds lack the hallucinogenic effects of classic psychedelics while retaining their therapeutic benefits. Due to the expected safety profile, the GM-200X molecules may deliver a long-term or subchronic maintenance therapy as well. Gilgamesh expects to nominate a clinical candidate from the GM-200X program in 2022.

The final program, GM-300X, is focused on novel analogs of naturally-occurring ibogaine, a plant-derived atypical psychoactive for the treatment of substance abuse. While it has been reported to dramatically reduce cravings for opiates for a period of months after a single administration, ibogaine has also been linked to QT prolongation and increased risks of cardiac arrhythmia. GM-300X molecules target the κ-opioid receptor (KOR) among others, but appear to lack ibogaine’s adverse cardiac effects. The program’s lead candidate nomination is also expected to take place this 2022.

Photo by Louis Reed on Unsplash