Gilgamesh Pharmaceuticals’ pipeline of new psychoactive drugs aimed at revolutionizing the treatment of psychiatric disorders

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

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

The Company’s preclinical technology platform characterizes existing molecules and integrates the results into the development of new therapies, creating a drug discovery cycle through high-resolution electrophysiology, disease-relevant models and evaluation. behavior of owner entities.

The Pipeline

The current portfolio includes four programs with material IP coverage composition. The first one, GM-1020is a NMDA receptor antagonist under development for depression and other indications. Preclinical studies have demonstrated that GM-1020 retains the rapid and robust efficacy of ketamine while avoiding first-pass metabolism, allowing for oral administration and attenuated dissociative side effects, making it potentially suitable for a home use. The new compound is is expected to enter clinical trials before the end of 2022.

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

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

The final program GM-300Xto focus on new ibogaine analogues of natural origin, an atypical plant-derived psychoactive for the treatment of drug addiction. Although it has been reported to significantly reduce opiate cravings for several months after a single administration, ibogaine has also been associated with QT interval prolongation and increased risks of cardiac arrhythmias. GM-300X molecules target the κ-opioid receptor (KOR) among others, but seem to lack the adverse cardiac effects of ibogaine. The appointment of the lead applicant for the program is also expected to take place in 2022.

picture by Louis Roseau on Unsplash

Alvin J. Chase