Perception Neuroscience’s lead development product is the glutamatergic modulator R-ketamine (PCN-101), a single isomer of ketamine. R-ketamine belongs to a new generation of compounds with the potential for rapid acting antidepressant (RAAD) activity. Most of the currently FDA-approved antidepressant therapies often take weeks to achieve maximal effectiveness.

A phase 2a Proof-of-Concept clinical trial of this exciting compound is currently ongoing.

Background 

Ketamine is a 50:50 mix of R-ketamine and S-ketamine (esketamine), two mirror image molecules (stereoisomers or enantiomers). Ketamine was approved in the US as a general anesthetic in 1970 and has seen wide use in this indication since then.

The first placebo-controlled study suggesting ketamine has antidepressant effects was reported in 2000. A single sub-anesthetic dose of ketamine given via intravenous infusion induced a rapid antidepressant response in patients. Since then, ketamine has been used off-label as a treatment for patients with poor response to antidepressants. By contrast, other antidepressants such as selective serotonin reuptake inhibitors, selective noradrenergic reuptake inhibitors, and tricyclic antidepressants, generally have high rates of non-response and may take several weeks for therapeutic benefits to become apparent. 

Esketamine, the S-enantiomer of ketamine, was approved in 2019 in the US as an intranasal formulation (Spravato®) for the treatment of TRD in adults and for the treatment of depressive symptoms in adults with MDD with acute suicidal ideation or behavior. Esketamine has concerns around safety and tolerability including dissociation, sedation, and the risks of misuse and abuse. This has necessitated a Risk Evaluation and Mitigation Strategies (REMS) with a number of restrictions including administration by an HCP in a supervised healthcare setting and the requirement for patients to be monitored for at least 2 hours following administration.

Nonclinical studies suggest that PCN-101 (R-ketamine) produces more sustained antidepressant effects while causing fewer psychomotor and behavioral adverse effects at therapeutic doses and has a lower potential for abuse compared to S-ketamine or racemic ketamine.

These nonclinical properties of R-ketamine were first discovered in the laboratories of Professor Kenji Hashimoto at Chiba University in Japan.  Perception Neuroscience has an exclusive license to this intellectual property which includes issued method-of-treatment claims.  

Corporate Highlights:

Phase 1 multiple ascending dose PK study in healthy volunteers completed in 2020

IND-enabling preclinical and toxicology studies completed with longer-term studies ongoing

US IND Approved 2022

The company initiated a Phase 2a proof-of-concept study in patients with Treatment-Resistant depression in 2021.  This trial is currently ongoing. 

Additionally, in 2021, Perception partnered with Otsuka Pharmaceuticals to develop PCN-101 in Japan.