Research over the past decades has elucidated on the role of various metabolites in ketamine's clinical efficacy profile in neuropathic pain, depression, and other neurological diseases.

Hydroxynorketamine (HNK), a ketamine metabolite formerly believed to be inactive, acts as a D-Serine modulator in neurons, is devoid of ketamine’s notorious psychomimetic properties and abuse liability, and has been demonstrated in various preclinical studies to contribute to or, in some indications, potentially even constitute the active principle of ketamine.

Studies with HNK suggest that its therapeutic effects may involve a molecular mechanism associated with decreased intracellular synthesis and extracellular transport of D-serine. D Serine is an endogenous NMDA receptor co-agonist, which plays a critical role in long-term potentiation (LTP) and NMDAR-induced neurotoxicity.

Spirify's proprietary novel candidates are derivates of HNK which aim at harnessing its pharmacological properties as a D-Serine modulator while further optimizing its clinical utility.