RL-007, a novel oral neuromodulator being developed to treat cognitive impairment associated with schizophrenia – A non-clinical and clinical overview

Background: Cognitive impairment associated with schizophrenia (CIAS) is observed in approximately 80% of schizophrenia patients and viewed as having the strongest influence on everyday functioning.

Methods: Data will be summarized from preclinical studies of RL-007 that have explored GABAergic and cholinergic neuromodulation. Data from a translational model of cognitive impairment was used to test the pro-cognitive effects in a series of animal and human studies. Safety and tolerability data will be summarized from over 500 participants from 10 clinical trials. A series of clinical studies of participants with cognitive impairment will be presented, including a Phase 2 pilot study in CIAS.

Results: RL-007 stimulates inhibitory signaling of GABAergic activity, through GABAb modulation, and enhances hippocampal synaptic plasticity and basal excitatory signaling in the cholinergic pathway. RL-007 is safe and well-tolerated, without GABAergic or cholinergic side effects. The scopolamine studies show reversal of learning and memory deficits across species. The clinical studies found improved cognitive performance, specifically for verbal learning and memory and processing speed as well as improved functional outcomes.

Discussion: RL-007 has shown a unique pharmacological profile that could assist in restoring neurotransmission abnormalities in CIAS patients, including GABAb modulating and inhibitory properties and enhanced cholinergic pathway activity. RL-007 was safe and well-tolerated in humans, without sedating or parasympathetic side effects. Consistent evidence was found for increasing cognition in non-clinical and clinical studies, specifically learning and memory, making RL-007 a compound to potentially treat CIAS. A large Phase 2 PBO-controlled clinical trial in CIAS is underway.