RL-007
RL-007 (a GABAB / cholinergic modulator) represents a novel pharmacological agent that enhances hippocampal plasticity and stimulates broad pro-cognitive activity. RL-007 modulates core abnormalities in synaptic function and neurotransmission mechanisms that are implicated with the cognitive impairments associated with schizophrenia and other central nervous system indications such as Alzheimer’s disease.
Preclinical evidence: RL-007 is a novel compound, which exhibits a modulating effect on two mechanisms that are central to learning and memory: the cholinergic and gamma‑aminobutyric acid type B (GABAB) receptor systems. RL-007 represents a novel pharmacological agent that enhances hippocampal plasticity and stimulates broad pro-cognitive activity. RL-007 modulates core abnormalities in synaptic function and neurotransmission mechanisms that are implicated with the cognitive impairments associated with schizophrenia. RL-007’s action is dependent upon GABAB receptors, evidenced by the blockade of the compound’s therapeutic activities by GABAB receptor antagonists, although it does not directly activate GABAB receptors. In contrast to other compounds that utilize GABAB receptors, RL-007 is non-sedating in nonclinical studies at doses approximately 1000‑times its effective dose.
RL-007 also influences the cholinergic system; its beneficial hippocampal activity is independent of acetylcholine, but it can enhance the activity of acetylcholine and reverses cognitive deficits induced by muscarinic receptor antagonism. RL-007 has been shown to enhance long term potentiation (LTP) in rat hippocampal slices, indicating a direct action on those brain regions involved with learning and memory processes. RL-007 enhances multiple cognitive and memory domains in mice, rats, and dogs in a range of testing paradigms including object recognition, social recognition, and working memory, and reverses age-associated cognitive deficits. Additionally, RL-007 has demonstrated anxiolytic properties in nonclinical models of unconditioned anxiety.
Prior evidence in humans: Overall, RL-007 is a Phase 2 asset that has been evaluated in ten clinical studies – seven Phase I studies and three Phase II studies – with over 500 unique subjects having been dosed to date. Four of these clinical trials demonstrated improvements in verbal learning and memory, including in a large Phase II study of subjects with peripheral neuropathic pain.
In all studies, RL‑007 was well tolerated and demonstrated an acceptable safety profile.