The GABAA α2 and α3 subunit receptors are expressed by nerves in the spinal cord that control the pain signalling to the brain. It is this control center which is malfunctioning in many patients with neuropathic pain. Saniona’s α2/α3 compounds selectively work on receptors containing the α2 and α3 proteins without efficacy on the main GABAA receptors in the brain, including the so-called α1 protein subunit, which is responsible for the sedative and hypnotic effects of unspecific GABAA compounds such as Valium®. By specifically modulating the GABAA α2 and α3 receptor subunits, Saniona’s α2/α3 compounds are expected to rebuild or improve the body's own pain regulating system in the spinal cord without promoting unwanted side effects such as sedation. Preclinical studies with AN363, and several other compounds from the series, have confirmed efficacy in animal models of neuropathic pain without the sedative effect. Also, human studies with an analogue (AN721) to AN363 supports that this concept can be extended to humans.
Neuropathic pain is caused by a lesion or dysfunction of the central or peripheral nervous system following diseases such as diabetes, varicella zoster, cancer and HIV or mechanical lesion and trauma or the use of drugs such as chemotherapy. Neuropathic pain is often chronic and irreversible. Well-known painkillers have no or little effect on neuropathic pain. Apart from narcotic analgesics (where tolerance development is a further complication), patients are typically treated with drugs developed for other indications including anti-epileptic drugs and antidepressants. According to Decision Resources, the market for neuropathic pain is about US$ 6 billion. The medical need is significant. It is estimated that about 40-60% of the treated patients do not respond to existing drugs and that the remaining patients in general achieve partial relief only.
Saniona has finalized the preclinical toxicology studies for AN363. In May 2016, Saniona announced that AN363 development is put on hold. Instead, extended non GLP preclinical studies on a backup compound to AN363 will be initiated with the aim to bring this compound forward towards clinical development.