SAN711 is a first-in-class pain and itch-relieving compound, which has the potential of being a first-line treatment option for pain management in patients suffering from untreatable neuropathic pain or itching disorders, either as standalone treatment or as an add-on medication to existing suboptimal therapies. SAN711 acts on the receptors for GABA, the main inhibitory signaling mediator in the nervous system. SAN711 works selectively on receptors containing the GABAA α3 subunit without efficacy on the main GABAA receptors in the brain including receptors containing the GABAA α1 protein. This is important, since the sedative and hypnotic adverse effects of current marketed product acting on the receptors of GABA, such as Valium®, are due to its action on the GABAA α1 containing receptors, whereas the pain killing and anti-itch effects relies on its effects on GABAA α3 containing receptors. This means that SAN711 may regulate the body's own pain and itch regulating system in the spinal cord without promoting unwanted side effects through activation of other GABA systems in the brain. Preclinical studies with the compound have confirmed efficacy in animal models of neuropathic pain and itching without the sedative effect.
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, irreversible and notoriously difficult to manage. According to industry estimates, neuropathic pain is believed to affect about 40 million people in seven major markets. Well-known painkillers, such as Aspirin®, Panodil®, and ibuprofen 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. It is estimated that 40-60% of the treated patients do not respond to existing drugs and that those that do respond to existing drugs in general achieve partial pain relief only, creating a significant medical need for more effective treatments. Furthermore, the existing drugs typically have severe and dose limiting side effects such as drowsiness, dizziness and somnolence.
Pruritus or itch is the most frequent symptom seen in dermatology including atopic dermatitis, urticaria and psoriasis. Pruritus is often defined as an unpleasant sensation associated with the desire to scratch and significantly reduces the quality of life of the affected individuals in a wide range of medical conditions. With a lifetime prevalence of up to 22% and a high rate of therapeutic failure due to suboptimal treatment options, chronic itch imposes a significant socio-economic burden. Antihistamines have traditionally been the first-line treatment option for most pruritic conditions despite low efficacy in the substantial number of pruritic diseases characterized by histamine-independent pruritus. Certain systemic diseases have long been known to cause pruritus that ranges in intensity from a mild annoyance to an intractable, disabling condition. Generalized pruritus may be classified into the following categories based on the underlying causative disease: renal pruritus, cholestatic pruritus, hematologic pruritus, endocrine pruritus, pruritus related to malignancy, and idiopathic generalized pruritus. The global combined market for treatment of atopic dermatitis and psoriasis amounts to approximately US$10 million and is expected to double over the next 10 years
Preclinical development of SAN711 will encompass scale-up of the manufacturing process, GMP production and various toxicology studies, which will form the basis for a regulatory application to initiate first-in-man clinical trials. Saniona is concurrently working with its development partners to initiate Phase 1 clinical trials in the first half of 2019.