SAN711 for treatment of chronic itching and neuropathic pain

SAN711 is a selective GABAA α3 modulator (PAM) which is derived from Saniona’s advanced ion channel platform and has demonstrated strong efficacy in rodent itching and pain models. The company has completed a comprehensive preclinical package, including full toxicology and GMP validation. The clinical candidate is ready for filing for clinical testing. Phase 1 clinical testing is scheduled to start over the summer 2019, either internally or together with a potential partner.

SAN711 has the potential to become a novel treatment of severe and untreatable itching conditions caused by renal failure and liver diseases as well as rare neuropathic itching diseases such as Brachioradial pruritus. Many chronic itching conditions are not related to skin reactions but are a result of chronic changes in sensory modulation in the spinal cord, mediated by GABAA α3 receptors, which SAN711 targets.

SAN711 also has the potential to become a novel and revolutionizing non-narcotic treatment concept for chronic pain conditions such as neuropathic pain, which has proven to be notoriously difficult to manage. It is estimated that 40-60% of patients do not respond to existing drugs and that the responders only achieve partial pain relief.

Narcotic analgesics such as morphine are effective for acute treatment of neuropathic pain, but patients need higher and higher doses to maintain pain relief due to tolerance development. In addition, the abuse potential of narcotic analgesics has proven to be a major problem for treatment of chronic neuropathic pain. As opposed to morphine, the effect of SAN711 is maintained after chronic treatment in neuropathic pain models. Moreover, SAN711 appears to be very well tolerated without abuse liability and other side effects such as drowsiness, dizziness and somnolence seen with strong analgesic.

Chronic itching/pruritus

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.

Neuropathic pain

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. Major indications include chronic low-back pain, painful diabetic neuropathy, post herpetic neuralgia (following shingles), neuropathic cancer pain and HIV related neuropathic pain. 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. The market for neuropathic pain is estimated to be approximately US$4 billion with an anti-epileptic drug being the current market leader. 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 only achieve partial pain relief, 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.