Pipeline

Ulcerative colitis (UC) and Crohn’s Disease are chronic inflammatory bowel diseases (IBD). Whereas Ulcerative colitis affects the large intestine including the colon and rectum causing inflammation in the innermost lining of the intestine, Crohn’s disease may develop anywhere in the BI tract from the mouth to the anus although it most commonly occurs at the end of the small intestine.

IBD affects men and women equally and although it may occur at any stage of life, it most often starts between the ages of 15 – 35. The causes are not fully understood but it is thought that a combination of genetics, environment and an overactive immune system are the culprits. While both diseases are chronic and require treatment over a patients’s lifetime they may vary in severity.

In the United States alone there are more than 3.5 million sufferers and current therapies benefit only a small fraction of the population. The current treatments of 5-ASA, cortiosteroids, immunomodulators, TNF-a inhibitors monocolonal antibodies (a4-integrin blockers) result in only a 30% refractory rate, induce sever side effects and have a high cost.

PafosPharma focuses on ulcerative colitis, an idiopathic chronic recurrent inflammatory condition that affects the colon. AM11095, a NAAA inhibitor, has shown effectiveness in preclinical models of Ulcerative Colitis (UC) and Crohn’s disease (CD). In colitis mouse models as well as in human biopsies it exhibited significant depression of inflammatory biomarkers. In treatment of TNBS-induced colitis mice NAAA has been shown to down regulate pro-inflammatory mediators and reduces systemic inflammation. In biopsies obtained from the most inflamed areas of the human colon or ileum AM11095 induced significant cytokine downregulation in mucosal expalants. Pafos is continuing its collaboration with a major hospital in testing human samples.

In the United States alone it is estimated that over 20 million people over the age of 12 have an addiction (these numbers exclude tobacco addiction). Progress in neurobiology has demonstrated that addictions are chronic diseases of the brain, similar to CNS pathologies such as depression of schizophrenia, involving several neuromediators and neuroreceptors in the endorphin, dopamine and other neurotransmitter pathways. In rodents and non-human primates we have shown that medication developed in our laboratory can be used as medications for addictive disorders for nicotine, cannabis and opium as well as alcohol. The new AM compounds are CB1 selective neutral antagonists that lack the undesirable effects of earlier designed CB1 antagonists. Our novel compounds exhibit a positive safety profile. AM4113 is in advanced preclinical development.

PTSD is a serious problem with estimates that it affects between 3.5% to as much as 8% (approximately 25 million people) of the population of the United States. Also, women are twice as likely as men to develop PTSD. Due to lack of treatment, misdiagnosis, and high utilization of healthcare services such as psychiatric treatments, the current estimated burden on the United States is 42.3 Billion annually. PTSD is also associated with a high co-morbidity rate with depression, alcoholism or substance abuse.

Currently there are few marketed treatments available for PTSD. One current treatment is clinically effective but limited in use due to CNS side effects and potential for abuse.

PafosPharma’s AM10843 is a highly potent CB1/CB2 receptor agonist. It is designed to incorporate “controlled-deactivation” methodology by controlling ADME properties while maintaining the desired biological activity. This decreases the potential for abuse while it improves PK/PD properties, and the compound has improved side effects when compared with others currently on the market.

Neuropathic pain results from a pathological abnormality in the nervous system itself. Treatment for the management of neuropathic pain is one of the greatest challenges facing today’s medical practice. Approximately 1.5% of the population (2.8 million people) in the United States suffers from moderate to severe neuropathic; pain associated with back pain, diabetic neuropathy, carpal tunnel syndrome, complex regional pain syndrome, HIV/AIDS neuropathy, phantom limb pain, spinal cord injury, post-herpetic neuralgia, trigeminal neuralgia, and neuropathic pain associated with cancer chemotherapy. A novel class of drugs, selective CB2 receptor agonists have demonstrated analgesic activity in preclinical animal models of nociceptive, inflammatory and neuropathic pain. Because this class of cannabinoid receptors is found outside the central nervous system, CB2 receptor agonists are anticipated to be devoid of the CNS side effects that are associated with non-specific and CB1 cannabinoid receptor agonists.

In the treatment of pain and inflammatory conditions, CB2 agonists activate the CB2 cannabinoid receptor in the periphery. CB2 receptors are not present in the brain in any significant extent and CB2 agonists produce none of the psychotropic effects that are characteristic of on selective cannabinoid agonists.

PafosPharma’s novel CB2 agonists bind selectively to the CB2 receptor and are active in models of neuropathic, inflammatory and peripheral pain and have exhibited a positive safety profile: (i) Highly selective for the CB2 receptor; (ii) No undesirable psychotropic effects; (iii) no gastrointestinal effects; (iv) no immunosuppressive effects; (v) no issues with tolerance; and (iv) exhibit a favorable toxicity profile.