TRK-820 (AC-820)

The most advanced program in Acologix is TRK-820 or AC-820, a highly selective kappa-opioid receptor agonist. The primary clinical indication of this compound is uremic pruritus, a severe systemic itch in kidney dialysis patients. According to the latest published research by DOPPS, or Dialysis Outcome and Practice Patterns Study, over 40% of dialysis patients suffer from this condition. This study involved over approximately 38,000 hemodialysis patients in 12 nations including Australia, Belgium, Canada, France, Germany, Italy, Japan, New Zealand, Spain, Sweden, the United Kingdom, and the United States. The severe itching in uremic pruritus patients can have a profound effect on their quality of life such as sleep. The DOPPS report demonstrated that the sleep disturbance by uremic pruritus significantly increases the mortality of the population (p<0.0001). Thus, treatment of pruritus in this population is more than just treating an “itch”. There are currently no U.S. Food and Drug Administration-approved therapies to address this condition. According to the United States Renal Data System, or USRDS, there were approximately 485,000 end stage renal diseases, or ESRD patients in the United States in 2005, with approximately 341,000 of these individuals receiving dialysis therapy.

TRK-820 has been evaluated in multiple clinical studies including the ones to treat uremic pruritus patients. In the latest pivotal Phase III clinical study conducted by Toray in Japan, TRK-820 demonstrated a highly significant reduction in itching intensity in uremic pruritus patients. In a separate long term study with uremic pruritus patients, TRK-820 exhibited high safety profile. Based upon these results, Toray filed for approval in Japan and anticipate the first regulatory approval on this molecule in the world. A similar Phase III clinical study is being prepared by Acologix in the United States and planned for 2008.

TRK-820 is believed to send an anti-itch signal by binding on kappa-opioid receptor. Therefore, it could reduce itching intensity regardless of their reasons. There are many diseases that are known to associate with severe itching such as a subpopulation of severe liver cirrhosis, eczema, psoriasis, and some cancer and infectious diseases. A typical effect of such severe itching is sleep disturbance of those patients. Acologix expects that TRK-820 could be useful to treat such other itch diseases than uremic pruritus and plans to explore its efficacy outside of renal fields.