RNAi therapeutic successful for treatment of SARS respiratory virus in Rhesus Macaque

Intradigm Corporation announced today its collaboration with Chinese academic and biotech groups has achieved clear evidence of prophylactic and therapeutic effects of siRNA (small interfering RNA) agents in Rhesus monkey to treat SARS coronavirus (SCV) respiratory infection.

The results are published as a research article in the September 2005 issue of Nature Medicine.

The published results show that potent siRNA inhibitors against SCV, validated in previous in vitro study (Antiviral Therapy 9:365-374), are active in vivo using a mouse model system and subsequently in a rhesus macaque (Macaca mulatta) SARS disease model, using a clinically viable delivery formulation by intranasal administration. The studies in macaques included two control groups and three treatment groups, using prophylactic, concurrent or early post exposure regimens, with a large number of animals in each group for statistically meaningful results. A pair of siRNA oligos, SC2 and SC5, targeting two different genes in the virus genome were administrated at 10 to 40 mg/kg. The numerous observations, including clinical SARS-like symptoms, lung histopathology and levels of viral RNA, confirm achievement of an siRNA- mediated inhibition of the respiratory virus and, importantly, no sign of siRNA treatment-mediated toxicity or off target effects. These results provide strong support for clinical investigation. Most importantly the results clearly illustrate the prospects for siRNA therapeutics to address unmet clinical need but also to dramatically reduce the time and cost of drug development. This capability is especially important in the critical area of newly emerging respiratory viral infections.

Nature Medicine also recognized the importance of the work in a news release entitled "New treatment against SARS effective in monkeys," which claimed that, "These results constitute the first successful therapeutic use of siRNA in primates, and significantly boost up the potential of this tool to prevent and treat SARS in people."

Dr. Patrick Lu, a corresponding author of the published paper and executive vice president of Intradigm pointed out, "The international collaborative effort was critical to the success of this study. Also, the clinically viable delivery formulation and route of administration are keys to achieve prophylactic and therapeutic efficacy of siRNA inhibitors in this non- human primate study." Dr. Martin Woodle, CSO of Intradigm, said, "The success of this study illustrates key advantages of siRNA-based therapeutic agents, including a massive reduction in discovery and development time for novel targeted therapeutics, essential for combating many emerging infectious diseases, and the coming revolution by combining siRNA sequences to allow rapid development of multi-targeted therapeutics."

"We are very excited by this Nature Medicine publication on the successful primate study with our siRNA-based antiviral therapeutics, which is further evidence that siRNA agents could become a very powerful drug modality for treatment of various diseases. With results from this study, we are more confident about our ongoing effort on ICS-283, an siRNA-based anticancer drug in late stage of preclinical development, expecting reach to the clinic in mid 2006," said John Spears, Chairman and CEO of Intradigm.

The study was conducted in collaboration and co-authored with scientists from Sun Yat-Sen University, Top Genomics, Ltd. of Guangzhou, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Guangzhou Institute of Respiratory Diseases of Guangzhou Medical College, Hong Kong University, in China, led by professors Nanshan Zhong and Bao-jian Li. This study is supported in part by Guangdong Provincial and Guangzhou Municipal Governments, and China World Trade Corporation.