Sirna Therapeutics, Inc. has announced that it has selected Sirna-AV34, a systemically delivered, chemically modified short interfering RNA compound, as its candidate for advancement to human clinical testing against Hepatitis C virus.
Sirna completed its preclinical evaluation of the efficacy of Sirna- AV34 and has begun cGMP manufacturing for its Phase I clinical studies.
Sirna expects to initiate IND-enabling toxicology studies in the first quarter of 2006 followed by the filing of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) by the fourth quarter of 2006.
Sirna-AV34 is a systemically delivered, nanoparticle-based therapeutic targeting the Hepatitis C virus.
The compound consists of multiple individual, chemically modified, siRNA sequences which target conserved sequences in the Hepatitis C viral genome.
Sirna-AV34 is designed to inhibit viral replication and reduce the selection of drug resistant mutant variants.
The design principles used in Sirna-AV34 were validated by demonstrating reduction in escape mutation frequency in the Hepatitis C virus sub-genomic replicon system in vitro.
No existing therapeutic approach has the potential to broadly inhibit Hepatitis C viral replication while reducing the probability of drug resistant variants.
"We are extremely pleased by the significant progress of our Hepatitis C antiviral program," stated Sirna Senior Vice President and Chief Scientific Officer, Barry Polisky, PhD.
"The selection of Sirna-AV34 as our clinical candidate reflects two major accomplishments of our research team."
"The first is the design, chemical modification and synthesis of a stable and potent siRNA compound which is effective broadly against the Hepatitis C virus."
"The second is the development of a proprietary nanoparticle delivery technology capable of efficient and specific delivery of the siRNA compound to hepatocytes."
"These two achievements have provided us with a unique opportunity to bring this groundbreaking therapy to the clinic."
As previously reported in a rodent model of Hepatitis B virus used as a surrogate for Hepatitis C virus, Sirna demonstrated that a chemically optimized and encapsulated siRNA had significant antiviral activity and prolonged duration of effect in vivo.
Recent data from a non-human primate model of Hepatitis C replication demonstrated that Sirna's systemically delivered siRNA compound suppressed Hepatitis C viral titers via an RNA interference mechanism.
"We are very excited to be moving a systemically delivered siRNA towards the clinic," stated Roberto Guerciolini, MD, Senior Vice President and Chief Medical Officer.
"Since the current treatments for chronic Hepatitis C remain highly unsatisfactory, we believe that the application of a siRNA compound targeting multiple components of the viral genome will result in a significant advancement in the treatment of this disease."