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Roberto Guerciolini, M.D."The biggest challenges in developing siRNA-based therapies are getting siRNAs inside cells and making sure they are stable to ensure a long-lasting effect. In our Phase 1 clinical trial of Sirna-027, we were able to halt the progression of the disease and in over half of the patients improve the ability to read letters on the eye chart. Successes such as these engender the kind of excitement that occurs when one is on the verge of the greatest medical breakthroughs"

– Roberto Guerciolini, M.D.
Senior Vice President of Development and Chief Medical Officer

Age-Related Macular Degeneration Overview:

Age-related macular degeneration macular degenerationA condition in which the cells of the macula lutea degenerate, resulting in blurred vision and ultimately blindness. The macula is a small area at the back of the eye, near the center of the retina, at which visual perception is most acute. Macular degeneration occurs most often with increasing age (age-related macular degeneration or AMD), but there are hereditary forms of the disease that affect children and teenagers as well. For more information, visit the MD Foundation web site (http://www.eyesight.org/).(AMD)AMDAge-related macular degeneration. A form of macular degeneration seen in adults over 60 years of age, and affecting over 15 million people in the United States alone. is an ocular disorder that alters central vision by damaging the macula, the central region of the retina.retinaA multilayered, light-sensitive membrane lining the inner eyeball and connected by the optic nerve to the brain. AMD is the leading cause of blindness in the United States in people over 50 with 200,000 new cases reported each year. Worldwide, 500,000 cases are reported annually. With an aging population in the US, the market for AMD products – expected to rise to $1.7 billion by 2007 -- is open to novel therapies with greater efficacy, convenient administration and longer duration of effect.

Sirna's AMD Program:

Sirna initiated its AMD program, the company’s first pipeline program, in 2002. The goal of the AMD program was to develop and identify a lead compound to treat chorodial neovascularization neovascularizationNew blood vessel formation in abnormal tissue (such as tumor tissue) or in abnormal positions (such as growth into the retina in macular degeneration).(CNV), new blood vessel growth in and around the retina, associated with AMD. The Sirna team fulfilled this goal in the fall of 2004, when the company filed an Investigational New Drug Application (IND)INDInvestigational New Drug: A new drug, antibiotic drug, or biological drug that is used in a clinical investigation. It also includes a biological product used in vitro for diagnostic purposes. Investigational New Drug is a status given to an experimental drug after the FDA agrees that it can be tested in people. and subsequently began human clinical trials with Sirna-027 – the first chemically-optimized siRNA siRNAshort interfering RNA. An intermediate in the RNAi process in which the long double-stranded RNA has been cut up into short (~21 nucleotides) double-stranded RNA. The siRNA stimulates the cellular machinery to cut up other single-stranded RNA having the same sequence as the siRNA.to be dosed in humans. Sirna-027 targets vascular endothelial growth factor receptor 1 (VEGFR-1).

Development Status - Sirna-027:

The Sirna-027 Phase 1 clinical trial began in November 2004 and completed enrollment and dosing in November 2005. Twenty-six patients were enrolled in the single dose escalation trial with six dose cohorts. The trial demonstrated that Sirna's short interfering RNA RNARibonucleic acid. A long chain polymer of genetic material similar to DNA except that it is usually found in a single-stranded form rather than as a double helix, it is made up of the ribo nucleotides A, G, C, and U (instead of T), it is somewhat less resistant to cellular degradation enzymes than DNA, and it functions most often as a transient messenger of genetic information rather than as a permanent store-house as is the case for DNA.(siRNA) molecule targeting Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) is safe and well tolerated. Twenty-five of 26 patients (96%) showed visual acuity stabilization and 23% of those patients experienced clinically significant improvement in visual acuity eight weeks after a single injection. The trial also showed a relevant decrease in central foveal thickness measured by ocular coherence tomography (OCT), which is the first demonstration of biological activity of a siRNA in humans.

Sirna anticipates that its strategic partner, Allergan, will begin Phase 2 studies with Sirna-027 in 2006.

Single Dose Visual Acuity Changes at 8 Weeks

Partnership Status:

In September 2005, Sirna announced a $250MM strategic alliance with Allergan for the continued development of Sirna-027 and to discover and develop other novel RNAi-based therapeutics against select ocular indications. In the alliance, Allergan will assume all responsibility for the continued clinical development of Sirna-027 as well as conducting and funding all pre-clinical development, clinical, regulatory, and commercialization activities for compounds arising from the alliance. Allergan will also provide its proprietary and novel delivery technologies to the development. Sirna will develop optimized lead compounds for the alliance.

Academic Collaborators:

  • Peter Campochiaro, MD: Professor of Ophthalmology and Neuroscience, Wilmer Ophthalmological Institute, Johns Hopkins Hospital School of Medicine
© 2007 Sirna Therapeutics
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