Sirnaomics has worked with its scientific founders and collaborators in developing siRNA therapeutic protocols using the multi-targeted siRNA cocktail approach. Several such protocols have been tested in animal disease models with very promising results for therapeutic applications. Strong ties with the Chinese biomedical community allow the progression of these products through high quality preclinical and clinical studies at low cost. In evaluating the optimal directions for application of siRNA therapeutics we take into account several key factors to determine where best to expend our effort and resources: We evaluate the potential market size for the therapeutics; we examine the advantage of siRNA therapeutics over other approaches (e.g. compared with small molecule or antibody based therapies), and we appraise the potential success of an siRNA therapeutic for a specific disease application.
Through the in-house research and development effort, and the collaboration with academic institutions, we currently have three drug candidates in the late stage preclinical development. The therapeutics areas of interests include siRNA therapeutics for skin scarless wound healing, respiratory influenza infection and ocular neovascularization diseases.
STP705 (Cutasil®) -
siRNA Therapeutics for Skin Scarless Wound Healing (SSWH)
According to The Mattson Jack Group, an independent research group, the US commercial market for reduction of scarring in the skin is valued at approximately US$4 billion a year. There are some 42 million patients each year who could potentially benefit from pharmaceuticals that prevent or reduce scarring in the skin. There are 41.8 million surgical procedures to the skin each year in Europe and 70 million procedures annually in the United States involving wounds, which could benefit from a drug that improves the appearance of the scar. Currently there are no related pharmaceuticals available in the market either in the US or Europe. Sirnaomics plans to be the first internationally to launch a marketed siRNA pharmaceutical drug for the reduction of scarring. What is needed for this space is a product that can accelerate the rate of wound closure while reducing the scar that typically forms in adult skin and which decreases the strength of the repair. Sirnaomics has demonstrated accelerated wound closure with a topically applied siRNA mixture that results in wound repair and a return of normal skin morphology (without a scar and with return of follicles). This product will have utility in treatment of wounds incurred on the battlefield, wounds from burns, or wounds from surgical intervention and may have utility in treatment of diabetic wounds – many of which require limb amputation as a cure. This product can be positioned within the armed forces for battlefield medical use, within hospitals for traumatic wounds and eventually into clinics and plastic surgery offices to improve healing in elective surgery. The candidate siRNA drug (Cutasil®) targeting both TGFβ1 and Cox-2 and packaged in HK polymer nanoparticles has been tested in mouse and swine skin excision wound models and demonstrated remarkable therapeutic benefit superior to the existing standard treatment. STP705 represents the First-in-Class drug with clear mechanism of action. It accelerates wound closure, minimizes scar formation, and decreases pain with anti-fungi activity.
STP702 (FluQuit®) -
siRNA Therapeutics against Influenza Infection (Pandemic Flu)
Our patented siRNA therapeutics (FluQuit®) shown to have efficacy against H5N1 (avian flu) have also demonstrated inhibitory activity against H1N1 (swine flu). With the recent pandemic of H1N1 the market for vaccines and therapeutics has increased dramatically in to $billions. With the rapid mutation rate of the flu virus we are seeing resistance to drugs such as amantadine and even tamiflu. Sirnaomics has licensed IP describing siRNA sequences for use in a therapeutic cocktail against flu and has identified a vehicle for administration of these siRNAs to the lung. We believe that an inhaled siRNA able to reduce viral load by preventing viral replication can capture a significant portion of the market for therapeutics in this space. Additionally, should new strains emerge (as they inevitably will), Sirnaomics will be poised to provide large numbers of doses of our drug ahead of vaccine production. We have developed siRNAs against conserved regions within the viral genome that should provide wide strain specificity and a multi-targeted siRNA cocktail will prevent escape of the virus from therapeutic pressure through mutation within a single gene segment. This antiviral approach may be applicable to other respiratory viruses such as Respiratory Syncytial Virus (RSV) infection.
STP601 (Acurita®) -
siRNA Therapeutics for AMD and Retinopathy
A multi-targeted siRNA cocktail nanoparticle formulation is developed for treatment of Age-related Macular Degeneration (AMD), Proliferative Diabetic Retinopathy (PDR) and Herpetic Stromal Keratitis (HSK), through intravitreous administration. This product has just completed a pre-IND meeting (May 14, 2008) with the USFDA and received a green light for IND enabling studies. Given a growing population of elderly and diabetics, blindness from these diseases is expected to be skyrocketing. Strong evidence suggests all arise from a similar VEGF-mediated neovascularization pathway, albeit they differ in how they are initiated and location within the eye. Thus they all are thought to be candidates for treatment by inhibiting this clinically validated pathway at the endothelial cells lining the interior of the growing blood vessels. Using small interfering RNA (siRNA) as a novel class of inhibitors, We are currently proposing a novel therapeutic approach combining three 25-mer siRNA duplexes targeting VEGF, VEGFR1 and VEGFR2 into one drug candidate, STP601, packaged with a biodegradable polypeptide formulation, for treatment of ocular neovascularization conditions including AMD, PDR and HSK. Since STP601 is an inhibitory drug blocking the production of targeted factors, it will be complementary to the existing antagonist small molecule and monoclonal antibody drugs blocking only the function of the targeted factors, in the same regimen.
STP503 (Trisilensa®) -
siRNA Therapeutics for Breast Cancer
More than 2 million women living in the U.S. have been treated for or are living with breast cancer, and more than 40,000 women are expected to die from the disease in 2006. Though breast cancer death rates are declining -- mostly due to earlier diagnosis -- the disease remains the second leading cause of cancer death in women (after lung cancer). Despite advances in detection, chemotherapy and other targeted therapeutic approaches, many women with breast cancer continue to die of this malignancy. New types of treatment are being tested in clinical trials including sentinel lymph node biopsy followed by surgery, high-dose chemotherapy with stem cell transplant, monoclonal antibodies as adjuvant therapy and tyrosine kinase inhibitors as adjuvant therapy. An attractive approach for therapeutic intervention is to inhibit all the targets along the pathways of EGFR, Raf-1 and mTOR which contribute to the breast cancer tumorigenesis. For siRNA therapeutic program STP503, we take the advantage of siRNA cocktails targeting EGFR, Raf-1 and mTOR genes as an RNAi therapeutic protocol for treatment of breast cancer. The siRNA drug will be delivered by our three generations of nanoparticle based delivery systems. This program is supported by an SBIR grant (1R43CA135958) from National Cancer Institute, National Institute of Health, with Dr. Patrick Y. Lu as the PI. This early discovery program is conducted in collaboration with Professor Luyuan Li’s Lab in University of Pittsburgh and Professor Anton Wellstein in Georgetown University, School of Medicine, Lambadi Cancer Research Center.