Sirnaomics, Inc. (www.sirnaomics.com), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, has published results of research obtained with its research and clinical collaborator - Shanghai 9th People’s Hospital, China. The manuscript is titled “Simultaneous silencing of TGF-β1 and COX-2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis” (Oncotarget, September, 2017). The study demonstrated dual-targeted gene silencing of TGF-β1 and COX-2 in human skin hypertrophic scar (HTS) primary cell and an HTS tissue implanted mouse model. This simultaneous silencing results in down regulation of a fibrosis biomarker and HTS reduction through activation of fibroblast apoptosis.
Dr. Patrick Lu, the President and CEO of Sirnaomics, commented: "This published result represents a collaborative effort between Sirnaomics scientists and our academic counterpart, to reveal the mechanism of action of a novel siRNA therapeutic product through a series of diligent experiments. We observed a synergistic effect when both TGF-β1 and COX-2 were silenced in human hypertrophic scar tissue and a significant reduction of the scar size.” Dr. Lu added, “This scientific achievement demonstrated the power of our Polypeptide Nanoparticle (PNP) delivery platform for RNAi therapeutic development.”
Professor Qingfeng Li from Shanghai 9th People’s Hospital, China and the co-senior author of the research article noted, “this drug candidate based on siRNA technology is one of the most effective agents towards hypertrophic scar reduction in our hands. It holds tremendous potential for treatment of the many patients suffering hypertrophic scar conditions and represents a solution to an unmet clinical need. We are excited to see this product progress into the clinical stage, and looking forward to its use in clinic practice.”
“It is critically important to have a clear understanding of the product candidate mechanism of action at the earliest possible stage in the product life cycle. This is a landmark pre-clinical study for Sirnaomics as we have been able to demonstrate not only target gene knockdown but also downstream biomarker reduction and subsequent cellular changes with fibroblast apoptosis. In this study we also see a positive result in the human Xenograft model with significant Hypertrophic scar reduction.” Dr. Michael Molyneaux, the Chief Medical Officer of Sirnaomics further emphasized, “The knowledge gained from this study has allowed us to expand the indications and therapeutic applications of STP705 that will be reported in the coming months.”
About Hypertrophic Scar
Hypertrophic scar formation is a major clinical problem in the developing and industrialized world. Burn injuries, traumatic injuries, and surgical procedures can give rise to exuberant scarring that results in permanent functional loss and the stigma of disfigurement. Hypertrophic scars form as a result of aberrations of physiologic wound healing and may arise following any insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patient’s quality of life, both physically and psychologically. Pathophysiology of hypertrophic scars entails a prolonged inflammatory and proliferative phase of wound healing after injury. Among various cytokines promoting hypertrophic scar formation TGF-β1 is known as a key regulator of the aberrant fibrogenic response, while COX-2 is a potent proinflammatory and proliferative mediator.
STP705 is composed of two siRNA oligonucleotides, targeting TGF-β1and COX-2 mRNA respectively, and formulated in nanoparticles with Histidine-Lysine Co-Polymer (HKP) peptide. Each individual siRNA was demonstrated to inhibit the expression of their target mRNAs and combining the two siRNA’s produced a synergistic effect that diminished pro-fibrogenic factors. Molecular analyses of the effects of administering the combination demonstrated that the inhibition of these targets had effects on downstream gene products associated with fibrosis including: α-SMA, Col1A1, and Col3A1. Additional data suggests that reductions in TGF-β1 and COX-2 led to proapoptotic effects in fibroblasts. This data also suggests that STP705 has the potential for broad application in many inflammatory and fibrotic driven disease states. The route of administration for STP705 for Scar Reduction will be via intradermal injection. The product based on this publication, STP705 or COTSIRANIB, is currently in a clinical Phase IIa study for Hypertrophic Scar Treatment in the US, and is approved for Phase I study in China. The paper can be obtained from following website: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path=20869&author-preview
About Sirnaomics, Inc.
Sirnaomics, Inc., a leading privately held biopharmaceutical company for discovery and development of RNAi therapeutics, is a Delaware corporation headquartered in Gaithersburg, Maryland, USA, with subsidiaries in Suzhou and Guangzhou, China. The company’s mission is to alleviate human suffering and advance patient care in areas of high unmet medical need. Members of the senior management team have extensive experience in the biopharmaceutical, financial, clinical and business management arenas in both the USA and China and the company is supported with funding from private investors, corporate partnerships and government grants. Sirnaomics has developed a strong portfolio of intellectual property with an enriched product pipeline. The therapeutic areas of interest include anti-fibrotic and anti-inflammatory disease states as well as cancer.
Michael Molyneaux, MD, MBA
Chief Medical Officer