Sirnaomics, Inc., a leading biopharmaceutical company in discovery and development of RNAi therapeutics, announces today that the U.S. Food and Drug Administration (FDA) has approved the company’s first oncology IND application. The IND approval will allow for the study of the Company’s lead product candidate, STP705, in patients with advanced cholangiocarcinoma (CCA).

Sirnaomics’ lead product candidate, STP705, is an anti-cancer/anti-fibrosis siRNA (small interfering RNA) therapeutic. It takes advantage of a dual-targeted inhibitory property and a proprietary polypeptide nanoparticle (PNP)-enhanced delivery system to target cells in the liver. It acts by directly inhibiting tumorigenesis through down regulation of Cancer Associated Fibroblast (CAF) activity and cell proliferation by silencing both TGF-β1 and COX-2 gene expression within the tumor micro-environment. In 2017, STP705 was granted Orphan Drug Designation from the FDA Office of Orphan Products Development (OOPD) for treatment of Cholangiocarcinoma (CCA) and Primary Sclerosing Cholangitis (PSC). The product has also received both US FDA and Chinese FDA IND approval for Hypertrophic Scar Reduction. The dual-targeted approach of STP705 is expected to have efficacy across many diseases in multiple therapeutic areas.

“The green light from the US FDA for Sirnaomics’ first oncology IND represents another major milestone for the company’s mission in discovery and development of novel siRNA therapeutics for unmet clinical needs. Building on our company’s anti-fibrosis therapeutic approach, Sirnaomics’ drug target selection and tumor targeting delivery should support a high rate of success for novel anticancer siRNA therapeutics,” said the Founder and CEO of the company, Dr. Patrick Y. Lu. “The latest success of Alnylam’s Patisiran drug validates the RNAi class of therapeutics and it is our belief that the industry will see great enthusiasm and expanded discovery and development of novel RNAi therapeutics for many disease applications. Sirnaomics is currently in a strong position to lead the RNAi community in the development of novel Oncology and Fibrosis therapeutics.”

“Cholangiocarcinoma is a devastating form of liver cancer with very high mortality and no effective therapy.  Based on our preclinical data, we are very hopeful that STP705 will have a positive impact on this disease. This IND approval is in line with our mission to target critical diseases with high unmet clinical need,” stated Chief Medical Officer, Michael Molyneaux M.D. “We expect that our rigorous clinical study design will enable us to gain great insights into the impact of STP705 on CCA. STP705 is able to achieve excellent uptake by the liver with a very good safety profile and it is expected this study will give us insight into other forms of liver cancer and fibrosis to support further indications in both oncology and fibrosis.”

About Cholangiocarcinoma

Cholangiocarcinoma (CCA) is the second most common hepatic primary malignancy (accounting for 15-20% of liver cancer).  CCA is also known as bile duct adenocarcinoma and biliary tract cancer. Although it is more common in Asia, its incidence in Europe and North America has increased significantly in recent decades. CCA is characterized by late diagnosis and fatal outcome with 5-year survival ranges from 2-30%.  CCA is an epithelial malignancy originating from transformed cholangiocytes, with preclinical studies suggesting hepatic progenitor cells as the cells of origin. Inflammation and cholestasis are key factors in cholangiocarcinogenesis.  Studies have shown high expression of TGF-β1 which is thought to become an oncogenic factor that induces invasion, angiogenesis, proliferation, and, in certain cases, metastasis.  Cyclooxygenase-2 (COX-2) also plays a role in the pathogenesis of CCA, activating growth factors that promotes cholangiocyte growth, such as MAPK, epidermal growth factor receptor (EGFR) and interleukin 6 (IL-6).

About STP705

STP705 is composed of two siRNA oligonucleotides, targeting TGF-β1 and 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 produces a synergistic effect that diminishes pro-fibrogenic and pro-inflammatory 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. Recent literature indicates that TGF-β1 is directly related to T cell exhaustion, PD-L1 and CTLA-4 upregulation in tumor micro-environment. These observations suggest that STP705 has the potential for broad application in many fibrotic and oncogenic driven diseases. Cell culture experiments with an intrahepatic cholangiocarcinoma cell line, HuCCT-1 treated with STP705, have demonstrated a significant target knockdown and tumor cell killing. HKP enhanced siRNA delivery has demonstrated preferential distribution in liver hepatocytes, liver sinusoidal endothelial cell (LSEC) and hepatic stellate cells (HSC). Following an intravenous administration of HKP/siRNA into mouse models, the enhanced permeability and retention (EPR) effect results in accumulation in the tumor micro-environment. In vivo studies using the HuCCT-1 cell xenograft tumor model in mice treated by STP705 administration, resulted in tumor growth inhibition in a dose-dependent manner.

About Orphan Drug Designation

The Orphan Drug Act (ODA) from US FDA provides for granting special status to a drug or biological product (“drug”) to treat a rare disease or condition upon request of a sponsor. This status is referred to as orphan designation (or sometimes “orphan status”). For a drug to qualify for orphan designation both the drug and the disease or condition must meet certain criteria specified in the ODA and FDA’s implementing regulations at 21 CFR Part 316. Orphan designation qualifies the sponsor of the drug for various development incentives of the ODA, including tax credits for qualified clinical testing.

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 develop novel therapeutics to alleviate human suffering and advance patient care in areas of high unmet medical need. The guiding principles of the company are: Innovation, Global Vision with a Patient Centered focus. Members of the senior management team have a great deal of combined experience in the biopharmaceutical industry, financial, clinical and business management in both the USA and China. The company is supported by funding from institutional investors and corporate partnerships. Sirnaomics has developed a strong portfolio of intellectual property with an enriched product pipeline. The therapeutic areas of focus include oncology and anti-fibrotic therapeutics. Learn more at www.sirnaomics.com.