Neoplastic Cell Transformation

Sirnaomics Ltd. (the "Company" or "Sirnaomics", stock code: 2257.HK), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, announced the start of a Phase I clinical trial for evaluation of the safety, tolerability and anti-tumor activity of the Company's siRNA (small interfering RNA) drug candidate, STP707 with intravenous (IV) administration in the United States. The first two patients in the clinical trial have received treatment. The Phase I clinical trial, a multi-center, open label, dose escalation and dose expansion study, will evaluate the safety, tolerability and anti-tumor activity of STP707. Thirty participants with advanced solid tumors, who have been unresponsive to standard therapies, will be enrolled in dose escalation. Once maximum tolerated dose or recommended Phase II dose has been established, up to 10 additional patients will be enrolled to confirm safety and explore anti-tumor activity. The study encompasses five cohorts who will receive one of five escalating doses of STP707 through IV administration on a 28-day cycle. The primary endpoints are to determine maximum tolerated dose and establish dosage recommendations for future Phase II studies. Additional secondary endpoints are to determine the pharmacokinetics of STP707, and to observe preliminary antitumor activity. "The first dosing of STP707 in patients with hepatocellular carcinoma and other types of solid tumors through IV administration is a significant milestone as we seek to advance this novel siRNA therapeutic, which has demonstrated promising activity in our preclinical efficacy and safety studies," said Patrick Lu, Ph.D., founder, chairman of the Board, Executive Director, President and CEO of Sirnaomics. "Our goal is to take advantage of polypeptide nanoparticle (PNP) formulated siRNA therapeutics for unmet clinical needs, specifically in the areas of oncology and fibrotic diseases. The Company is inspired to lead the RNAi community in development of novel oncology therapeutics, and initiating this study helps us work towards achieving that." "Sirnaomics' mission is to leverage research in RNAi therapeutics to develop drug candidates, which includes STP707, that are able to solve critical unmet needs for patients with a variety of cancers," said Michael Molyneaux, M.D., Executive Director and Chief Medical Officer at Sirnaomics. "With the start of this Phase I clinical trial, we can expand our therapeutic reach using IV administration as a modality. In doing so it opens us up to more opportunities to explore the impact of STP707, including the appropriate dosage and anti-tumor activity that we've already seen in previous studies." STP707 takes advantage of a dual-targeted inhibitory property and a PNP-enhanced targeted delivery to solid tumors and metastatic tumors via intravenous administration. An initial preclinical study has demonstrated that simultaneously knocking down TGF-β1 and COX-2 gene expression in the tumor microenvironment increases active T cell infiltration. A further combination study demonstrated synergistic antitumor activity between STP707 and a PD-L1 antibody using a mouse orthotopic liver cancer model. About STP707 STP707 is composed of two siRNA oligonucleotides, targeting TGF-β1 and COX-2 mRNA respectively, formulated in nanoparticles with a Histidine-Lysine Co-Polymer (HKP+H) peptide as the carrier. The specific carrier peptide is distinct from the carrier used in Sirnaomics' STP705 product. 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-inflammatory factors. Over-expression of TGF-β1 and COX-2 have been well-characterized in playing key regulatory roles in tumorigenesis. In preclinical studies with STP707, IV administration resulted in knock-down of TGF-β1 and COX-2 gene expressions in various organs including liver and lung. In addition, in preclinical models STP707 had antitumor activity in various solid tumor types. About Sirnaomics Sirnaomics is an RNA therapeutics biopharmaceutical company with product candidates in preclinical and clinical stages that focuses on the discovery and development of innovative drugs for indications with medical needs and large market opportunities. Sirnaomics is the first clinical-stage RNA therapeutics company to have a strong presence in both China and the United States, and also the first company to achieve positive Phase IIa clinical outcomes in oncology for an RNAi therapeutics for its core product, STP705.