On January 24, 2024 Sirnaomics Ltd. (the "Company", Stock Code: 2257, together with its subsidiaries, the "Group" or "Sirnaomics"), a leading biopharmaceutical company engaging in discovery and development of advanced RNAi therapeutics, reported that the Company published a research article with NAR Cancer (Press release, Sirnaomics, JAN 24, 2024, View Source [SID1234639459]). The article reveals a novel mechanism of action of lead RNAi cancer drug candidate, STP707, a polypeptide nanoparticle (PNP) formulation comprised of two active siRNA (small interfering RNA) inhibitors targeting TGF-β1 and COX-2 for intravenous treatment of solid tumors. The publication provides support to the company’s ongoing clinical studies and a strong rationale for combination treatment with immune-checkpoint inhibitors.
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The published study, ‘Codelivery of TGFβ and Cox2 siRNA inhibits HCC by promoting T-cell penetration into the tumor and improves response to Immune Checkpoint Inhibitors’ demonstrates how PNP delivered the siRNA to multiple cell types besides hepatocytes in the liver. It also demonstrates that STP707 can simultaneously deliver the siRNAs targeting TGF-β1 and COX-2 to tumor cells. Systemic administration of the PNP packaged with dual-targeted siRNAs (2mg/kg) in mice bearing orthotopic hepatocellular carcinoma (HCC) tumors induced tumor growth inhibition to an undetectable level. A combination study with a lower dosage of the siRNAs (1mg/kg) and PD-L1 mAbs revealed an additive effect on tumor growth inhibition and an increase in penetration of CD4+ and CD8+ T-cells into the tumor microenvironment. These study results provide a scientific rationale for further exploration using STP707 for the treatment of HCC and potentially other solid tumors.
"By publishing Sirnaomics’ pioneering efforts in cancer RNAi therapeutics with the leading peer-reviewed journal in the field of nucleic acid therapeutics, it demonstrates strong scientific rationale for developing STP707," said Dr. Patrick Lu, Founder, Chairman of the Board, Executive Director, President and Chief Executive Officer of Sirnaomics. "The newly described mechanism of action of dual-targets TGF-β1 and COX-2 siRNAs for enhancing antitumor immunogenicity provides further scientific foundation for recent successes from our Phase I clinical study for STP707, as a single drug and, potentially, in combination with immune check point inhibitors."
The corresponding author of the publication, Dr. David Evans, Executive Director and Head of Discovery of Sirnaomics, commented, "The discovery from this study illustrates for the first time that silencing both TGF-β1 and COX-2 simultaneously in the tumor microenvironment may enhance antitumor activity through recruitment of activated CD4+ and CD8+ T-cells. Tumor inhibition is further augmented when an immune checkpoint inhibitor is added to STP707."