Sirnaomics Publishes Novel Mechanism of Action Study for STP707, an RNAi-Based Therapy for Solid Tumors, in NAR Cancer

This study was published in the frontier peer-reviewed journal of nucleic acid therapy, *Nucleic Acid Research Cancer*.

Hong Kong, Germantown, Maryland, and Suzhou, ChinaJanuary 24, 2024/PR Newswire/ --Sirnaomics Ltd.（"Company", Stock Code: 2257, together with its subsidiaries, collectively referred to as"Group"Or"Sirnaomics"Sirnaomics, Inc.

Published in this issue"Promoting T Cell Penetration and Suppressing HCC via TGFβ and COX2 siRNA Delivery to Enhance Response to Immune Checkpoint Inhibitors"Demonstrates the mechanism of PNP delivering siRNA to various cell types in the liver other than hepatocytes and shows that siRNA delivered by STP707 to tumor cells can simultaneously target TGF-β1 and COX-2. Systemic administration of PNPs loaded with dual-targeting siRNAs (2 mg/kg) in mice bearing orthotopic hepatocellular carcinoma (HCC) tumors suppressed tumor growth to undetectable levels. A study on low-dose siRNA (1 mg/kg) combined with a PD-L1 monoclonal antibody showed that siRNAs have an additive effect on inhibiting tumor growth and further increase the infiltration of CD4+ and CD8+ T cells into the tumor microenvironment. These findings provide a scientific basis for further exploration of STP707 for the treatment of HCC and other solid tumors.

SirnaomicsFounder, Chairman of the Board, Executive Director, President and Chief Executive Officer, Dr. Yang LuIndicates:"The publication of Sirnaomics' groundbreaking research in the field of cancer RNAi therapeutics, featured in a leading peer-reviewed journal in nucleic acid therapeutics, has provided robust scientific support for the development of STP707. The novel mechanism of action described in the paper, highlighting the dual targeting of TGF-β1 and COX-2 siRNA to enhance anti-tumor immunogenicity, further strengthens the scientific foundation behind the recent success of STP707’s Phase I clinical study. STP707 can be used as a monotherapy or in combination with immune checkpoint inhibitors."

The corresponding author of this paperSirnaomicsExecutive Director and Head of Drug Development & CollaborationDavid EvansPh.D.Indicates:"The findings of this study indicate for the first time that simultaneously silencing TGF-β1 and COX-2 in the tumor microenvironment can enhance anti-tumor activity by recruiting activated CD4+ and CD8+ T cells. The addition of an immune checkpoint inhibitor to STP707 may further enhance its tumor-suppressing effects."

AboutSirnaomics Ltd. (Stock Code: 2257)
Sirnaomics is an RNA therapeutics biopharmaceutical company with candidate products in clinical and preclinical stages, focusing on exploring and developing innovative drugs for the treatment of indications with significant medical needs and large market opportunities. Sirnaomics is the first clinical-stage RNA therapeutics biopharmaceutical company to hold a significant market position in both Asia and the United States. With its proprietary delivery technologies — the peptide nanoparticle delivery platform and the second-generation GalNAc conjugate delivery platform — the group has established a very rich pipeline of drug candidates. Following multiple successes in the clinical programs of STP705 and STP707, Sirnaomics is now at the forefront internationally in advancing RNAi drugs for cancer treatment. STP122G is the first GalAhead™ technology candidate to enter clinical development. With the establishment of Sirnaomics’ clinical production facilities, the group is currently making the leap from a biotech company to a biopharmaceutical company. For more information about the company, please visit:www.sirnaomics.com。