Sirnaomics Shows Strong Antitumor Activity of New Oligonucleotide-Chemo

Sirnaomics Ltd., a pioneering biopharmaceutical company in RNAi therapeutics, recently announced a significant breakthrough with its novel Oligonucleotide-Chemodrug Conjugate (ODC) agent. This breakthrough has been documented in the latest edition of the Journal of Oncology Research and Therapy. The ODC has shown remarkable antitumor activity in various tumor cell lines and a pancreatic tumor model in mice, laying a strong foundation for Sirnaomics' RNAi-based cancer therapeutic program using its proprietary Antibody-Oligonucleotide-Chemodrug Conjugate (AODC) modality.

Building on previous research published in NAR Cancer in 2020, Sirnaomics' current study continues to advance its anticancer ODC agent. The agent comprises a double-stranded siRNA that targets CHK1 mRNA, replacing cytidines in the sense strand with gemcitabine, a small molecule anticancer drug. This combination significantly enhances the IC50 value by approximately 100-fold in different cell lines, signifying its potent efficacy.

The latest research utilizes chemically modified bases within the ODC construct to improve stability, thereby increasing its potency and efficacy against CHK1 gene expression. In vitro tests have demonstrated strong antitumor activities of the gemcitabine-containing CHK1 specific siRNA, validated through various cell culture models, including Pancreatic, NSCLC, TNBC, and Ovarian. Furthermore, the construct has shown efficacy in a pancreatic tumor xenograft model in mice, effectively abating the tumor when administered intravenously using Sirnaomics' proprietary polypeptide nanoparticle formulation.

Dr. David Evans, Head of Discovery Research at Sirnaomics and corresponding author of the publication, emphasized the potential of oligonucleotide-drug conjugates (ODCs) in enhancing the efficacy and duration of small molecule therapeutics. He pointed out that many small molecule drugs initially show effectiveness but eventually encounter resistance due to the upregulation of certain protein expressions by tumor cells. By identifying these proteins and designing specific siRNAs to target them, the ODC constructs can overcome such resistance, minimize systemic toxicity, and potentiate the efficacy of chemodrugs.

Dr. Patrick Lu, founder, Chairman, and CEO of Sirnaomics, highlighted the company's commitment to innovation in RNAi therapeutics. He stated that the latest advancement of Sirnaomics' proprietary ODC agent underscores the company's continuous efforts in developing novel cancer treatments. He also noted the ongoing clinical studies of STP705 for skin cancer, STP707 for solid tumors, and STP122G for anticoagulation therapy. Dr. Lu expressed optimism that Sirnaomics' AODC agents could offer an alternative approach to cancer treatment, inspired by the success of ADCs, and could open up extensive partnership opportunities.

An exemplar of this novel approach is STP888, an Oligonucleotide-Drug Conjugate (ODC) that targets CHK1 with a siRNA duplex containing gemcitabine. This conjugate works by degrading CHK1 mRNA, subsequently reducing CHK1 protein levels. The sense strand's degradation releases gemcitabine, thereby enabling a synergistic anticancer effect. The chemically stabilized construct allows for precise targeting of tumor cells, enhancing efficacy and reducing toxicity. Sirnaomics plans to couple this construct with antibodies against tumor-specific markers, forming the basis for Antibody Oligonucleotide-Drug Conjugates (AODC).

Sirnaomics Ltd. is a clinical-stage RNA therapeutics company, holding a leadership position in advancing RNAi therapeutics for oncology applications. With a robust presence in both Asia and the United States, the company leverages proprietary delivery technologies, including Polypeptide Nanoparticle Formulation and the second generation of GalNAc conjugation. Sirnaomics' current clinical programs include STP705 (Phase IIa, IIb), STP707 (Phase I), and STP122G, which is the first drug candidate of GalAhead™ technology to enter clinical development, showing promising therapeutic efficacy and safety.