HONG KONG, GERMANTOWN, Md. and SUZHOU, China, June 13, 2024 /PRNewswire/ -- Sirnaomics Ltd. (the "Company"; together with its subsidiaries, "Sirnaomics" or the "Group"; stock code: 2257), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, today announced that the Group has published a major advancement of its novel Oligonucleotide-Chemodrug Conjugate (ODC) agent. The ODC demonstrated potent antitumor activity in multiple tumor cell lines and a pancreatic tumor model in mice. The work was published in the latest issue of Journal of Oncology Research and Therapy (06, 2024: p1-16, Volume 9, issue 02). This groundbreaking work creates a solid foundation for the Company's RNAi-based cancer therapeutic program using a proprietary Antibody-Oligonucleotide-Chemodrug Conjugate (AODC) modality.

The published results are the extension of prior work (NAR Cancer, 2020, Vol. 2, No. 3. p1-12) using a proprietary anticancer ODC agent comprising a double-stranded siRNA targeting CHK1 mRNA incorporating gemcitabine into its Sense Strand in place of Cytidines. Gemcitabine (a small molecule anticancer drug) is synergistic with CHK1 inhibition increasing the IC50 of the combination about 100-fold in different cell lines. In the latest work, the ODC construct contained chemically modified bases to improve stability and this construct improved potency and efficacy against CHK1 gene expression. In vitro tests have shown potent antitumor activities of gemcitabine containing CHK1 specific siRNA validated using Pancreatic, NSCLC, TNBC and Ovarian cell culture models. The construct also provides efficacy against a pancreatic tumor in a xenograft model in mice, ablating the tumor upon Intravenous administration using Sirnaomics proprietary polypeptide nanoparticle formulation.

"Antibody Drug Conjugates (ADCs) have demonstrated exceptional specificity and efficacy for cancer treatment. Sirnaomics expects to harness similar benefits with its ODC constructs, to improve potency or duration of effect of small molecule therapeutics. Many small molecule drugs show efficacy initially but encounter drug resistance later due to upregulation of certain protein expression by tumor cells. Identifying those proteins and designing specific siRNAs against these targets provides a powerful approach to overcome these chemodrug induced resistances." Dr. David Evans, Head of Discovery Research of Sirnaomics and the corresponding author of the publication, indicated, "Building an oligonucleotide-drug conjugate (ODC) construct will minimize resistance and potentiate chemodrug efficacy, while reducing systemic toxicity of the chemodrug. Together with an antibody derived targeting property, this will provide a novel drug modality Antibody Oligonucleotide Drug Conjugate (AODC) for improvement of cancer treatment."