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."
Dr. Patrick Lu, the founder, Chairman and CEO of Sirnaomics, comments, "The latest advancement of Sirnaomics proprietary ODC agent demonstrates the Company's continuing innovative effort for novel cancer RNAi therapeutics, while pushing our clinical studies of STP705 for the treatment of skin cancer, STP707 for the treatment of solid tumors and STP122G for anticoagulation therapy. We expect Sirnaomics' AODC agents will provide an alternative approach to treat various cancers based on tremendous success of ADCs and bring broad partnership opportunities."
About STP888
An example of an Oligonucleotide-Drug Conjugate (ODC) - CHK1 siRNA duplex containing Gemcitabine (STP888) targets the gene CHK1 which has been shown to synergize with the small molecule Gemcitabine in inducing anticancer efficacy. Upon binding, the mRNA is degraded and eventually the protein level of CHK1 is reduced. The Sense strand is degraded, releasing the gemcitabine and allowing the synergistic effect to be observed. The chemically stabilized construct will allow direct targeting to tumor cells (leaving adjacent normal cells) which will improve efficacy and reduce toxicity. Sirnaomics will pursue delivery using this construct coupled to an antibody against markers upregulated in the tumor but not in normal cells. This will be the foundation of Antibody Oligonucleotide-Drug Conjugates (AODC).
About Sirnaomics Ltd. (Stock Code: 2257)
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 Asia and the United States. Based on its proprietary delivery technologies: Polypeptide Nanoparticle Formulation and the 2nd generation of GalNAc conjugation, the Group has established an enriched drug candidate pipeline. Sirnaomics is currently holding a leadership position on advancing RNAi therapeutics for oncology application with multiple successes of its clinical programs for STP705 (Phase IIa, IIb) and STP707 (Phase I). The ongoing Phase I study of STP122G represents the first drug candidate of GalAhead™ technology entering clinical development with an encouraging therapeutic efficacy and safety readouts for the first two cohorts. Learn more at: www.sirnaomics.com.
source: Sirnaomics
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