Sirnaomics Announces Major Advancement in Novel Oligonucleotide-Chemodrug Conjugate (ODC) Platform

On June 14, 2024, Sirnaomics Ltd. announced that the group had published significant progress on its novel oligonucleotide-drug conjugate (ODC). The ODC demonstrated potent anti-tumor activity in various tumor cell lines and a mouse model of pancreatic cancer. This research was published in the latest issue of the Journal of Cancer Research and Treatment (June 2024: p1-16, Volume 9, Issue 02). This breakthrough work lays a solid foundation for the company’s RNAi-based cancer therapeutics program, which utilizes a proprietary antibody-oligonucleotide-drug conjugate (AODC) platform.

The published results are an extension of prior research (NAR Cancer, 2020, Vol. 2, No. 3, p1-12). Using a proprietary anticancer ODC agent, which contains double-stranded siRNA targeting CHK1 mRNA, the double-stranded siRNA incorporates gemcitabine into its sense strand in place of cytidine. Gemcitabine (a small-molecule anticancer drug) synergizes with CHK1 inhibitors, increasing the combined IC50 by approximately 100-fold across various cell lines. In the latest study, the ODC construct includes chemically modified bases to enhance stability, improving the potency and efficacy of anti-CHK1 gene expression. In vitro testing demonstrated potent antitumor activity of gemcitabine-containing CHK1-specific siRNA using pancreatic, NSCLC, TNBC, and ovarian cancer cell culture models. The construct also showed efficacy against pancreatic tumors in mouse xenograft models—eliminating tumors when administered intravenously using Sirnaomics' proprietary polypeptide nanoparticle formulation.

"Antibody-drug conjugates (ADCs) have demonstrated exceptional specificity and efficacy in cancer treatment. Sirnaomics aims to leverage the similar advantages of its ODC structure to enhance the potency or duration of small-molecule therapies. Many small-molecule drugs initially show effectiveness but later encounter resistance due to tumor cells upregulating the expression of certain proteins. Identifying these proteins and designing specific siRNAs targeting them offers a powerful approach to overcoming resistance induced by these chemotherapeutic agents," said Dr. David Evans, Head of Discovery Research at Sirnaomics and the corresponding author of the publication. "Constructing oligonucleotide-drug conjugates (ODC) will minimize resistance, enhance the efficacy of chemotherapeutic agents, and reduce their systemic toxicity. Combined with antibody-derived targeting properties, this creates a new drug modality for improving cancer treatment—antibody-oligonucleotide drug conjugates (AODC)."

Dr. Yang Lu, Founder, Chairman, and CEO of Sirnaomics, stated: "The latest advancements in Sirnaomics' proprietary ODC formulation demonstrate the company's ongoing innovation and efforts in novel cancer RNAi therapies, while also advancing our clinical research on STP705 for skin cancer, STP707 for solid tumors, and STP122G for anticoagulation therapy. We hope that Sirnaomics' AODC formulation will achieve great success in ADC.""On the basis of providing an alternative method for treating various cancers and bringing about extensive collaboration opportunities."

About STP888

An Oligonucleotide Drug Conjugate (ODC) Targeting the CHK1 Gene – A CHK1 siRNA Duplex Containing Gemcitabine (STP888), Has Demonstrated Synergistic Anticancer Effects with Small Molecule Gemcitabine. Upon conjugation, mRNA is degraded, ultimately reducing the protein level of CHK1. The sense strand is degraded, releasing gemcitabine, thereby observing a synergistic effect. The stable chemical structure allows for direct targeting of tumor cells (leaving adjacent normal cells unaffected), which will enhance efficacy and reduce toxicity. Sirnaomics will utilize this structure conjugated with an antibody (targeting markers that are upregulated in tumors but not in normal cells) for delivery.

AboutSirnaomics

Sirnaomics is an RNA therapeutics biopharmaceutical company with its 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 have a significant market presence in both Asia and the United States.