Sirnaomics Ltd., a leading biopharmaceutical company in discovery and development of RNAi therapeutics, recently announced that its scientific research team has published significant findings in the prestigious international journal NAR Cancer (2026, Vol. 8, DOI: 10.1093/narcan/zcag002).

 

The study details the success of STP355, a novel dual-targeting siRNA nanoparticle therapy designed to inhibit TGFβ1 and VEGFR2. In in vivo melanoma experiments, STP355 demonstrated superior therapeutic efficacy by significantly inhibiting tumor growth and metastasis while enhancing the immune system's attack on tumors. Notably, the therapy exhibited a safety profile far exceeding that of traditional chemotherapy, offering a revolutionary potential solution for the treatment of advanced melanoma.

 

 

Melanoma remains the most aggressive form of skin cancer, with incidence rates rising globally. Patients with advanced stages often suffer from multi-organ metastasis (lung, liver, brain, bone) and face a poor prognosis, with a 5-year survival rate of less than 30%. While immune checkpoint inhibitors have improved outcomes, a significant number of patients still face challenges regarding drug resistance and disease progression, creating an urgent need for therapeutic modalities with novel mechanisms of action.

 

STP355 utilizes an innovative dual-targeting strategy to simultaneously silence two critical targets within the Tumor Microenvironment (TME):

 

• TGFβ1: A core molecule in tumor immune suppression that hinders immune cell infiltration and promotes metastasis.

 

• VEGFR2: A key regulator of tumor angiogenesis; its overexpression drives the formation of new blood vessels that supply nutrients for tumor growth and spread.

 

The research team successfully screened and identified high-efficiency siRNA sequences with 100% homology across human, mouse, and non-human primate species, laying a solid foundation for clinical translation.

 

To achieve efficient delivery, the two specific siRNAs were encapsulated using Sirnaomics' clinically validated Polypeptide Nanoparticle (PNP) vector. Upon intravenous injection, the STP355 nanotherapeutic precisely targets the TME to achieve synchronous silencing of both targets.

 

Key Findings in Melanoma Models:

 

Superior Efficacy: Compared to the traditional chemotherapy drug Cisplatin (which reduced tumor weight by 61%), STP355 achieved a significant reduction in tumor weight of 70%.

 

Enhanced Safety: While Cisplatin caused a 10% weight loss in subject mice, the STP355 group maintained stable body weight with no obvious toxic side effects.

 

Survival & Metastasis: STP355 increased the survival rate from 0% (control group) to 100% and reduced lung metastatic burden by over 50%.

 

 

Synergy with Immunotherapy

A critical finding of the study is STP355’s ability to remodel the immune microenvironment. Treatment resulted in a nearly 4-fold increase in the infiltration of immune cells (including T cells and Natural Killer cells) into tumor tissue.

 

Furthermore, when combined with immune checkpoint inhibitors (such as PD-L1 or CTLA4 antibodies), STP355 demonstrated a synergistic effect, achieving a tumor inhibition rate of up to 73%, far surpassing single-agent immunotherapy (maximum 50%). This suggests a promising new strategy for overcoming immunotherapy resistance.

 

 

Management Commentary

"The publication of this research further validates the universality, efficacy, and safety of the company’s PNP delivery platform," stated Dr. Weiwei Tian, Vice President of R&D at Sirnaomics. "It confirms that the PNP technology platform is safe and possesses definitive efficacy for systemic administration in the treatment of solid tumors. We will continue to advance the application of this technology platform in the development of novel small nucleic acid drugs."

 

Future Outlook

The innovative dual-targeting design and the application of the PNP carrier address the technical bottlenecks of in vivo siRNA delivery while significantly reducing immunogenicity. With STP355 sequences being highly conserved across species, the path for subsequent development is streamlined.

 

Currently, STP355 has completed multiple preclinical studies demonstrating excellent efficacy and safety. The research team will next proceed with toxicology and pharmacokinetics studies in non-human primates, laying the groundwork for human clinical trials. This achievement not only opens a new path for melanoma treatment but also serves as a vital reference for RNA interference therapies in other solid tumors, potentially expanding the application of nucleic acid drugs in oncology.