On December 20, 2022 Sirnaomics Ltd. (Stock Code: 2257.HK) (the "Company", together with its subsidiaries, "Sirnaomics" or the "Group"), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, reported the interim results from a Phase I clinical trial evaluating the safety, tolerability and anti-tumor activity of the Company’s siRNA (small interfering RNA) drug candidate, STP707 with intravenous (IV) administration in the United States (Press release, Sirnaomics, DEC 20, 2022, View Source [SID1234625462]). This is a basket study which enrolls various solid tumor types. The analysis included the first three cohorts in a five-cohort dose escalation study.

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The multi-center, open label, dose escalation and dose expansion tumor basket study evaluates the safety, tolerability and anti-tumor activity of STP707. Twenty participants with advanced solid tumors, who have been unresponsive to standard therapies, are included in the dose escalation analysis. Once maximum tolerated dose or recommended Phase II dose has been established, additional patients will be enrolled to confirm safety and explore anti-tumor activity. The study encompasses five total cohorts who will receive escalating doses of STP707 through IV administration on a 28-day cycle including 3 mg, 6 mg, 12 mg, 24 mg and 48 mg dosing cohorts. The interim analysis involves subjects from the 3 mg, 6 mg, and 12 mg dosing cohorts. The subjects were dosed once per week for a total of 4 doses over a 28-day treatment cycle and will continue to be dosed in the study until they exhibit progressive disease. Additional secondary endpoints are to determine the pharmacokinetics of STP707 and to observe preliminary anti-tumor activity. This interim data is from the first three cohorts treated with three different doses of STP707.

"We are very excited to see STP707, our leading siRNA drug product for treatment of multiple solid tumors through an intravenous administration in which the first three cohorts with twenty patients have been completed showing strong safety profile and efficacy readouts. This is the first time that an RNAi (RNA interference) cancer therapeutic has demonstrated a very promising clinical potential for metastasized tumors. The interim data of STP707 will allow us to expand our research with additional cohorts — a positive step forward in moving this treatment into the next phase," said Dr. Patrick Lu, Founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics. "This Phase I basket clinical study result encourages us to proceed to a potential combination study with immune check point inhibitor drugs. We look forward to expanding clinical trials with STP707 that has the potential to address the unmet needs of patients with solid tumors and other cancers."

"The progress of our dose escalation STP707 solid tumor basket study is a significant milestone as we seek to advance this novel siRNA oncology therapeutic," said Dr. Michael Molyneaux, M.D., Executive Director and Chief Medical Officer of Sirnaomics. "We have passed each of the first three cohorts’ safety requirements for dose escalation and anticipate dosing our fourth cohort in the first quarter 2023. To date, STP707 has exhibited a strong safety profile when compared to other novel oncology therapeutics."

Dr. Molyneaux added, "The 20 subject data set demonstrates an encouraging efficacy signal with duration of response equal to or exceeding two treatment cycles or 56 days in 8 subjects examined over all dosing cohorts. There have also been a number of tumor types including liver, pancreatic, colon and uveal melanoma cancers that have exhibited stable disease beyond 100 days of treatment. It is important to emphasize the fact that the subjects in this study have received multiple forms of prior treatments including surgery, radiation, and tumor specific first- and second-line therapies. As all subjects demonstrated progressive disease on prior treatment regimens, this group of subjects represents a subset of resistant tumor types that have not responded to all prior therapies. It is encouraging to see very good safety combined with duration of response in such resistant tumor types, and we look forward to continuing this study."

STP707 takes advantage of a dual-targeted inhibitory property and a PNP-enhanced targeted delivery to solid tumors and metastatic tumors via intravenous administration. An initial preclinical study has demonstrated that simultaneously knocking down TGF-β1 and COX-2 gene expression in the tumor microenvironment increases active T cell infiltration. A further combination study demonstrated synergistic anti-tumor activity between STP707 and a PD-L1 antibody using a mouse orthotopic liver cancer model.

For more information about Sirnaomics’ clinical trials, please visit ClinicalTrials.gov (Identifier NCT05037149) and the Company’s website at www.sirnaomics.com.

About STP707

STP707 is composed of two siRNA oligonucleotides, targeting TGF-β1 and COX-2 mRNA respectively, formulated in nanoparticles with a Histidine-Lysine Co-Polymer (HKP+H) peptide as the carrier. The specific carrier peptide is distinct from the carrier used in Sirnaomics’ sTP705 product. Each individual siRNA was demonstrated to inhibit the expression of their target mRNAs and combining the two siRNA’s produces a synergistic effect that diminishes pro-inflammatory factors. Over-expression of TGF-β1 and COX-2 have been well-characterized in playing key regulatory roles in tumorigenesis. In preclinical studies with STP707, IV administration resulted in knock-down of TGF-β1 and COX-2 gene expressions in various organs including liver, lung and xenograft tumor. In addition, in preclinical models STP707 had shown strong anti-tumor activity in various solid tumor types. Using a mouse liver orthotopic tumor model, a combination regimen of STP707 with an immune checkpoint antibody has demonstrated a potent anti-tumor activity.