Sirnaomics Announces Completion of STP707 Phase I Clinical Study with Strong Safety Profile and Disease Activity for the Treatment of Pancreatic Cancer Patients

HONG KONG, GERMANTOWN, Md. and SUZHOU, China, June 28, 2024 /PRNewswire/ -- Sirnaomics Ltd. (the "Company", together with its subsidiaries, the "Group" or "Sirnaomics"; stock code: 2257), a leading biopharmaceutical company engaging in discovery and development of advanced RNAi therapeutics, today announced that the Group has completed STP707 Phase I clinical study with strong safety profile and stable disease activity for treatment of pancreatic cancer patients. This is a dose escalation study conducted in 11 oncology clinics in the U.S. The study involved six cohorts, consisting of 50 patients with various cancers, of which 11 had pancreatic cancer.

In an earlier news release from the Company in August 2023, the Group noted completion of all dosing regimens for its Phase I study of STP707 for the treatment of multiple solid tumors. This basket study has enrolled patients suffering from various types of late-stage cancers and failing after multiple rounds of treatments. The study is to evaluate the safety, tolerability and anti-tumor activity of the Group's siRNA (small interfering RNA) drug candidate, STP707, through intravenous infusion (IV) with six cohorts of escalating doses. Patients including pancreatic, colorectal, liver, melanoma and other cancers, with advanced/ metastatic or surgically unresectable solid tumors, refractory to standard therapy, were recruited. Six dose levels (3mg, 6mg, 12mg, 24mg, 36mg and 48mg) were explored in ascending doses. Patients received IV infusion on Day 1, 8, 15 and 22 of a 28-days cycle.

11 pancreatic patients (five males and six females, average age 64 years) were enrolled in the study. Patients were heavily pre-treated and received, on average, three lines of therapy prior to enrollment in the study (including Gemcitabine, Paclitaxel and Folfirinox). The preliminary results indicated that the mean treatment cycles completed was three cycles (average 12 doses). The average days for stable disease for all 11 patients with STP707 treatment was 92 days, while 31 days for the 12mg group, 65 days for 24mg group and 112 days for 48mg group, including one patient ongoing at 281 days. No treatment related adverse events (TRAE) were reported for the 11 patients, except for one patient with a Grade 2 infusion reaction. Non-treatment related adverse events were secondary to their advanced metastatic disease including intestinal obstruction, abdominal distention, gastrointestinal obstruction, embolism, gastrointestinal hemorrhage, tumor pain, hypoxia and dyspnea.

The maximum tolerated dose of STP707 for all 50 late-stage cancer patients was not reached even at 48mg dosage level. STP707 was very well-tolerated in a heavily pretreated cancer patient population. The 11 pancreatic subset of patients showed low toxicity and relatively long stable disease at various dosages (106, 281 and 302 days), and warrants further study with STP707 alone or in combination with immune check point inhibitors, given the preclinical documented ability of STP707 to recruit T-cells to the tumor microenvironment (TME). This is the first time a polypeptide nanoparticle-based siRNA cancer therapeutic has demonstrated early positive safety and efficacy results for the treatment of late-stage pancreatic cancer patients.

"We are very excited to see STP707, our leading siRNA drug product for the treatment of heavily pre-treated pancreatic cancer (one of the deadliest tumor types), shows these strong results upon intravenous administration. This is a very promising result for RNAibased cancer therapeutics for the treatment of metastasized tumors." said Dr. Patrick Lu, Ph.D., Founder, Chairman of the Board, Executive Director, President and Chief Executive Officer of Sirnaomics. "The strong safety profile, long-lasting stable disease efficacy and dose-dependent antitumor activity of this intravenously administered STP707 formulation, present a potential novel cancer therapeutic, either as a single drug or in combination with immune check point inhibitor drugs."

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 antitumor 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 antitumor activity.

About Sirnaomics

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 conjugates, the Group has established an enriched drug candidate pipeline. Sirnaomics is advancing RNAi therapeutics for oncology application with multiple successes of its clinical programs for STP705 and STP707. STP122G represents the first drug candidate of GalAhead™ technology entering clinical development. With the establishment of the Group's manufacturing facility, Sirnaomics currently is undergoing a transition from a biotech company to a biopharma corporation. Learn more at: www.sirnaomics.com.