Science & technology


Pancreatic ductal adenocarcinoma is the most common pancreatic neoplasm, responsible for 95% of pancreatic cancer cases. It evolves from a progressive cascade of cellular, morphological and architectural changes, which are associated with somatic mutations in oncogenes and tumor suppressor genes.

Most notably, almost all pancreatic ductal adenocarcinomas involve mutations in the K-RAS oncogene, with the vast majority of them are gain-of-function mutations at codon 12 of the oncogene. Substitution of the Glycine at codon 12 to aspartate (G12D) is the most common K-RAS mutation in human pancreas adenocarcinoma. In pancreatic ductal adencarcinoma, the cancer cells are addicted to the expression of the mutated K-RAS.

Out of the 13 patients evaluable for efficacy measures, patients showed very promising efficacy signs in all measures: extended progression free survival period compared with historical data, disease stability or tumor response on CT imaging in all patients, tumor marker CA 19-9 response in the majority of the patients, and extended median overall survival of 15 months based on a predictive Kaplan-Meier analysis. (Golan et al 2015 )

Based on this Phase 1 study, the company nearly coming multinational Phase 2 study is planned to assess the response rate of the investigational agent siG12D-LODER  in patients with unresectable locally advanced pancreatic cancer. Phase 2 is a single dose study, of 2.8mg (eight high-dose 350ug siG12D-LODERs) to be administered combined with chemotherapy treatment (Gemcitabine + nab Paclitaxel).