MT-5745 / Mitsubishi Tanabe - LARVOL DELTA

Robust pancreatic tumor suppression by a novel combination treatment with anti-PD-1 immune checkpoint antibody and stroma modifying RNA oligonucleotide STNM01 in mice. (ASCO 2024) - "The present work represents the first report of robust synergy between systemic anti-PD-1 antibody and single stroma modifying agent through intratumoral route of administration. Combination usage of STNM01 would provide a novel and clinically feasible therapeutic option to trigger remarkable effect of immune checkpoint inhibitors to this most hard-to-treat solid tumor."

Preclinical • Stroma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • FOXP3

STNM01, the RNA oligonucleotide targeting carbohydrate sulfotransferase 15, as second-line therapy for chemotherapy-refractory patients with unresectable pancreatic cancer: An open label, phase I/IIa trial. (PubMed, EClinicalMedicine) - "This was an open-label, dose-escalation study of STNM01 as second-line therapy in gemcitabine plus nab-paclitaxel-refractory PDAC...It prolonged survival by enhancing T cell infiltration in tumor microenvironment. The present study was supported by the Japan Agency for Medical Research and Development (AMED)."

Journal • P1/2 data • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8

A clinical study following phase I/IIa trial of STNM01 to investigate the overall survival and tumor microenvironment in patients with unresectable pancreatic cancer. (ASCO 2022) - "Locoregional injection of STNM01 was able to reactivate and augment tumor-infiltrating T cells while repress MDSCs. These changes in tumor immune cell profiles correlate with prolong prognosis in patients with first-line refractory, unresectable PDAC."

Biomarker • Clinical • P1/2 data • Tumor microenvironment • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD33 • CD8

LOCOREGIONAL INJECTION OF THE RNA OLIGONUCLEOTIDE TARGETING CARBOHYDRATE SULFOTRANSFERASE 15 IS ABLE TO ACCELERATE TUMOR-INFILTRATING T CELLS IN PATIENTS WITH UNRESECTABLE PANCREATIC CANCER, REFRACTORY TO FIRST-LINE CHEMOTHERAPY (DDW 2022) - "STNM01 application showed a good tolerability and safety profile. Conclusion : EUS-guided locoregional injection of STNM01 was well tolerated and able to prolong prognosis by enhancing T cell infiltration in patients with refractory, unresectable pancreatic cancer."

Clinical • IO biomarker • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8

[VIRTUAL] A phase I/IIa trial of the RNA oligonucleotide STNM01 by EUS-FNI to investigate the safety and efficacy in patients with first-line refractory, unresectable pancreatic cancer. (ASCO 2021) - "Repeated locoregional injection of STNM01 is safe and well tolerated in patients with unresectable PDAC as combined 2L therapy . The 6-month survival rate of 10,000 nM of STNM01 was 83.3%, which is remarkable compared with previously reported data . Unexpected mode of action for tumoral lymphocyte infiltration also suggests the promising potential of locoregional injection of STNM01 as a new therapeutic option for PDAC."

Clinical • P1/2 data • Gastrointestinal Cancer • Hepatology • Oncology • Pain • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD20 • CD8

Notice of discontinuation of development of nucleic acid drug "MT-5745 (STNM01)" for ulcerative colitis and occurrence of impairment loss (non-recurring item) [Google translation] (Mitsubishi Tanabe Press Release) - "Mitsubishi Tanabe Pharma Corporation...has been involved in the discontinuation of development of MT-5745 (STNM01, assumed indication: ulcerative colitis)...various non-clinical trials were conducted to supplement the data of Steric Co., Ltd. toward the start of full-scale clinical trials of ulcerative colitis. I could not confirm it and the project was canceled."

Discontinued • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Submucosal injection of the RNA oligonucleotide STNM01 in active ulcerative colitis induces mucosal healing and reverses tissue remodeling (UEGW 2017) - "In conclusion, the present study demonstrates that targeting CHST15 by submucosal injection of the CHST15 blocker STNM01 could allow refractory UC patients to achieve mucosal healing and clinical remission. Local application of STNM01 would thus be a unique novel therapeutic approach for reversal of tissue remodeling in refractory UC"

Clinical • Fibrosis • Immunology • Inflammation • Inflammatory Bowel Disease

Overexpression of carbohydrate sulfotransferase 15 in pancreatic cancer stroma is associated with worse prognosis. (PubMed, Oncol Lett) - "Our previous study reported the safety and efficacy of EUS-guided fine-needle injection (EUS-FNI) of STNM01, a double-stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer...Overexpression of CHST15 in cancer cells was associated with tumor stage. These results suggested that targeting therapy for CHST15 may be useful for stroma fibroblasts and cancer cells."

Journal

Oligonucleotides-A Novel Promising Therapeutic Option for IBD. (PubMed, Front Pharmacol) - "...Alicaforsen, selectively targets ICAM-1 mRNA...An antisense oligonucleotide against SMAD7 mRNA (mongersen) demonstrated pre-clinical and phase II efficacy in CD, but a phase III clinical trial was stopped due to lack of efficacy...Topical application of cobitolimod was studied in UC patients. We will also discuss two other novel oligonucleotides which act on the GATA3 transcription factor (SB012) and on carbohydrate sulfotransferase 15 (STNM01), which could both represent novel promising therapeutic options for the treatment of UC."

Journal • Review

Carbohydrate Sulfotransferase 15 in Pancreatic Cancer Associated with Mature Fibrosis and Prognosis (USCAP 2019) - "...Previously, we reported the safety and efficacy of EUS-guided fine-needle injection (EUS-FNI) of STNM01, the double-stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer... The present study revealed that overexpression of CHST15 in stroma was associated with worse overall survival and immature fibrosis. Overexpression of CHST15 in cancer cells was associated with tumor stage. These results suggest that targeting therapy for CHST15 might be useful for stroma fibroblasts and cancer cells."