Dicerna Presents New β-catenin Data from Multiple Tumor Models at the 2015 RNA & Oligonucleotide Therapeutics Meeting

Dicerna Pharmaceuticals, Inc.

, a leader in the development of RNAi therapeutics, today announced promising new in vivo data for CTNNB1 DsiRNA in multiple patient-derived xenograft (PDX) and other models of diverse tumor types. CTNNB1 DsiRNA is an extended Dicer substrate short interfering RNA (DsiRNA-EX) therapeutic targeting β-catenin delivered using Dicerna's proprietary next generation EnCore™ lipid nanoparticle (LNP) technology. β-catenin, encoded by the CTNNB1 gene, is a well-studied oncology target that is validated by human genetic and functional evidence in a variety of cancers, including hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), and intrahepatic cholangiocarcinoma (IHCC). The data are being presented at the 2015 RNA & Oligonucleotide Therapeutics Meeting at Cold Spring Harbor Laboratory, held April 8-11, 2015 in Cold Spring Harbor, N.Y. The findings will be presented today in an oral presentation titled "Advances in Delivery of Dicer Substrate siRNAs (DsiRNAs) to Tumors" and were also presented yesterday in a poster presentation titled "Delivery of Dicer-substrate siRNAs (DsiRNAs) to Patient-derived Xenograft Tumors." The findings demonstrate CTNNB1 DsiRNA's favorable pharmacokinetic (PK) and biodistribution properties as well as robust messenger RNA (mRNA) knockdown and tumor exposure in models of HCC, CRC, melanoma, leukemia, genetic hepatoblastoma, and other tumor types including PDX models. "Dicerna's second generation EnCore LNP system has been further refined and is more broadly active than the first generation EnCore technology," said Douglas M. Fambrough, Ph.D., chief executive officer of Dicerna. "As a result, Dicerna is now able to show consistent gene knock down in an even wider range of tumor types, greater efficiency of tumor delivery, and delivery to both subcutaneous and orthotopic tumors. These findings provide us with a deeper understanding of the parameters that drive EnCore mediated tumor delivery and will help to inform our clinical development strategy as we move forward." In an orthotopic HCC PDX model, a single dose of CTNNB1 DsiRNA yielded up to 90% knockdown of CTNNB1 and downstream effectors. Furthermore, Dicerna scientists observed rapid dampening of Wnt signaling in the tumor cells, but not in the adjacent normal liver tissue. In addition to the HCC findings, Dicerna showed mRNA knockdown in models of hepatoblastoma, melanoma, leukemia and CRC, providing further insights into the efficacy and delivery of EnCore mediated CTNNB1 DsiRNA in other tumor types. In one example, CTNNB1 DsiRNA delivery resulted in robust tumor growth inhibition in β-catenin-dependent CRC tumors. Dicerna continues to advance its EnCore LNP platform through extensive structure-function analyses to identify advanced formulation components and manufacturing processes. These advances have yielded a greater mechanistic understanding of tumor delivery, improved potency, and up to 10-fold improvements in tumor-specific delivery.