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

Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA), 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.

About RNAi

RNA interference (RNAi) is a highly potent and specific mechanism for regulating the activity of a targeted gene. In this biological process, certain double-stranded RNA molecules known as short interfering RNAs (siRNAs) bind to complementary messenger RNAs (mRNAs) and recruit proteins that break the chemical bonds that hold mRNAs together, preventing the mRNAs from transmitting their protein-building instructions.

RNAi therapeutics have the potential to treat a number of human diseases by "silencing" disease-causing genes. The discoverers of RNAi, a gene silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine.

About Dicer Substrate Technology

Dicerna's proprietary RNAi molecules are known as Dicer substrates, or DsiRNAs, so called because they are processed by the Dicer enzyme, which is the initiation point for RNAi in the human cell cytoplasm. Dicerna's discovery approach is believed to maximize RNAi potency because the DsiRNAs are structured to be ideal for processing by Dicer. Dicer processing enables the preferential use of the correct RNA strand of the DsiRNA, which may increase the efficacy of the RNAi mechanism, as well as the potency of the DsiRNA molecules relative to other molecules used to induce RNAi. Dicerna’s DsiRNA Extended (DsiRNA-EX) molecules resemble DsiRNA molecules but have an extended region at one end of the molecule which is engineered to provide additional functionality to the DsiRNA-EX molecules. Dicerna can also use this extended region to generate its DsiRNA-EX-Conjugates, where a drug delivery agent is linked directly to the extended region of the DsiRNA-EX molecule, enabling the ability to deliver DsiRNA-EX Conjugates to patients through a subcutaneous injection.

About Dicerna

Dicerna Pharmaceuticals, Inc. is a biopharmaceutical company focused on the discovery and development of innovative treatments for rare, inherited diseases involving the liver and for cancers that are genetically defined. The company is using its proprietary RNA interference technology platform to build a broad pipeline in these therapeutic areas. In both rare diseases and oncology, Dicerna is pursuing targets that have been difficult to address using conventional approaches, but where connections between targets and diseases are well understood and documented. The company intends to discover, develop and commercialize novel therapeutics either on its own or in collaboration with pharmaceutical partners.

Cautionary Note on Forward-Looking Statements

This press release includes forward-looking statements. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Applicable risks and uncertainties include those relating to our preclinical research and other risks identified under the heading "Risk Factors" included in our most recent Form 10-Q filing and in other future filings with the SEC. The forward-looking statements contained in this press release reflect Dicerna's current views with respect to future events, and Dicerna does not undertake and specifically disclaims any obligation to update any forward-looking statements.