Dicerna Pharmaceuticals
May 14, 2015

Dicerna Announces Expansion of Ongoing DCR-MYC Phase 1 Study to Evaluate Safety and Efficacy in Patients with Advanced Pancreatic Neuroendocrine Tumors (PNETs)

New Cohort Added Based on Signs of Clinical Activity in PNET Patients

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA), a leader in the development of RNAi therapeutics, today announced it is expanding its ongoing Phase 1 study of DCR-MYC in solid tumors, multiple myeloma, or lymphoma to include a cohort of patients with pancreatic neuroendocrine tumors (PNETs) following early signs of clinical and metabolic response and tumor shrinkage in PNET patients. DCR-MYC is an investigational Dicer substrate short-interfering RNA (DsiRNA) therapeutic targeting the MYC oncogene and the first MYC-targeting short-interfering RNA (siRNA) to enter clinical trials.

"Based on the clinical activity seen in two out of three patients with PNET, evidence of a complete metabolic response (based on FDG-PET) and a partial response (based on RECIST criteria), as well as published evidence on the role of MYC in growth and maintenance of PNET tumors, we are adding a PNET expansion cohort in the ongoing Phase 1 study," said Pankaj Bhargava, M.D., chief medical officer of Dicerna. "Most patients with PNET have unresectable or metastatic disease at the time of diagnosis. Despite recent improvements in treatment, advanced PNET remains an incurable disease. There are only two approved targeted therapies (Sutent® and Afinitor®) for advanced PNET, both with modest response rates, and there are no approved treatments for patients who progress after standard therapies. Therefore, there remains a clear unmet medical need for patients with advanced PNET."

The ongoing Phase 1 study, initiated in April 2014, is a multi-center, dose-escalation trial designed to assess the safety and tolerability of DCR-MYC in patients with solid tumors, multiple myeloma, or lymphoma who are refractory or unresponsive to standard therapies. The study is designed to identify the maximum tolerated dose (MTD), the pharmacokinetic profile, potential pharmacodynamic effects, and antitumor activity of DCR-MYC. Once the MTD is established, an expansion cohort will be opened to enroll patients with PNET. This multi-center expansion cohort will enroll up to 20 patients with low- to intermediate-grade PNET who have demonstrated disease progression after treatment with standard therapies.

Preliminary safety, tolerability, clinical, and metabolic response data from the ongoing Phase 1 trial of DCR-MYC will be presented at the 2015 ASCO Annual Meeting during the Tumor Biology Oral Abstract Session on Monday, June 1, 2015.

About Pancreatic Neuroendocrine Tumors (PNETs)

PNETs are a group of rare tumors that develop in endocrine cells found in the pancreas. Although PNETs are rare, their incidence has been rising significantly over the last 20 years, currently representing approximately 1-2% of all pancreatic cancers and comprising 7% of all neuroendocrine tumors.1 In the United States, the incidence of PNET has increased approximately 80% from 2007-2012, with PNETs representing an estimated 5.7% of all pancreatic tumors.2 While the cause of PNETs is unknown, people who have family members with an endocrine disorder called multiple endocrine neoplasia type 1 (MEN1) are at increased risk of the disease. Surgical resection, when feasible, is the primary treatment for patients. However, most patients with PNETs are diagnosed in advanced stages of the disease when surgical resection is no longer an option. Patients with non-resectable disease are generally treated with approved medical therapies. Currently, there are two targeted therapies approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with advanced stages of PNET.

About DCR-MYC

DCR-MYC, Dicerna's investigational Dicer substrate siRNA (DsiRNA) therapeutic, is designed to silence the MYC oncogene. MYC is a key target in oncology because it is implicated in a large number of cancers. DCR-MYC contains MYC-targeted DsiRNA delivered via Dicerna's EnCoreTM lipid nanoparticle (LNP) tumor delivery system. In preclinical research involving human tumors implanted in mice, and in mice that were genetically engineered to develop tumors, DCR-MYC substantially reduced the level of MYC expression and slowed or halted tumor progression. Dicerna is conducting a clinical trial program to explore the therapeutic activity of DCR-MYC across multiple tumor types. The Company has a Phase 1 clinical trial of DCR-MYC in patients with solid tumors, multiple myeloma or lymphoma, and a Phase 1b/2 trial in patients with hepatocellular carcinoma (HCC).

About RNAi

RNA interference (RNAi) is a biologic process in which certain double-stranded RNA molecules inhibit the expression of disease-causing genes by destroying the messenger RNAs (mRNAs) of those genes. It reflects a new approach in the development of specific and powerful therapies for genetic cancers and rare inherited diseases involving the liver. RNAi has the potential to treat these diseases through some of the most promising, yet previously inaccessible drug targets.

Traditional classes of drugs, small molecules and antibodies, have been used successfully for diseases with well-defined targets and proteins encoded by disease-associated genes. However, both of those classes are limited by the nature of the targets they can inhibit. RNAi offers the potential to overcome these limitations. Rather than targeting and binding to proteins to inhibit their activity, RNAi exerts its effects one step earlier in the process by targeting the mRNA, the instruction set that directs the building of the protein. In this manner, RNAi can potentially attack any target. Potential targets include disease-causing genes that are expressed exclusively inside cells and which lack good small-molecule binding pockets, putting them beyond the reach of traditional antibody and small-molecule technology.

About Dicer Substrate Technology

Dicerna's innovative Dicer substrate short-interfering RNA (DsiRNA) technology platform fuels a pipeline of promising, precisely targeted therapies designed to overcome many of the challenges of earlier generations of RNAi therapeutics. Dicerna's DsiRNA and DsiRNA-EX molecules are at the core of its therapeutic candidates. Each are chemically optimized double-stranded RNAs designed to potently induce RNAi. Dicerna has further developed the ideas behind DsiRNAs to create its DsiRNA-EX molecules, which carry additional benefits.

Dicerna's proprietary RNAi molecules are known as Dicer substrates because they are designed to be processed by the Dicer enzyme, which is the initiation point for RNAi in the human cell cytoplasm. Dicerna's discovery approach seeks to maximize RNAi potency through optimized structuring of DsiRNAs 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 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, whereby a drug delivery agent is linked directly to the extended region of the DsiRNA-EX molecule, potentially enabling the delivery of DsiRNA-EX Conjugates to patients through a subcutaneous injection.

About Dicerna Pharmaceuticals, Inc.

Dicerna 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 seeks to use 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 historically been difficult to inhibit 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. For more information, please visit www.dicerna.com.

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. DsiRNA-EX Conjugate-mediated delivery technology is in preclinical development, and the process by which a preclinical technology could potentially lead to an approved product is long and subject to significant risks and uncertainties. Interim clinical data relating to our DCR-MYC Phase I study are preliminary and could differ materially from final clinical data. Moreover, Phase 1 clinical data may not be replicated in subsequent clinical trials and may fail to indicate whether a drug candidate is potentially approvable. Applicable risks and uncertainties include those relating to our preclinical research and clinical development 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.

References

1 Sadaria MR, Hruban RH, Edil BH. Advancements in pancreatic neuroendocrine tumors. Expert Rev. Gastroenterol. Hepatol. 2013;7(5):477-490.

2 National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program, 2015. 18 Regs Research Data, 1973-2012.

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Source: Dicerna Pharmaceuticals, Inc.

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