Dicerna Presents Preliminary Safety and Efficacy Data from DCR-MYC Phase 1 Study at ASCO 2015

Evidence of Clinical Anti-tumor Activity Seen in Two Patients with Advanced Pancreatic Neuroendocrine Tumors

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA), a leader in the development of RNAi therapeutics, today presented preliminary safety and efficacy data from an ongoing Phase 1 study of DCR-MYC in patients with advanced solid tumors, multiple myeloma, or lymphoma at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting. DCR-MYC is an investigational Dicer substrate short interfering RNA (DsiRNA) therapeutic targeting the MYC oncogene. The interim data provide evidence of clinical and metabolic response in patients across several dose levels. Of particular significance, evidence of clinical anti-tumor activity was observed in two patients with advanced, treatment refractory pancreatic neuroendocrine tumors (PNETs).

Anthony W. Tolcher, M.D., FRCP©, director of clinical research at South Texas Accelerated Research Therapeutics (START) and a principal investigator in the study, presented the data during the ASCO Tumor Biology oral abstract session. The presentation is titled Safety and activity of DCR-MYC, a first-in-class Dicer substrate small interfering RNA (DsiRNA) targeting MYC, in a phase 1 study in patients with advanced solid tumors.

"We are very pleased that DCR-MYC has been well-tolerated thus far," said Dr. Tolcher. "The evidence of anti-tumor activity seen in patients with advanced PNET is particularly exciting. It was remarkable to see a metabolic response in a patient with PNET following just one cycle of treatment, followed by a response to re-treatment after a break of almost a year during which the patient remained progression-free. The data in PNET patients merit further exploration of DCR-MYC in this difficult to treat tumor."

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 advanced solid tumors, multiple myeloma, or lymphoma who are refractory or unresponsive to standard therapies. The study is also designed to identify the compound's maximum tolerated dose (MTD), the pharmacokinetic (PK) profile, potential pharmacodynamic (PD) effects using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging, and anti-tumor activity based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

In the study, DCR-MYC is administered as a two-hour intravenous (IV) infusion once-weekly for two weeks, followed by a one week break (3 weeks = 1 cycle). All patients receive premedications with dexamethasone, diphenhydramine, and an H-2 blocker. The starting dose was 0.1 mg/kg, with current dosing at 0.68 mg/kg. Dose-escalation will continue until the MTD is established. Pre- and post-dosing tumor biopsies will be obtained in a cohort of patients enrolled at MTD.

As of May 12, 2015, 26 patients were treated with DCR-MYC, with 18 patients evaluable for response. Anti-tumor activity was seen in two out of three patients with advanced, treatment refractory PNET. Specifically, evidence of a complete metabolic response based on imaging with FDG-PET was seen in one patient, and a partial tumor response (34% reduction in tumor size) based on RECIST 1.1 criteria in another. Both patients were treated with multiple therapies for PNET prior to starting the study.

Based on these interim study findings, Dicerna announced in May 2015 an expansion of the ongoing DCR-MYC Phase 1 trial to include a cohort of patients with PNET. Once the MTD is established, the 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.

"The preliminary Phase 1 safety and efficacy results are encouraging and support further study of DCR-MYC for use as a new treatment option for patients with cancer," said Pankaj Bhargava, M.D., Dicerna chief medical officer. "We are currently enrolling patients in the seventh cohort of the study. Once the maximum tolerated dose is established, we will open enrollment for a multi-center expansion cohort in patients with advanced PNET. In addition to the Phase 1 study, we continue to enroll patients in our Phase 1b/2 trial of DCR-MYC in patients with hepatocellular carcinoma (HCC). We are pleased with the progress of both of these studies."

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). DCR-MYC is the first MYC-targeting short interfering RNA (siRNA) to enter clinical trials.

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. This approach may enable 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 drug candidates designed to potentially 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. Dicerna seeks to chemically optimize its double-stranded RNAs to potently induce RNAi. Dicerna has further developed the ideas behind DsiRNAs to create its DsiRNA-EX molecules, which potentially 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 DsiRNA 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 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 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. Interim clinical data 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.