Dicerna Pharmaceuticals
Feb 2, 2015

Dicerna Pharmaceuticals Announces First Patient Dosed in Phase 1b/2 Clinical Trial of DCR-MYC, an Investigational RNAi Therapeutic Targeting the MYC Oncogene, in Patients with Advanced Hepatocellular Carcinoma

Trial to Evaluate Safety, Tolerability and Preliminary Antineoplastic Effect of DCR-MYC

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA), a leader in the development of RNAi therapeutics, today announced that the first patient has been dosed in a global Phase 1b/2 clinical trial of DCR-MYC, an investigational Dicer substrate short interfering RNA (DsiRNA) therapeutic, in patients with advanced hepatocellular carcinoma (HCC). This new trial expands the development program for DCR-MYC, which is also being studied in a Phase 1 clinical trial in patients with solid tumors and hematological malignancies.

DCR-MYC targets the driver oncogene MYC, which is central to the growth of many tumor types, including HCC. Patients with HCC frequently show amplification of the MYC oncogene, suggesting an important role for MYC activity in a significant portion of people with the disease.

"We are pleased to enroll our first patient in our second clinical trial with DCR-MYC, which is focused on advanced HCC," said Pankaj Bhargava, M.D., chief medical officer of Dicerna. "MYC is a highly relevant target in many cancers, including HCC, but remains challenging to drugs with conventional modalities. The potential of inhibiting the MYC pathway with DsiRNA therapeutics is very exciting and could be of tremendous therapeutic value for patients."

The multi-center, open-label study will enroll approximately 72 patients with locally advanced unresectable or metastatic HCC at sites in the United States, South Korea and Singapore. The Phase 1b portion of the study is designed to assess safety, tolerability, maximum tolerated dose, and recommended Phase 2 dosing of DCR-MYC. The Phase 2 portion of the study will evaluate preliminary antineoplastic activity of DCR-MYC in addition to safety and tolerability.

The study will enroll patients who do not respond to or do not tolerate standard-of-care sorafenib therapy, or patients who lack access to sorafenib or for whom no suitable therapy is available. DCR-MYC will be administered by two-hour intravenous infusion (IV) once a week for two weeks, followed by a week of rest, with the potential to evaluate dosing every other week.

"The incidence of HCC is on the rise in the United States and Europe, primarily due to the prevalence of chronic hepatitis C infection," said Andrew X. Zhu, M.D., Ph.D., associate professor of medicine at Harvard Medical School, director of liver cancer research at Massachusetts General Hospital Cancer Center, and an investigator in the DCR-MYC Phase 1b/2 study. "Liver cancer has become the second leading cause of cancer-related mortality worldwide. Patients with advanced HCC have limited treatment options, and there are no approved therapies for those who are intolerant of, or progress after treatment with sorafenib. We hope to address a significant unmet medical need in this patient population and look forward to working closely with Dicerna on this innovative trial."

For more information about Dicerna's DCR-MYC-102 clinical study in HCC, please visit https://clinicaltrials.gov.

About Hepatocellular Carcinoma (HCC)

Liver cancer is the second leading cause of cancer-related deaths worldwide, with 745,000 deaths per year.1 Hepatocellular carcinoma (HCC) is the most common form of liver cancer in adults. Most cases of HCC result from infection with the hepatitis B or C virus, which can lead to cirrhosis of the liver.2 However, non-alcoholic fatty liver disease, associated with obesity and diabetes, is also an important risk factor for HCC.3 Early-stage HCC is generally treated with surgery, which is potentially curative; however, given the nonspecific symptoms that are characteristic of HCC, the substantial majority of patients are diagnosed only after HCC is at an advanced stage. Patients with advanced HCC have limited treatment options, and the disease is associated with poor patient outcomes and high mortality.

About DCR-MYC

DCR-MYC, Dicerna's investigational Dicer substrate siRNA (DsiRNA) molecule, is a synthetic double-stranded RNA delivered via the company's proprietary EnCore™ LNP delivery system. DCR-MYC is designed to serve as a potent and specific inhibitor of the MYC oncogene. MYC is a key target in oncology because it has been demonstrated to cause or promote cancer when abnormally expressed or activated. The MYC oncogene encodes for a small intracellular protein that lacks a good binding site, making it a challenging target for monoclonal antibodies or traditional small molecules. However, DsiRNA therapeutics may be able to overcome these challenges by "silencing" the MYC oncogene in cancer cells. In pre-clinical studies, Dicerna has shown that DCR-MYC inhibits gene transcript activity and reduces tumor volume in multiple mouse tumor models. Dicerna is investigating DCR-MYC in a variety of tumor types, including HCC, other solid tumors, multiple myeloma, and lymphoma.

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.

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.

References

1 World Health Organization, http://www.who.int/mediacentre/factsheets/fs297/en/

2 American Cancer Society, http://www.cancer.org/cancer/livercancer/detailedguide/liver-cancer-risk-factors

3 Gambarin-Gelwan M. Viral hepatitis,non-alcoholic fatty liver disease and alcohol as risk factors for hepatocellular carcinoma. Chin Clin Oncol 2013;2(4):32. doi:10.3978/j.issn.2304-3865.2013.09.02

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Source: Dicerna Pharmaceuticals, Inc.

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