Dicerna Pharmaceuticals
Nov 17, 2014

Dicerna Reports on Progress of Development Programs

-- Company to Host First R&D Webcast on December 15 --

WATERTOWN, Mass.--(BUSINESS WIRE)-- Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA), a leader in the development of RNA interference (RNAi) based therapeutics, today announced that it will host its first R&D webcast to review the company's strategy, technology, and expanding pipeline of innovative RNAi therapies. The R&D webcast will take place on Monday, December 15 at 4:30 p.m. To register, please visit www.dicerna.com.

In the R&D webcast, the company will discuss details of its DCR-PH1 program, its treatment for the orphan disease primary hyperoxaluria type 1 (PH1). Expected to enter the clinic in 2015, DCR-PH1 incorporates a new and proprietary extended Dicer substrate molecule (DsiRNA-EX) and in-licensed lipid nanoparticle (LNP) delivery technology from Tekmira Pharmaceuticals. The company will also describe, for the first time, its proprietary conjugate-mediated delivery technology, which will enable subcutaneous delivery of RNAi therapy and will be featured in future liver-targeted programs. These liver delivery technologies complement Dicerna's proprietary oncology-focused EnCore LNP delivery system.

"Dicerna continues to make rapid progress in engineering highly precise and targeted RNAi-based treatments for rare, inherited diseases involving the liver and for cancers that are genetically defined," said Douglas Fambrough, Ph.D., Chief Executive Officer of Dicerna. "Our entire organization is focused on realizing the full clinical and commercial potential of these proprietary therapies by applying our own industry-leading delivery platforms and, when appropriate, licensing proven delivery platforms. This approach will streamline development of our programs and allow us to focus our resources most effectively."

Dicerna management will also include a summary of recent developments in the company's presentations at the Stifel 2014 Healthcare Conference in New York on November 18 and the Jefferies 2014 Global Healthcare Conference in London on November 20. To access the live webcast or replay of the presentations, please visit www.dicerna.com.

Update on the DCR-PH1 Development Program

Dicerna expects to release initial data from a phase 1 clinical trial of DCR-PH1 in patients with PH1 by the end of 2015. DCR-PH1 is an investigational extended Dicer substrate RNA (DsiRNA-EX) molecule delivered via LNP technology. In the DCR-PH1 DsiRNA-EX molecule, one of the two RNA strands carries a 10-base extension. This extended structure improves the immunosilencing and stability properties of the DsiRNA-EX molecule. DsiRNA-EX technology is covered by Dicerna patent 8,349,809 and other Dicerna patent applications and is distinct from other existing RNAi patent estates. As announced earlier today, the DCR-PH1 delivery system has been in-licensed from Tekmira. This system has been demonstrated in both non-human primate studies and human clinical studies to provide potent, safe and effective RNA delivery to hepatocytes (liver cells). Use of the Tekmira LNP is expected to streamline the development path for DCR-PH1 and allow Dicerna to focus its proprietary EnCore LNP delivery platform on its oncology pipeline.

DCR-PH1 addresses the pathology of PH1 by seeking to target and destroy the messenger RNA produced by HAO1, a gene implicated in the excessive production of oxalate in PH1 patients. Oxalate is the key driver of pathogenesis in PH1. By reducing oxalate production, this approach is expected to prevent the kidney damage and other complications associated with PH1. In preclinical studies, DCR-PH1 induces potent and long-term inhibition of HAO1 and significantly reduces urinary oxalate levels, while demonstrating long-term tolerability in animal models of PH1.

First Disclosure of the DsiRNA-EX Conjugate-Mediated Subcutaneous Delivery Platform

Dicerna has developed a proprietary DsiRNA-EX conjugate-based delivery system to advance the development of its pipeline of liver-targeted RNAi therapies. These conjugates do not involve lipid nanoparticles and are built on the DsiRNA-EX platform, using an extension to one strand of the double-stranded DsiRNA molecule. DsiRNA-EX conjugates can be delivered subcutaneously, while still retaining capability for intravenous administration, allowing flexibility in mode of administration. The DsiRNA-EX conjugate technology is covered by Dicerna patent 8,349,809 and other Dicerna patent applications and is distinct from other existing RNAi conjugate-mediated delivery patent estates.

Identification of Additional Liver-Targeted RNAi Therapies

Following an extensive review of rare diseases with gene targets expressed in the liver, Dicerna has prioritized a broad portfolio of research and development opportunities. The company is currently pursuing discovery research on several rare diseases involving the liver and intends to add additional programs over time. Dicerna expects to declare its first DsiRNA-EX conjugate clinical candidate in 2015 for an undisclosed rare disease involving the liver. For competitive reasons, the company does not plan to specify disease areas or therapeutic targets until a program has reached a late preclinical stage.

About Primary Hyperoxaluria Type 1 (PH1)

PH1 is a rare, inherited liver disorder that often results in severe damage to the kidneys. The disease can be fatal unless the patient undergoes a liver-kidney transplant, a major surgical procedure that is often difficult to perform due to the lack of donors and which carries substantial risk. In the event of a successful transplant, the patient must live the rest of his or her life on immunosuppressant drugs, which have substantial associated risks. Currently, there are no FDA-approved treatments for PH1.

PH1 is characterized by a genetic deficiency of the liver enzyme alanine:glyoxalate-aminotransferase (AGT), which is encoded by the AGXT gene. AGT deficiency induces overproduction of oxalate by the liver, resulting in the formation of crystals of calcium oxalate in the kidneys. Oxalate crystal formation often leads to chronic and painful cases of kidney stones and subsequent fibrosis (scarring), which is known as nephrocalcinosis. Many patients progress to end-stage renal disease (ESRD) and require dialysis or transplant. Aside from having to endure frequent dialysis, PH1 patients with ESRD may experience a build-up of oxalate in the bone, skin, heart and retina, with concomitant debilitating complications. While the true prevalence of primary hyperoxaluria is unknown, it is estimated to be one to three cases per one million people.1 Fifty percent of patients with PH1 reach ESRD by their mid-30s.2

About RNAi

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 Contact 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 that LNP technology may fail to deliver DCR-PH1 to the liver in human beings or otherwise fail to accelerate clinical development, clinical trials may not demonstrate the effectiveness of DCR-PH1, and the DsiRNA-EX conjugate-based delivery system may fail to advance the development of Dicerna's pipeline of liver-targeted RNAi therapies. Additional risks, including those relating to Dicerna's preclinical research and clinical development and other risks, are 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.


1 Cochat, P, Rumsby, G. Primary Hyperoxaluria. The New England Journal of Medicine 2013; 369(7): 649-658.

2 Rare Kidney Stone Consortium. Primary Hyperoxaluria. 2010. Available at: http://www.rarekidneystones.org/hyperoxaluria/physicians.html. Accessed October 14, 2014.

Westwicke Partners
Yolanda Taylor, 617-366-6803
Alex Van Rees, 973-442-1555 ext. 111

Source: Dicerna Pharmaceuticals, Inc.

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