FDA Grants Orphan Drug Designation for DCR-PH1, Dicerna’s Investigational Therapy for the Treatment of Primary Hyperoxaluria Type 1 (PH1)

Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA), a leading developer of RNA interference (RNAi) therapeutics, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to DCR-PH1, the company’s therapeutic candidate for the treatment of primary hyperoxaluria type 1 (PH1). PH1 is a severe, rare, inherited disorder of the liver that often results in kidney failure, and for which there are no approved therapies.

The Orphan Drug Designation program, administered by the FDA’s Office of Orphan Products Development (OOPD), provides orphan status to drugs which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a therapeutic drug. DCR-PH1 is Dicerna’s proprietary DsiRNA-EX-based therapeutic candidate being developed for the treatment of PH1. In a genetic mouse model of PH1, Dicerna has shown that DCR-PH1 knocks down the gene transcript that encodes for the enzyme glycolate oxidase (GO) and reduces the excretion of oxalate in the urine.

"The Orphan Drug Designation is an important regulatory milestone as we further our development of DCR-PH1 in PH1, a disease that currently does not have an approved treatment option,” said Ted Ashburn, M.D., Ph.D., senior vice president of product strategy and operations of Dicerna. "We are encouraged by the progress of this program to date, and our aim is to rapidly advance the development of DCR-PH1 as a potential new treatment option for PH1 patients.”

DCR-PH1 incorporates a proprietary, lipid nanoparticle (LNP) technology which allows it to be efficiently delivered to the liver after intravenous (IV) administration. Dicerna obtained rights to this delivery technology by way of a licensing agreement signed in November 2014 with Tekmira Pharmaceuticals Corporation.

About Primary Hyperoxaluria Type 1 (PH1)

PH1 is a rare, inherited liver disorder in which excess oxalate production 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 the threat of organ rejection. 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 DCR-PH1

Dicerna is developing DCR-PH1, which is in preclinical development, for the treatment of PH1. DCR-PH1 is engineered to address the pathology of PH1 by targeting and destroying the messenger RNA (mRNA) produced by HAO1, a gene implicated in the pathogenesis of PH1. HAO1 encodes glycolate oxidase, a protein involved in producing oxalate. By reducing oxalate production, this approach seeks to prevent the complications of PH1. In preclinical studies, DCR-PH1 has been shown to induce potent and long-term inhibition of HAO1 and to significantly reduce levels of urinary oxalate, while demonstrating long-term efficacy and tolerability in animal models of PH1.

About Dicerna’s Dicer Substrate Technology

Dicerna’s proprietary RNAi molecules are known as Dicer substrate short-interfering RNA molecules, 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 (RNAi) 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. DCR-PH1 is in preclinical development, and the process by which a preclinical therapeutic candidate could potentially lead to an approved drug is long and subject to significant risks and uncertainties. Orphan Drug Designation does not assure a faster or more probable regulatory path. Applicable risks and uncertainties include those relating to our preclinical and clinical research and other risks identified under the heading "Risk Factors" included in our most recent Form 10-K 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 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.