Dicerna Pharmaceuticals
Sep 2, 2015

Dicerna Pharmaceuticals Submits Investigational New Drug (IND) Application for DCR-PH1, an Investigational Therapy for Primary Hyperoxaluria Type 1 (PH1)

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA), a leading developer of RNA interference (RNAi) therapeutics, today announced the submission of an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for 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 IND submission is an important milestone for the DCR-PH1 program, as it takes us one step closer to bringing this novel therapy to patients with primary hyperoxaluria type 1," said Pankaj Bhargava, M.D., chief medical officer at Dicerna. "We look forward to working with the FDA during the review process in order to rapidly initiate clinical development of DCR-PH1."

DCR-PH1 incorporates small interfering RNA (siRNA) formulated in a proprietary lipid nanoparticle (LNP) technology that is being investigated as a system for efficient delivery to the liver after intravenous (IV) administration. Dicerna obtained rights to this delivery technology by way of a licensing agreement with Arbutus Biopharma Corporation, formerly Tekmira Pharmaceuticals Corporation.

About Primary Hyperoxaluria Type 1 (PH1)

PH1 is a rare, inherited genetic disorder of the AGXT gene in the liver which causes excess oxalate production.1 The AGXT gene encodes for the liver enzyme alanine:glyoxylate-aminotransferase (AGT). The kidneys are unable to eliminate the large amount of oxalate that is produced and the accumulation can result in severe damage to the kidneys and other organs. Currently, there are no approved therapies for the treatment of PH1 in the US and the EU.

Patients with this disease often undergo combined liver and kidney transplant, a major surgical procedure, and subsequently must take immunosuppressant drugs for the rest of their lives, and there is a potential for a future re-transplant and possible cancers. Patients with decreased renal function may also experience oxalosis, which involves a build-up of oxalate in other organs such as the bone, skin, heart and retina, possibly causing other concomitant, debilitating complications. The estimated genetic prevalence of PH1 is 1 in 151,887, which suggests more than 5,000 patients in the US and EU.2 The median age at first symptoms is 5.8 years.3 The median age at diagnosis is between 4.2 and 11.5 years depending on whether or not nephrocalcinosis is present.4 Fifty percent of patients with PH1 reach ESRD by their mid-30s.5

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 (GO), an enzyme involved in producing oxalate. This approach seeks to prevent the complications of PH1 through the reduction of oxalate production. In preclinical studies, DCR-PH1 induced inhibition of HAO1 and significantly reduced levels of urinary oxalate 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 seeks to maximize RNAi potency through development of DsiRNAs that are thought to be ideally structured 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. The Investigational New Drug application 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-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. Cochat, P, Rumsby, G. Primary Hyperoxaluria. The New England Journal of Medicine 2013; 369(7): 649-658.

2. Hopp, K, Cogal, A, Bergstralh, E, Seide, B, Olson, J, Meek, A, Lieske, J, Milliner, D and Harris, C on behalf of the Rare Kidney Stone Consortium. Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria, Journal of the American Society of Nephrology 2015; 26: February 2, 2015.

3. van der Hoeven SM, van Woerden CS, Groothoff JW. Primary hyperoxaluria type 1, a too often missed diagnosis and potentially treatable cause of end-stage renal disease in adults: results of the Dutch cohort. Nephrology, Dialysis, Transplantation 2012; 27(10):3855-3862.

4. Tang X, Bergstrath EJ, Mehta RA, Vrtiska TJ, Milliner DS, Lieske JC. Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria Kidney International 2015; 87:623-631.

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

Dicerna
Investor:
Westwicke Partners
Peter Vozzo, 443-213-0505
peter.vozzo@westwicke.com
or
Media:
SmithSolve
Alex Van Rees, 973-442-1555 ext. 111
alex.vanrees@smithsolve.com

Source: Dicerna Pharmaceuticals, Inc.

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