Dicerna Pharmaceuticals
May 11, 2016

Dicerna Reports Potent Preclinical Activity with GalNAc-DsiRNA-EX Conjugates

TIDES Presentation Highlights Proprietary Approach to Hepatic Delivery of RNAi-based Therapy via Subcutaneous Injection, with Potential Utility against Multiple Therapeutic Targets

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA), a leading developer of investigational RNA interference (RNAi) therapeutics, today will present updated preclinical data demonstrating the potency of its proprietary GalNAc-DsiRNA-EX Conjugate technology in enabling direct delivery of RNAi-based therapy to the liver via subcutaneous (SC) injection, with potential utility against multiple therapeutic targets. The presentation will take place at the 18th Annual TIDES: Oligonucleotide and Peptide Research, Technology and Product Development Conference in Long Beach, Calif.

Bob D. Brown, Ph.D., chief scientific officer and senior vice president of research at Dicerna, will present an updated case study of the application of the GalNAc-DsiRNA-EX Conjugate technology to a well-characterized hepatic disease gene, Alpha-1-antitrypsin (SERPINA1), resulting in a reduction of serum Alpha-1-antitrypsin (A1AT) in a transgenic mouse model of liver disease. Dr. Brown will also present data showing approximately 80% knockdown of SERPINA1 messenger RNA (mRNA) with a single 3-mg/kg dose of the GalNAc-DsiRNA-EX Conjugate, as well as approximately 88% knockdown of HAO1, a gene implicated in the pathogenesis of primary hyperoxaluria type 1 (PH1), a rare, inherited liver disorder that often results in progressive and severe kidney damage, at the same 3-mg/kg dose.

"Our proprietary DsiRNA-EX Conjugates exhibit potent in vivo activity in rodents and monkeys, suggesting utility against multiple therapeutic targets," said Dr. Brown. "In addition to facilitating efficient delivery and gene target knockdown in the liver, the ‘Tetraloop' configuration of the GalNAc-DsiRNA-EX Conjugates confers the advantages of potency, stability and ease of chemical modification without loss of activity. Extensive testing of sequence versus chemical modifications in vitro and in vivo has enabled efficient design of molecules by stamping patterns on sequences, which are starting to yield predictable in vivo performance. Moreover, the platform is remarkably tolerant of conjugate linker lengths and chemistries, offering a significant degree of flexibility in conjugate-mediated delivery to the liver."

"Our DsiRNA-EX Conjugate platform continues to generate robust preclinical data supporting development as subcutaneously delivered, gene-targeted therapies," commented Douglas Fambrough, Ph.D., president and chief executive officer of Dicerna. "We look forward to releasing additional data throughout 2016 showing short- and long-term gene knockdown in various animal models of liver disease."

Dicerna has developed investigational DsiRNA-EX Conjugates for liver-related diseases by attaching N-acetyl galactosamine (GalNAc) sugars to one or more points on DsiRNA-EX molecules, yielding multiple proprietary conjugate delivery configurations. The GalNAc sugars specifically bind to receptors on target cells, leading to internalization and access to the RNAi machinery within the cells.

Earlier this year, Dr. Brown presented data showing a greater than 75% reduction in serum A1AT in non-human primates treated with a prototype SERPINA1 GalNAc-DsiRNA-EX Conjugate, with effects lasting more than seven weeks after the last of five SC doses. At the TIDES conference in Long Beach, he reported that the prototype conjugate provided almost six months of A1AT protein knockdown in monkeys. Dr. Brown also noted that Dicerna scientists have identified GalNAc-DsiRNA-EX Conjugates with in vivo half maximal inhibitory concentrations (IC50, the concentration needed to inhibit a biological or biochemical function by half) of ≤1.0 mg/kg against multiple targets.

"We have initiated non-human primate studies of our DsiRNA-EX Conjugates against multiple therapeutic targets with high-potency leads, and plans are in place for additional programs," Dr. Brown said. "As we continue to advance this platform, we hope to benefit from enhanced understanding of GalNAc conjugate medicinal chemistry, which appears to offer a unique therapeutic approach to diseases of the liver and other potential indications."

Dr. Brown's presentation will be available at 12:30 p.m. ET on Wednesday, May 11, 2016 on the Events & Presentations page in the Investors & Media section of the Dicerna website.

About Dicerna Pharmaceuticals, Inc.

Dicerna Pharmaceuticals, Inc., is an RNA interference-based biopharmaceutical company focused on the discovery and development of innovative treatments for rare, inherited diseases involving the liver, for other therapeutic areas in which the liver plays a key role, 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 many cases, 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 these 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. DsiRNA-EX Conjugate-mediated delivery technology is in preclinical development, and the process by which a preclinical technology could potentially lead to an approved product is long and subject to significant risks and uncertainties. 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.

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Source: Dicerna Pharmaceuticals, Inc.

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