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Dicerna Expands Lead GalXCDevelopment Program to Encompass All Forms of Primary Hyperoxaluria and Reveals New Therapeutic Target for DCR-PHXC.

M2 PHARMA-July 20, 2017-Dicerna Expands Lead GalXCDevelopment Program to Encompass All Forms of Primary Hyperoxaluria and Reveals New Therapeutic Target for DCR-PHXC


- US-based ribonucleic acid interference therapeutics developer Dicerna Pharmaceuticals, Inc. (NASDAQ: DRNA) has presented new preclinical data suggesting the potential utility of DCR-PHXC, a GalXC-based investigational therapy, for treating all forms of primary hyperoxaluria, the company said.

In a series of presentations at the 12th International Workshop on Primary Hyperoxaluria for Professionals, Patients and Families in Tenerife, Spain from July 14-16, 2017, Dicerna scientists presented research from animal models demonstrating how DCR-PHXC inhibits the lactate dehydrogenase A gene, which Dicerna has identified as potentially being an optimal therapeutic target in patients with PH, a group of severe, rare, inherited disorders of the liver that often result in kidney failure.

In patients with PH, the liver over-produces oxalate, a metabolite that can accumulate throughout the body and particularly in the kidneys, often resulting in end-stage renal disease and the need for both kidney and liver transplants.

DCR-PHXC, the lead investigational product candidate in Dicerna's pipeline of therapies targeting rare diseases of the liver, yields potent, liver-specific LDHA inhibition in animal models of PH, an effect that reduces oxalate to near-normal levels, which may prevent the damage caused to kidneys and other organs by oxalate accumulation.

At the 12th International Workshop, Dicerna presented research findings on LDHA inhibition, which was shown in animal models to reduce oxalate to normal or near-normal levels in PH types 1, 2, and ethylene glycol-induced PH.

In contrast, research findings showed that inhibiting the enzyme glycolate oxidase, a common target of investigational therapies for PH, including Dicerna's earlier IV-administered program for PH1, does not appear to have the potential to treat PH2 or IPH.

In animal models of PH2 and ethylene glycol-induced PH, LDHA knockdown with DCR-PHXC nearly normalised oxalate levels within one-month post-treatment, whereas oxalate levels remained unchanged and elevated in animals receiving GO-targeted therapy.

LDHA reduction has a linear correlation with oxalate reduction and offers a minimal metabolic intervention, unlike GO reduction.

These benefits of LDHA inhibition may translate into consistent therapeutic activity even in the event of a missed dose. There are numerous case reports of LDHA deficiency naturally occurring in humans, with no reported adverse effects due to deficiency in the liver.

DCR-PHXC is the most advanced product candidate utilizing Dicerna's GalXC technology, a proprietary platform that advances the development of next-generation RNAi-based therapies designed to silence disease-driving genes in the liver. GalXC compounds are intended to be broadly applicable across multiple therapeutic areas, including rare diseases, chronic liver diseases, cardiovascular diseases, and viral infectious diseases.

GalXC enables subcutaneous delivery of RNAi therapies to hepatocytes in the liver and offers several distinct potential benefits, as extensively demonstrated in various animal models. Such benefits could include potent silencing of LDHA and other genes; highly specific targeting to hepatocytes, sparing other cell types in the body; a long duration of action; and a simple, infrequent dosing regimen.

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Publication:M2 Pharma
Date:Jul 20, 2017
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