Developing next-generation RNAi therapies.
Dicerna has a growing pipeline of product candidates to address unmet medical needs in diseases involving the liver, including rare diseases, chronic liver diseases, cardiovascular diseases, and viral infectious diseases. Our optimized, subcutaneously administered GalXCTM molecules are designed to potently and selectively silence genes that are implicated in these disorders. We have qualified dozens of disease-associated genes in clinical indications where we believe an RNAi-based inhibitor may provide substantial benefit to patients, providing expansive therapeutic opportunities. In addition, Dicerna has developed hits and/or optimized GalXC conjugate inhibitors against almost 40 of these qualified targets.
We choose to attack disease targets where we have high confidence that successful silencing of the target gene will provide substantial benefit to patients, and for which we can move rapidly through the drug approval process. Whether focusing on our core area of rare diseases or on serious, life-threatening, chronic diseases, the common threads are the expression of faulty genes in the liver and a substantial need for new treatment options. In making these choices, we are working to improve the lives of patients suffering from potentially debilitating conditions.
FOCUSED PATIENT POPULATIONS (RARE DISEASES)
Primary Hyperoxaluria Type 1 (PH1)
We are developing DCR-PHXC for the treatment of PH1. PH1 is a rare inborn error of metabolism in which the liver produces excessive levels of oxalate, which in turn causes damage to the kidneys and to other tissues in the body. In preclinical models of PH, DCR-PHXC reduces oxalate production to near-normal levels, ameliorating the disease condition. DCR-PHXC is in preclinical development, and has advanced into IND-enabling studies. We plan to file an Investigational New Drug (IND) submission and/or Clinical Trial Application (CTA) for DCR-PHXC in late 2017 and commence human clinical trials shortly thereafter.
In the third quarter of 2016, we announced that we had transitioned our PH1 program to DCR-PHXC from DCR-PH1, a lipid nanoparticle (LNP) formulated RNAi compound, as we move forward with the GalXC RNAi technology platform. DCR-PH1 was being studied in two clinical trials, DCR-PH1-101 in patients with PH1 and DCR-PH1-102 in normal healthy volunteers (NHVs).
We presented initial data from the NHV study at the 17th Congress of the International Pediatric Nephrology Association (IPNA) in Iguaçu, Brazil on September 22, 2016. We believe these data provide the proof of concept for the pharmacological activity of RNAi-based therapy in PH1.
Genetic Orphan Disease
Dicerna launched a GalXC research program that targets a liver-expressed gene involved in a serious rare disease. The compound is currently in preclinical development.
COMPLEX DISEASES WITH LARGE PATIENT POPULATIONS
Hypercholesterolemia (PCSK9 targeted therapy)
We are using our GalXC RNAi platform to develop a therapeutic that targets the PCSK9 gene for the treatment of hypercholesterolemia. PCSK9 is a validated target for hypercholesterolemia, and there are United States (U.S.) Food and Drug Administration (FDA)-approved therapies targeting PCSK9 that are based on monoclonal antibody (MAb) technology. Based on preclinical studies, we believe that our GalXC RNAi platform can produce a PCSK9-targeted therapy with more attractive commercial properties than existing MAb therapies, based on comparatively smaller subcutaneous injection volumes and less frequent dosing, while providing equal or superior control of serum cholesterol.
An undisclosed rare disease involving the liver
We are developing a GalXC-based therapeutic, targeting a liver-expressed gene involved in a serious rare disease. For competitive reasons we have not yet publicly disclosed the target gene or disease. We have selected this target gene and disease based on criteria that include having a strong therapeutic hypothesis, a readily-identifiable patient population, the availability of a potentially predictive biomarker, high unmet medical need, favorable competitive positioning, and what we believe is a rapid projected path to approval. We plan to file an IND for this program in the second quarter of 2018.
Chronic Hepatitis B Virus infection
We are using our GalXC RNAi platform to investigate potential pharmaceutical treatments for chronic Hepatitis B Virus (HBV). More than 350 million people are infected with HBV worldwide. Current therapies rarely lead to a long-term immunological cure as measured by the clearance of HBV surface antigen (HBsAg). Based on preclinical studies, Dicerna believes that its GalXC RNAi platform has the potential to produce an experimental HBV-targeted therapy that eliminates HBsAg expression in HBV patients and can be delivered in a commercially attractive subcutaneous dosing paradigm.
Chronic Liver Disease
Dicerna is using its GalXC RNAi platform to investigate potential pharmaceutical therapeutic options for the treatment of chronic liver diseases (CLDs) such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), progressive familial intrahepatic cholestasis (PFIC), and other indications. Estimates suggest that more than three million Americans live with some form of chronic liver disease. Based on preclinical studies, Dicerna believes that its GalXC RNAi platform enables exquisite targeting of hepatocytes and the silencing of injury-responsive mRNAs that result in release of profibrotic damage signals offering a novel approach to developing potential therapeutics for the treatment of CLD.