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 (PH)
DCR-PHXC, a subcutaneously delivered GalXC-based investigational therapy for treating all forms of primary hyperoxaluria (PH), is the lead investigational product candidate in Dicerna’s pipeline of therapies targeting rare diseases of the liver. Dicerna is preparing to file a clinical trial application in the EU in the fourth quarter, 2017, and plans to begin Phase 1 clinical trials in early 2018 as the Company pursues its goal of developing new therapies that address the full range of patients with PH.
PH is a family of severe, rare, genetic liver disorders characterized by overproduction of oxalate, a natural chemical in the body that is normally eliminated as waste through the kidneys. In patients with PH, the kidneys are unable to eliminate the large amount of oxalate that is produced, and the accumulation of oxalate can result in severe damage to the kidneys and other organs. Currently, there are no approved therapies for the treatment of PH in the US.
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. Based on the Company’s candidate development work during the fourth quarter of 2016, Dicerna is positioned to advance DCR-PCSK9, which targets the PCSK9 gene and will be evaluated for the treatment of statin-refractory patients with hypercholesterolemia, into formal preclinical development. PCSK9 is a validated target for hypercholesterolemia, and there are FDA-approved therapies targeting PCSK9 that are based on monoclonal antibody technology. Based on preclinical studies, we believe that our GalXC RNAi platform can produce a PCSK9-targeted therapy with attractive commercial properties, such as small subcutaneous injection volumes and less frequent dosing.
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
Dicerna is using its GalXC RNAi platform to investigate potential pharmaceutical treatments for HBV. Current therapies for HBV rarely lead to a long-term immunological cure as measured by the clearance of HBV surface antigen (“HBsAg”) and sustained HBV deoxyribonucleic acid (“DNA”) suppression. Based on preclinical studies, we are evaluating whether our GalXC RNAi platform can produce an experimental HBV-targeted therapy that profoundly reduces HBsAg expression in HBV patients and that has the potential to be delivered in a commercially attractive subcutaneous dosing paradigm. Dicerna would expect to file an IND or a CTA around the end of 2018.
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.