Novo Nordisk and Dicerna Announce Collaboration to Develop RNAi Therapies for Cardiometabolic Diseases Affecting the Liver

Today, Novo Nordisk and Dicerna Pharmaceuticals announced a research agreement to jointly develop RNAi therapies for the treatment of liver-related cardiometabolic diseases, leveraging Dicerna’s proprietary GalXC RNAi technology platform. The collaboration aims to explore more than 30 hepatocyte targets, potentially yielding multiple clinical candidates for chronic liver disease, non-alcoholic steatohepatitis (NASH), type 2 diabetes, obesity, and rare diseases. Also today, The Medicines Company released robust efficacy and safety data for its RNAi therapy inclisiran, signaling that the RNAi therapeutic modality is increasingly being applied to treat common diseases with larger patient populations.

RNA interference is a biological process in which certain RNA molecules inhibit the expression of disease-causing genes by degrading their messenger RNA (mRNA). Rather than targeting and binding to proteins to inhibit their activity, RNAi acts at an earlier stage by targeting and silencing the mRNA that directs protein synthesis. This mechanism enables RNAi to target any molecule, including disease-causing genes that are inaccessible to conventional antibodies and small-molecule drugs. Furthermore, RNAi therapies can reduce dosing frequency and prolong therapeutic effects, offering greater convenience for patients.

Dicerna’s GalXC RNAi technology platform is designed to advance the development of next-generation RNAi therapeutics for silencing disease-causing genes in the liver and other tissues. GalXC therapeutics are processed by the Dicer enzyme, which represents the natural entry point of the RNAi pathway in human cells. Dicerna’s researchers use GalXC to directly conjugate N-acetylgalactosamine (GalNAc) sugars to Dicer-substrate small interfering RNA (DsiRNA) molecules, which can only be cleaved by the Dicer enzyme. This approach stabilizes the RNAi duplex while enabling flexible and efficient conjugation of targeting ligands. Dicerna believes that this chemical modification enables subcutaneous delivery of RNAi therapeutics to the liver, where they specifically bind to receptors on target cells, thereby facilitating cellular uptake of the RNAi therapeutics. By leveraging Dicer as the processing enzyme for RNAi, the activity of the RNAi pathway is optimized to operate with maximal specificity and efficacy.

▲Dicerna’s RNAi therapy design (Image source: Dicerna official website)

Under the terms of the agreement, Dicerna will be responsible for the preclinical development of each candidate drug, while Novo Nordisk will be responsible for the further development of selected candidates. Both parties are eligible to commercialize the developed drugs. Dicerna will receive an upfront payment of $175 million and a $50 million equity investment. Additionally, upon completion of the development of the planned RNAi therapies, Dicerna will be eligible to receive an additional $75 million in payments over the first three years, as well as potential milestone payments of $357.5 million per developed drug and future sales royalties.

“We are pleased to expand the therapeutic scope of the GalXC platform to a broad range of hepatocyte targets, thereby increasing our development opportunities in the field of severe liver disease,” said Dr. Douglas M. Fambrough, President and Chief Executive Officer of Dicerna. “Novo Nordisk’s expertise in cardiovascular diseases and its years of experience in developing and commercializing innovative therapies globally will help us develop novel RNAi therapeutics to benefit the large patient population with unmet medical needs.”

“Dicerna’s RNAi therapeutics platform has the potential to yield multiple treatment candidates across disease areas such as diabetes, obesity, cardiovascular disease, and NASH,” said Marcus Schindler, Senior Vice President of Global Drug Research and Development at Novo Nordisk. “We will collaborate with Dicerna to leverage this emerging technology to achieve greater success in drug development.”

References:

[1] Dicerna and Novo Nordisk Enter Agreement to Discover and Develop RNAi Therapies for Liver-Related Cardio-Metabolic Diseases, Retrieved November 18, 2019, from https://www.businesswire.com/news/home/20191118005269/en

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