Dicerna Receives $10M Milestone Payment from Lilly as FDA Authorizes IND for RNAi Therapy LY3561774

Compiled by Hemingway

On November 16, Dicerna Pharmaceuticals, Inc., a developer of RNA interference (RNAi) gene therapy drugs, announced that the U.S. FDA has authorized the Investigational New Drug (IND) application for LY3561774, a novel drug candidate developed in collaboration with Eli Lilly and Company. This marks the first clinical-stage candidate from the partnership between Dicerna and Eli Lilly.

The approval of this authorization triggered a $10 million milestone payment from Eli Lilly to Dicerna. Meanwhile, Eli Lilly will conduct Phase I clinical trials for LY3561774 in the later stage. According to prior planning, patient enrollment for this trial was expected to be completed by the end of 2020, primarily for the treatment of a cardiovascular metabolic disease with unknown causes.

In addition, Dicerna is eligible to receive up to $350 million in development and commercialization milestone payments for applications of the GalXC™ platform in hepatic metabolic diseases, as well as $355 million in milestone payments for non-hepatic metabolic disease applications, along with tiered royalty fees ranging from mid-single digits to low double digits on potential product sales.

Dicerna’s collaboration agreement with Eli Lilly was reached in 2018, focusing on the discovery, development, and commercialization of potential new therapies for metabolic diseases, neurodegenerative diseases, and pain. Since the establishment of the partnership, the two parties have initiated more than ten development programs. The Investigational New Drug (IND) application for LY3561774 marks the first milestone achievement under the global licensing and research collaboration between Dicerna and Eli Lilly established in 2018. This collaboration leverages Dicerna’s RNA interference (RNAi) technology and platform to develop investigational cardiometabolic therapies and future treatments.

For Eli Lilly, this provides strong support for launching RNAi therapeutic candidates into the market in 2021 and beyond, thereby enhancing its R&D pipeline. Meanwhile, RNAi-based drugs have the potential to become effective and convenient treatment options for severe diseases with significant unmet medical needs.

Dicerna’s proprietary RNAi technology platform, known as GalXC™, is designed to advance the development of next-generation RNAi-based therapeutics capable of silencing driver genes in liver diseases. Additionally, GalXC-based compounds enable subcutaneous delivery of RNAi therapeutics by specifically binding to receptors on hepatocytes, thereby facilitating cellular internalization and intracellular RNAi activity.

The advantage of the GalXC approach is that it optimizes the activity of the RNAi pathway, enabling it to function in the most specific and effective manner. Dicerna is currently exploring new applications for its RNAi technology beyond the liver, targeting other tissues and enabling novel therapeutic applications.

RNA interference (RNAi) is a biological process in which certain double-stranded RNA molecules inhibit the expression of disease-causing genes by degrading their messenger RNA (mRNA). It represents a novel avenue for developing specific and effective therapies. Rather than targeting and binding to proteins to inhibit their activity, RNAi acts earlier in the gene silencing pathway by targeting mRNA—the set of instructions that guide protein synthesis. By leveraging this instructional framework, RNAi is considered capable of targeting any molecule, including disease-causing genes that are inaccessible to conventional antibodies and small-molecule drugs. Therefore, by silencing pathogenic genes, the RNAi platform holds the potential to address diseases that are difficult to treat with other modalities.

Reference Source: Dicerna Announces FDA Acceptance of Lilly’s Investigational New Drug (IND) Application for First GalXC™ RNAi Candidate Under Companies’ Global Research Collaboration and Licensing Agreement