INDIANAPOLIS & CAMBRIDGE, Mass.—Toward the end of 2018, Eli Lilly and Co. and Dicerna Pharmaceuticals Inc. announced the closing of a global licensing and research collaboration announced in October, following clearance under the Hart-Scott Rodino Antitrust Improvements Act of 1976. The collaboration focuses on discovery, development and commercialization of gene-silencing targets in the areas of cardio-metabolic disease, neurodegeneration and pain using Dicerna’s proprietary GalXC RNA interference (RNAi) technology platform.
Under the terms of the agreement, Lilly has agreed to an upfront payment of $100 million, as well as purchasing a $100 million stake in Dicerna at a premium—according to report in Reuters, Lilly agreed to purchase these shares at $18.47 per share, which represents a 42-percent premium to Dicerna’s close at $13 per share prior to the announcement. Additionally, Dicerna is eligible to receive up to approximately $350 million per target in development and commercialization milestones, as well as tiered royalties on product sales.
“Dicerna will develop the GalXC molecule in the preclinical development phase,” says Dr. Douglas M. Fambrough, president and CEO of Dicerna. “Lilly will then be responsible for conducting the clinical trials and potential commercialization of GalXC molecules as part of this collaboration.”
“The two companies anticipate collaborating on more than 10 targets,” he adds.
The GalXC platform invented by Dicerna was designed to promote the development of next-generation RNAi-based therapies that target and silence disease-driving genes by inhibiting the expression of specific genetic material and blocking the production of targeted proteins. Compounds produced via GalXC have been used extensively in liver gene targets, and are intended to be broadly applicable to multiple therapeutic areas and tissue types.
“For liver gene targets, a straightforward application of our GalXC platform should generate clinical candidate molecules without great challenge,” says Fambrough. “Indeed, this simplicity of application is part of what attracted Lilly … Our GalXC technology platform optimizes the activity of the RNAi pathway so that it operates in the most specific and potent fashion, and Lilly recognized that the platform can generate drug candidates objectively with excellent pharmaceutical properties.”
“In addition, the proprietary RNA structure in the GalXC platform is particularly amenable to exploring delivery to non-liver tissues,” he notes. “With the partnership with Lilly, we look forward to exploring new tissues, such as additional organs in the cardio-metabolic system and neural tissues relevant to neurodegeneration and pain indications.”
“Taking the GalXC platform to additional tissues, through modifications of the chemistries and perhaps with new targeting ligands, may present some technical challenges that we believe are highly solvable,” says Fambrough. “We’ve initiated work in animal models for delivery to neural tissues using our GalXC molecules, and we’ve already generated high potency RNAi activity.”
Gene silencing and RNAi represent a cutting edge of medical research that has the potential to treat a variety of diseases with well-validated but previously inaccessible drug targets. Several large pharmaceutical companies, including Lilly and Johnson & Johnson, are investing heavily in this field of research.
“At Lilly, we go to where breaking science meets unmet medical needs,” Dr. Daniel M. Skovronsky, Lilly’s senior vice president and chief scientific officer, said in a media release announcing the agreement. “We are excited to collaborate with Dicerna and utilize their RNAi expertise to study targets that up until now have proven to be very technically challenging. RNAi has the potential to treat an array of diseases that are of strategic importance to Lilly.”
According to Tamara Mathias, reporting for Reuters in October 2018, Alnylam Pharmaceuticals Inc.’s compound Onpattro (patisiran) became the first RNAi drug approved for use in the United States. In August, the U.S. Food and Drug Administration approved the drug for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis, a rare disease with no previous form of treatment.
“Lilly and Dicerna started talking about the GalXC technology back in 2016, but things really kicked into high gear in 2018,” Fambrough comments. “I believe Lilly has recognized the emerging power of nucleic acid modalities such as RNAi. As conversations progressed, we decided to collaborate both on GalXC and extending GalXC to additional tissues.”
Dicerna has inked several high-profile collaboration deals in recent years. The company announced a $200-million deal with Boehringer Ingelheim in November 2017. Only a week before the Lilly partnership was announced, Dicerna also struck a deal with Alexion Pharmaceuticals worth a potential total of more than $140 million.
“Our business’ strategy is to retain full or substantial ownership stake in its key rare disease programs, while pursuing partnerships for more complex diseases with multiple gene dysfunctions and larger patient populations,” explains Fambrough. “This partnership with Lilly fits in very well with our partnering strategy.
“The collaboration with Lilly provided an exceptional opportunity for Dicerna to leverage its proprietary GalXC platform in order to generate new medicines for cardio-metabolic diseases, and to establish a presence in new fields including neurodegeneration and pain,” he continues. “With Lilly’s demonstrated leadership in each of these fields, it is an ideal partner for extending the range of Dicerna’s proprietary GalXC technology.”