Eli Lilly will apply Dicerna Pharmaceuticals’ GalXC™ RNA interference (RNAi) technology platform to discover, develop, and commercialize new treatments based on more than 10 targets in cardio-metabolic disease, neurodegeneration, and pain, through a collaboration that could generate more than $3.7 billion for Dicerna, the companies said today.
GalXC is designed to advance the development of next-generation RNAi-based therapies that are intended to work by silencing disease-driving genes across multiple therapeutic areas.
Among those therapeutic areas previously cited by Dicerna have been cardiovascular diseases, as well as chronic liver diseases, rare diseases, and viral infectious diseases.
But in disclosing its global licensing and research collaboration agreement with Lilly, Dicerna said it foresaw expanding RNAi treatments beyond those areas.
“The collaboration with Lilly provides an exceptional opportunity to leverage our 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,” Dicerna President and CEO Douglas M. Fambrough, Ph.D., said in a statement. “Lilly, with its demonstrated leadership in each of these fields, is an ideal partner for extending the range of Dicerna’s proprietary GalXC technology.”
GalXC molecules are structured to be processed by the enzyme Dicer, the initiation point for RNAi in the human cell cytoplasm. GalXC-based therapies are processed by the Dicer enzyme, which is the natural initiation point for RNAi within the human cell.
Using GalXC, Dicerna researchers attach N-acetylgalactosamine sugars directly to the extended region of the proprietary Dicer substrate short-interfering RNA (DsiRNA) molecules, yielding multiple conjugate delivery configurations that according to the company allow flexible and efficient conjugation to the targeting ligands while stabilizing the RNAi duplex.
In addition to advancing new GalXC therapies into clinical development and commercialization, the companies said, they will partner on developing a new nucleic acid platform technology to generate next-generation oligonucleotide therapies.
Lilly agreed to pay Dicerna $100 million upfront; make a $100 million equity investment at an undisclosed premium; and pay up to approximately $350 million per target in payments tied to achieving development and commercialization milestones—in addition to a $5 million payment “due when the first non-hepatocyte target achieves proof of principle,” Dicerna disclosed in a regulatory filing.
10+ Targets Anticipated
“The two companies anticipate collaborating on more than ten targets,” Lilly and Dicerna stated.
Lilly also agreed to pay Dicerna tiered royalties ranging from the mid-single to low-double digits on product sales. The companies’ collaboration agreement deal is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions.
“At Lilly, we go to where breaking science meets unmet medical needs,” added Daniel M. Skovronsky, M.D., Ph.D., Lilly SVP and CSO. “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. Together with Dicerna, we aim to employ this emerging modality for greater success in drug development.”
The partnership with Dicerna appears to mesh with two of Lilly’s scientific areas of interest: Neuroscience, and “emerging technology and innovation,” overseen by a team whose goals include “access to novel pathways and new therapeutic modalities.”
Investors appeared to share Lilly’s enthusiasm for the collaboration, responding with a stock-buying surge that sent Dicerna’s share price climbing nearly 17% from Friday’s close of $13.00 on the NASDAQ Global Select Market, to $15.10 a share as of 9:40 a.m.
For Dicerna, the agreement with Lilly is the second big-money RNAi collaboration with a biopharma giant in as many weeks. On Wednesday, Dicerna and Alexion Pharmaceuticals agreed to partner on discovering and developing RNAi therapies for complement-mediated diseases, through a collaboration that could generate more than $637 million for Dicerna.
Dicerna’s pipeline is led by one GalXC-generated clinical rare-disease candidate—the primary hyperoxaluria treatment DCR-PHXC, which last month generated positive preliminary results in the ongoing Phase I PHYOX trial (NCT03392896). On Thursday, Dicerna announced additional data associating DCR-PHXC with normalization or near-normalization of urinary oxalate levels in a majority of adult patients with primary hyperoxaluria types 1 and 2 (PH1 and PH2).
The rest of Dicerna’s pipeline consists of one clinical and two earlier “research” phase candidates for undisclosed rare diseases; preclinical candidates for hepatitis B virus (DCR-HBVS), hypercholesterolemia (DCR-PCSK9); a research-phase candidate for nonalcoholic steatohepatitis (NASH; DCR-LIV1) being developed through a potentially more-than-$201 million collaboration with Boehringer Ingelheim launched in November 2017; and four research-phase candidates for undisclosed cardiometabolic disorders.