Eli Lilly bets on an RNA base editing outfit leveraging the body's own enzymes to reverse mutations
With its controversial Alzheimer’s med donanemab nearly ready for FDA scrutiny, Eli Lilly has grown more emboldened in its efforts to become the top dog in neuroscience. A new partnership with a quiet RNA editing player focused around neuroscience could now add even more bite to Lilly’s bark.
Lilly will pay $50 million in upfront cash and equity and up to $1.25 billion in downstream milestones for access to five RNA editing candidates from Dutch biotech ProQR Therapeutics, which is using edited oligonucleotides to kick off an RNA base editing system initiated by the body’s own enzymes, the partners said Wednesday.
ProQR’s oligonucleotide platform, dubbed Axiomer, recruits “endogenous” enzymes in the cell — which are known as adenosine deaminases acting on RNA, or ADARs — to attach to target RNA and induce an adenosine to inosine base switch, what’s called A-to-I.
When that edited RNA is transcribed, the inosine is interpreted as guanosine, effectively creating an A-to-G switch. That’s important because ProQR thinks its platform could address around 20,000 known G-to-A mutations that are associated with human disease. The first targets in the collab are liver and nervous system diseases, ProQR said, and represent a change of pace for the biotech’s pipeline, which is currently focused on genetic eye disease with a lead candidate in late-stage clinical testing.
“RNA editing is an exciting emerging technology, which allows transient, reversible editing, which in some indications may be an extremely attractive therapeutic approach,” said Andrew Adams, Lilly’s VP for new therapeutic modalities, in a statement. “Through this collaboration with ProQR, we hope to utilize this technology to unlock novel treatments to improve the lives of patients across a spectrum of diseases.”
It’s an approach similar to the technology for which Roche recently earmarked more than $3 billion in a tie-up with Shape Therapeutics, also targeting ADARs. That family of enzymes is particularly attractive for brain cell RNA editing, potentially due to naturally high levels of expression there. Roche and Shape say they’re going after Alzheimer’s and Parkinson’s, among other diseases, and it’s not a stretch to say that Lilly — with Alzheimer’s candidate donanemab near filing — could be interested in those targets as well.
This partnership represents a continued effort on Lilly’s part to expand its next-gen RNA therapeutics wing as well as its work in neuroscience, which has received a big shot in the arm from donanemab’s resurrection after the controversial Aduhelm approval. Late last month, Lily announced it would spin its umbrella BioMedicines unit off into two new business areas — neuroscience and immunology — indicating the company’s renewed focus on the central nervous system.
Meanwhile, Lilly has inked deals in RNA therapeutics and gene editing, taking a broad swing at next-gen meds. In April 2019, the drugmaker signed a deal with Avidity Biosciences worth $35 million upfront and $405 million per opt-in for the biotech’s platform that combines monoclonal antibodies and oligonucleotide-based therapies targeting RNA. The initial focus area for the partnership was immunology, the partners said at the time.
More than a year later, in November, Lilly agreed to a partnership with Precision BioSciences worth $100 million upfront for molecules out of that biotech’s in vivo gene editing platform based on the I-Crel enzyme with an initial focus in Duchenne muscular dystrophy.
ProQR, meanwhile, has been working on edited oligonucleotides, what it calls EONs, for quite some time but primarily focused on genetic eye disease. The biotech’s lead drug, sepofarsen for Leber congenital amaurosis 10, is currently in Phase II/III testing with an interim readout scheduled for the first half of 2022.
According to CEO Daniel de Boer, ProQR’s platform can touch a range of genetic mutations across organs, putting liver and brain disease well within range. Those certainly aren’t easy therapeutic areas and ones that require a high degree of tissue specificity, but de Boer thinks having Lilly on board will help in terms of refining areas of therapeutic need.
“We said, ‘what if we can enable others to use this technology but for other therapeutic areas that are non-core to us?'” de Boer said. “That’s what led to this partnership with Lilly where we will help on the RNA side but they will eventually take the drugs into development. So it’s really combining our expertises where we contribute all our know-how on the RNA science and they bring in the therapeutic area expertise.”
With its platform “ready for primetime,” ProQR will likely declare its first candidate in this partnership within the next 12 months, de Boer said.