Entos Pharmaceuticals’ star is rising. Just a few short months after the biotech’s nucleic acid delivery tech helped land a deal with BioMarin, the Edmonton, Alberta-based Canadian company has teamed up with Eli Lilly for $50 million upfront to drive its proteolipid vehicles (PLVs) toward a range of nervous system targets.
Eli Lilly has picked up exclusive right to Entos’ Fusogenix nucleic acid delivery technology, which it will use to research, develop and potentially sell nucleic acid-based therapeutics against targets in the central and peripheral nervous systems, the companies said Thursday.
The deal breaks down like this: Lilly and Entos will collaborate on multiple programs that wed Lilly-supplied therapeutic cargo to Entos’ PLVs. Entos is on deck to generate, develop and optimize those PLVs on its proprietary Fusogenix platform. Lilly will then select PLVs to take into the clinic.
Entos is in line to receive $50 million upfront from the R&D pact, which includes an equity investment in the company by Lilly. Each program under the collaboration could net Entos up to $400 million more in potential development and commercial milestones, plus royalties should any of the products reach the market.
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“Overcoming barriers to the safe and effective delivery of [nucleic acid-based therapies] to specific target cells is essential to realizing their potential,” Andrew Adams, vice president of genetic medicine at Eli Lilly, said in a statement. Entos’ Fusogenix platform could hold the key to overcoming those challenges.
Nucleic-acid based therapies hold great potential, but they’re also hamstrung by the need to deliver genetic payloads directly to target cells without significant toxicity, Entos says on its website. “Gene therapy-clinical trials using cationic or ionizable lipid nanoparticle platforms have been disappointing due to high toxicity and an inability to target organs other than the liver,” the company continues.
Fusogenix, for its part, “combines the best features of viral and lipid-based approaches without the downsides of either,” Entos CEO and founder John Lewis, Ph.D., said in an emailed statement.
Entos’ PLVs are formulated with so-called fusion-associated small transmembrane proteins, or FAST proteins, plus neutral lipids for better tolerability. Fusogenix, which can be used to deliver a range of therapy types, such as gene therapy, mRNA, miRNA, RNAi and CRISPR, delivers mRNA or DNA into target cells through direct fusion.
Thanks to its tolerability, Fusogenix has the potential to work in a “wide variety” of tissues outside the liver, teeing up delivery of nucleic acid medicines “throughout the body,” Entos has said. It’s also suitable for repeat dosing because it isn’t immunogenic, meaning it doesn’t provoke an immune response. This makes the delivery technology ideal for long-term treatment of healthy patients, the company says.
“Because PLVs deliver nucleic acids through direct fusion, we are able to avoid the immune toxicity associated with endosomal uptake and escape,” Lewis explained. “Using FAST proteins has allowed us to re-imagine the lipid nanoparticle to create a safe, effective and redosable delivery platform suitable for gene knockdown, gene therapy, gene expression or gene editing approaches.”
Lilly isn’t the only pharma major showing interest in Fusogenix. Back in November, the company teamed up with BioMarin to apply its delivery tech to certain candidates in the company’s gene therapy pipeline. That deal will see Entos leverage Fusogenix to create specially formulated BioMarin drugs aimed at “multiple undisclosed genetic disease indications,” the companies said in November.
Further, the Lilly deal helps validate the idea that “the key to successful development of breakthrough genetic medicines is not the cargo, but the delivery vehicle that brings that cargo safely to the right cells in the right tissue at the right time,” Lewis said.
Editor's note: This story has been updated with additional comments from Entos.