5:21 PM
 | 
May 02, 2019
 |  BC Innovations  |  Product Development

With a deal and a debut, targeted oligo delivery gets a boost from ADCs

How antibody-oligonucleotide conjugates could bring out the best of both modalities

The marriage of antibody-drug conjugates and oligonucleotides won two votes of confidence last month with a deal between Lilly and Avidity, and the debut of Atlas-backed Dyne Therapeutics. The approach promises delivery of oligos to tissues outside the liver, taking advantage of advances in both ADCs and oligo therapeutics, but faces design challenges to ensure the payload reaches intracellular targets at the right time and in the right dose.

On April 22, Eli Lilly and Co. obtained global rights to antibody-oligo conjugate technology from Avidity Biosciences LLC to develop therapies for immunology indications. Lilly paid $20 million up front and made a $15 million investment in Avidity, which is also eligible for up to $405 million in milestones per target. The identity and number of targets are undisclosed.

Prior to the deal, Avidity had raised a total of $30 million in venture financing since launching in 2014.

On April 3, Dyne Therapeutics Inc., which was founded and incubated by Atlas Venture, debuted with a $50 million series A to develop antibody-oligo conjugates. Forbion and MPM Capital also participated in the round.

The hope is that the modality will solve a problem that has dogged the oligo field -- the inability to deliver the therapies to tissues outside the liver. Naked siRNA and antisense oligos aren’t stable in circulation, and companies typically pack them into lipid nanoparticles (LNPs). But incorporating cell-specific targeting ligands into LNPs is difficult. Consequently, most are taken up by the liver, which filters them out of circulation.

“We’d rather not engineer a whole new system when we can take advantage of the learnings from ADCs.”

Arthur Levin, Avidity Biosciences

The first major breakthrough in cell type-specific delivery came with conjugation of oligos to GalNAc, a technique used by both Ionis Pharmaceuticals Inc. and Alnylam Pharmaceuticals Inc. The sugar moiety binds to a receptor on hepatocytes, however, so it does not solve the extra-hepatic delivery problem.

While a handful of companies have...

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