Ionis pays Bicycle $45M to expand oligonucleotide delivery toolkit

Ionis pays Bicycle $45M to expand oligonucleotide delivery toolkit

Ionis Pharmaceuticals is paying $45 million upfront for the exclusive right to binders for the delivery of oligonucleotides to tissues expressing TfR1. The deal leaves Bicycle Therapeutics free to license the small molecules for the delivery of all molecular payloads outside of oligonucleotides.

Bicycle granted Ionis an option on the binders late last year. Since then, the partners have shown the synthetic bicyclic peptides developed by Bicycle can selectively deliver oligonucleotide therapeutics to TfR1-expressing tissues. TfR1, also known as CD71, is involved in cellular iron uptake, has been explored for drug delivery into the brain and is highly expressed in cardiac and skeletal muscle.

Ionis’ interest in TfR1 is part of its broader push to enable the targeted delivery of oligonucleotides by attaching them to ligands that bind to receptors found on specific cell types. Having landed the license, Ionis will work with Bicycle to develop ligand conjugated antisense medicines that hit TfR1.

The project builds on Ionis’ work to conjugate molecules such as GalNAc and a GLP–1 peptide to antisense oligonucleotides to get more of its drug compounds to targets including hepatocytes and beta cells in the pancreas. The Bicycle project puts a twist on the idea by using a class of binder that is designed to combine the best attributes of biologics and small molecules.

“This approach offers several potential advantages over related strategies in development, including increased potency, more convenient administration, less complex manufacturing processes and reduced cost of goods,” Eric Swayze, executive vice president of research at Ionis, said in a statement.

Ionis secured rights to the binders by paying $45 million and committing to development, regulatory and commercial milestone payments and royalties for each program developed through the alliance. The upfront payment includes an $11 million equity investment.

Bicycle retains the rights to use the binders in the delivery of modalities other than oligonucleotides. Having shown the molecules have broad conjugation potential across multiple payloads, Bicycle sees potential to use the binders in the treatment of multiple diseases affecting skeletal and cardiac muscles as well as the central nervous system. Bicycle is also studying the molecules in dementia.

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