Ionis Pharmaceuticals has exercised its option and entered into an exclusive worldwide license and collaboration agreement with Bicycle Therapeutics for tissue-targeted delivery of oligonucleotide therapeutics using Bicycle’s proprietary bicyclic peptides with high affinity to the transferrin receptor (TfR1).
 
Ionis had an option for an exclusive license under the terms of a December 2020 evaluation and option agreement. The agreement granted Ionis the right to evaluate tissue-targeting TfR1 binding Bicycles as vehicles to deliver oligonucleotide therapeutics to specific organ systems and an option to obtain an exclusive license at the end of the evaluation period.
 
Bicycle receives a total of $45 million upfront, which includes a license fee, an option fee, and an $11 million equity investment. Bicycle is eligible to receive development, regulatory and commercial milestone payments and royalties for each program developed under the collaboration.
 
“This agreement stems from a highly successful collaboration with Ionis that began earlier in the year, during which Bicycles were shown to selectively deliver oligonucleotide payloads into TfR1-expressing tissue,” said Kevin Lee, Ph.D., chief executive officer of Bicycle Therapeutics. “These data build upon our own work, and that of our partners, which have shown Bicycles targeted to tumor antigens can rapidly and selectively deliver a variety of payloads into solid tumors. This tissue-targeting payload-delivery capability is facilitated by the unique nature of Bicycles that inherently enables the conjugation of a diverse range of molecular cargos without impacting the pharmacology of the target. We believe Bicycles have the potential to become the targeting technology of choice for the development of precision medicines.”
 
Bicycle has identified binders that it believes to be the first small molecules to target TfR1 with high specificity without modifying TfR1’s natural function. These binders present broad conjugation potential across multiple payloads, thereby resulting in the potential to treat diseases in multiple therapeutic areas, including the skeletal and cardiac muscles and of the central nervous system. Bicycle is currently also collaborating with the Dementia Discovery Fund (DDF) to advance potential TfR1 Bicycles for treating dementia.
 
Under the terms of the license and collaboration agreement, Ionis and Bicycle will collaborate to develop a pipeline of oligonucleotide therapeutic product candidates delivered using the tissue-targeting TfR1 Bicycle technology, while Bicycle retains the rights to use TfR1 Bicycles for all non-oligonucleotide therapeutic purposes, including within its existing collaboration with DDF targeting dementia.