Circio (CRNA) R&D Update summary

Market and industry update

• Circular RNA is drawing strong commercial interest: Vertex-Orna agreed to a deal with $65M upfront and up to $635M in milestones, while Novartis-Kate announced a $1.1B deal.

• First clinical dosing of a circular RNA therapeutic occurred in April, marking a field milestone.

R&D progress: circVec platform

• After one systemic administration in mice monitored for up to six months, circVec-AAV showed 50% higher total expression than mRNA-AAV; early heart-specific data indicated up to 10-fold higher potency.

• In vivo and in vitro studies showed up to 35-fold higher protein expression in heart tissue and 10-fold in muscle, with higher on-target expression and reduced liver effects.

• DNA format #1 boosted circVec expression more than sixfold over plasmid DNA; LNP-circVec enables selective spleen expression and liver de-targeting, with potential for in vivo cell therapy.

• Muscle, heart and spleen are priority tissues, with potential applications in muscle and cardiac genetic disease and cell therapies; development includes AAV and DNA delivery approaches.

Business development and partnerships

• Collaborations with AAV, DNA and delivery technology specialists are underway to validate circVec externally and advance tissue-specific delivery.

• Seeking research and commercial partnerships, with plans to outlicense circVec while advancing selected programs in-house.