Circio (CRNA) R&D Update summary

Market and industry update

• Circular RNA is gaining traction in biotech due to its superior durability and expression over mRNA, with major deals like Vertex-Orna ($65M upfront, up to $635M milestones) and Novartis-Kate ($1.1B) highlighting strong commercial interest.

• The first clinical dosing of a circular RNA therapeutic occurred in April, marking a milestone for the field.

R&D progress and technology platform

• circVec technology enables in vivo expression of circular RNA, aiming to enhance AAV gene therapy potency and durability, especially for muscle and cardiac diseases affecting over 150,000 patients.

• circVec-AAV demonstrates up to 35-fold increased protein expression in heart tissue and 10-fold in muscle, with tissue-specific expression validated in vivo and sustained over time.

• DNA format #1 for circVec offers over 6x expression compared to plasmid DNA, with reduced cost, repeat dosing, and larger payload capacity.

• LNP-circVec achieves selective spleen expression, opening new avenues for in vivo CAR T and cell therapies, and enables de-targeting of liver expression.

• circVec demonstrates higher on-target expression in muscle and heart, with reduced off-target effects in the liver.

Business development and partnerships

• Multiple collaborations are underway with AAV, DNA, and delivery technology companies to validate circVec in external settings and expand tissue-specific applications.

• The company is actively seeking research and commercial partnerships, aiming to outlicense circVec while advancing select programs in-house.