Circio (CRNA) investor relations material

Technology overview

• Developed a circular RNA-based gene expression platform (circVec) that enables enhanced and prolonged gene expression for vector-based therapeutics.

• circVec offers a novel alternative to conventional mRNA approaches, with unique intellectual property and know-how in circRNA gene expression.

• Circular RNA is naturally resistant to degradation and has a half-life exceeding 600 hours, compared to ~10 hours for mRNA.

Performance and efficacy

• circVec achieves up to 75x longer half-life and up to 50x higher protein expression than mRNA-based vectors.

• In heart tissue, circVec-AAV delivers 40x higher gene expression than conventional mRNA-AAV, with consistent performance across a wide dose range.

• Enables at least 10-20x dose reduction while maintaining or enhancing gene expression levels.

• 80% of heart cells show positive circRNA expression at low doses, a substantial improvement over benchmarks.

Specificity and safety

• circVec increases on-target heart activity and reduces off-target liver expression, with 35x higher total heart expression and very low liver expression.

• Advantage is driven by a 96x increase in RNA transcript levels in target tissue, with no significant difference in vector copy number.

• circVec-AAV shows consistently reduced cellular stress response and less activation of the UPR pathway, indicating lower toxicity compared to mRNA vectors.