Circio (CRNA) R&D update summary

R&D and Technology Update

• circVec AAV technology demonstrated up to 50x higher gene expression in the eye and 40x in the heart, with 80% of heart cells positive after systemic delivery, validating robust, reproducible performance across organs.

• circVec enables enhanced and prolonged gene expression, with expression advantage driven by RNA transcript levels rather than vector copy number.

• Dose-sparing potential allows for 10-20x lower doses while maintaining or improving efficacy, reducing toxicity and cost.

• circVec reduces off-target expression, particularly in the liver, and shows less cellular stress and improved safety profiles compared to traditional gene therapy.

• Optimized vector generations (3.0 and 4.0) achieved significant increases in protein yield and tissue specificity, especially in heart and eye.

Market Landscape, Competitive Positioning, and Industry Impact

• Circular RNA is a rapidly emerging field with high-value acquisitions and notable M&A activity, while circVec is differentiated by in vivo production and outperforms conventional gene therapy on expression, specificity, and toxicity.

• circVec is positioned as a platform technology with no direct competitors, offering unique advantages in gene and cell therapy and a differentiated window for in vivo cell therapy with >6 months expression on a single dose.

• The technology is complementary to other AAV enhancements and could be combined with targeted capsids for further improvements.

• Ongoing collaborations with big pharma and other partners aim to expand applications and delivery systems, with active pursuit of new partnerships targeting high unmet medical needs.

• Recognized in scientific and industry press for pioneering circular RNA technology.

Pipeline Progress, Future Plans, and Milestones

• Focus areas include gene therapy for heart, eye, and CNS, with ongoing preclinical work, disease-specific constructs, and collaborations in each.

• In vivo CAR program leverages circVec for long-lasting, non-integrating expression in immune cells, targeting cancer and autoimmune diseases.

• Remove and replace technology offers dual activity for diseases with toxic gene accumulation, under active exploration.

• Multiple data readouts and milestones are expected in Q2 and the second half of the year, including disease model efficacy and T-cell delivery results, with 2-3 new R&D collaborations targeted in 2026.

• Next steps include additional partnerships and further validation in disease models, with value inflection points anticipated from animal disease model data and T-cell targeting results.