Circio (CRNA) R&D update summary

R&D Progress and Technology Validation

• circVec AAV technology demonstrated up to 50x improved gene expression in the eye and 40x in the heart, with reproducible results and up to 80% of heart cells positive after systemic delivery, validating broad applicability.

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

• circVec enables enhanced and prolonged gene expression, with high tissue specificity and reduced off-target expression, especially in the heart and eye, improving safety profiles.

• Expression advantage is driven by RNA transcript levels, not vector copy number.

• Ongoing work includes moving from reporter genes to disease-relevant constructs for heart and eye, with in vivo studies and key data readouts planned.

Competitive Landscape and Differentiation

• circVec is differentiated by delivering genetic instructions for in vivo circular RNA production, unlike competitors using synthetic circRNA.

• Recent high-value acquisitions and notable M&A activity in the circRNA and AAV space highlight industry interest, but circVec occupies a unique, non-overlapping niche.

• circVec's approach is complementary to other AAV enhancement technologies, with potential for future collaborative combinations.

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

In Vivo CAR and Cell Therapy Applications

• circVec enables long-lasting, non-integrating gene expression in immune cells (up to 6 months), filling a gap between short-lived RNA and permanent lentiviral approaches.

• Avoids liver expression and targets spleen-resident immune cells, supporting cancer-focused in vivo CAR applications.

• Active research and collaborations are ongoing to optimize delivery systems for in vivo CAR, with updates expected in Q2/Q3.