Circio (CRNA) R&D update summary

R&D and Technology Advancements

• circVec AAV technology demonstrated up to 50x improved gene expression in the eye and 40x in the heart, validated across multiple organs and with 80% of heart cells positive after systemic delivery.

• circVec enables enhanced, prolonged gene expression and significant dose-sparing (10-20x), reducing toxicity and cost while maintaining efficacy.

• Optimized vector generations (3.2 and 4.0) achieved tissue specificity, reduced off-target liver expression, and less cellular stress.

• Remove and replace technology allows for dual activity: knocking down toxic RNA and expressing functional proteins, expanding therapeutic potential.

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

Competitive Positioning and Industry Impact

• circVec differs from competitors by enabling in vivo circular RNA production, not synthetic RNA delivery, and outperforms conventional gene therapy on expression, specificity, and toxicity.

• Offers >6 months expression duration on a single dose, addressing major AAV gene therapy limitations like high dose requirements and toxicity.

• Recent high-value acquisitions and notable M&A/licensing activity in the RNA and AAV space highlight sector momentum, with circVec occupying a unique, non-overlapping niche.

• circVec's durability and tissue specificity make it suitable for genetic diseases requiring long-term expression.

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

Pipeline Progress and Future Plans

• Active programs in heart, eye, and CNS, with early CNS data showing promising improvements; collaborations with big pharma are ongoing.

• Disease-specific constructs for Danon disease (heart) and wet AMD (eye) are being developed and tested in vitro and in vivo.

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

• Multiple readouts expected in Q2, including CNS data, disease gene constructs, and T-cell delivery results.

• Aiming for 2-3 new R&D technology collaborations in 2026, with value inflection points from animal disease model data and T-cell targeting results.