Circio (CRNA) R&D Update summary

Technology and Platform Development

• circVec 3.0 achieves up to 27-fold higher protein expression than initial designs and fourfold over the previous generation, with a new enhancer element to boost future designs.

• Circular RNA from circVec demonstrates up to 75 times longer in vivo half-life than linear mRNA, with over 600 hours observed in mouse muscle.

• In vivo studies show circVec maintains high expression for at least 170 days, outperforming mRNA vectors, especially at low and mid doses.

• circVec platform enables patient cells to act as circRNA factories, offering potent and durable protein expression for gene therapy and vaccines.

• Ongoing R&D includes optimization, new delivery methods, validation in new tissues, and collaborations to expand tissue targeting and non-viral delivery.

Preclinical Data and Performance

• circVec 2.1 shows 15x longer RNA half-life and up to 10x higher protein expression than mRNA in vitro.

• In vivo, circVec 2.1 achieves over 6 months of expression from a single injection in immuno-competent mice.

• At low doses, circVec 2.1 delivers up to 15x higher expression than mRNA at 170 days post-injection.

• circVec-AAV vectors validated in vivo, with expression levels on par or better than mRNA-AAV after 30 days.

• Bioinformatic modeling indicates up to 75x longer in vivo half-life for circVec vs. mRNA, with peak expression after 38 days.

Therapeutic Applications and Pipeline

• Lead focus is on gene therapy, aiming to improve potency, reduce dosing, and lower costs by enabling higher and longer-lasting protein expression.

• circVec is being explored for cell therapy and chronic diseases, with initial disease targets in muscular dystrophies such as limb-girdle and myotonic dystrophy.

• The platform allows for mono-, bi-, or tri-modal constructs, enabling protein expression, knockdown, and neutralization of disease-causing RNAs.

• Ongoing in vivo experiments target muscle, heart, lung, and brain, with prioritization based on upcoming data expected December–January.

• Lead candidate selection is expected by mid-2026, with clinical entry targeted within three years.