Circio (CRNA) Corporate presentation summary

Platform performance

• circVec uses intracellular circular RNA accumulation to extend expression; platform materials report up to 60x higher protein expression than mRNA-based approaches.

• Design evolution from circVec 1.1 to 4.x delivered ~40x higher protein yield; optimized architecture outperformed conventional circRNA constructs by ~36x.

• In vivo intramuscular testing showed 75x prolonged RNA half-life and 15x higher peak expression versus mVec, with expression peaking at 38 days versus 2.3 days.

AAV gene therapy

• AAV9-circVec achieved 40x higher heart expression than mRNA-based AAV; heart-optimized designs reached ~190x expression advantage and 95% on-target heart expression with <1% off-target liver expression.

• RNAscope showed RNA in 80% of heart cells at 5e12 vg/kg; transcript levels per positive cell were 34x–58x higher than mVec, with reduced unfolded protein response activation.

• AAV-circVec showed up to 60x expression advantage in CNS and up to ~50x in the eye; cardiac dose-sparing potential was reported at 10–20x.

• Next steps include testing in genetic heart disease models, single-cell analysis for eye and CNS programs, and validation in non-human primates.

Nonviral DNA-LNP and cell therapy

• LNP-formulated DNA is being developed for repeat-dose in vivo cell therapy, with systemic delivery and liver and spleen targeting; the format delivers DNA rather than RNA.

• After one systemic dose, circVec spleen expression was confirmed for 6 months, versus mainly short-term liver expression for mVec; targeted LNP delivery produced spleen signal at all tested doses with >2 months’ durability.

• In vitro Jurkat T-cell testing showed enhanced and prolonged circVec expression versus mVec.

• Pipeline areas include in vivo CAR-T for B-cell malignancies and autoimmunity, plus AAV programs for heart, eye and CNS disease.