Circio (CRNA) Company presentation summary

Platform and market

• circVec is a proprietary circRNA-based gene-expression platform designed to deliver genes and produce stronger, longer-lasting expression than mRNA; cited platform comparisons report up to 75x longer RNA lifetime and up to 60x more protein.

• circRNA is presented as more durable than mRNA, flexible and versatile, with a low immune response; three major industry transactions were highlighted over the prior 9 months, including deals valued at up to $2.5B.

• circVec targets gene therapy for inherited heart, eye and nervous-system diseases, plus cell therapy for cancer and autoimmunity.

Preclinical gene therapy evidence

• In animal studies, AAV-circVec showed up to 40x higher cardiac gene expression than mVec; the advantage was also demonstrated with therapeutic LAMP2B expression for Danon disease.

• Heart studies reported 35x higher total expression, reduced unwanted liver expression and 96x more cardiac RNA than mVec, with no significant difference in vector-copy number.

• AAV-circVec showed up to 50x higher eye expression; a low dose produced 12x more expression than a 10x higher mVec dose.

• CNS studies showed ~10x–60x expression advantages across three delivery methods; further analyses and systemic testing were ongoing.

• circVec generation 5 has potential for >200x improvement versus mRNA-based AAV; milestones include disease-model studies, larger-animal data and therapeutic-gene validation.

In vivo cell therapy

• circVec DNA is positioned to enable redosable in vivo CAR-T treatment, with >6 months of effect from one dose while avoiding genome integration.

• T-cell-targeted LNP studies showed spleen-specific circVec expression for >3 months; cell-type mapping, LNP screening and immune-silent DNA-vector testing were underway.

• The approach combines an expression system, vector and delivery technology; T-cell-targeted LNPs are intended to reduce off-target effects.