Circio Holding

Circio Holding ASA (“Circio” or “the Company”) published, on the 28th of October 2026, the materials for its oral and two poster presentations at the European Society of Gene and Cell Therapy (ESGCT) Annual Congress in Hamburg. The materials present a new heart-optimized AAV9 circVec 5.2 design reaching approx. 200x higher gene expression than conventional mRNA-based AAV9, with approx. 95% of the expression occurring in the heart (25%) and less than 1% in the liver (9%).

---

Analyst Group’s View on the ESGCT Data

The expression multiples for heart, eye and CNS had already been disclosed, as had the 200x target for the fifth generation, set out at Circio’s R&D update in September. What the materials add is the circVec 5.2 design, delivering the 200x in vivo alongside a sharper split between on-target and off-target expression, both measured with a reporter gene.

Among the additions, the specificity data carry the most weight. A vector delivered into the bloodstream distributes beyond its target organ, and protein produced outside the heart, principally in the liver, contributes nothing therapeutically while raising the risk profile. The posters track this across successive generations, with the share of expression occurring in the heart rising from 25% for conventional AAV to approx. 65% for circVec 3.2 and approx. 95% for circVec 5.2, while the share in the liver falls from 9% to approx. 4% and then below 1%. This matters because viral dose is the binding constraint in AAV gene therapy. Higher viral dose means both greater risk of serious side effects and higher manufacturing cost, and Analyst Group assesses that a construct delivering more protein to the heart and less elsewhere allows a lower viral dose for the same effect, which is often what decides whether an indication is treatable at all.

Circio presented the fifth generation at its September R&D update as having the potential to exceed conventional AAV by 200x or more. That figure has now been measured in vivo in heart, compared to approx. 40x for circVec 3.2. Analyst Group considers the demonstration more significant than the number itself, as a stated ambition has been fulfilled two months after it was set out. The measurement used a reporter gene, establishing the platform’s expression power rather than a therapeutic effect for a therapeutic protein.

The expression data reported for heart, eye and CNS to date rest on firefly luciferase, a reporter gene whose expression can be tracked in a living animal but which has no therapeutic function, leaving a standing question for prospective partners as to whether the advantage holds for a therapeutic protein. Using LAMP2B, a protein relevant in genetic heart disease, circVec 3.2 produced materially more RNA and more protein in heart than conventional AAV across two separately optimized versions of the gene. The advantage therefore carries over, addressing the question Analyst Group identified in its H1-26 analysis as outstanding, though these remain initial results generated with circVec 3.2. Reporter expression in heart has since risen from approx. 40x with that construct to approx. 200x with circVec 5.2, and Analyst Group would expect the therapeutic-protein data to improve as the newer designs are applied.

In summary, Analyst Group views the ESGCT materials as adding precision to the platform’s characterization alongside the step up in heart expression, with the cardiac specificity the most important addition. What remains open is whether the additional protein makes diseased animals better, which the in vivo heart disease-model studies are designed to establish. Circio expects those studies to begin in Q1-27, with read-outs during the year, in line with the six-to-twelve-month guidance given in September, while the R&D webcast at the end of November, presenting in vivo heart and eye results expected to complete during the month, is the nearer-term test.

---

About ESGCT

The European Society of Gene and Cell Therapy (ESGCT) is the principal professional organization for gene and cell therapy in Europe. Its annual meeting is the largest conference in the field in Europe and the second largest globally, attended by academic researchers, pharmaceutical and biotechnology companies, patient advocacy organizations and life science media, and only a limited share of submitted abstracts are selected for oral presentation.