· Two posters demonstrate in vivo superiority of circular RNA vs. linear mRNA
-based expression and technical proof-of-concept for CircioŽs Žremove-&-replaceŽ
gene therapy format for the unmet medical need AATD
  · The posters were presented at the American Society of Gene & Cell Therapy
(ASGCT) 2024 annual meeting 7-11 May in Baltimore, USA

Oslo, Norway, 13 May 2024 - Circio Holding ASA (OSE: CRNA), a biotechnology
company developing circular RNA-based gene therapy, today announces that it has
presented two posters that demonstrate in vivo proof-of-concept for its powerful
and differentiated circVec platform approach to gene therapy. The two posters
were presented at the American Society of Gene & Cell Therapy (ASGCT) 2024
annual meeting 7-11 May in Baltimore, USA

"Circio has generated results demonstrating that the circVec 2.1 design performs
very well in vitro. We have now confirmed this in vivo with statistically
significant higher expression level and durability for circVec 2.1 DNA vectors
compared to standard linear mRNA-based expression. These results provide an
important technical proof-of-concept for CircioŽs technology platform in an
animal model. We now have confirmation for our expectation that this could
translate into improved gene therapies for patients in the future," said Dr.
Thomas B Hansen, CTO at Circio. "In recent experiments, Circio has observed up
to four months circVec durability in vivo. This substantially outperforms mRNA
vector expression. Following these results, we can rapidly advance to design and
test circVec in several AAV and DNA-based vectors. This will validate these very
promising data in therapeutically relevant formats."

At ASGCT, Circio also presented the dual-function 'remove-&-replace' concept for
Alpha-1-antitrypsin deficiency (AATD). This genetic disease causes severe
symptoms in the lung and liver. There are currently no satisfactory therapeutic
options available for this indication and AATD still represents a major unmet
medical need. There are over 200,000 AATD patients affected in the USA and EU
alone. With the technologically differentiated circVec remove-&-replace format,
Circio has developed a unique gene therapy concept that can deal with both the
lung and liver-associated symptoms in one single therapeutic.

"AATD is a challenging genetic disease to treat. This is in part due to the two
distinct pathologies in the liver and lung," said Dr. Victor Levitsky, CSO at
Circio. "We have now established and technically validated circVec constructs
that can both replenish functional wild-type AAT and specifically remove more
than 90% of the mutated protein. This is challenging to achieve because the
functional and mutant forms are very similar. By using circular RNA-based AAT
expression, Circio is uniquely able to separate the two species for mutant
-specific knockdown, thereby solving two problems with one single product."

Optimization and In Vivo Performance of circVec, a Vector-Based Circular RNA
Expression Platform