· circVec 2.1 DNA vectors have now demonstrated higher and more durable
expression vs. conventional mRNA-based expression in vivo for up to five months
  · Machine learning sequence optimization has resulted in a new and enhanced
circVec 2.2 design, which increases protein expression by 2-4 -fold vs. circVec
2.1
  · The enhanced circVec expression durability can deliver substantial
improvement over current gold-standard gene therapy approaches
  · Circio management presents and discusses these data in a webcast published
today, 17 June 2024, watch the webcast here (https://redeye
-3.wistia.com/medias/bst2y63ily)

Oslo, Norway 17 June 2024 - Circio Holding ASA (OSE: CRNA), a biotechnology
company developing next generation circular RNA vector technology for gene
therapy, today announces updated in vivo data. This new data demonstrates a
substantial durability advantage of Circio's circVec technology over
conventional mRNA expression. In addition, Circio has undertaken sequence
optimization resulting in a new and enhanced circVec 2.2 design. The new data
are presented by CircioŽs scientific leadership team in a
webcast (https://redeye-3.wistia.com/medias/bst2y63ily) released today 17 June
2024.

"The circVec 2.1 design is performing very well in vivo, and Circio has now
validated expression for up to five months. This is a clear demonstration of a
substantial, and statistically significant, advantage over mRNA-based
expression. As a result, the data provides an important proof-of-concept for
CircioŽs circular RNA platform, which we expect will translate into improved
gene therapies for patients in the future," said Dr. Thomas B Hansen, CTO at
Circio. "In parallel, we have deployed machine learning to optimize circVec
sequence composition. This has enabled us to generate a new and even more
powerful circVec 2.2 design, which increases protein expression by 2-4 -fold vs.
circVec 2.1 constructs."

In parallel to the in vivo characterization, Circio has tested and incorporated
further features into the circVec platform. A dual-function 'remove-&-replace'
concept has been designed and validated in vitro for Alpha-1-antitrypsin
deficiency (AATD). This concept has the ability to both replace functional AAT
protein and remove the disease variant. AATD is a genetic disease that causes
severe symptoms in the lung and liver. There are currently no satisfactory
therapeutic options available, and AATD represents a major unmet medical need
with over 200,000 patients affected in the USA and EU.

"In recent months, Circio has made important progress with its circVec AATD gene
therapy constructs. We have now technically validated a very efficient and
selective 'remove' functionality to complement the robust and durable circular
RNA 'replace' expression of the AAT protein," said Dr. Victor Levitsky, CSO at
Circio. "Almost all gene therapies today are based on the AAV vector. We are
confident that circVec-based expression can enhance this format. CircioŽs first
circular RNA AAV constructs have now been validated in vivo, and their
performance compared to conventional mRNA-AAVs will be tracked over the coming
months. We expect that these data will be of considerable interest to
prospective gene therapy partners."

The new circVec data is presented and discussed by CircioŽs CEO, CSO and CTO in
a webcast released today 17 June 2024 available via CircioŽs webpage and the
Redeye platform.
Watch the webcast here (https://redeye-3.wistia.com/medias/bst2y63ily).

For further information, please contact:
Erik Digman Wiklund, CEO
Phone: +47 413 33 536
Email: erik.wiklund@circio.com

Lubor Gaal, CFO
Phone: +34 683343811
Email: lubor.gaal@circio.com

About Circio

Building next generation RNA therapeutics

Circio Holding ASA is a biotechnology company developing novel circular RNA gene
therapies and immunotherapy medicines.

Circio has established a unique circular RNA (circRNA) platform for genetic
medicine. The proprietary circVec technology is based on a modular genetic
cassette design for efficient biogenesis of multifunctional circRNA from DNA and
viral vectors, which can be deployed in multiple disease settings. The circVec
platform has demonstrated enhanced and more durable protein expression than
classic mRNA vector systems, and has the potential to become the new gold
-standard for DNA and virus-based therapeutics in the future. The circRNA R&D
activities are being conducted by the wholly owned subsidiary Circio AB based at
the Karolinska Institute in Stockholm, Sweden.

In addition, Circio is developing a cancer vaccine, TG01, targeting KRAS driver
mutations. TG01 is currently being tested in three clinical trials: RAS-mutated
pancreatic cancer and lung and non-resectable pancreatic cancer in US, and
multiple myeloma in Norway. These studies are being run through academic
collaborative networks, supported by prestigious research grants from Innovation
Norway and the Norwegian Research Council, creating read-outs and future
optionality for the program at low cost to Circio.