· New circVec 2.0 design boosts protein expression by up to 10-fold vs. circVec
1.0
  · Bioinformatic simulation indicates 10-30-fold higher maximum protein
expression vs. mRNA-based systems
  · circVec has the potential to replace mRNA as the preferred expression system
for all viral and DNA-based therapeutics in the future

Circio established the first generation circVec 1.0 genetic cassette based on
"NatureŽs best design" for human circRNA expression. Following rational,
targeted optimization of specific sequences and regulatory elements, Circio has
been able to further improve the circRNA biogenesis and translation rate,
resulting in up to 10-fold increase in protein payload expression. To CircioŽs
knowledge, circVec 2.0 far exceeds any other known intra-cellular circRNA
expression system, both in terms of circRNA biogenesis efficiency and protein
yield.

Thomas Birkballe Hansen, VP and head of Research at Circio said: "We are
continuing to evolve our circVec platform, and the enhanced 2.0 design drives
potent and persistent protein expression. Durability and toxicity are major
issues facing todayŽs gold-standard gene therapy approaches, which we believe
can be overcome by switching from current mRNA-based expression to our circVec
system. We have not reached the full potential of our technology yet, and we are
continuously exploring further optimization strategies towards circVec 3.0 and
beyond."

The data presented at ESGCT 2023 demonstrates the importance of optimizing both
the DNA genetic cassette and the circRNA design to maximize protein payload
expression. By modifying the flanking inverted repeat elements (IR), circRNA
biogenesis was improved by 2-3 -fold vs. circVec 1.0. Screening and selecting
novel internal ribosome entry site (IRES) elements increased the protein
translation rate by 2-6 -fold. Combining these modifications, the resulting
protein payload expression was enhanced by 3-10-fold vs. circVec 1.0 (depending
on cell type), and outcompeted mRNA already at early time points.

Furthermore, bioinformatic modelling of long-term dynamics, based on CircioŽs
experimental results and externally published data, showed substantially
elevated and more durable expression levels from circRNA compared to
conventional mRNA vectors. This characteristic can enable improved therapeutic
potency, lower dosing, and reduced toxicity. As such, circRNA is expected to
replace mRNA as the preferred expression system for all viral and DNA-based
therapeutics in the future.

Please see the poster here: 2023 ESGCT
poster (https://mb.cision.com/Public/17093/3862401/9989516e464d88da.pdf)

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

Renate Birkeli, Investor Relations
Phone: +47 922 61 624
Email: renate.birkeli@circio.com (renate.birkeli@targovax.com)

About Circio

Building next generation RNA therapeutics

Circio Holding ASA (OSE: CRNA) is a biotechnology company developing novel
circular RNA and immunotherapy medicines.

Circio has established a unique circular RNA (circRNA) platform to develop novel
circRNA medicines for rare disease, vaccines, and cancer. 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 for many purposes. 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 two clinical trials in RAS-mutated
pancreatic cancer and multiple myeloma in the USA and 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.