Circio announces novel circVec 3.0 generation and circular mRNA half-life up to 75 times longer than linear mRNA in vivo

04 Dec 2024 08:00 CET

· Novel circVec 3.0 design feature achieves 27- and 4-fold improvement vs.
circVec 1.1 and 2.1 generation, respectively
· circVec circular mRNA shows up to 75 times longer half-life than
conventional linear mRNA in vivo
· Muscle-specific circVec 2.0-AAV vectors validated by systemic delivery in
vivo
· The results will be discussed in a live
webcast (https://teams.microsoft.com/l/meetup
-join/19%3ameeting_YWU3YjYwMDktMWJmOC00NTdjLWFmMjYtOTUyMWNjNzJlNmJl%40thread.v2/
0
?context=%7b%22Tid%22%3a%2266b0661a-3ec3-48a8-a966
-5b0cce82b3fe%22%2c%22Oid%22%3a%223f5f84b0-5521-4c04-bd8a-e185546abe04%22%7d) at
10am CEST on 4 December 2024

Oslo, Norway 4 December 2024 - Circio Holding ASA (OSE: CRNA), a biotechnology
company developing powerful circular RNA technology for next generation nucleic
acid medicine, today announces an R&D update showcasing the latest powerful
circVec 3.0 generation circular mRNA expression system and bioinformatic
analysis of long-term expression data in mouse muscle. The analysis demonstrates
up to 75 times prolonged half-life vs linear mRNA in vivo.

"With Circio´s circVec 2.1 construct we have already demonstrated the potential
of our powerful circular RNA technology to outperform mRNA-based expression
systems both in vitro and in vivo. Continued optimization of the circVec genetic
cassette has now resulted in the discovery of a novel enhancer element, which
brings up to 27- and 4-fold improvement over the previous circVec 1.1 and 2.1
generations, respectively. This new component will be added as a standard design
feature in circVec generation 3.0," said Dr. Thomas B Hansen, CTO at Circio. "We
are very eager to explore how this new feature can further boost circVec protein
expression level and durability in vivo, with the aim to improve potency and
safety of nucleic acid medicines. Our science team is now rapidly advancing to
implement the new circVec 3.0 design into AAV and DNA-based vector formats for
future therapeutic applications."

In addition, Circio presents bioinformatic analysis of long-term in vivo
expression data showing an estimated circular mRNA half-life of more than 600
hours vs. less than 10 hours for linear mRNA in mouse muscle. This translates to
up to 75 times prolonged half-life in vivo, substantially higher than the 15
times enhancement previously reported in vitro.

"Reaching this level of unprecedented RNA half-life in vivo, combined with the
added power of circVec generation 3.0, represents the latest major milestone for
our circular mRNA expression platform," said Dr. Erik Digman Wiklund, CEO at
Circio. "We are demonstrating that our technology has the potential to
substantially enhance current gold-standard nucleic acid medicines, and bring
benefit to patients with difficult-to-treat diseases for which there are no
cures available today."

Circio also reports interim in vivo results for the AAV gene therapy vector
format. Protein expression from an AAV9 construct with the circVec 2.0 genetic
cassette has now been validated by systemic administration in vivo, showing a
similar expression pattern to current gold-standard mRNA-AAV for the first 30
days. The experiment is continuing, and previous evidence suggests that the
circVec expression advantage usually emerges 4 weeks after injection and then
increases over time. circVec generation 3.0 AAV constructs are currently being
designed and will enter in vivo testing during 1Q 2025.

The circVec 3.0 data and recent in vivo results will be presented and discussed
by Circio management in a live webcast (https://teams.microsoft.com/l/meetup
-join/19%3ameeting_YWU3YjYwMDktMWJmOC00NTdjLWFmMjYtOTUyMWNjNzJlNmJl%40thread.v2/
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-5b0cce82b3fe%22%2c%22Oid%22%3a%223f5f84b0-5521-4c04-bd8a-e185546abe04%22%7d) at
10:00am CEST on 4 December 2024. A recording of the webcast will be made
available on the Circio webpage (http://www.circio.com/).

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

Neil Hunter, Hunter PR
Phone:+44 7821 255568 (http://tel:+447821255568)
Email: neiljameshunter@gmail.com

About Circio

Building next generation RNA technology for nucleic acid medicine

Circio Holding ASA is a biotechnology company developing powerful circular RNA
vector expression technology for next generation nucleic acid medicine.

Circio has established a unique circular RNA (circRNA) vector expression
platform for novel DNA, RNA and viral therapeutics. The proprietary circVec
technology is based on a modular genetic cassette design for efficient
biogenesis of multifunctional circRNA inside cells, which can be deployed in
multiple therapeutic settings, including genetic medicine, cell therapy and
chronic disease. The circVec platform has demonstrated up to 15-fold enhanced
and more significantly more durable protein expression vs. classic mRNA vector
systems and has the potential to become a new gold-standard platform technology
for nucleic acid and viral 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 pan-RAS cancer vaccine, TG01, targeting KRAS
driver mutations. TG01 is currently being tested in two clinical trials: RAS
-mutated pancreatic and lung cancer in the USA and multiple myeloma in Norway.
These studies are being run through academic and industry 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.

More information:
Access the news on Oslo Bors NewsWeb site

633791_Circio_webcast_slides_4Dec24.pdf