Circio presents pre-clinical proof-of-concept data for its circVec gene therapy platform at the ASGCT 2024 meeting

· Two posters demonstrate in vivo superiority of circular RNA vs. linear mRNA-based expression and technical proof-of-concept for Circio´s´remove-&-replace´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 biotechnologycompany developing circular RNA-based gene therapy, today announces that ithaspresented two posters that demonstrate in vivo proof-of-concept for itspowerfuland differentiated circVec platform approach to gene therapy. The two posterswere presented at the American Society of Gene & Cell Therapy (ASGCT) 2024annual meeting 7-11 May in Baltimore, USA

"Circio has generated results demonstrating that the circVec 2.1 designperformsvery well in vitro. We have now confirmed this in vivo with statisticallysignificant higher expression level and durability for circVec 2.1 DNA vectorscompared to standard linear mRNA-based expression. These results provide animportant technical proof-of-concept for Circio´s technology platform in ananimal model. We now have confirmation for our expectation that this couldtranslate into improved gene therapies for patients in the future," said Dr.Thomas B Hansen, CTO at Circio. "In recent experiments, Circio has observed upto four months circVec durability in vivo. This substantially outperforms mRNAvector expression. Following these results, we can rapidly advance to designandtest circVec in several AAV and DNA-based vectors. This will validate theseverypromising data in therapeutically relevant formats."

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

"AATD is a challenging genetic disease to treat. This is in part due to thetwodistinct pathologies in the liver and lung," said Dr. Victor Levitsky, CSO atCircio. "We have now established and technically validated circVec constructsthat can both replenish functional wild-type AAT and specifically remove morethan 90% of the mutated protein. This is challenging to achieve because thefunctional and mutant forms are very similar. By using circular RNA-based AATexpression, 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 RNAExpression Platform;   O´Leary et al. ASGCT 2024

Expressing AAT from circular RNA-encoding vectors as a promising gene therapyapproach for Alpha 1-antitrypsin deficiency; O´Leary et al. ASGCT 2024

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

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

About Circio

Building next generation RNA therapeutics

Circio Holding ASA is a biotechnology company developing novel circular RNAgenetherapies and immunotherapy medicines.

Circio has established a unique circular RNA (circRNA) platform for geneticmedicine. The proprietary circVec technology is based on a modular geneticcassette design for efficient biogenesis of multifunctional circRNA from DNAandviral vectors, which can be deployed in multiple disease settings. The circVecplatform has demonstrated enhanced and more durable protein expression thanclassic 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&Dactivities are being conducted by the wholly owned subsidiary Circio AB basedatthe Karolinska Institute in Stockholm, Sweden.

In addition, Circio is developing a cancer vaccine, TG01, targeting KRASdrivermutations. TG01 is currently being tested in three clinical trials:RAS-mutatedpancreatic cancer and lung and non-resectable pancreatic cancer in US, andmultiple myeloma in Norway. These studies are being run through academiccollaborative networks, supported by prestigious research grants fromInnovationNorway and the Norwegian Research Council, creating read-outs and futureoptionality for the program at low cost to Circio.

For more information please contact:

Neil Hunter

Hunter PRneiljameshunter@gmail.com+44 7821 255568

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