Circio Holding ASA

Investor Presentation • May 28, 2025

circio

Circular RNA expression systems for enhanced gene and cell therapies

R&D and corporate update webcast 28 May 2025

This report contains certain forward-looking statements based on uncertainty, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on the results of operations and the financial condition of Circio Holding ASA and the Circio Group. Such forward-looking statements reflect the current views of Circio and are based on the information currently available to the company. Circio cannot give any assurance as to the correctness of such statements.

There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied in these forward-looking statements. These factors include, among other things, risks or uncertainties associated with the success of future clinical trials; risks relating to personal injury or death in connection with clinical trials or following commercialization of the company's products, and liability in connection therewith; risks relating to the company's freedom to operate (competitors patents) in respect of the products it develops; risks of non-approval of patents not yet granted and the company's ability to adequately protect its intellectual property and know-how; risks relating to obtaining regulatory approval and other regulatory risks relating to the development and future commercialization of the company's products; risks that research and development will not yield new products that achieve commercial success; risks relating to the company's ability to successfully commercialize and gain market acceptance for Circio's products; risks relating to the future development of the pricing environment and/or regulations for pharmaceutical products; risks relating to the company's ability to secure additional financing in the future, which may not be available on favorable terms or at all; risks relating to currency fluctuations; risks associated with technological development, growth management, general economic and business conditions; risks relating to the company's ability to retain key personnel; and risks relating to the impact of competition.

• 1. circVec R&D update
• 1. Corporate update

Continued high deal activity in circular RNA space

\$65m up-front

+ up to \$635m in milestones

LNP-circRNA for in vivo gene editing in blood diseases

• circRNA (oRNA) manufacturing and LNP delivery platform
• Develop two novel therapeutic candidates for sickle cell disease and beta thalassemia

\$1.1b

in up-front +

AAV gene therapy for muscular dystrophies

• AAV capsid engineering technology platform
• Three preclinical neuromuscular therapeutic candidates for DM1, DMD and FSHD

Circio's circVec platform is technologically differentiated, opportunity in next generation gene and cell therapies

Muscle and cardiac genetic disease

Tissue-specific AAV format

150,000 patients in target diseases, with no approved therapies

Next Gen AAV

Auto-immune disease, oncology

LNP: DNA format, redosable

Very large patient population, only autologous options available today

In vivo CAR

1. Corporate update

AAV protein expression, in vitro f-Luc

circVec-AAV feasibility validated, testing and optimization of constructs ongoing

AAV-circVec, muscle specific Quantification of signal (luminescence)

Tissue-specific signal from AAV-circVec Post mortem ex vivo analysis (luminescence)

AAV circVec, heart specific – two AAV designs Quantification of signal (luminescence), high dose

AAV-circVec, heart specific – two AAV designs Quantification of signal, high/low dose comparison

AAV circVec, heart specific – two AAV designs Quantification of signal (luminescence), high dose

AAV circVec, heart specific Vertical signal profile from head to tail

AAV circVec, heart specific – two AAV designs Quantification of signal (luminescence), high dose

AAV circVec, heart specific Total signal (luminescence), heart region

circVec validated in AAV format, multiple designs tested Identified tissue-specific circVec AAV expression profile 10-fold increased potency vs. mRNA for heart-specific AAV
Further exploration and enhancement of tissue-specific circVec performance using AAV vectors
Development and testing of AAV-circVec for treatment of muscular dystrophies and cardiomyopathies in relevant mouse disease models
Establish research collaborations with AAV specialist companies in tissue / target specific setting External testing and validation of circVec-AAV advantage

1. Corporate update

Testing and validation of circVec in therapeutic vectors

DNA vector expression relative to plasmid DNA Quantification of in vivo signal, time course

• Reduced cost vs. current approaches
• Repeat-dosable
• Larger payload capacity than AAV
• Longer expression than RNA
• ➢ Considered the future format for gene and cell therapy
• ➢ Substantial efforts ongoing to establish enhanced vectors and delivery systems
• ➢ Technologies to target and extend expression are highly sought after

LNP-mVec (mRNA), luminescence Systemic I.V. delivery, single dose on Day 0

LNP-circVec (circRNA), luminescence Systemic I.V. delivery, single dose on Day 0

LNP collaboration partner

circVec de-targets liver expression

	Novel therapeutically relevant DNA format identified circVec LNP-delivery to spleen confirmed
	Analysis of circVec spleen delivery at cellular level
	Testing new DNA format in advanced and targeted LNP formulations and non-LNP delivery systems
	Establish platform for durable circVec in vivo CAR approach using circVec DNA + spleen delivery system
	Several ongoing collaborations with innovative DNA delivery companies: Certest, Entos, 4BB and others Seeking collaboration partners for in vivo cell therapy

	Validate heart data Test additional tissues Testing in disease models	Establish collaborations with AAV companies External circVec AAV testing
	Replicate findings w/new format circVec CAR expression Ex vivo T cell experiments	Establish collaborations with in vivo CAR companies External circVec DNA testing
	Test additional LNP formulations Test other delivery systems Validate w/new DNA format	Several ongoing collaborations Certest, Entos, 4BB + others, data during 2H´2025

* Expected data package necessary to drive interest to initiate partnering discussions and negotiations

Data & Timeline: current best estimates - experiments have uncertain outcomes and may need to be repeated, impacting plans and timelines

	The Board selected to withdraw the proposals after careful consideration of the current situation Evaluating alternatives to manage OSE share price rule
	Proposed 40% level enables more flexibility for fundraising in tough market conditions Higher likelihood to attract new and international investors
	RSU/option program important compensation component Aligns shareholder and employee long-term goals Reduces cash expenditure for the company

circio

Q& A Session