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2 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.
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3 2. circVec R&D update 3. Corporate update
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Feb 2021 $80M Series A Series A+B $490M May/Aug 2021 Jul 2022 $42M Series A Licensing $150M Upfront $3,5B deal value Aug 2022 Aug 2022 $221M Series B Series A $270M April 2023 4 Jan 2025 $65M Upfront Aug 2023 $30M Series A May 2024 M&A April 2025 First patient dosed with circRNA Licensing
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5 Licensing $65m up-front + up to $635m in milestones circRNA (oRNA) manufacturing and LNP delivery platform Develop two novel therapeutic candidates for sickle cell disease and beta thalassemia LNP-circRNA for in vivo gene editing in blood diseases M&A $1.1b in up-front + AAV capsid engineering technology platform Three preclinical neuromuscular therapeutic candidates for DM1, DMD and FSHD AAV gene therapy for muscular dystrophies
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´ Lead program, in house focus Next step / partnership
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7 3. Corporate update
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8 2019 2022 2023 LUXTURNA AAV Retinal Dystrophy ZOLGENSMA AAV SMA ADSTILADRIN AdV NMIBC HEMGENIX AAV Hemophilia B UPSTAZA AAV AADC ELEVIDYS AAV DMD ROCTAVIAN AAV Hemophilia A VYJUVEK HSV DEB 2017 AAV format has substantial caveats: Insufficient gene expression level High dose requirement → toxicity & cost Not repeat-dosable 8 AAV: Adeno-Associated Virus, currently best known vector for long-term protein expression in humans
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RNA Protein circVec-AAV feasibility validated, testing and optimization of constructs ongoing AAV protein expression, in vitro f-Luc Enhanced durability Enhanced expression AAV-circVec AAV-mVec ~2x Aim: at least 3-5x enhanced potency vs. mVec-AAV 9
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10 AAV-circVec, muscle specific Quantification of signal (luminescence) Diaphragm Heart Liver Tissue-specific signal from AAV-circVec Post mortem ex vivo analysis (luminescence) n = 4 per group circVec advantage from D60, stabilizing at +50% expression up to D170 Higher circVec expression in heart and diaphragm, lower in liver circVec mVec circVec mVec circVec mVec Diaphragm Heart Liver
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11 Same effect as mRNA-AAV at 10x reduced dose AAV-circVec, heart specific – two AAV designs Quantification of signal, high/low dose comparison 35x 9X mVec circVec#1 circVec#2 AAV circVec, heart specific – two AAV designs Quantification of signal (luminescence), high dose 10 17 28 42 56 10 17 28 42 56 10 17 28 42 56Day
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12 AAV circVec, heart specific Vertical signal profile from head to tail Heart region Head Tail cm distance mVec circVec#1 circVec#2 AAV circVec, heart specific – two AAV designs Quantification of signal (luminescence), high dose 10 17 28 42 56 10 17 28 42 56 10 17 28 42 56Day
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13 AAV circVec, heart specific Total signal (luminescence), heart region Significant increase in heart-expression from both circVecs, p<0.01, mixed model mVec circVec#1 circVec#2 AAV circVec, heart specific – two AAV designs Quantification of signal (luminescence), high dose 10 17 28 42 56 10 17 28 42 56 10 17 28 42 56Day
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14 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 Establish research collaborations with AAV specialist companies in tissue / target specific setting External testing and validation of circVec-AAV advantage 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
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15 3. Corporate update
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Technical development Non-therapeutic applications Repeat-dosable non-viral gene therapy Repeat-dosable gene therapy Vaccines Classic viral gene therapy Single dose only ✓ ✓ ✓ 16 ✓
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17 DNA vector expression relative to plasmid DNA Quantification of in vivo signal, time course DNA format #1 identified as promising therapeutic vector format for circVec >6x expression vs. plasmid DNA DNA format #1 DNA format #2 DNA format #3 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 afterEqual level to plasmid DNA
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18 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 Mainly short-term liver expression No liver expression Accumulation in spleen from week 3-12 circVec de-targets liver expression LNP collaboration partner
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19 Novel therapeutically relevant DNA format identified circVec LNP-delivery to spleen confirmed Several ongoing collaborations with innovative DNA delivery companies: Certest, Entos, 4BB and others Seeking collaboration partners for in vivo cell therapy 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
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21 Validate heart data Test additional tissues Testing in disease models Replicate findings w/new format circVec CAR expression Ex vivo T cell experiments Test additional LNP formulations Test other delivery systems Validate w/new DNA format Establish collaborations with AAV companies External circVec AAV testing Establish collaborations with in vivo CAR companies External circVec DNA testing Several ongoing collaborations Certest, Entos, 4BB + others, data during 2H´2025
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1H´25 2H´25 1H´26 * 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 R&D process Tissue screening Delivery testing Disease model testing In vivo testing and optimization of circVec designs Select vector and delivery route + technology Disease testing and candidate construct optimization Value inflection point 1: * circVec-AAV in vivo validation Example: oRNA-Vertex deal Value inflection point 2: * Disease model validation Example: Novartis-Kate M&A ASGCT 2025 conference, mid-May Premier global gene therapy event Data from ongoing in vivo program 22 2H´26
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23 RSU/option program important compensation component Aligns shareholder and employee long-term goals Reduces cash expenditure for the company Proposed 40% level enables more flexibility for fundraising in tough market conditions Higher likelihood to attract new and international investors The Board selected to withdraw the proposals after careful consideration of the current situation Evaluating alternatives to manage OSE share price rule