Circio : Company update 17 April 2024

Disruptive circRNA technology for genetic medicine

Company update 17 April 2024

Important notice and disclaimer

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.

2

1	The challenge

2. The circVec approach

3. Therapeutic application of circVec

4. 2023 financials

5. Intended financing

3

Gene therapy for rare disease is rapidly gaining momentum

with investors, pharma and regulators

Focus area for regulators à Fastest growing class of new approvals à Commercial success

Circio aims to improve current gold-standard gene therapy:

6 out of 8 approved gene therapies are AAV-based

LUXTURNAZOLGENSMA

AAV	AAV
Retinal Dystrophy	SMA

2017

2019

8 gene therapies approved 2017-2023:

100% utilizing viral vectors

75% utilizing an AAV vector

75% approved for rare diseases

HEMGENIX ELEVIDYSROCTAVIAN

AAV	AAV	AAV
Hemophilia B	DMD	Hemophilia A

2022

2023

ADSTILADRIN

UPSTAZA

VYJUVEK

AdV	AAV	HSV
NMIBC	AADC	DEB

55

The need for high dosing is a major limitation for

current gold-standard AAV gene therapy

Limited applicability

Low expression level not sufficient

for many genetic diseases

Low expression à High dosing

Safety issues, liver and immunological toxicity

High dosing à High cost

High dose requirement drives

high manufacturing cost

circRNA can

boost potency

and reduce

toxicity and cost

of AAV gene

therapy

6

2	The circVec approach

3. Therapeutic application of circVec

4. 2023 financials

5. Intended financing

7

The circVec expression system:

making circRNA from a DNA starting point

DNA

circVec

DNA or viral

vector

Inject

circRNA

biogenesis

circRNA	Protein	Potent and durable
		protein expression

8

circVec expression has been validated for a broad

set of different protein and cell types

20 payloads validated

Broad size-range

Confirmed in multiple cell and tissue types

Intra-cellular,membrane-bound and secreted proteins Various reporter genes

Immunological proteins

Infectious disease vaccine antigens

20 - 170 kDa (150 - 1,270 amino acid residues) 460 - 3,800 nt open reading frame (ORF)

Maximum size limit not yet reached

6 different cell lines

Skin, lung, liver and muscle cell types Mouse tissue: liver and muscle

9

circVec substantially outperforms the expression

level and durability of mRNA-based systems

Increased expression level

circVec vs. mRNA luciferase reporter expression; time course

Prolonged durability

Enhanced therapeutic potency

50 >135h

45 circRNA

40

35

• 9h

life mRNA

15 x

circVec 2.1

"Due to its significant advantages, circRNA systems can be expected to replace mRNA-based expression for DNA format therapeutics in the future

• just as synthetic circRNA can be expected to replace current mRNA formats"

Dr. Alex Wesselhoeft

Scientific founder oRNA Therapeutics

Relative luminescence

30

25

20

15

10

5

0

48

>8.5x expression at Day 8 for circVec 2.1 vs. mRNA

mRNA

96	144	192
	Hours

10