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.
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1 | The challenge |
2. The circVec approach
3. Therapeutic application of circVec
4. 2023 financials
5. Intended financing
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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 |
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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
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2 | The circVec approach |
3. Therapeutic application of circVec
4. 2023 financials
5. Intended financing
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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 |
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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
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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 |
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Disclaimer
Circio Holding ASA published this content on 16 April 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 17 April 2024 06:21:01 UTC.