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IP - Circio presents new and differentiating circVec data and corporate update in live webcast - Attachment: 250528_Circio_Webcast.pdf

Company: Circio Holding ASA Date: 2025-05-28 Language: English Register to download
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# 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.

- 2. circVec R&D update
- 3. Corporate update

# Continued high deal activity in circular RNA space

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# **\$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

![](_page_4_Picture_7.jpeg)

**\$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

![](_page_5_Figure_1.jpeg)

Muscle and cardiac genetic disease

Tissue-specific AAV format

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

![](_page_5_Picture_5.jpeg)

Next Gen AAV

Auto-immune disease, oncology

LNP: DNA format, redosable

Very large patient population, only autologous options available today

![](_page_5_Picture_10.jpeg)

In vivo CAR

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3. Corporate update

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### **AAV protein expression,** in vitro f-Luc

![](_page_8_Figure_3.jpeg)

**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)

![](_page_9_Figure_3.jpeg)

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

![](_page_10_Picture_2.jpeg)

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

![](_page_10_Figure_4.jpeg)

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

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

![](_page_11_Figure_4.jpeg)

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

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

![](_page_12_Figure_4.jpeg)

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

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3. Corporate update

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# Testing and validation of circVec in therapeutic vectors

![](_page_15_Figure_1.jpeg)

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

![](_page_16_Figure_2.jpeg)

- 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

![](_page_17_Figure_3.jpeg)

![](_page_17_Picture_4.jpeg)

**LNP collaboration partner**

**circVec de-targets liver expression**

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

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

![](_page_21_Figure_1.jpeg)

**\*** 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<br>consideration of the current situation<br>Evaluating alternatives to manage OSE share price rule |
|--|----------------------------------------------------------------------------------------------------------------------------------------------------------------|
|  | Proposed 40% level enables more flexibility for fundraising<br>in tough market conditions<br>Higher likelihood to attract new and international investors      |
|  | RSU/option program important compensation component<br>Aligns shareholder and employee long-term goals<br>Reduces cash expenditure for the company             |

# circio

# Q& A Session