Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Corporate Update (December 2024)
29 slides from Circio Holding Asa's corporate update, Dec 4, 2024
Slide 1: Disruptive circRNA technology for nucleic acid medicine
Disruptive circRNA technology for nucleic acid medicine Company update webcast 4 December 2024
Slide 2: circVec introduction
1 circVec introduction 2. circVec generation 3.0 3. circVec in vivo data 4. circVec therapeutic application 5. Warrant exercise information 2
Slide 3: The unique circVec expression system
The unique circVec expression system: Turning the patient´s cells into circRNA factories circVec DNA or viral vector DNA Inject circRNA biogenesis circRNA Protein Potent and durable protein expression 3
Slide 4: The circVec platform is technologically differentiated and creates novel opportunities for circRNA
The circVec platform is technologically differentiated and creates novel opportunities for circRNA Main Suitable Existing Expression Delivery opportunity for gene CDMO manu- durability system in vaccines therapy facturing circVec months Viral or vector to years DNA-LNP approach Synthetic circRNA- 7-
Slide 5: Circio is being recognized by industry media as an emerging leader in the circRNA space
Circio is being recognized by industry media as an emerging leader in the circRNA space 5
Slide 6: circVec generation 3.0
2 circVec generation 3.0 3. circVec in vivo data 4. circVec therapeutic application 5. Warrant exercise information 6
Slide 7: circVec 2.1 has shown 15x prolonged circRNA half-life and up to 10x protein expression vs. mRNA in vitro
circVec 2.1 has shown 15x prolonged circRNA half-life and up to 10x protein expression vs. mRNA in vitro circVec vs. mRNA luciferase reporter expression; in vitro time course circVec in vitro RNA half-life >8.5x expression at Day RT-qPCR, nascent vs. total RNA 8 circVec 2.1 vs. mRNA 50 45 Relative l
Slide 8: The starting point for the circVec construct is based on nature's best design
The starting point for the circVec construct is based on nature´s best design mRNA Expression of human endogenous circRNA AAAAAAAA NGS analysis of 300+ RNAseq datasets Linear splicing Backsplicing circRNA Maximum biogenesis-rate Circular RNA expression cassette of endogenous promoter SA SD circRNA I
Slide 9: Optimizing nature's best design to build circVec 3.0
Optimizing nature´s best design to build circVec 3.0 circVec generation 1.X – 3.X, design schematics circVec protein expression, Western blot circVec 1.1 IR SA SD IR IRES + ORF DNA RNA Therapeutic protein Control 9
Slide 10: Optimizing nature's best design to build circVec 3.0
Optimizing nature´s best design to build circVec 3.0 circVec generation 1.X – 3.X, design schematics circVec protein expression, Western blot circVec 1.1 IR SA SD IR IRES + ORF circVec 2.0 IRES + ORF Therapeutic protein DNA RNA Control 10
Slide 11: Optimizing nature's best design to build circVec 3.0
Optimizing nature´s best design to build circVec 3.0 circVec generation 1.X – 3.X, design schematics circVec protein expression, Western blot circVec 1.1 IR SA SD IR IRES + ORF circVec 2.0 IRES + ORF Therapeutic protein circVec 2.1 IRES + ORF Control DNA RNA 10
Slide 12: Optimizing nature's best design to build circVec 3.0
Optimizing nature´s best design to build circVec 3.0 circVec generation 1.X – 3.X, design schematics circVec protein expression, Western blot circVec 1.1 IR SA SD IR IRES + ORF circVec 2.0 IRES + ORF Therapeutic protein circVec 2.1 IRES + ORF Control circVec 3.0 IRES + ORF 10 DNA RNA
Slide 13: Optimizing nature's best design to build circVec 3.0
Optimizing nature´s best design to build circVec 3.0 circVec generation 1.X – 3.X, design schematics circVec protein quantification, Western blot circVec 1.1 ~27x increase for SA SD IR IRES + ORF IR circVec 3.0 vs 1.1 Relative protein quantity ~4x circVec 2.0 IRES + ORF ~2x circVec 2.1 ~3x IRES + OR
Slide 14: circVec in vivo data
3 circVec in vivo data 4. circVec therapeutic application 5. Warrant exercise information 11
Slide 15: circVec 2.1 achieves >6 month expression durability on one single injection in immuno-competent mouse muscle
circVec 2.1 achieves > 6 month expression durability on one single injection in immuno-competent mouse muscle mRNA-vector-Luciferase circVec 2.1-Luciferase Intra-muscular injection BALB/c Immuno-competent mice Left hindleg Right hindleg 3 dose levels Monitor expression over time mRNA circRNA Low dos
Slide 16: circVec 2.1 dose response in vivo - strongest advantage vs. mRNA observed at low dose
circVec 2.1 dose response in vivo - strongest advantage vs. mRNA observed at low dose, high therapeutic relevance Absolute expression (luminescence) Relative expression (luminescence) circVec 2.1 vs. mRNA pDNA vector expression -fold change circVec 2.1 vs. mRNA expression 1.8x higher 3.8x higher 15x
Slide 17: Bioinformatic analysis of circVec 2.1 in vivo data indicates up to 75 times increased half-life of circRNA vs. mRNA
Bioinformatic analysis of circVec 2.1 in vivo data indicates up to 75 times increased half-life of circRNA vs. mRNA Inferred RNA half-life (hours), bioinformatic modelling Inferred peak expression (days) >75x longer in vivo 38d half-life vs. mRNA 610h 233h Peak expression 135h 135h after >1 month 2.
Slide 18: Deploying circVec to enhance AAV gene therapy
Deploying circVec to enhance AAV gene therapy AAV protein expression, luminescence AAV vector AAV-circVec2.0 AAV-mVec ~2x Standard circVec mRNA approach circRNA approach Enhanced RNA durability Enhanced Protein expression Enhanced circVec-AAV expression vs. mRNA-AAV, validated by multiple experiment
Slide 19: AAV9 circVec 2.0 vs. mRNA in vivo experiment ongoing: circVec functionality validated systemically
AAV9 circVec 2.0 vs. mRNA in vivo experiment ongoing: circVec functionality validated systemically circVec 2.0 mVec High dose Experimental set-up Day 10 14 30 Day 10 14 30 Vector: AAV9, muscle- #1 #1 specific promoter High dose circVec version: circVec 2.0 #2 #2 AAV-circVec2.0 Payload: Firefly lucif
Slide 20: Ongoing R&D activities aim to further evolve circVec platform and validate activity in new tissues in vivo
Ongoing R&D activities aim to further evolve circVec platform and validate activity in new tissues in vivo Implement circVec 2.2 feature in 3.0 → circVec 3.1 circVec Set up circVec 3rd generation in vivo testing platform Implement circVec 3.0 feature into AAV vectors File patent(s) to cover circVec
Slide 21: circVec therapeutic application
4 circVec therapeutic application 5. Warrant exercise information 18
Slide 22: circVec is a platform that can be deployed in multiple disease areas and therapeutic settings
circVec is a platform that can be deployed in multiple disease areas and therapeutic settings Initial focus Mid-term Long-term High durability ´Remove & Non-integrating approach for Durable expression of Replace´ concept for rare genetic safer, repeat dosable biologics for auto-immune and disease im
Slide 23: circVec offers multiple modes-of-action (MoA) customizable to each specific target and disease
circVec offers multiple modes-of-action (MoA) customizable to each specific target and disease customized circVec cassette 2 1 3 Removal of mutant or Best-in-class protein Neutralization of pathogenic mRNA expression and durability pathogenic miRNAs AAA circVec is a unique platform to build mono-, b
Slide 24: Gene therapy development plan
Gene therapy development plan Modality and disease to be selected based on experimental data Therapeutic Ongoing in vivo Pipeline modality screening opportunities Myotonic and Limb-girdle dystrophy, Muscle Sarcopenia AAV-circVec Heart Fabry, Danon disease Payload: reporter LNP-DNA circVec gene Lung
Slide 25: circVec lead muscular genetic disease targets
Muscle disease circVec lead muscular genetic disease targets Limb-Girdle muscular dystrophy Myotonic dystrophy (type 2) (type 1) Progressive muscle- Adult onset muscle- wasting in hip and wasting Pathology shoulder Prolonged muscle- Breathing and heart contraction issues Issues in other organs >100,
Slide 26: circVec R&D update summary
circVec R&D update summary New circVec 3.0 generation has been established circVec o 27x / 4x improvement vs. circVec 1.1 / 2.1, respectively 3.0 o circVec 1.1 was 1.5-2x better than mRNA in vitro, depending on time and context >600 hours circRNA half-life in vivo vs. <10 hours for mRNA circRNA o >7
Slide 27: Warrant exercise
Warrant exercise 26 circio
Slide 28: Exercise of warrants issued in connection with the rights issue completed in July 2024
Exercise of warrants issued in connection with the rights issue completed in July 2024 Exercise period 4 – 18 December Exercise price NOK 0.60 Total number of warrants 13,864,852 Maximum gross proceeds NOK 8.32m Publication of outcome 19 December Subscribed shares will be transferred as soon Share s
Slide 29: How to exercise warrants
How to exercise warrants Complete and send signed warrant exercise form in PDF 1 format to email: contact@circio.com The exercise form is available on the Circio webpage 2 Request the holding bank to transfer the warrants to: Nordea VPS account number 06001.2222.000 Transfer the subscription amount