Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Corporate Update (April 2024)
26 slides from Circio Holding Asa's corporate update, Apr 17, 2024
Slide 1: Disruptive circRNA technology for genetic medicine
Disruptive circRNA technology for genetic medicine Company update 17 April 2024
Slide 2: Important notice and disclaimer
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
Slide 3: The challenge
1 The challenge 2. The circVec approach 3. Therapeutic application of circVec 4. 2023 financials 5. Intended financing 3
Slide 4: Gene therapy for rare disease is rapidly gaining momentum
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
Slide 5: Circio aims to improve current gold-standard gene therapy
Circio aims to improve current gold-standard gene therapy: 6 out of 8 approved gene therapies are AAV-based LUXTURNA ZOLGENSMA HEMGENIX ELEVIDYS ROCTAVIAN AAV AAV AAV AAV AAV Retinal Dystrophy SMA Hemophilia B DMD Hemophilia A 2017 2019 2022 2023 8 gene therapies approved 2017-2023: ADSTILADRIN UPST
Slide 6: The need for high dosing is a major limitation of AAV gene therapy
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 circRNA can Low expression à High dosing boost potency Safety issues, liver and and reduce immunological toxicity toxicity and
Slide 7: The circVec approach
2 The circVec approach 3. Therapeutic application of circVec 4. 2023 financials 5. Intended financing 7
Slide 8: The circVec expression system: making circRNA from a DNA starting point
The circVec expression system: making circRNA from a DNA starting point circVec DNA or viral vector DNA Inject circRNA biogenesis circRNA Protein Potent and durable protein expression 8
Slide 9: circVec expression validated for a broad set of proteins and cell types
circVec expression has been validated for a broad set of different protein and cell types Intra-cellular, membrane-bound and secreted proteins 20 payloads Various reporter genes validated Immunological proteins Infectious disease vaccine antigens 20 - 170 kDa (150 - 1,270 amino acid residues) Broad
Slide 10: circVec substantially outperforms expression level and durability of mRNA-based systems
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 50 >135h ½ 9h 45 life circRNA mRNA Enhanced therapeutic potency 40 circVec 2.1 Relative luminescenc
Slide 11: In vivo reporter pilot study: circVec 2.1 outperforms mRNA over time
In vivo reporter pilot study: circVec 2.1 outperforms mRNA over time and shows >4 month durability circVec 2.1-Luciferase mRNA-vector-Luciferase Intra-muscular injection of pDNA Single dose given on Day 0 Left hindleg Right hindleg Monitor expression over time circVec expression ongoing after 4 mont
Slide 12: Confirmatory in vivo study validates circVec expression advantage vs. mRNA
Confirmatory in vivo study validates circVec expression advantage vs. mRNA up to 3 months Day 3 Day 7 Day 10 Day 14 Day 17 Day 21 Day 24 Day 28 Day 35 Day 42 Day 49 Day 56 Day 70 Day 90 mRNA-vector circVec in Consistently superior circVec in left hindleg right hindleg expression from week 4
Slide 13: circVec 2.1 in vivo data analysis demonstrates statistically significant improvement
circVec 2.1 in vivo data analysis demonstrates statistically significant improvement over mRNA vector expression Luciferase signal in vivo, -fold change Statistical modelling of long-term expression circVec 2.1 vs. mRNA pDNA vector expression circVec 2.1 vs. mRNA expression dynamics, 2 years Up to 2
Slide 14: circVec can be deployed to enhance AAV gene therapy
circVec can be deployed to enhance AAV gene therapy AAV protein expression, luminescence AAV vector 3 2 days 4 days Luminescence (relative to mRNA) 2,5 Standard circVec mRNA approach circRNA approach 2 1,5 1 Enhanced RNA durability 0,5 0 Mock mRNA circRNA Enhanced Protein expression Enhanced circVec
Slide 15: circVec 2.0 AAV vector functionality validated in vivo
circVec 2.0 AAV vector functionality validated in vivo circVec-AAV luminescence; F-luc at Day 14 post injection Experimental set-up Vector: AAV8 circVec version: circVec 2.0 Payload: Firefly luciferase (F-luc) Mouse strain: NOD/SCID/IL- 2Rγnull immuno- deficient mice Delivery route: Intravenous tail
Slide 16: Therapeutic application of circVec
3 Therapeutic application of circVec 4. 2023 financials 5. Intended financing 16
Slide 17: Lead indication: Alpha-1 antitrypsin deficiency (AATD)
Current treatment options Lead indication: Alpha-1 antitrypsin deficiency (AATD) AATD is a major unmet medical need manifested in liver and lung Lung-associated AATD Replacement therapy with an alpha-1 proteinase inhibitors Weekly IV infusions Bronchodilators and inhaled steroids used for mild sympt
Slide 18: Lead gene therapy program: circVec Remove-&-Replace for AATD
Lead gene therapy program for proof-of-concept: circVec ´Remove-&-Replace´ for AATD wt AAT circVec AAT circVec AAT AAV8 circVec 2.1 AAT R&R design circVec Rep ove & Rep ove & expression o ve o ve ce e ce e promoter IR SA SD IR lac lac Rem Rem la la AAT gene Remover Rem Rem load IRES Pay- PME Rep Rep
Slide 19: circVec validated in both viral and synthetic DNA vector formats
circVec has been validated in both viral and synthetic DNA vector formats for therapeutic applications Viral Synthetic DNA AAV Adenovirus DNA format 1 DNA format 2 Application Gene therapy, incl. Vaccines Gene therapy, incl. Gene therapy AATD AATD Cell therapy Oncology Vaccines Improved expression S
Slide 20: R&D summary – boosting gene therapy
R&D summary – boosting gene therapy Gene therapy market is expected to grow sharply during the next decade The However, high cost and safety issues are holding back progress challenge Urgent need for strategies that can increase potency, improve safety and reduce cost à effective and affordable gene
Slide 21: 2023 financial report
4 2023 financial report 5. Intended financing 21
Slide 22: 2023 financials – substantially reduced spend in 2H'23
2023 financials1 – substantially reduced spend in 2H´23 NOK m 1H22 2H22 1H23 2H23 Total revenue 0 10 0 0 Payroll cost R&D expenses2 -23 -24 -42 -7 reduced by 45% Payroll and related expenses -30 -22 -22 -12 Other operating expenses3 -7 -398 -8 -9 Total operating expenses -60 -4444 -73 -28 Operating
Slide 23: Resources focused to maximize R&D output
Resources focused to maximize R&D output Staff level reduced from 23 to 10 FTEs Organization Board and management streamlined R&D staff prioritized, minimal back-office Building a strong technology platform R&D strategy Focusing on gene therapy, AATD lead program Using collaborations to complement c
Slide 24: Intended financing
Intended financing 24 eircio
Slide 25: Intended rights issue of NOK 50-60 million planned during 2Q 2024
Intended rights issue of NOK 50-60 million planned to be completed during 2Q 2024 Partially guaranteed rights issue Completion by June 2024 Transaction Target size NOK 50-60m gross proceeds structure Circio board and mgmt have pre-committed NOK 1.5m Atlas is supportive and will contribute to the tra
Slide 26: Q & A Session
Q & A Session Company update 17 April 2024