Circio Holding Asa · OSL:CRNA
Circio Holding Asa — H1 2024 Earnings Presentation
24 slides from Circio Holding Asa's earnings presentation, Aug 29, 2024
Slide 1: Disruptive circRNA technology for genetic medicine
circio “ Disruptive circRNA ° technology for genetic medicine First half-year report 29 August 2024
Slide 2: Forward-looking statements
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 C
Slide 3: Agenda
2. circVec gene therapy 3. 1H 2024 financials 3
Slide 4: Financing and deal activity in the circRNA field
Licensing Series A Series A Series A+B $150M Upfront $490M $3,5B deal value $270M $300M M&A May/Aug 2021 Aug 2022 April 2023 May 2023 May 2024 Feb 2021 Jul 2022 Aug 2022 Oct 2022 Aug 2023 $80M $42M $221M Undisclosed $30M Series A Series A Series B M&A Series A 4
Slide 5: circVec platform mechanism
´ circVec DNA or viral vector DNA Inject circRNA biogenesis circRNA Protein Potent and durable protein expression 5
Slide 6: circVec vs. mRNA relative expression
circVec vs. mRNA protein expression assay; time course >8.5x expression circVec RNA stability 50 at Day 8 circVec 45 2.1 vs. mRNA 40 Relative expression 35 30 circVec 2.1 25 circVec 2.0 20 circVec 1.0 15 mRNA 10 5 0 48 96 144 192 Hours 6
Slide 7: circVec 2.1 enhanced durability vs. mRNA in vivo
Day 1 Day 8 Day 14 Day 21 Day 28 Day 35 Day 42 Day 57 Day 71 Day 91 Day 119 circRNA mRNA circRNA mRNA circRNA mRNA circRNA mRNA circRNA mRNA circRNA mRNA circRNA mRNA circRNA mRNA circRNA mRNA circRNA mRNA circRNA mRNA circVec 2.1 pDNA constructs show statistically significant enhanced durability vs
Slide 8: circVec vs. mRNA luciferase expression in vivo
circVec vs. mRNA Luciferase expression, single intra-muscular injection of pDNA @ day 0 Day 175 mRNA circVec 8
Slide 9: circVec 2.1 vs. mRNA expression fold change
Absolute expression (luminescence) Relative expression (luminescence) circVec 2.1 vs. mRNA pDNA vector expression -fold change circVec 2.1 vs. mRNA expression 2.0x higher 3.2x higher 14x higher expression at D84 expression at D84 expression at D84 P<0.001 P<0.05 9 HD: High dose MD: Mid dose LD: Low
Slide 10: Machine learning model validation, circVec 2.x performance
Machine learning model validation circVec 2.x performance Commercial#1 Commercial#2 circVec 2.2 shows 2-4x circVec 2.2 circVec 2.1 improved expression Actual experimental result compared 2.1 design Validation protein Control Predicted result by model 10
Slide 11: Recognized by industry media as a leader in circRNA
BIOCENTURY ARTICLE | PRODUCT DEVELOPMENT Emerging circular RNA field split on what to deliver and how to deliver it The rising therapeutic modality is more durable than linear MRNA, promising efficacy and manufacturing advantages BY DANIELLE GOLOVIN, BIOPHARMA ANALYST August 17, 2023 11:34 PM UTC J
Slide 12: circVec gene therapy
circVec gene therapy 3. 1H 2024 financials 12 circio
Slide 13: circVec applications across therapy areas
Gene therapy Vaccines Gene therapy Gene therapy Oncology Vaccines Cell therapy Improved expression Single-dose vaccine Enable repeat-dosing Improved uptake and reduced dosing Therapeutic protein for gene therapy Reduced vs. mRNA AAV delivery to tumors Enhanced nuclear uptake immunogenicity Advantage
Slide 14: Approved gene therapies 2017-2023 and AAV vectors
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 UPSTAZA VYJUVEK 100% utilizing viral vectors 75% utilizing an AAV vector 75% approved for rare diseases AdV AAV
Slide 15: AAV protein expression vs. mRNA
AAV protein expression, luminescence 3 2 days 4 days Luminescence (relative to mRNA) 2.5 2 1.5 1 Enhanced RNA durability 0.5 0 Mock mRNA circRNA Enhanced Protein expression Enhanced circVec-AAV expression vs. mRNA-AAV, validated by multiple experimental methods in vitro 15
Slide 16: circVec-AAV experimental set-up
circVec-AAV luminescence, F-luc at Day 20 Experimental set-up Intra-muscular (I.M.) Vector: AAV8 circVec version: circVec 2.0 Payload: Firefly luciferase (F-luc) Mouse strain: NOD/SCID/IL- 2Rγnull immuno- deficient mice Tail vein (I.V.) Delivery route: Tail vein or intra- muscular injection Single i
Slide 17: Robust expression in muscle with AAV8
AAV expression (luminescence), I.M single inj. Day 13 Day 34 Day 69 Robust expression in muscle circVec-AAV (bioluminescence) achieved with AAV8 expression virus (liver optimized strain) Not yet evident advantage vs. mRNA-AAV (ongoing experiment, week 10 data) Continuous tracking, testing of lower d
Slide 18: Next steps for circVec development
circVec 2.2 generation testing in vivo Establish and test circVec 3.0 generation in vitro Two new patent filings at drafting / planning stage Explore muscle-specific AAV and lower dose level Test delivery and expression in additional tissues Implement circVec 2.2 (→ 3.0) features Entered / entering
Slide 19: 1H 2024 financials
1H 2024 financials 19 circio
Slide 20: Financing and restructuring highlights
Gross proceeds: NOK 19.6m, completed in July 2024 - NOK 9.4m pre-subscriptions (incl. NOK 1.75m from Board and Management) - NOK 8.7m in additional subscriptions Financing commitment by Atlas until 30 June 2025 Waiver of total loan value of NOK 71.3m (EUR 6.2m) Saves NOK 9-11m in annual down-payment
Slide 21: Financial results 1H 2024
NOK m 1H23 2H23 1H24 Total revenue 0 0 0 R&D expenses2 -42 -7 -7 Payroll and related expenses -22 -12 -10 Payroll cost: - 50% Other operating expenses3 -8 -9 -5 Other operating: - 30% Total operating expenses -73 -28 -23 Operating loss -73 -28 -23 Waiver of ONCOS-102 Net financial items -3 -7 67 R&D
Slide 22: Lean organisation and reduced cash burn
Lean and efficient organisation – 10 FTEs R&D staff prioritized, majority of employees Minimal administration as public company Generate data package for deal or investment Focus on low hanging fruits /short term gains Using collaborations to generate new data Cash burn rate reduced to NOK ~4m / mon
Slide 23: Financing secured until June 2025
Financing secured until 30 June 2025 Financing commitment from Atlas available from October 2024 Warrant exercise period December 2024 Aiming to enter first strategic partnership in 2025 Continuous specialist investor dialogues 23
Slide 24: Q&A Session
Circle Q&A Session First half-year report 29 August 2024