Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Investor Presentation (April 2024)
32 slides from Circio Holding Asa's investor presentation, April 2024
Slide 1: Disruptive circRNA technology for genetic medicine
Disruptive circRNA technology for genetic medicine Company presentation 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: Circio executive summary
Circio executive summary Gene therapy market is expected to grow sharply during the next decade The However, suboptimal vectors, cost and safety issues hold back progress challenge Urgent need for strategies that can increase potency, improve safety and reduce cost à effective and affordable gene th
Slide 4: The challenge
1 The challenge 2. The circVec approach 3. Therapeutic application of circVec 4. Additional cancer vaccine opportunity 5. Summary & finance 4
Slide 5: Gene therapy for rare disease is rapidly gaining momentum with investors, pharma and regulators
Gene therapy for rare disease is rapidly gaining momentum with investors, pharma and regulators 10% Focus area for regulators à Fastest growing class of new approvals à Commercial success
Slide 6: 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 7: The need for high dosing is a major limitation for current gold-standard 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 Safety issues, liver and à boost potency immunological toxicity à lower toxicity à r
Slide 8: circRNA offers increased durability and expression rate, enhancing gene therapy potency
circRNA offers increased durability and expression rate, thus enhancing the potency of gene therapy Extended RNA durability Higher protein expression 15x half-life vs. mRNA 5x translation rate vs. mRNA circRNA will outcompete linear mRNA due to its enhanced stability microRNA sponging Modular & mult
Slide 9: circRNA is gaining strong industry momentum as a superior RNA platform
Based on these advantages, circRNA is gaining strong industry momentum as a superior RNA platform Licensing Series A Series A Series A+B $150M Upfront $490M $3,5B Total deal value $270M $300M May/Aug 2021 Aug 2022 April 2023 May 2023 Feb 2021 Jul 2022 Aug 2022 Oct 2022 Aug 2023 $80M $42M $221M Undis
Slide 10: The circVec approach
2 The circVec approach 3. Therapeutic application of circVec 4. Additional cancer vaccine opportunity 5. Summary & finance 10
Slide 11: The circRNA field was established by Circio scientists
The circRNA field was established by Circio scientists Dr Thomas B Hansen Dr Erik D Wiklund 6,373 citations 30 September 2011 922 citations 2,291 citations 11
Slide 12: 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 Enhanced and durable protein expression 12
Slide 13: The circVec platform is technologically differentiated and creates novel possibilities for circRNA
The circVec platform is technologically differentiated and creates novel possibilities 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 14: circVec substantially outperforms the 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 luminescence
Slide 15: circVec 2.1 outperforms mRNA-based expression in vivo with >4 month durability
circVec 2.1 outperforms mRNA-based expression in vivo with >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 months; mRNA very low >1
Slide 16: Statistical analysis of in vivo data demonstrates significant advantage vs. mRNA
Statistical analysis of in vivo data demonstrates significant advantage vs. mRNA increasing over time 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 20x circVec
Slide 17: circVec expression has been validated for a broad set of different protein 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 18: Therapeutic application of circVec
3 Therapeutic application of circVec 4. Additional cancer vaccine opportunity 5. Summary & finance 18
Slide 19: 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 20: 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 21: Lead indication: Alpha-1 antitrypsin deficiency (AATD)
Current treatment options Lead indication: Alpha-1 antitrypsin deficiency (AATD) AATD is a genetic disease 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 symptoms Lack
Slide 22: Lead circVec gene therapy program: Differentiated Remove-&-Replace concept for AATD
Lead circVec gene therapy program: Differentiated´Remove-&-Replace´concept for AATD circVec AAT circVec AAT wt AAT AAV-circVec2.0 AATD R&R design circVec Rep ove & Rep ove & o ve o ve ce e ce e SA SD promoter IR IR expression lac lac Rem Rem la la AAT gene Remover Rem Rem load IRES Pay- PME Rep Rep
Slide 23: circVec has been 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 24: circVec R&D summary and next steps
circVec R&D summary and next steps circVec 2.1 generation outperforms mRNA by 10x In vitro Validated in various cells, tissues and 20 payloads validation Platform potential, three patent applications filed Statistically significant improvement over mRNA- In vivo based expression Multiple delivery an
Slide 25: Additional cancer vaccine opportunity
4 Additional cancer vaccine opportunity 5. Summary & finance 25
Slide 26: Ongoing low-cost phase 2 program with legacy KRAS cancer vaccine
Ongoing low-cost phase 2 program with legacy KRAS cancer vaccine Academic study sponsor and industry partners: Multiple Myeloma TG01 monotherapy Phase 1 post 1L treatment n = 20 patients Pancreatic Cancer Pancreatic Cancer TG01 + chemotherapy TG01 + anti-PD1 Phase 1 Phase 1/2 post-surgery post-surge
Slide 27: TG01 KRAS cancer vaccine legacy program
TG01 KRAS cancer vaccine legacy program More than 100 patients treated in total Past Promising phase 1 data in post-surgery pancreas cancer 10 year survival benefit shown in legacy study Phase 2 program with three active studies in different Present indications and combinations à multiple shots on g
Slide 28: Summary & finance
Summary & finance 28 circio
Slide 29: Active strategy to develop shareholder value through revenue-generating partnerships
Active strategy to develop shareholder value through revenue-generating partnerships 2023 1H 2024 2H 2024 2025 Initiate partner Tailor R&D Generate Enter revenue- dialogues strategy requested data generating deals Indication of interest R&D strategy adapted Revisit partners when Partner negotiations
Slide 30: R&D & BD value inflection points: Targeting first partnering deal during 1H'25
R&D & BD value inflection points: Targeting first partnering deal during 1H´25 1H´24 2H´24 1H´25 2H´25 Technical AAV AAV circVec circVec 3.0 AATD TG01 First Lead in vivo functionality vs. mRNA generation disease clinical strategic candidate PoC in vivo in vivo technical PoC model data data BD deal s
Slide 31: Circio planned short- and long-term deliverables
Circio planned short- and long-term deliverables Pre-clinical PoC and first deal à Q2 2025 Clinical readiness à 2026 and beyond Further enhance platform and expand IP portfolio Clinical entry of AAV-circVec AATD gene therapy - Establish circVec 3.0 generation - Phase 1 safety and biomarker data (AAT
Slide 32: Full team in place with strong blend of expertise
Full team in place with strong blend of expertise to build and capitalize on Circio´s platform Dr Erik D Wiklund Dr Lubor Gaal Dr Thomas B Hansen Dr Victor Levitsky Ola Melin CEO CFO & CBO CTO CSO COO Overall strategy Securing financing Building technology Leading immunology and Operational and exec