Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Targovax — Redeye Fight Cancer Day 2023
23 slides from Circio Holding Asa's conference presentation, Jan 19, 2023
Slide 1: Redeye Fight Cancer Day 2023
WT ° targovax Redeye — Fight Cancer Day 2023 Victor Levitsky, Chief Scientific Officer
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 Targovax and the Targovax Gr
Slide 3: Building next generation immune activator therapies
ONCOS-102: oncolytic immunotherapy with demonstrated clinical efficacy and excellent safety profile in multiple solid tumors and treatment combinations Highly competitive response rate: 35% ORR in anti-pd-1 resistant melanoma, responses in non-injected lesions and deep mechanistic analyses Building
Slide 4: Product candidates and 2023 milestones
Preclinical Clinical Product candidate Discovery IND- Phase 1 Phase 2 Phase 3 / Milestones enabling pivotal PD-1 Resistant Melanoma 1H 2023 Re-challenge combination w/aPD-1 & CTLA-4 Initiation of phase 2 trial (USA) ONCOS-102 Mesothelioma 1H 2023 Combination w/Standard-of-Care (SoC) Publication in o
Slide 5: Melanoma and Mesothelioma
i. Melanoma ii. Mesothelioma 5
Slide 6: ONCOS-102 mechanism of action
Reverses immuno-suppressive defence mechanisms in the tumor Primes anti-cancer T-cell responses Delivers immune stimulatory payloads 6
Slide 7: PD-1 resistance incidence and addressable patients
Total ~50,000 patients per year diagnosed with Incidence unresectable advanced malignant melanoma globally ~50% of cases become PD-1 resistant PD-1 resistance Total ~25,000 patients per year Estimated 10,000 – 20,000 patients per year addressable Addressable with intra-tumoral therapies >100,000 pat
Slide 8: ONCOS-102 response rate versus competing therapies in PD-1 resistant melanoma
CR PR 35% ORR ONCOS-102 5% 30% (7/20 pts.) 35% ORR BNT111 0% 35% (6/17 pts.) 29% ORR RP1 13% 16% (18/61 pts.) Anti-PD1 23% ORR Vidutolimod 7% 16% retreatment (23/98 pts.) 21% ORR Lenvatinib 3% 18% (22/103 pts.) 19% ORR TAVO 3% 16% (19/101 pts.) 15% ORR Sotigalimab 0% 15% (5/33 pts.) 7% ORR T-VEC 0%
Slide 9: Response in individual tumors
Response in individual tumors % change from baseline; injected and non-injected target lesions Injected (n=16)1 Non-injected (n=36) Part 1 o 12 of 36 (33%) non-injected Part 2 target lesions reduced in size o 8 of 15 (53%) patients had reduction in non-injected target lesions o 6 of 15 patients (40%
Slide 10: CD8+ T-cell infiltration increased over time
CD8+ T-cell tumor infiltration CD8+ T-cell infiltration increased over time Tumor biopsy IHC, patient case example in patients with clinical benefit (CR+PR+SD) p = 0.01 Progression on 3x ONCOS-102 only 6x ONCOS-102 pembrolizumab monotherapy 2x pembrolizumab Prior therapies: T-vec (oncolytic virus) D
Slide 11: Phase 2 trial design with botensilimab
1 ONCOS-102 2 ONCOS-102 + monotherapy balstilimab Expand to n=37 high dose1 high dose3 Confirm safety Randomize 3 Select dose for Safety run-in n=6 ONCOS-102 + expansion 2 ONCOS-102 + botensilimab Expand first to n=18, then n=37 balstilimab low2 → high dose 4 ONCOS-102 + Safety run-in n=6 10 patient
Slide 12: Phase 2 opportunity in PD-1 resistant melanoma
✓ Opportunity to achieve best-in-class data in PD-1 resistant melanoma setting ✓ Differentiated botensilimab combination, with strong scientific and strategic rationale and clinically validated activity in cold tumors ✓ Design and size to enable licensing decisions for big pharma partners ✓ Confirm
Slide 13: Circular RNA pipeline program
Circular RNA pipeline program
Slide 14: mRNA therapeutics: oncology is the next frontier
USD 50b total 2022 Remarkable speed - first mRNA sales for COVID therapeutics were approved in 2020 mRNA vaccines mRNA outcompeted more established concepts in COVID vaccine race Oncology is the next frontier for mRNA SOURCE: Statista analysis January 2023 14
Slide 15: Challenges with RNA therapeutics
RNA is chemically unstable – mRNA vaccines have required significant modifications Efficient delivery of RNA therapeutics is currently limited to vaccines and liver disease Challenging to achieve sufficient spread and half-life in tumors 15
Slide 16: Initial circRNA papers establishing the field
Initial circRNA papers establishing the field Dr Thomas Hansen Dr Erik D Wiklund 16
Slide 17: Versatility of circRNA provides a toolbox for novel medicines
The versatility of circRNA provides a toolbox to create a novel class of medicines for multiple applications . ais O Maximize payload expression Extra-cellular trafficking Ob 2D Circular RNA is resistant to exonuclease degradation, leading to vastly increased half-life O-O Onco-microRNA sponging
Slide 18: Highly versatile, multi-modal MoA, excellent stability
Therapeutic product Inject circRNA Gene therapy / Inside the Onco-microRNA protein translation patient sponge Encode tumor Immunological antigens activation Highly versatile – Multi-modal MoA – Excellent stability 18
Slide 19: Enhanced intra-cellular stability and delivery
Enhanced Does not Suitable Delivery Existing Delivery intra-cellular require vaccination to solid GMP manu- to liver stability packaging platform tumors facturing circAde vector approach Synthetic circRNA Synthetic mRNA o Targovax has the only approach for circRNA delivery to solid tumors o Vector-b
Slide 20: Competing circRNA companies
USD 325m USD 490m raised to date raised to date Main backers: Main backers: Merck (MSD), MPM Capital & BioImpact Capital Flagship Pioneering, Fidelity, Invus & Blackrock Approach: synthetic circRNA, LNP delivered Approach: synthetic circRNA, LNP delivered oRNA – engineered, IRES driven circRNAs eRNA
Slide 21: World-leading circRNA experts in-house
World-leading experts in-house with over 10 years circRNA experience Led by circRNA pioneer Dr. Thomas Hansen circAde system is applicable for many therapeutic areas Technical PoC established, in vivo PoC studies initiated Ability for broad and rapid library-based screening Vector GMP manufacturing
Slide 22: Outlook
Outlook
Slide 23: Outlook and opportunities
Opportunity to become best-in-class in PD-1 resistant melanoma Data from differentiated combination with botensilimab +/- PD-1 Phase 2 designed and sized to be attractive for big pharma partnering Validate platform and prepare for clinical introduction of first candidate In vivo PoC demonstrating pl