Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Presentation (November 2022)
31 slides from Circio Holding ASA's investor presentation, November 2022
Slide 1: Targovax Company overview November 2022
° targovax Company overview November 2022
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: Management team
Former consultant in the BD and finance Extensive experience Deeply experienced 25 years experience in 20 years in the pharma Pharma & Healthcare industry executive with across the global tumor immunology Biologics development, and biotech industry practice of McKinsey & 25 years experience oncology
Slide 5: Product candidates and 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/anti PD-1 Initiation of phase 2 trial (USA) ONCOS-102 Mesothelioma 1H 2023 Combination w/Standard-of-Care (SoC) Publication in oncolo
Slide 6: Melanoma and Mesothelioma
i. Melanoma ii. Mesothelioma 6
Slide 7: ONCOS-102 mechanism of action
Reverses immuno-suppressive defence mechanisms in the tumor Primes anti-cancer T-cell responses Delivers immune stimulatory payloads 7
Slide 8: Melanoma incidence and PD-1 resistance
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 9: ONCOS-102 response rate vs competitors in PD-1 resistant melanoma
CR PR 35% ORR ONCOS-102 5% 30% (7/20 pts.) 37% ORR RP1 12% 25% (6/16 pts.) 35% ORR BNT111 0% 35% (6/17 pts.) 28% ORR TAVO 8% 20% (15/50 pts.) Anti-PD1 23% ORR retreatment Vidutolimod 7% 16% (23/98 pts.) 21% ORR Lenvatinib 3% 18% (22/103 pts) 15% ORR Sotigalimab 0% 15% (5/33 pts.) 7% ORR T-VEC 0% 7%
Slide 10: 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 11: CD8+ T-cell tumor infiltration
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 12: CTLA-4 blockade rationale
CTLA-4 blockade depletes inhibitory regulatory T-cells both within the tumor and systemically CTLA-4 blockade enhances the priming of tumor-specific cytotoxic T-cells Enhanced tumor-specific T-cell priming leads to better systemic effect 12
Slide 13: Phase 2 melanoma trial design
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 14: Opportunity for best-in-class data in melanoma
✓ Opportunity to achieve best-in-class data in PD-1 resistant melanoma setting ✓ Differentiated combinations vs. competitors, with strong scientific and strategic rationale ✓ Design and size to enable licensing decisions for big pharma partners ✓ Confirm ONCOS-102 high dose and address FDA requireme
Slide 15: Mesothelioma: high unmet medical need
Mesothelioma Malignant pleural mesothelioma - high unmet medical Surgery Radiotherapy ws i Only 10% of patients suitable Rarely effective due to tumor for resection shape — Often diagnosed too Hard to focus radiation j Pe late for surgery Mainly s Technically challenging palliative care an Chemother
Slide 16: Mesothelioma survival data vs other trials
mPFS months 11 Targovax experimental 10 ONCOS-102+Pem/cis Pem/cis (or carbo) Checkpoint trials 9 8 Targovax control8 Baas6 Zalcman5 7 control Nowak7 Ceresoli3 chemo/durva Scagliotti4 Forde8 Baas6 6 Vogelzang2 Ipi/nivo chemo/durva Tsao1 5 mOS months 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Slide 17: Mutant KRAS
Mutant KRAS
Slide 18: Mutant KRAS program rationale
RAS mutations drive 30% of all cancers Current treatment options only address the KRAS G12C mutation, mainly relevant in lung cancer Only two other known polyvalent KRAS vaccines in clinical development Targovax focusing on differentiated cancer indications International collaborations established t
Slide 19: Circular RNA pipeline program
Circular RNA pipeline program
Slide 20: The circRNA discoverers work for Targovax
The circRNA discoverers work for Targovax Dr Thomas Hansen Dr Erik D Wiklund 20
Slide 21: circRNA toolbox for a novel class of medicines
circRNA provides a toolbox to create a novel class of medicines . ais O Maximize payload expression Extra-cellular trafficking Ob 2D Circular RNA is resistant to exonuclease degradation, leading to vastly increased half-life oo = => O O Onco-microRNA sponging Immune response booster O Hn
Slide 22: Highly versatile, multi-modal MoA, excellent stability
2022 objectives for the Targovax circRNA program: o Establish technical proof-of- concept (PoC) for circRNA vector approach Circular RNA o Optimize vector expression constructs and circRNA structural design Gene therapy / Onco-microRNA protein translation sponge o Explore and validate advantages of
Slide 23: Functional vector and effective circRNA design
Functional vector established Highly effective circRNA design identified Payload expressed from vector-encoded circRNA Plasmid-expressed circRNA, transfected cells Insertion Vector Protein expression strategy function V1 V2 ⍺-payload 1 V3 ⍺-payload 1 V4 ⍺-Loading Ctrl o circRNA design strategy is cr
Slide 24: 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 Targovax circRNA vector approach Synthetic circRNA Synthetic mRNA o Targovax has only approach with ability to deliver to solid tumors o
Slide 25: circRNA proof-of-concept results
✓ Functional vector design established, with efficient circRNA generation and transgene payload expression ✓ Superior circRNA design identified ✓ Extended circRNA half-life confirmed ✓ Enhanced and prolonged circRNA protein payload production over mRNA 25
Slide 26: circRNA focus areas and expansion
1 Activate validated immuno-stimulatory targets that face Core initial Oncology systemic toxicity issues focus for Solid tumors Modulate key cancer signalling and metabolic pathways in-house development Immunize against tumor neoantigens 2 Vaccines Enhance potency, durability and logistics over mRNA
Slide 27: circRNA competitive strengths
World-leading circRNA experts in-house with deep technical experience Led by circRNA pionéer Dr. Thomas Hansen Unique vector system for circRNA delivery to solid tumors Technical PoC established, vector turns cancer cells into circRNA factory GMP manufacturing at scale using commercially available e
Slide 28: Outlook
A Outlook
Slide 29: Outlook and strategy
Out-license ONCOS-102 with results from phase 2 melanoma trial Aim to “knock-it-out-of-the-park” with novel triple combination Study designed and sized to be attractive for big pharma partners Create optionality and multiple shots on goal in mutant RAS cancers Two TG01 clinical trials set to open du
Slide 30: Cash, market cap and shareholders
Net cash flow in 3Q - 30 -3 Shareholder Estimated ownership1 Shares million Ownership NOK million USD million HealthCap 12.4 6.6 % Avanza Bank AB (nom.) 7.4 3.9 % Cash at end of 3Q 96 9.6 Goldman Sachs Int. (nom.) Nordnet Bank AB (nom.) 5.2 4.7 2.8 % 2.5 % NOK million USD million Bækkelaget Holding
Slide 31: Want to learn more?
.e) targovax Want to learn more? CEO Dr. Erik Digman Wiklund Contact —[email protected] www.targovax.com