Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Targovax — Investor Presentation (November 2021)
36 slides from Circio Holding Asa's investor presentation, November 2021
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER Company presentation November 2021 OSE: TRVX
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 future and which, by their nature, will have an impact on the results of operations and the financial condition of
Slide 3: Targovax at a Glance
TARGOVAX AT A GLANCE ONCOS-102: Novel immune activator with clinical efficacy in several solid tumors in monotherapy and in combination with anti-PD1 and chemotherapy MoA confirmed in multiple indications: Broad local and systemic immune activation associated with clinical outcome ONCOS-102 is the b
Slide 4: High and Growing Medical Need for Immune Activators
HIGH AND GROWING MEDICAL NEED FOR IMMUNE ACTIVATORS CPIs are revolutionizing …but most patients …leading to a high medical cancer therapy… do not respond… need for immune activators $25bn Global CPI market 44% Patients eligible for CPI2: 60 - 90% Non-responders 1 Immune Checkpoint Inhibitors Markets
Slide 5: ONCOS-102 Immune Activation
ONCOS-102 IMMUNE ACTIVATION Unblinds the tumor to the immune system Activates the body´s own T-cells against the cancer Reverses immuno-suppresive defence mechanisms in the tumor 5
Slide 6: ONCOS-102 Initiates a Strong Immune Response That Triggers Anti-Tumor Immunity
ONCOS-102 INITIATES A STRONG IMMUNE RESPONSE THAT TRIGGERS ANTI-TUMOR IMMUNITY 1 Virus injection 2 Immune activation 3 T-cell generation 4 Anti-tumor immunity Intratumoral or intra- Oncolysis of tumor cells Antigen processing T-cell tumor infiltration peritoneal injection Inflammatory response by st
Slide 7: Clinical and Preclinical Pipeline
CLINICAL AND PRECLINICAL PIPELINE Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma 2022 Platform IO combination trial First patient Mesothelioma 2H 2021 ONCOS-102 Combination w/pemetrexed/cisplatin Survival update Metastatic Colorectal cancer 1H 2022 Comb
Slide 8: Refractory Melanoma
Refractory Melanoma 2. Mesothelioma 3. Metastatic Colorectal cancer 4. NextGen ONCOS vectors 5. Novel mutRAS concepts 6. Corporate strategy and finance 8
Slide 9: PD1 Refractory Melanoma Market Opportunity
MELANOMA PD1 REFRACTORY MELANOMA MARKET OPPORTUNITY ~100.000 new stage III/IV cases of malignant Incidence melanoma per year in the major markets ~50% recur and become unresectable Unresectable Total ~50.000 patients per year ~50% of cases become PD resistant PD1 resistance Total ~25.000 patients pe
Slide 10: ONCOS-102 Has Demonstrated Class-Leading Efficacy in PD1-Refractory Melanoma
MELANOMA ONCOS-102 HAS DEMONSTRATED CLASS-LEADING EFFICACY IN PD1-REFRACTORY MELANOMA CR PR Comment 35% ORR o Adenovirus expressing GM-CSF ONCOS-102 5% 30% (7/20 pts.) 35% ORR o Four melanoma antigens, mRNA BNT111 0 35% (6/17 pts.) retreatment Anti-PD1 6% 25% 31% ORR o Herpes virus expressing GM-CSF
Slide 11: Best-in-Class Response Rate with ORR of 35%
MELANOMA BEST-IN-CLASS RESPONSE RATE WITH ORR OF 35% Relative change (percent) in tumor burden from baseline to best response 100 Complete response Partial response 80 Stable disease 60 Progressive disease 40 IV III IV III III 20 IV IV III IV IV 0 III III -20 III -40 III IV IV III -60 IV -80 III -10
Slide 12: Multiple Examples of Systemic (Abscopal) Effect
MELANOMA MULTIPLE EXAMPLES OF SYSTEMIC (ABSCOPAL) EFFECT TWO PATIENTS WHERE A NON-INJECTED LESION COMPLETELY DISAPPEARED No universally agreed definition of abscopal effect: o 12 of 36 (33%) non-injected target lesions reduced in size o 8 of 15 patients with reduction in non-injected target lesions
Slide 13: Case Example: Patient with Complete Response
MELANOMA CASE EXAMPLE: PATIENT WITH COMPLETE RESPONSE Tumor response, 1 of 1 injected lesion Baseline Week 3 Week 9 Week 18 Week 27 (EoS) Tumor regression Discoloring and scar following ONCOS-102 tissue from injections only priming phase and biopsies Progression on 3x ONCOS-102 only 3x ONCOS-102 & 3
Slide 14: Case Example: Tumor T-cell Infiltration
MELANOMA CASE EXAMPLE: PATIENT WITH COMPLETE RESPONSE TUMOR T-CELL INFILTRATION T-cell infiltrate, 1 of 1 injected lesion Baseline Week 3 Week 9 Total level of T-cells Wk 3 CD8+ T-cells Wk 9 Low CD8+ 15x increase CR, mainly necrotic tissue; BL level at baseline from baseline some T-cells still prese
Slide 15: Highest Increase in Tumor T-cell Infiltrates Observed in Melanoma Responders
MELANOMA HIGHEST INCREASE IN TUMOR T-CELL INFILTRATES OBSERVED IN MELANOMA RESPONDERS T-cell infiltrate (TIL) for individual patients; tumor mIHC, relative level Average T-cell level per group Baseline Baseline Week 3 Week 3, ONCOS only Week 9 * w/o pseudo-progressor CD8+ T-cells CR PR SD PD CR 1 PR
Slide 16: Gene Expression Data Confirms IHC Observations
MELANOMA GENE EXPRESSION DATA CONFIRMS IHC OBSERVATIONS AND DETAILS BROAD PRO-INFLAMMATORY TUMOR RE-PROGRAMING RNAseq gene expression provides further insights: Change Day 64 vs. baseline o Pro-inflammatory “hot” tumor remodeling through multiple pathways and molecular mechanisms o ”Hot” tumor remod
Slide 17: Strength and Breadth of ONCOS-102 Clinical Data Package Opens Broad Opportunities
STRENGTH AND BREADTH OF ONCOS-102 CLINICAL DATA PACKAGE OPENS BROAD OPPORTUNITIES Class-leading ONCOS-102 drives meaningful clinical benefit, efficacy competitive with leading drug candidates ONCOS-102 data package is highly consistent Highly across tumor types, survival, clinical response, consiste
Slide 18: Next Step: Melanoma Platform Trial
NEXT STEP: MELANOMA PLATFORM TRIAL TO EXPLORE MULTIPLE ONCOS-102 COMBINATIONS DRIVEN BY PHASE 1 DATA Part 1 – run-in Part 2 – multi-cohort extension 1 ONCOS-102 4 ONCOS-102 + monotherapy PD1 + CTLA4 Assess contri- o Additional cohorts to explore Randomize bution of novel combinations components ONCO
Slide 19: Mesothelioma
Mesothelioma 3. Metastatic Colorectal cancer 4. NextGen ONCOS vectors 5. Novel mutRAS concepts 6. Corporate strategy and finance 19
Slide 20: High Unmet Medical Need in Malignant Pleural Mesothelioma
MESOTHELIOMA THERE IS A HIGH UNMET MEDICAL NEED IN MALIGNANT PLEURAL MESOTHELIOMA Surgery Radiotherapy Only 10% of patients Rarely effective due to suitable for resection tumor shape Often diagnosed too Hard to focus radiation late for surgery Mainly Technically challenging palliative care Chemother
Slide 21: ONCOS-102 mOS in 1L Will Be Between 21.9–25.0 Months
MESOTHELIOMA ONCOS-102 mOS IN 1L WILL BE BETWEEN 21.9–25.0 MONTHS, WHICH IS THE BEST SURVIVAL DATA REPORTED IN 1L MESOTHELIOMA ONCOS-102 +Pem/cis mPFS Pem/cis (or carbo) months Checkpoint trials 11 Targovax experimental8 10 21.9–25.0 months 9 8 Targovax control8 Baas6 Zalcman5 7 control Nowak7 Ceres
Slide 22: Improved Survival Associated with Powerful ONCOS-102 Induced Immune Activation
MESOTHELIOMA IMPROVED SURVIVAL OUTCOME IS ASSOCIATED WITH POWERFUL ONCOS-102 INDUCED IMMUNE ACTIVATION Immuno-modulation in tumor tissue; Mesothelioma, Day 36 vs. baseline 22
Slide 23: Immune Marker Data Build Rationale for New Combinations
MESOTHELIOMA IMMUNE MARKER DATA BUILD STRONG RATIONALE FOR SEVERAL NEW COMBINATIONS WITH ONCOS-102 Immuno-modulation in tumor tissue; Mesothelioma, Day 36 vs. baseline Co-stims: Help T-cells expand, survive and kill Anti-PD1: T-cell engagers: Block the tumor´s “don´t Exploit T-cell cytotoxic machine
Slide 24: Metastatic Colorectal Cancer
Metastatic Colorectal cancer 4. NextGen ONCOS vectors 5. Novel mutRAS concepts 6. Corporate strategy and finance 24
Slide 25: Phase 1/2 Trial Combining ONCOS-102 and Imfinzi
COLORECTAL CANCER PHASE 1/2 TRIAL COMBINING ONCOS-102 AND IMFINZI Collaborators Primary colorectal cancer with peritoneal metastases Patient population Failed prior standard-of-care platinum chemotherapy 6 ONCOS-102 intraperitoneally infusion (once per week) Treatment regime 12 cycles of Imfinzi (st
Slide 26: NextGen ONCOS Vectors
NextGen ONCOS vectors 5. Novel mutRAS concepts 6. Corporate strategy and finance 26
Slide 27: Novel RNA Delivery Formats: RNA Exists Naturally in Circular Form
NOVEL RNA DELIVERY FORMATS: RNA EXISTS NATURALLY IN CIRCULAR FORM 768 citations 27
Slide 28: Two Recent Circular RNA Biotech Launches Attracted Mega Series A Rounds
TWO RECENT LAUNCHES OF CIRCULAR RNA BIOTECHS HAVE ATTRACTED MEGA SERIES A ROUNDS 28
Slide 29: ONCOS Provides an Ideal, Clinically Validated Platform for Circular RNA
ONCOS PROVIDES AN IDEAL, CLINICALLY VALIDATED PLATFORM FOR CIRCULAR RNA Novel ONCOS circular RNA vectors Circular RNA Express transgenes Encode tumor antigens Immunological activation Onco-microRNA sponge Highly versatile delivery system 29
Slide 30: Novel mutRAS Concepts
Novel mutRAS concepts 6. Corporate strategy and finance 30
Slide 31: Additional Opportunity: Novel Mutant RAS Concepts Through Strategic Partnerships
ADDITIONAL OPPORTUNITY: NOVEL MUTANT RAS CONCEPTS THROUGH STRATEGIC PARTNERSHIPS Targovax mutRAS immunotherapy strategy Ongoing mutRAS initiatives o Enhanced versions of Option to license TG vaccines for TG01/TG02 vaccines Greater China and Singapore Expand mutRAS clinical use o Novel therapeutic Cl
Slide 32: Corporate Strategy and Finance
Corporate strategy and finance 32
Slide 33: Targovax Core Development Strategy
TARGOVAX CORE DEVELOPMENT STRATEGY Let the science guide us: 1 Make smart, scientifically based decisions based on data and insights generated in the phase 1/2 program Advance ONCOS-102 in aPD1 refractory melanoma: 2 Boost response rates beyond the current 35% ORR by identifying the best combination
Slide 34: R&D Strategy: Validating ONCOS as a Versatile Delivery Tool
R&D STRATEGY: VALIDATING ONCOS AS A VERSATILE DELIVERY TOOL AND IDENTIFY BEST COMBINATION APPROACH o Lead clinical-stage product candidate Clinical o Phase 2 multi-cohort trial in melanoma ONCOS-102 platform trial o Assess multiple combinations in parallel to identify best partner and schedule Two-p
Slide 35: 3Q Financial Snapshot
3Q FINANCIAL SNAPSHOT Key figures Shareholder base1 Net cash flow in 3Q Ownership by professional -17 -2.0 institutions, e.g. • HealthCap, Nordea, 30% NOK million USD million Radforsk, AP4, MP Pension Cash at end of 3Q1 54 6.4 Largest shareholder 14% NOK million USD million • HealthCap Market cap 50
Slide 36: Targovax Summary
TARGOVAX SUMMARY ONCOS-102 - Best clinically documented immune activator in solid tumors o Compelling clinical and immune data in >200 patients as monotherapy, in combo with chemo and CPIs o Poised to lead and grow the global market for checkpoint inhibitors (CPIs) Mechanism of action confirmed in m