Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Presentation (October 2020)
31 slides from Circio Holding ASA's investor presentation, October 2020
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER Investor presentation October 2020
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 Immune activation ➢ Addressing high medical need for immune activators like oncolytic viruses to enhance cancer immunotherapies Leader in the field ➢ ONCOS-102 is one of the most promising oncolytic viruses with >200 patients treated ➢ Encouraging clinical and immune data in mon
Slide 4: Track Record of Strong Execution with Multiple Upcoming Value Inflection Points
TRACK RECORD OF STRONG EXECUTION WITH MULTIPLE UPCOMING VALUE INFLECTION POINTS 2019 2020 2021 H1 H2 H1 Mesothelioma ✓ Mesothelioma ✓ Mesothelioma Mesothelioma 18 month survival 24 month survival Safety lead-in 12 month data follow-up follow-up ✓ Merck: ✓ Melanoma Part 2 data Mesothelioma Melanoma O
Slide 5: Growing Need for Immune Activators
GROWING NEED FOR IMMUNE ACTIVATORS Checkpoint inhibitors are revolutionizing cancer …but minority of patients …leading to a high medical therapy… respond… need for immune activators 22 bn USD Global CPI market1 44 % Patients eligible for CPI2: 10 - 40 % Responders 1 Immune Checkpoint Inhibitors Mark
Slide 6: Several Significant Oncolytic Virus Transactions
SEVERAL SIGNIFICANT ONCOLYTIC VIRUS TRANSACTIONS Acquirer Target Type of deal Deal value Strategic collaboration USD 120m near-term Co-development of multiple USD >900m total value vaccinia viruses, Pre-clinical M&A USD 400m RNA virus, Phase II cash acquisition M&A USD 140m up-front Herpes virus, Pr
Slide 7: ONCOS-102 Is an Oncolytic Adenovirus Armed with an Immune Activating Transgene
ONCOS-102 IS AN ONCOLYTIC ADENOVIRUS SEROTYPE 5 ARMED WITH AN IMMUNE ACTIVATING TRANSGENE 1 2 3 Selective replication Boosting the immune Enhanced infection in cancer cells activation of cancer cells ∆24 bp ∆6.7K/gp19K ∆Ad5 knob E1A E3 Fiber knob ITR ITR GM-CSF Transgene Ad3 knob 7
Slide 8: ONCOS-102 Drives a Strong Immune Response Triggering Anti-Tumor Immunity
ONCOS-102 DRIVES A STRONG IMMUNE RESPONSE TRIGGERING 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 stimulat
Slide 9: ONCOS-102 Development Strategy Centered Around Checkpoint Inhibitor Combinations
ONCOS-102 DEVELOPMENT STRATEGY IS CENTERED AROUND CHECKPOINT INHIBITOR COMBINATIONS 1 Establish path-to-market Mesothelioma o ~15.000 patients o Niche indication, potential for first line 2 Activate refractory tumors Anti-PD1 refractory melanoma o Few alternatives for ~50.000 patients o Competitive
Slide 10: Development Program Focused on Strategic Therapeutic Combinations and Partnerships
DEVELOPMENT PROGRAM FOCUSED ON STRATEGIC THERAPEUTIC COMBINATIONS AND PARTNERSHIPS Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma 2H 2020 Combination w/ pemetrexed/cisplatin Survival data Melanoma 2H 2020 Combination w/Keytruda Part 2 clinical data ONCOS
Slide 11: Pipeline: ONCOS-102
Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma ONCOS-102 Combination w/ pemetrexed/cisplatin Melanoma Combination w/Keytruda Colorectal Combination w/Imfinzi Prostate Combination w/DCvac ONCOS-200 series Next Gen viruses Novel mutRAS concepts 11
Slide 12: High Need for New Treatment Approaches in Malignant Pleural Mesothelioma
HIGH NEED FOR NEW TREATMENT APPROACHES IN MALIGNANT PLEURAL MESOTHELIOMA Surgery Radiotherapy Only 10% of patients Rarely effective due to suitable for resection tumor shape and location Often diagnosed too Hard to focus radiation late for surgery Mainly Technically challenging palliative care Chemo
Slide 13: Encouraging Clinical Outcomes in First Line
ONCOS-102 MESOTHELIOMA PHASE I/II COMBINATION WITH SOC CHEMO ENCOURAGING CLINICAL OUTCOMES IN FIRST LINE Trial design Disease control rate Experimental Control First and second (or later) line ONCOS-102: 6 intra-tumoral injections Standard of Care (SoC) Chemo: Pemetrexed and cisplatin, 6 cycles 90%
Slide 14: First Line ORR and PFS Data Compare Favorably to Historical Control
FIRST LINE ORR AND PFS DATA COMPARE FAVORABLY TO HISTORICAL CONTROL ORR / BORR 50 45 Scagliotti Baas 20194 20205 40 35 Baas ipi/nivo 20205 Targovax experimental 30 Targovax control group, ORR7 25 Vogelzang 20032 Zalcman Tsao Ceresoli 20166 20 20191 2006, BORR3 15 10 5 0 4,5 5,0 5,5 6,0 6,5 7,0 7,5 8
Slide 15: A Broad and Powerful Immune Activation Pattern Confirms ONCOS-102 Mode of Action
A BROAD AND POWERFUL IMMUNE ACTIVATION PATTERN CONFIRMS ONCOS-102 MODE OF ACTION CD8+ T-cells ONCOS-102 treated - Alive -fold change ONCOS-102 treated - Deceased Control - Alive Control - Deceased Cytotoxic CD8+ T-cells PD-L1 expression -fold change -fold change • Powerful immune activation compared
Slide 16: Powerful Immune Activation Associated with Improved Clinical Outcome
PRELIMINARY DATA THIS POWERFUL IMMUNE ACTIVATION IS ASSOCIATED WITH IMPROVED CLINICAL OUTCOME ONCOS-102 treated patients with disease control (SD/PR) vs progression (PD) Fraction of modulated genes1, Day 36 vs Baseline (%) Broad immune activation observed in patients with disease control Low immune
Slide 17: Clinical and Immune Data Support Triple Combination with Checkpoint Inhibitor
CLINICAL AND IMMUNE DATA SUPPORT TRIPLE COMBINATION WITH CHECKPOINT INHIBITOR Excellent safety profile confirmed ONCOS-102 and SoC chemotherapy combination is well-tolerated Clear clinical activity Favorable mPFS of 8.9 months in first line ONCOS-102 treated patients ONCOS-102 mode-of-action confirm
Slide 18: Pipeline: ONCOS-102
Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma Combination w/ pemetrexed/cisplatin ONCOS-102 Melanoma Combination w/Keytruda Colorectal Combination w/Imfinzi Prostate Combination w/DCvac ONCOS-200 series Next Gen viruses Novel mutRAS concepts 18
Slide 19: ONCOS-102 Anti-PD1 Refractory Melanoma: 33% ORR and Robust Immune Activation
ONCOS-102 ANTI-PD1 REFRACTORY MELANOMA PART 1 33% ORR AND ROBUST IMMUNE ACTIVATION Advanced, unresectable melanoma Disease progression following prior treatment with anti-PD1 Patient population Poor prognosis, with few treatment alternatives Part 1: 9 patients. Part 2: 12 patients (ongoing, fully re
Slide 20: Robust Local and Systemic Immune Activation
PART 1 ROBUST LOCAL AND SYSTEMIC IMMUNE ACTIVATION Patients with activation Patients without activation Inflammatory response and innate immune activation Pro-inflammatory cytokine increase: IL-6 and / or TNFa Increase in systemic IFNγ expression Fever/chills Adaptive immune activation T-cell tumor
Slide 21: Tumor Regression Observed in PD1-Refractory Patients
TUMOR REGRESSION OBSERVED IN PD1-REFRACTORY PATIENTS BEST PERCENT CHANGE IN TARGET LESIONS 100 80 Best % change in tumor burden from baseline 60 40 IV * III * III 20 III 0 IV -20 * -40 III -60 IV -80 III -100 * III * Progressive Disease due to non target progression 21 Letters and numbers indicating
Slide 22: Case Example: Early and Durable Complete Response
PART 1 CASE EXAMPLE: EARLY AND DURABLE COMPLETE RESPONSE Tumor response, 1 of 1 injected lesion Baseline Week 3 Week 9 Week 18 Week 27 (EoS) Progression on 3x ONCOS-102 only 3x ONCOS-102 & 3x ONCOS-102 & 5x 3x ONCOS-102 & 8x Keytruda 2x Keytruda Keytruda Keytruda Patient characteristics Tumor stage
Slide 23: ONCOS-102 Efficacy Competitive to Leading Candidates in PD1 Refractory Melanoma
ONCOS-102 HAS PRODUCED EFFICACY DATA COMPETITIVE TO LEADING DRUG CANDIDATES IN PD1 REFRACTORY MELANOMA CR PR Comment 11% 22% 33% ORR o Adenovirus expressing GM-CSF ONCOS-102 (3/9 pats.) 31% ORR o Herpesvirus expressing GM-CSF retreatment RP1 0 31% (5/16 pats.) and GALV Anti-PD1 25% ORR o TLR-9 agoni
Slide 24: Pipeline: ONCOS-102
Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma Combination w/ pemetrexed/cisplatin Melanoma Combination w/Keytruda ONCOS-102 Colorectal Combination w/Imfinzi Prostate Combination w/DCvac ONCOS-200 series Next Gen viruses Novel mutRAS concepts 24
Slide 25: Strong Collaboration in Colorectal Cancer with Phase I/II Trial Combining ONCOS-102 and Imfinzi
STRONG COLLABORATION IN COLORECTAL CANCER WITH PHASE I/II TRIAL COMBINING ONCOS-102 AND IMFINZI Collaboration Patient population Primary ovarian or colorectal cancer with peritoneal metastases Refractory to standard-of-care platinum chemotherapy Intraperitoneal admin of ONCOS-102 Dose escalation Exp
Slide 26: Tumor Change and Responses in Safety Lead-In
TUMOR CHANGE AND RESPONSES IN SAFETY LEAD-IN CPI MONOTHERAPY HAS SHOWN RESPONSES <5%1 Cohort C Tumor change2 and best overall response Cohort B Colorectal3 (CRC) Ovarian (OC) Cohort A 120 120 PD 100 100 80 80 PD PD PD PD 60 Cohort C 60 40 PD PD 40 20 SD 20 PD PD SD PD PD SD PR SD/PR 0 0 -20 -20 -40
Slide 27: Pipeline: ONCOS-102
Product candidate Preclinical Phase I Phase II Collaborator Next expected event Mesothelioma Combination w/ pemetrexed/cisplatin Melanoma Combination w/Keytruda ONCOS-102 Colorectal Combination w/Imfinzi Prostate Combination w/DCvac ONCOS-200 series Next Gen viruses Novel mutRAS concepts 27
Slide 28: Next Generation ONCOS Viruses Have Double Transgenes and Distinct Modes of Action
NEXT GENERATION ONCOS VIRUSES HAVE DOUBLE TRANSGENES AND DISTINCT MODES OF ACTION Mode of action Target tumors ONCOS-210 & -212 o Interfere with tumor’s ability to o Highly invasive or Inhibition of tumor growth break down surrounding tissue metabolic tumors and vascularization o Induce cell cycle a
Slide 29: Establishing Pipeline of First-in-Class Mutant RAS Concepts Through Strategic Partnerships
ESTABLISHING PIPELINE OF FIRST-IN-CLASS MUTANT RAS CONCEPTS THROUGH STRATEGIC PARTNERSHIPS Targovax mutRAS immunotherapy strategy Next generation mutant RAS pipeline o Enhanced versions of Boost TG01/02 immunogenicity - Enhanced mutRAS TG01/TG02 vaccines Next gen. adjuvants vaccination o Novel thera
Slide 30: Sufficiently Funded to Advance Clinical Program Beyond Value Inflection Points
SUFFICIENTLY FUNDED TO ADVANCE CLINICAL PROGRAM BEYOND VALUE INFLECTION POINTS The company The shareholders Cash end of 2Q Estimated ownership1 101 11 Shareholder HealthCap Shares million Ownership 12.4 16.3 % NOK million USD million RadForsk 4.4 5.8 % Nordea 4.3 5.7 % Net cash flow - total 2Q Fjard
Slide 31: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER BEST-IN-CLASS ENCOURAGING NEWS FLOW IMMUNE ACTIVATION CLINICAL EFFICACY Rich news flow 2020-21 from ONCOS-102 has clinically This powerful immune ongoing clinical program demonstrated a broad and activation translates into Collaboration with Mer