Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Presentation (February 2020)
36 slides from Circio Holding ASA's investor presentation, February 2020
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER Company Presentation February 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: Activating the Immune System to Fight Cancer
ACTIVATING THE IMMUNE SYSTEM TO FIGHT CANCER Growing need for immune activators Immune activators can enhance the efficacy of checkpoint inhibitors ONCOS oncolytic adenovirus platform targets hard-to-treat solid tumors ONCOS-102 lead clinical asset One of the furthest developed OVs with >180 patient
Slide 4: Oncolytic Viruses Increasingly Important in Future Cancer Therapy Landscape
ONCOLYTIC VIRUSES INCREASINGLY IMPORTANT IN THE FUTURE CANCER THERAPY LANDSCAPE Targovax focus Immune Immune activators modulators Oncolytic viruses Checkpoint inhibitors Surgery - Radio - Chemo Immune Targeted boosters therapy CAR-Ts, TCRs TKIs, PARPs, etc. 4
Slide 5: ONCOS-102 Is an Oncolytic Adenovirus Armed with GM-CSF Transgene
ONCOS-102 IS AN ONCOLYTIC ADENOVIRUS SEROTYPE 5 ARMED WITH A GM-CSF 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 5
Slide 6: ONCOS-102 Mode of Action
ONCOS-102 MODE OF ACTION 1 Virus injection Local delivery 2 Oncolysis Immune activation 3 Antigen processing T-cell activation 4 T-cell response Anti-tumor immunity Intra-tumoral or intra- Lysis of tumor cells Antigen processing T-cell tumor infiltration peritoneal injection Inflammatory response T-
Slide 7: Benefits of ONCOS-102 Adenovirus
BENEFITS OF ONCOS-102 ADENOVIRUS Highly immunogenic, TLR-9 agonist, stimulates inflammation Well-characterized, well-tolerated and few safety concerns Versatile DNA backbone, ability to carry multiple transgenes 7
Slide 8: Significant BD Transactions in the Oncolytic Virus Space 2018-2019
SEVERAL SIGNIFICANT BD TRANSACTIONS IN THE ONCOLYTIC VIRUS SPACE IN 2018-2019 Acquirer Target Type of deal Deal value M&A USD 400m RNA virus, Phase II cash acquisition M&A USD 140m up-front Herpes virus, Pre-clinical USD 1b total value M&A USD 250m VSV virus, Pre-clinical cash acquisition R&D partne
Slide 9: The OV Development Landscape
THE OV DEVELOPMENT LANDSCAPE OVERVIEW OF MOST RELEVANT OVS IN CURRENT DEVELOPMENT Company Asset/ Program MoA Highest Phase Approved 2015 as mono H Imlygic HSV with GM-CSF transgene, IT only Phase III PD1 combo R Cavatak Coxsackievirus, non gene modified, IT focus, IV and IP trial ongoing Phase II A
Slide 10: ONCOS Development Strategy
ONCOS DEVELOPMENT STRATEGY 1 Path-to-market as orphan drug Mesothelioma o ~15.000 patients1 o Focused market entry in niche indication o Potential as frontline therapy, limited competition 2 Activating CPI refractory tumors Anti-PD1 refractory melanoma o No/few alternatives for ~50.000 patients1 o B
Slide 11: ONCOS-102 Clinical Development Program
ONCOS-102 CLINICAL DEVELOPMENT PROGRAM o Randomized trial Mesothelioma o Combination with SoC chemo 1 Phase I/II 31 patients o First data set with encouraging clinical and immune data Anti-PD1 refractory o Combination with Keytruda Compassionate use Various tumors o program 115 patients Phase I 12 p
Slide 12: ONCOS-102 Clinical Development Program
ONCOS-102 CLINICAL DEVELOPMENT PROGRAM o Randomized trial Mesothelioma o Combination with SoC chemo 1 Phase I/II 31 patients o First data set with encouraging clinical and immune data Anti-PD1 refractory Compassionate use Various tumors program 115 patients Phase I 12 patients 2 melanoma Phase I up
Slide 13: High Need for New Treatment Approaches
MALIGNANT PLEURAL MESOTHELIOMA HIGH NEED FOR NEW TREATMENT APPROACHES Surgery Radiotherapy Only 10% of patients Rarely effective due to suitable for resection tumor shape Technically challenging Shape of tumors make due to location them hard to target Diagnosis often too Mainly late for surgery pall
Slide 14: Rationale for ONCOS-102 Go-to-Market Strategy in Mesothelioma
RATIONALE FOR ONCOS-102 GO-TO-MARKET STRATEGY IN MESOTHELIOMA Become frontline therapy Orphan Drug Designation Limited competition o Data so far indicate o High unmet medical o Few other viruses in activity in mesothelioma need; orphan drug development designation o Ongoing randomized trial o ONCOS-
Slide 15: Study Design
ONCOS-102 MESOTHELIOMA PHASE I/II TRIAL IN COMBINATION WITH CHEMO STUDY DESIGN Experimental group n=14 Patient population Safety lead-in ONCOS-102 plus Non- n=6 SoC Chemo (6 cycles) Advanced malignant randomized Randomized pleural mesothelioma ONCOS-102 First and second (or later) plus SoC Chemo (6
Slide 16: Patient Characteristics and Outcomes
ONCOS-102 MESOTHELIOMA PHASE I/II COMBINATION WITH SOC PATIENT CHARACTERISTICS AND OUTCOMES ITT: N = 31 (20+11) Experimental Control Comments PP: N = 30 (19+11) n= 20 n= 11 Tumor and disease characteristics at enrollment - Number of lesions 4.3 3.5 - Tumor burden mm (RECIST 1.1) 87 46 Generally more
Slide 17: First Line ONCOS-102 ORR and Early PFS Compare Favorably to Historical Control
FIRST LINE ONCOS-102 ORR AND EARLY PFS DATA COMPARE FAVORABLY TO HISTORICAL CONTROL ORR / BORR • Vogelzang 2003 was the basis for FDA approval of Pemetrexed 50 • FDA review disputed data, reducing confirmed BORR to 21% (Hazarika 2005) 45 Vogelzang 40 2003, BORR 35 Targovax control 30 group, ORR 25 T
Slide 18: Increased T-cell Infiltration in Experimental Group
ONCOS-102 MESOTHELIOMA IMMUNE ACTIVATION INCREASED T-CELL INFILTRATION IN EXPERIMENTAL GROUP CD8+ T-cell infiltration -fold change from baseline to day 36 (n=201) Partial response (PR) Stable disease (SD) Progressive disease (PD) Average -fold change in CD8+ • 3.3-fold in experimental group • No cha
Slide 19: Next Step: ONCOS-102 + Anti-PD1/L1 + Chemo Triple Combination
NEXT STEP: ONCOS-102 + ANTI-PD1/L1 + CHEMO TRIPLE COMBINATION IN FIRST LINE MESOTHELIOMA Study population – malignant pleural mesothelioma: First line, unresectable, advanced and/or metastatic disease ca. 100 patients Experimental arm ONCOS-102 + anti-PD1/L1 + Chemo Safety lead-in Go / No go decisio
Slide 20: Summary and Next Steps
ONCOS-102 MESOTHELIOMA PHASE I/II TRIAL SUMMARY AND NEXT STEPS Excellent safety profile ONCOS-102 and SoC chemotherapy combination is well-tolerated Clinical activity observed Emerging data suggest benefit for ONCOS-102 treated patients and compare favorably to historical control Increased T-cell in
Slide 21: Strategy and Indicative Timelines
ONCOS-102 DEVELOPMENT PATH IN MALIGNANT PLEURAL MESOTHELIOMA STRATEGY AND INDICATIVE TIMELINES 2019 2020 2021 2022 2023 2024 Ongoing Phase I/II randomized, N=31 Preparation for phase II Phase II lead-in Randomized phase II ONCOS-102 + CPI + SoC safety part, N=12 N=90 o Phase I/II trial of ONCOS-102
Slide 22: ONCOS-102 Clinical Development Program
ONCOS-102 CLINICAL DEVELOPMENT PROGRAM Mesothelioma 1 Phase I/II 31 patients Anti-PD1 refractory o Combination with Keytruda Compassionate use Various tumors o program 115 patients Phase I 12 patients 2 melanoma Phase I o PI at Memorial Sloan Kettering CC Part 1 completed with 33% ORR up to 21 patie
Slide 23: 33% ORR and Robust Immune Activation
ONCOS-102 ANTI-PD1 REFRACTORY MELANOMA PART 1 33% ORR AND ROBUST IMMUNE ACTIVATION Advanced, unresectable melanoma with disease progression following prior treatment with anti-PD1 Patient population Typically treated with 2-3 immunotherapies prior to inclusion Median age 73 years (40-87) Poor progno
Slide 24: Best Percentage Change in Target Lesions
BEST PERCENTAGE 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 24 Letters and numbers indicating disease stage Preliminary data
Slide 25: Case Example: Patient with Complete Response
CASE EXAMPLE: PATIENT WITH 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 at enrolment
Slide 26: Robust Local and Systemic Immune Activation
ROBUST LOCAL AND SYSTEMIC IMMUNE ACTIVATION Inflammatory response and innate immune activation Pro-inflammatory cytokine increase: IL-6 (8/8 pts), TNFa (7/8 pts) Increase in systemic IFNγ expression (8/8 pts) Fever/chills (7/9 pts) Adaptive immune activation T-cell tumor infiltration Tumor specific
Slide 27: Increase in CD8+ T-cell Infiltration Necessary, Not Sufficient, for Response
INCREASE IN CD8+ T-CELL INFILTRATION APPEARS TO BE NECESSARY, BUT NOT SUFFICIENT, FOR RESPONSE CD8+ T-cell infiltration into injected lesions, -fold change from baseline Clinically responding patients All 9 patients had low or very low CD8+ T-cell infiltration at baseline * CR PR PR PD PD PD PD PD P
Slide 28: ONCOS-102 + Keytruda Data in Context
ONCOS-102 + KEYTRUDA DATA IN CONTEXT ANTI-PD1 REFRACTORY MELANOMA BENCHMARK DATA CR PR Comment 33% ORR ONCOS-102 11% 22% (3/9 pats.) 25% ORR o Checkmate Pharma, TLR-9 agonist retreatment CMP-001 3% 22% o Data from high dose cohort (21/83 pats.) Anti-PD1 3% 17% 21%ORR o Dynavax, TLR-9 agonist SD-101
Slide 29: Melanoma Part 2 Is Recruiting
MELANOMA PART 2 IS RECRUITING UP TO 12 PATIENTS: 12 ONCOS-102 INJECTIONS COMBINED WITH 5 MONTHS KEYTRUDA Part 1: BL 1 2 3 6 9 12 15 18 21 24 27 Weeks 3 ONCOS-102 injections CPO ONCOS-102 KEYTRUDA Part 2: BL 1 2 3 6 9 12 15 18 21 24 27 Weeks 12 ONCOS-102 injections CPO ONCOS-102 ONCOS-102 + KEYTRUDA
Slide 30: ONCOS-102 Clinical Development Program
ONCOS-102 CLINICAL DEVELOPMENT PROGRAM Mesothelioma 1 Phase I/II 31 patients Anti-PD1 refractory Compassionate use Various tumors program 115 patients Phase I 12 patients 2 melanoma Phase I up to 21 patients Peritoneal o Combination with Imfinzi o Completed 3 malignancies Phase I/II o Intraperitonea
Slide 31: Phase I/II Trial in Combination with Imfinzi
ONCOS-102 IN PERITONEAL MALIGNANCIES PHASE I/II TRIAL IN COMBINATION WITH IMFINZI Collaboration with US-based Cancer Research Institute, Ludwig Cancer Research (trial sponsor) and AstraZeneca Patient population: peritoneal disease who have failed prior standard chemotherapy and have histologically c
Slide 32: Pipeline with Rich Near-Term News Flow
PIPELINE WITH RICH NEAR-TERM NEWS FLOW Product candidate Preclinical Phase I Phase II Phase III Next expected event 1H 2020 Mesothelioma Updated clinical and Combination w/ pemetrexed/cisplatin immune data 1H 2020 Melanoma Clinical and immune Combination w/Keytruda activation data ONCOS-102 Peritone
Slide 33: Next Generation ONCOS Viruses Have Double Transgenes
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 34: TG01/02 IOVaxis Option Agreement
TG01/02 IOVAXIS OPTION AGREEMENT CEO: John Wang HQ: Nantong, China Founded: 2018 R&D focus: Shared and personalized cancer vaccines Topic o Exclusive option to license TG01/02 Terms o US$250.000 option fee vaccines for Greater China and Singapore o US$3m up-front fee upon option exercise o License o
Slide 35: 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 3Q Estimated ownership1 104 11 Shareholder HealthCap Shares, million 12.4 Ownership 19.6 % NOK million USD million RadForsk 4.4 7.0 % Nordea 3.7 5.8 % Net cash flow - total 3Q Thor
Slide 36: Activating the Immune System to Fight Cancer
ACTIVATING THE IMMUNE SYSTEM TO FIGHT CANCER CLINICALLY PROVEN INNOVATIVE RICH NEWS FLOW PIPELINE One of the furthest developed Next generation Clinical and immune activation oncolytic viruses virus platform in from mesothelioma and pre-clinical testing melanoma trials Strong single agent data Poten