Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Presentation (July 2021)
35 slides from Circio Holding ASA's investor presentation, July 2021
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER Company presentation July 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 combination with anti-PD1 and chemotherapy, and as monotherapy MoA confirmed in multiple indications: Broad local and systemic immune ONCOS-102 is the activation associated with clinical outcome
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 immunosuppresive defense mechanisms in the tumor 5
Slide 6: 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 6
Slide 7: 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 8: Early-Stage Development Successfully Completed – Entering Late-Stage Development
EARLY-STAGE DEVELOPMENT SUCCESSFULLY COMPLETED – ENTERING LATE-STAGE DEVELOPMENT Expansion opportunities Late-stage development Mesothelioma Colorectal cancer Early-stage development PD-1 refractory melanoma Other indications Other IO combinations Clinical efficacy Platform development Immune activa
Slide 9: Clinical and Preclinical Pipeline
CLINICAL AND PRECLINICAL PIPELINE Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma 1H 2022 Combination w/anti PD1 First patient Mesothelioma 2H 2021 ONCOS-102 Combination w/pemetrexed/cisplatin Survival update Metastatic Colorectal cancer 1H 2022 Combinat
Slide 10: Product Candidate Pipeline
Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma Combination w/anti PD1 Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin Metastatic Colorectal cancer Combination w/anti PDL1 Next Gen viruses Novel mutRAS concepts 10
Slide 11: 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 12: 35% ORR and Systemic Effect in Anti-PD1 Refractory Melanoma
MELANOMA 35% ORR AND SYSTEMIC EFFECT IN ANTI-PD1 REFRACTORY MELANOMA Advanced, unresectable melanoma Patient population Disease progression despite prior treatment with anti-PD1 20 patients, 11 stage III and 9 stage IV Part 1: 3 ONCOS-102 injections followed by 5 months of Keytruda Treatment regime
Slide 13: Patient Demographics – More Advanced Disease in Part 2
MELANOMA PATIENT DEMOGRAPHICS – MORE ADVANCED DISEASE IN PART 2 Part 1 Part 2 Total Parameters (n=8) (n=12) (N=20) Age (median) 70.5y 72y 72y Time from diagnosis to start of ONCOS-102 (median) 6.9y 2.9y 4.5y Number of treatments prior to study (average) 5.3 5.9 5.6 - Surgery (average) 2.1 1.9 2.0 -
Slide 14: 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 15: Responders Typically Had Reduction in Tumor Burden Already at Week 9
MELANOMA RESPONDERS TYPICALLY HAD REDUCTION IN TUMOR BURDEN ALREADY AT WEEK 9 Change in tumor volume through study; normalized to baseline (BL=100) Complete response (CR) Partial response (PR) Stable disease (SD) Progressive disease (PD) + 20% No change Pseudo-progression • RECIST1.1: PD - 30% • irR
Slide 16: Previous Treatments – 6 of 7 Responders Had Last Anti-PD1 Treatment <3 Months Prior
MELANOMA PREVIOUS TREATMENTS – 6 OF 7 RESPONDERS HAD LAST ANTI-PD1 TREATMENT <3 MONTHS PRIOR TO TRIAL Checkpoint inhibitor treatment prior to ONCOS-102 BOR CR All patients had min. PR 2 cycles of anti-PD1 (nivo or pembro) All patients had PD, confirmed by CT at SD baseline 15 / 20 patients last aPD1
Slide 17: 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 18: Case Example 1: Patient with Complete Response
MELANOMA CASE EXAMPLE 1: 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 &
Slide 19: Case Example 1: Tumor T-Cell Infiltration
MELANOMA CASE EXAMPLE 1: 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 pre
Slide 20: 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 21: ONCOS-102 Is a Well-Validated Program in Anti-PD1 Refractory Melanoma
MELANOMA ONCOS-102 IS A WELL-VALIDATED PROGRAM IN ANTI-PD1 REFRACTORY MELANOMA Clinical benefit Biomarker data ORR in PD-1 Stage of Abscopal Monotherapy Combination Combination TLR-9 Inflammatory T-cell PD-L1 Company Asset Type of molecule Refractory Development effect data w/ aPD1 with chemo signal
Slide 22: Top International KOLs Consulted for Advice on Next Steps
MELANOMA TOP INTERNATIONAL KOLs CONSULTED FOR ADVICE ON NEXT STEPS KOLs consulted Q1 2021 KOL feedback and recommendations for next steps Jedd Wolchok o ORR of >30% viewed as positive, uniform MSK, New York, USA recommendation to continue development Mario Sznol Yale, New Haven, USA o Systemic effec
Slide 23: Targeting Accelerated Approval in PD1 Refractory Melanoma
MELANOMA TARGETING ACCELERATED APPROVAL IN PD1 REFRACTORY MELANOMA Rationale Study design – current thinking Next steps • Highly competitive • ONCOS-102 + anti-PD1 • Finalize study design and clinical data • Single arm, ~100 patients enrolment criteria • No standard of care • Primary endpoint: ORR •
Slide 24: Product Candidate Pipeline
Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma Combination w/anti PD1 Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin Metastatic Colorectal cancer Combination w/anti PDL1 Next Gen viruses Novel mutRAS concepts 24
Slide 25: 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 26: Encouraging Clinical Outcomes in 1st Line Mesothelioma
MESOTHELIOMA ONCOS-102 MESOTHELIOMA PHASE 1/2 COMBINATION WITH SoC CHEMO ENCOURAGING CLINICAL OUTCOMES IN 1ST LINE Trial design Oncos-102 + SoC, n=8 SoC, n=6 Median PFS, months 1st and 2nd (or later) line ONCOS-102: 6 intra-tumoral injections 9.8 7.6 SoC chemo: pemetrexed and cisplatin, 6 cycles Ali
Slide 27: 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 28: Improved Survival Outcome 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; Day 36 vs. baseline • Powerful immune activation compared to control across all parameters • Immune activation pattern suggests ONCOS-102 induces sensitivity to c
Slide 29: Good Safety Profile, Immune Activation, Median Survival and Fast Track Status
MESOTHELIOMA GOOD SAFETY PROFILE, IMMUNE ACTIVATION, MEDIAN SURVIVAL AND FAST TRACK STATUS PROVIDE OPPORTUNITIES ONCOS-102 is well tolerated as combination therapy Clear survival benefit in first line patients Broad and powerful immune activation FDA-granted Fast Track designation in mesothelioma Ne
Slide 30: Product Candidate Pipeline
Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma Combination w/anti PD1 Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin Metastatic Colorectal cancer Combination w/anti PDL1 Next Gen viruses Novel mutRAS concepts 30
Slide 31: 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 32: Product Candidate Pipeline
Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma Combination w/anti PD1 Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin Metastatic Colorectal cancer Combination w/anti PDL1 Next Gen viruses Novel mutRAS concepts 32
Slide 33: Targovax's Pipeline Strategy
TARGOVAX’S PIPELINE STRATEGY Next Generation ONCOS viruses o Build new functionality into clinically proven ONCOS backbone o Boosted immunological activity and anti-tumor transgenes o Proprietary development and external collaborations Novel mutant RAS concepts o Novel combinations and adjuvant tech
Slide 34: Financial Snapshot
FINANCIAL SNAPSHOT The company Top 20 Shareholders - Estimated ownership Shares m Relative HealthCap 12,4 14,3 % Cash at end of 1Q Nordea 4,5 5,2 % 95 11 RadForsk AP4 Goldman Sachs & Co. LLC 4,4 4,0 2,0 5,1 % 4,6 % 2,3 % NOK million USD million Thorendal Invest AS 1,8 2,0 % Bækkelaget Holding AS 1,7
Slide 35: Targovax Summary
TARGOVAX SUMMARY Novel immune activator ONCOS-102 with clinical efficacy in multiple settings 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