Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Presentation (September 2021)
33 slides from Circio Holding ASA's investor presentation, September 2021
Slide 1: Activating the Patient's Immune System to Fight Cancer
ACTIVATING THE PATIENT’S IMMUNE SYSTEM TO FIGHT CANCER Company presentation September 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 ONCOS-102 is MoA confirmed in multiple indications: Broad local and systemic immune activation associated with clinical outcome 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 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: Clinical and Preclinical Pipeline
CLINICAL AND PRECLINICAL PIPELINE Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma 2022 Platform trial First patient Mesothelioma 2H 2021 ONCOS-102 Combination w/pemetrexed/cisplatin Survival update Metastatic Colorectal cancer 1H 2022 Combination w/anti
Slide 9: Product Candidate Pipeline
Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma Platform trial Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin Metastatic Colorectal cancer Combination w/anti PDL1 Next Gen viruses Novel mutRAS concepts 9
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: 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 12: 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 13: 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 14: 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 15: 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 16: 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 17: 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 18: 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 19: 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 20: 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 21: Melanoma Phase 2 Platform Trial to Explore Multiple ONCOS-102 Combinations
MELANOMA PHASE 2 PLATFORM TRIAL TO EXPLORE MULTIPLE ONCOS-102 COMBINATIONS Part 1 – run-in Part 2 – multi-cohort extension 1 ONCOS-102 4 ONCOS-102 + monotherapy PD1 + aCTLA4 Randomize o Additional cohorts to explore Assess novel combinations ONCOS-102 + 2 ONCOS-102 + PD1 contribution of 5 (PD1) + co
Slide 22: Product Candidate Pipeline
Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma Platform trial Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin Metastatic Colorectal cancer Combination w/anti PDL1 Next Gen viruses Novel mutRAS concepts 22
Slide 23: 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 24: Encouraging Clinical Outcomes in 1st Line
ENCOURAGING CLINICAL OUTCOMES IN 1ST LINE PHASE 1/2 COMBINATION WITH SoC CHEMO 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 Alive after 24 months Safety Experi- Co
Slide 25: 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 26: Improved Survival Associated with Powerful ONCOS-102 Induced Immune Activation
IMPROVED SURVIVAL OUTCOME IS ASSOCIATED WITH POWERFUL ONCOS-102 INDUCED IMMUNE ACTIVATION Immuno-modulation in tumor tissue; Mesothelioma, Day 36 vs. baseline 26
Slide 27: Immune Marker Data Build Strong Rationale for New Combinations
IMMUNE MARKER DATA BUILD STRONG BIOLOGICAL 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 machinery
Slide 28: Product Candidate Pipeline
Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma Platform trial Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin Metastatic Colorectal cancer Combination w/anti PDL1 Next Gen viruses Novel mutRAS concepts 28
Slide 29: 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 30: Product Candidate Pipeline
Product candidate Preclinical Phase 1 Phase 2 Phase 3 Next expected event Refractory Melanoma Platform trial Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin Metastatic Colorectal cancer Combination w/anti PDL1 Next Gen viruses Novel mutRAS concepts 30
Slide 31: 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 32: 2Q Financial Snapshot
2Q FINANCIAL SNAPSHOT Key figures Shareholder base1 Net cash flow in 2Q Ownership by professional -24 -2.7 institutions, e.g. NOK million USD million • HealthCap, Nordea, Radforsk, AP4, Arctic 31% Cash at end of 2Q Aurora, MP Pension 71 8.4 NOK million USD million Largest shareholder • HealthCap 14%
Slide 33: Targovax Summary
TARGOVAX SUMMARY ONCOS-102 is the 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