Circio Holding ASA · OSL:CRNA
Circio Holding ASA — Targovax — Investor Day (February 2021)
81 slides from Circio Holding ASA's investor day presentation, Feb 18, 2021
Slide 1: Capital Markets Day Agenda & speakers
PLEASE JOIN US FOR OUR CAPITAL MARKETS DAY Agenda & speakers With strong clinical data generated on ONCOS-102, 2:30-2:40 PM Welcome Øystein Soug, CEO, Targovax is moving into late-stage clinical development. Targovax In addition, a broad pipeline of preclinical assets creates a broad horizon of oppo
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: Welcome
Welcome 2. Anti-PD1 refractory melanoma 3. ONCOS-102 development program 4. Immune activation 5. Preclinical pipeline update 6. 4Q update 7. Closing remarks
Slide 4: The Immuno-Oncology Revolution
THE IMMUNO-ONCOLOGY REVOLUTION > 500,000 patients treated per year > 3,000 ongoing clinical trials > 40% of US cancer patients eligible > 10 approved products 4 SOURCE: Research&Markets; Haslam & Prasad 2019, JAMA; Vaddepally et al. 2020, Cancers
Slide 5: First Generation Immuno-Oncology: Checkpoint Inhibitors
FIRST GENERATION IMMUNO-ONCOLOGY: CHECKPOINT INHIBITORS Cornerstone of current cancer treatment Deep and durable responses $25b annual sales globally 7 products approved to date, many more in development 5 SOURCE: GlobalData, Research&Markets
Slide 6: The Challenge: Make PD1 Checkpoint Inhibitors Work for More Patients
THE CHALLENGE: MAKE PD1 CHECKPOINT INHIBITORS WORK FOR 0-40% of treated patients respond MORE PATIENTS of responding >50% patients relapse 1 PD-1 checkpoint inhibitor monotherapy not sufficient 6 6 SOURCE: Haslam & Prasad, 2019, JAMA
Slide 7: The Solution: ONCOS-102 Immune Activation
THE SOLUTION: ONCOS-102 IMMUNE ACTIVATION Activates the body´s own T-cells against the cancer Unblinds the tumor to the immune system Reverses immunosuppressive defense mechanisms in the tumor 7
Slide 8: Targovax at a Glance
TARGOVAX AT A GLANCE Lead product candidate o Class-leading data in monotherapy and combinations with chemo and aPD-1 o Powerful immune activation ONCOS-102 o Ideal combination partner to aPD-1 Vision: o Path to market Unlock greater clinical benefits in cancer patients by deploying multifunctional
Slide 9: Clinical and Preclinical Pipeline
CLINICAL AND PRECLINICAL PIPELINE Product candidate Preclinical Phase 1 Phase 2 Collaborator Melanoma Combination w/Keytruda Colorectal cancer ONCOS-102 Combination w/Imfinzi Mesothelioma Combination w/pemetrexed/cisplatin ONCOS-200 series Next Gen viruses Novel mutRAS concepts 9 All rights to ONCOS
Slide 10: 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 PD1 refractory melanoma Other indications Other IO combinations Clinical efficacy Platform development Immune activat
Slide 11: ONCOS-102 Pipeline
Product candidate Preclinical Phase 1 Phase 2 Collaborator ONCOS-102 Melanoma Combination w/Keytruda Colorectal cancer Combination w/Imfinzi Mesothelioma Combination w/pemetrexed/cisplatin ONCOS-200 series Next Gen viruses Novel mutRAS concepts 11
Slide 12: Dr. Alexander N. Shoushtari, Memorial Sloan Kettering Cancer Center
DR. ALEXANDER N. SHOUSHTARI, MEMORIAL SLOAN KETTERING CANCER CENTER Renowned expert in melanoma, with a research focus on checkpoint refractory melanomas Clinical Director and Assistant attending physician, Melanoma Services, Dept of Medicine, Memorial Sloan Kettering Cancer Center Principal investi
Slide 13: Anti-PD1 refractory melanoma
Anti-PD1 refractory melanoma Dr. Shoushtari 3. ONCOS-102 development program 4. Immune activation 5. Preclinical pipeline update 6. 4Q update 7. Closing remarks
Slide 14: Melanoma and oncolytic adenoviruses
Melanoma and oncolytic adenoviruses Alexander Shoushtari, MD Assistant Attending Physician Melanoma and Immunotherapeutics Service Memorial Sloan Kettering Cancer Center New York, NY February 18, 2021 @alexshoushtari
Slide 15: Immunotherapy has revolutionized the treatment of malignant melanoma
Immunotherapy has revolutionized the treatment of malignant melanoma Real world example – Patient in an ipilimumab checkpoint inhibitor trial Prior to starting ipilimumab One year of ipilimumab treatment 2 Photo courtesy Jedd Wolchok
Slide 16: PD-1 blockade has surpassed CTLA-4 as cornerstone of melanoma treatment
PD-1 blockade has surpassed CTLA-4, and become the cornerstone of melanoma treatment Nivo + Ipi Nivo Ipi Source: Larkin et al, NEJM 2019 3
Slide 17: SITC treatment algorithm for late stage melanoma
SITC treatment algorithm for late stage melanoma Checkpoint inhibitors and BRAFi/MEKi are the mainstay frontline therapy in unresectable melanoma Few alternatives exist following progression on CPI and/or BRAFi/MEKi Treatment resistance – option of clinical trial or best supportive care 4 SOURCE: So
Slide 18: PD-1 checkpoints are effective in melanoma
PD-1 checkpoints are effective in melanoma Two main checkpoint inhibitor (CPI) treatment choices o Anti-PD-1 monotherapy: Pembrolizumab or Nivolumab o Anti-PD-1 + anti-CTLA4 combination therapy: Nivolumab plus Ipilimumab 45 - 60% objective response rate o Responses can last for years, but not foreve
Slide 19: Post PD-1/CTLA4/BRAF-MEKi progression options
Post PD-1/CTLA4/BRAF-MEKi progression, only experimental and off-label options are available Standard options post PD-1 Non-standard options post PD-1 After PD-1 monotherapy Clinical Trials (selected) o BRAF-MEK, if V600 mutant o PD-1 combination with: o Nivolumab plus ipilimumab − Oncolytic virus o
Slide 20: Response rates in PD-1 refractory melanoma trials
Response rates reported from PD-1 checkpoint inhibitor refractory melanoma clinical trials 5% 30% 35% ORR o Adenovirus expressing GM-CSF ONCOS-102 (7/20 pts.) CR PR Company Comment 31% ORR o Herpes virus expressing GM-CSF RP1 6% 25% and GALV (5/16 pts.) retreatment Anti-PD1 30% ORR o IL-12, DNA plas
Slide 21: Promising experimental therapies for PD-1 resistant patients
Promising experimental therapies available for PD-1 resistant patients Oncolytic viruses TLR-9 agonists • Trigger oncolysis and inflammatory • Stimulate innate immune response response via TLR-9 and other via TLR-9 danger signaling • Reverses local immuno-suppression • Trials ongoing in combination
Slide 22: Overview of the most common oncolytic virus classes
Overview of the most common oncolytic virus classes Small RNA viruses Adenovirus Herpes viruses Vaccinia virus o Highly oncolytic o Highly inflammatory o Large payload capacity o Large payload capacity o Highly inflammatory o Versatile DNA backbone o Only approved virus class o Used as vector for fi
Slide 23: Study design of ONCOS-102 phase I trial in melanoma
Study design of ONCOS-102 phase I trial in PD1 checkpoint-refractory melanoma Part 1 (n=8): BL 1 2 3 6 9 12 15 18 21 24 27 Weeks 3x ONCOS-102 injections Sequential treatment CPO ONCOS-102 pembrolizumab Part 2 (n=12): BL 1 2 3 6 9 12 15 18 21 24 27 Weeks 12x ONCOS-102 injections Combination treatment
Slide 24: Patient and disease characteristics
Patient and disease characteristics 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 - Treatments ex. surgery (aver
Slide 25: Objective responses in 7 of 20 patients (35% ORR)
Objective responses observed in 7 out of 20 patients (35% ORR) 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 -
Slide 26: Responders had last aPD1 treatment less than 3 months prior
6 of 7 responders had last aPD1 treatment less than 3 months prior to entering the trial Best Checkpoint inhibitor treatment prior to ONCOS-102 response CPI treatment prior to Part 1 001-02-002 PD trial inclusion: 001-01-001 PD 001-01-005 CR 001-01-009 PR 15 / 20 patients last 001-01-004 SD 001-02-0
Slide 27: Case example – patient with complete response
Case example 1 – patient with complete response Tumor stage at enrollment: IIIc Prior therapies: Surgery T4a, N2b, M0 Radiation Ipilimumab RECIST 1.1: CR Dabrafenib + Trametinib Pembrolizumab Baseline Week 3 Week 9 Week 18 Week 27 (EoS) Target lesion 1 of 1 Progression on 3x ONCOS-102 3x ONCOS-102 &
Slide 28: Case example – PR following 2 lines of prior PD-1 blockade
Case example 2 - Patient with PR following 2 separate lines of prior PD-1 blockade Tumor images, 3 of 3 injected lesions Baseline Week 3 Week 9 Week 18 Week 27 (EoS) Stage IIIC at Lesion 1 of 3 enrollment, 7 lesions in total 3 non-target lesions injected Prior therapies: - Surgery Lesion 2 of 3 - Ni
Slide 29: Evidence of systemic (abscopal) effect
Evidence of systemic (abscopal) effect – responses observed in several non-injected lesions Conservative definition of abscopal effect per lesion: o ≥30% tumor reduction from baseline o ≥ 5mm absolute reduction Abscopal effect observed in 4 / 20 patients (20%) o 1 / 8 patients in Part 1 (12.5%) o 3
Slide 30: ONCOS-102 with pembrolizumab is safe and well tolerated
ONCOS-102 and the combination with pembrolizumab is safe and well tolerated Adverse Event, Preferred term Subjects, n Events, n Grade 1 / 2 events Grade 3 Grade 4 AEs related to ONCOS-102 +/- CPO Pyrexia 10 24 24 - - Chills 9 23 23 - - Nausea 6 10 10 - - Injection site pain 4 6 6 - - Myalgia 3 6 6 -
Slide 31: Modulation of immune-related gene expression in Part 2
Broad and persistent modulation of immune-related gene expression observed in Part 2 of the trial Modulation of gene expression following ONCOS-102 treatment; % modulated genes Day 22 vs. Baseline Day 64 vs. Baseline Part 1 Part 2 Day 22 & Day 64 (n=2) Day 22 (n=10) & Day 64 (n=7) Baseline (n=6) Bas
Slide 32: ONCOS-102 + Keytruda data compares well to previous reports
ONCOS-102 + Keytruda data compares well to previous reports in PD-1 refractory melanoma Company Comment CR PR 5% 30% 35% ORR o Adenovirus expressing GM-CSF ONCOS-102 (7/20 pts.) 31% ORR o Herpes virus expressing GM-CSF RP1 6% 25% retreatment (5/16 pts.) and GALV Anti-PD1 30% ORR o IL-12, DNA plasmid
Slide 33: Successful phase I trial warrants further development of PD1 combination
Successful ONCOS-102 phase I trial warrants further development of PD1 combination Safety - ONCOS-102 is well-tolerated, with no safety concerns - Combines well with pembrolizumab, including concomitant dosing - Broad and general immune activation pattern observed in Immune ONCOS-102 injected lesion
Slide 34: Melanoma: Small indication, but influential
Melanoma: Small indication, but influential o We usually set trends followed by the bigger histologies o Easily accessible tissue o Relatively aggressive disease o Hot (cutaneous) vs cold (uveal) vs mixed (mucosal) models o Patient buy-in for biomarker heavy trials 21
Slide 35: What is next in melanoma? Ongoing trials and new combinations
What is next in melanoma? Ongoing trials and new combinations to watch Example compounds Trials to watch o LAG-3 relatimab in combination with Nivolumab in stage IV Novel immune Anti-LAG-3, TIM-3, IO naïve melanoma checkpoint inhibitors TIGIT o TIM-3 mono and in combination with anti-PD-1 in IO pret
Slide 36: First Line Trials in Melanoma: Big Ones
First Line Trials in Melanoma: Big Ones Randomized, PD-1 +/- XYZ o LAG-3: Nivolumab +/- Relatlimab (NCT03470922) o IL-2 directed: Nivolumab +/- BEMPEG (NCT03635983) o VEGF: Pembrolizumab +/- Lenvatinib (NCT03820986) BRAF-MEK +/- PD-1: Enco-Bini-Spartalizumab (NCT02967692) T-VEC: Pembrolizumab +/- T-
Slide 37: First Line Trials in Melanoma: Overall Survival
First Line Trials in Melanoma: Big Ones o Large, randomized trials, 500-700+ patients o What do we need for a new standard? – Overall Survival (OS), not just PFS and ORR – Tolerability – Schedule / ease of use o We are a few years away from making a new frontline standard o Existing frontline treatm
Slide 38: Post PD-1 Trials: Trends
Post PD-1 Trials: Trends o Critical need to develop new treatments, but it’s getting harder to do it well o Rigidly defining “PD-1 resistance” o Slowly relaxing prior toxicity requirements (…too slowly) o Highly selective trials (e.g. lifileucel) o The specter of ipilimumab: 20% ORR, durability o Si
Slide 39: Thanks!
Thanks! 2020 MSKCC Melanoma Disease Management Group
Slide 40: ONCOS-102 development program
ONCOS-102 development program 4. Immune activation 5. Preclinical pipeline update 6. 4Q update 7. Closing remarks
Slide 41: 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 PD1 refractory melanoma Other indications Other IO combinations Clinical efficacy Platform development Immune activat
Slide 42: Checkpoint Inhibitors in the Clinic
CHECKPOINT INHIBITORS IN THE CLINIC Huge impact since the launch of Yervoy in 2011 o aPD1 standard of care in several solid tumor indications o Varying response rates − Melanoma ca. 40% ORR − Lung ca. 30% ORR − Head & Neck ca. 20% ORR CPI refractory cancer is a significant medical need o Primary ref
Slide 43: PD1 Refractory Melanoma Market Opportunity
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 per year Es
Slide 44: Accelerated Approval in Anti-PD1 Refractory Melanoma Is Our Priority
ACCELERATED APPROVAL IN ANTI-PD1 REFRACTORY MELANOMA IS OUR PRIORITY Rationale Preliminary trial design – Next steps registration directed • Highly • Conclude trial design discussions competitive • Single arm, < 200 patients with KOLs in US, EU and Australia clinical data • Refractory status • Consu
Slide 45: Pipeline: ONCOS-102
Product candidate Preclinical Phase 1 Phase 2 Collaborator Melanoma Combination w/Keytruda Colorectal cancer ONCOS-102 Combination w/Imfinzi Mesothelioma Combination w/pemetrexed/cisplatin ONCOS-200 series Next Gen viruses Novel mutRAS concepts 45
Slide 46: Colorectal Cancer: Phase 1/2 Trial Combining ONCOS-102 and Imfinzi
COLLABORATION IN COLORECTAL CANCER WITH PHASE 1/2 TRIAL COMBINING ONCOS-102 AND IMFINZI Patients Primary colorectal cancer with peritoneal metastases Failed prior standard-of-care platinum chemotherapy Dose escalation Expansion Safety lead-in Simon’s two- Part 1 stage design Part 2 ONCOS-102 13 pati
Slide 47: Pipeline: ONCOS-102
Product candidate Preclinical Phase 1 Phase 2 Collaborator Melanoma Combination w/Keytruda Colorectal cancer Combination w/Imfinzi Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin ONCOS-200 series Next Gen viruses Novel mutRAS concepts 47
Slide 48: Mesothelioma: Phase 1/2 Trial in Combination with Chemo
ADVANCED MALIGNANT PLEURAL MESOTHELIOMA PHASE 1/2 TRIAL IN COMBINATION WITH CHEMO Experimental group n=14 Trial design ONCOS-102 plus 1st and 2nd line Safety lead-in SoC Chemo n=6 Randomized Standard of Care (SoC) pemetrexed/cisplatin +/- ONCOS-102 ONCOS-102 plus SoC Chemo Control group n=11 SoC Che
Slide 49: Clinical Outcomes in 1st Line Compare Favorably to Historical Control
CLINICAL OUTCOMES IN 1ST LINE COMPARE FAVORABLY TO HISTORICAL CONTROL ONCOS-102 +Pem/cis mPFS Pem/cis (or carbo) months Checkpoint trials 11 Targovax experimental8 10 Min. 9 8 Targovax control8 Min. Max. Zalcman5 7 Nowak7 Ceresoli3 Baas5 chemo/durva Scagliotti4 control Ipi/Nivo 6 Vogelzang2 just app
Slide 50: Fast Track Designation and Evolving Survival Data Provide Opportunities
FAST TRACK DESIGNATION AND EVOLVING SURVIVAL DATA PROVIDE OPPORTUNITIES Well tolerated combination therapy Clear clinical activity in 1st line patients Interim survival data promising even without CPI FDA granted Fast Track designation in mesothelioma Next steps Continue follow patients to determine
Slide 51: ONCOS-102 Opportunities Beyond Melanoma and Mesothelioma
ONCOS-102 OPPORTUNITIES BEYOND MELANOMA AND MESOTHELIOMA COLORECTAL o Large medical need and strong scientific o Data expected during 1H 2022 rationale for CPI combination o Review opportunity and o Met predetermined efficacy threshold in development with AstraZeneca Simon two-stage trial FURTHER OP
Slide 52: Clinical and Preclinical Pipeline
CLINICAL AND PRECLINICAL PIPELINE Product candidate Preclinical Phase 1 Phase 2 Collaborator Next expected event Melanoma 1H 2022 Combination w/anti PD1 First patient Colorectal cancer Update by collaborator – ONCOS-102 Combination w/Imfinzi clinical data expected 1H22 Mesothelioma 1H 2021 Combinati
Slide 53: Immune activation
Immune activation 5. Preclinical pipeline update 6. 4Q update 7. Closing remarks
Slide 54: The Importance of Immunological Read-outs
THE IMPORTANCE OF IMMUNOLOGICAL READ-OUTS o Understand mechanism- o Strength of immune of-action of ONCOS-102 responses o Confirm delivery of o Breadth of ONCOS-102 into the immunological tumor remodelling Function Power o Persistence of the Duration Impact o Association between immune response immu
Slide 55: Four Critical Phases of Tumor-Specific Immune Response
FOUR CRITICAL PHASES OF TUMOR-SPECIFIC IMMUNE RESPONSE T-cell migration and 2 infiltration into the tumor 1 Access to tumor antigens, cross-presentation by APCs and priming of T-cells Expansion and survival m 3 of T-cells in the tumor 4 Tumor cell recognition and elimination 55 Adapted from Chen & M
Slide 56: Four Critical Phases of Tumor-Specific Immune Response: Problems
FOUR CRITICAL PHASES OF TUMOR-SPECIFIC IMMUNE RESPONSE T-cell migration and 2 infiltration into the tumor 1 Access to tumor antigens, cross-presentation by APCs Problem: T-cells do not and priming of T-cells reach the tumor Problem: Low tumor immunogenicity and Expansion and survival ineffective T-c
Slide 57: ONCOS-102 Activates Danger Signaling: Mesothelioma
ONCOS-102 ACTIVATES DANGER SIGNALING: MESOTHELIOMA TLR9 expression in tumor RNAseq -fold change D36 vs. baseline1, mesothelioma Injected lesion Non- Control injected lesion 57 1 Unpublished company data
Slide 58: ONCOS-102 Activates Danger Signaling: Melanoma
ONCOS-102 ACTIVATES DANGER SIGNALING: MELANOMA * * 001-01-13 – no data for Day 64 58 Unpublished company data
Slide 59: Robust Increase of Tumor Infiltration by T-Cells
ROBUST INCREASE OF TUMOR INFILTRATION BY T-CELLS FOLLOWING ONCOS-102 TREATMENT ONCOS-102 induced tumor T-cell infiltration Ovarian cancer patient case example, monotherapy Tumor biopsy mIHC – CD8+ T-cells o >1000-fold increase of CD8+ T-cells in tumor o Ovarian cancer patient – stable disease for th
Slide 60: T-Cell Tumor Infiltration: Mesothelioma
ROBUST INCREASE IN T-CELL TUMOR INFILTRATION FOLLOWING ONCOS-102 TREATMENT: MESOTHELIOMA 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 M1:M2 macrophage Ratio of cyt
Slide 61: Immune-Permissive Reshaping of Tumor Microenvironment: Melanoma
IMMUNE-PERMISSIVE RESHAPING OF TUMOR MICROENVIRONMENT BY ONCOS-102: MELANOMA Modulation of gene expression; Fraction (%) of genes modulated within the indicated gene groups Day 22 vs. Baseline Day 64 vs. Baseline Part 1 Part 2 Day 22 & Day 64 (n=2) Day 22 (n=10) & Day 64 (n=7) Baseline (n=6) Baselin
Slide 62: Increased Cytotoxic Potential of Intratumoral T-Cells: Mesothelioma
ONCOS-102 TREATMENT INCREASES CYTOTOXIC POTENTIAL OF INTRATUMORAL T-CELLS: MESOTHELIOMA Relative level of cytotoxic GrB+ / CD8+ T-cells at Modulation of tumor gene expression, Fraction day 36 of genes Alive vs. deceased at 12 months, mesothelioma ONCOS-102 treated vs. untreated, mesothelioma ONCOS-1
Slide 63: Increased Cytotoxic Potential of T-Cells: Melanoma
ONCOS-102 TREATMENT INCREASES CYTOTOXIC POTENTIAL ON INTRA-TUMORAL T-CELLS: MELANOMA 63 Unpublished company data
Slide 64: ONCOS-102 Immune Activation - Conclusions
ONCOS-102 IMMUNE ACTIVATION - CONCLUSIONS ONCOS-102 activates the immune system and counteracts multiple mechanisms of immuno-suppression operating at different steps of the cancer immunity cycle Multifaceted modulation of the tumor micro-environment induced by ONCOS-102 is linked to clinical benefi
Slide 65: Preclinical pipeline update
Preclinical pipeline update 6. 4Q update 7. Closing remarks
Slide 66: Pipeline: ONCOS-102
Product candidate Preclinical Phase 1 Phase 2 Collaborator Melanoma Combination w/Keytruda Colorectal cancer Combination w/Imfinzi Mesothelioma ONCOS-102 Combination w/pemetrexed/cisplatin ONCOS-200 series Next Gen viruses Novel mutRAS concepts 66
Slide 67: Targovax's Three-Pillar R&D Pipeline Strategy
TARGOVAX´S THREE-PILLAR R&D PIPELINE STRATEGY Novel ONCOS-102 combinations o Maximize clinical impact of ONCOS-102 through novel clinical combinations with complementary mechanism of action o Strong scientific rationale from existing clinical immune data Next Generation ONCOS viruses o Build new fun
Slide 68: Next Generation ONCOS: ONCOS-211 Prioritized
NEXT GENERATION ONCOS: ONCOS-211 PRIORITIZED FOR FURTHER DEVELOPMENT Adenosine – a key suppressor of immune cells Transgene activity Transgene 1 – ICOS-L o ICOS-ligand binds to ICOS on the T- cell surface, providing a strong stimulatory signal o Enhanced cytotoxicity Transgene 2 – ADA o ADA degrades
Slide 69: ICOS-L Expression Tied to Deep Clinical Response to ONCOS-102
ICOS-L EXPRESSION CAN BE TIED TO DEEP CLINICAL RESPONSE TO ONCOS-102 Immune cell infiltrate at Baseline, mIHC Co-stimulatory receptor expression, gene expression High Medium Low PD SD PR CR PD SD PR CR CR patient was …but high level of ICOS-L immunologically providing co-stimulatory signal “cold” at
Slide 70: Building Tyrosine Kinase Inhibitor Functionality into ONCOS
BUILDING TYROSINE KINASE INHIBITOR FUNCTIONALITY INTO ONCOS Collaboration partner Target – Tyrosine kinase inhibition Papyrus Therapeutics OPCML protein o OPCML is a potent tumor suppressor, inactivated in ca. 50% of all cancers o OPCML shuts down the oncogenic signaling function of at least 8 RTKs
Slide 71: Novel Mutant RAS Vaccination Concepts
NOVEL MUTANT RAS VACCINATION CONCEPTS INCORPORATING IMMUNOLOGICAL POWER OF ONCOS Merging ONCOS and TG technology ONCOS used as carrier for mutRAS peptides Combining the power of mutRAS vaccination ONCOS-102 Modified TG ONCOS-TG and oncolysis peptides PeptiCRAd 71
Slide 72: R&D Pipeline Strategy Addresses Key Components of the Cancer Immunity Cycle
THE R&D PIPELINE STRATEGY IS DESIGNED TO ADDRESS KEY COMPONENTS OF THE CANCER IMMUNITY CYCLE T-cell migration and 2 infiltration into the tumor Antigen release, cross- 1 presentation and priming of T-cells • Secretion of chemokines • Antigen release by ICD • TLR activation Expansion and survival of
Slide 73: 4Q update
4Q update 7. Closing remarks ° targovax °
Slide 74: 4Q Highlights and Subsequent Events
4Q HIGHLIGHTS AND SUBSEQUENT EVENTS Announced 35% response rate in ONCOS-102 trial in anti-PD1 refractory melanoma patients and regression on non-injected lesions Completed Part 1 in the colorectal cancer trial, combining ONCOS-102 with ONCOS-102 Imfinzi (duravalumab), recruitment in Part 2 opened A
Slide 75: Update on IOVaxis License
UPDATE ON IOVAXIS LICENSE CEO: John Wang HQ: Nantong, China Founded: 2018 R&D focus: Shared and personalized cancer vaccines Description Update o Exclusive option to license TG01/02 o IOVaxis is still in IND application vaccines for Greater China and process with NMPA (Chinese FDA) Singapore o NMPA
Slide 76: Continued Cost Control in 4Q20
CONTINUED COST CONTROL IN 4Q20 NOK m 4Q19 1Q20 2Q20 3Q20 4Q20 Total revenue 2 0 0 0 -0 External R&D expenses -25 -13 -14 -9 -8 Payroll and related expenses -11 -11 -11 -9 -12 Other operating expenses -5 -5 -5 -4 -3 Total operating expenses -42 -30 -30 -22 -23 76
Slide 77: Currently Funded into 2022
CURRENTLY FUNDED INTO 2022 The company Share liquidity Cash at end of 4Q ~170% of shares traded last 12 months 122 14 Share turnover per month1 NOK million USD million Million shares Net cash flow - total 4Q 45 5.3 Capital raise in Oct 2020 NOK million USD million Market cap 850 100 NOK million USD
Slide 78: Closing remarks
Closing remarks ° targovax °
Slide 79: Track Record of Strong Execution with Upcoming Value Inflection Points
TRACK RECORD OF STRONG EXECUTION WITH UPCOMING VALUE INFLECTION POINTS 2020 2021 H1 H2 Melanoma ✓ Melanoma Part 2 data Prepare and set up new trial Mesothelioma ✓ Mesothelioma ✓ Mesothelioma ONCOS-102 Merck collaboration Fast Track designation 24-month survival 18 month survival follow-up follow-up
Slide 80: Clinical and Preclinical Pipeline
CLINICAL AND PRECLINICAL PIPELINE Product candidate Preclinical Phase 1 Phase 2 Collaborator Next expected event Melanoma 1H 2022 Combination w/anti PD1 First patient Colorectal cancer Updates by collaborator ONCOS-102 Combination w/Imfinzi expected 1H22 Mesothelioma 1H 2021 Combination w/pemetrexed
Slide 81: 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 PD1 refractory melanoma Other indications Other IO combinations Clinical efficacy Platform development Immune activat