Circio Holding Asa · OSL:CRNA
Circio Holding Asa — Targovax — Investor Day (June 2017)
67 slides from Circio Holding Asa's investor day presentation, Jun 26, 2017
Slide 1: Arming the immune system to fight cancer
Arming the immune system to fight cancer Capital Markets Update June 26th 2017 www.targovax.com
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: Capital Markets Update - Agenda
Capital Markets Update - Agenda Introduction – CEO, Øystein Soug Targovax’s technology and trials – CMO, Dr Magnus Jäderberg A physician’s view on pancreatic cancer – Prof Daniel Palmer Financial update – CFO, Erik Wiklund Q&A www.targovax.com 3
Slide 4: Targovax develops two novel cancer immunotherapy drugs
Targovax develops two novel cancer immunotherapy drugs – both with promising phase I/II data TG01 ONCOS-102 Cancer vaccine Oncolytic virus Therapeutic vaccine Injected into the tumor Mimics antigens Releases antigens Stimulates “killer” white blood Stimulates “killer” white blood cells (
Slide 5: Immunotherapy market expected to reach 30-50b USD by 2025
Immunotherapy is considered to have enormous potential, and the market is expected to reach 30-50b USD by 2025 Estimated market size ($Bn)* ~15% p.a. o 8 products currently on the market o Market estimated to reach 40b USD in 2025 o Estimated that 2/3 of cancers will be treated with immunotherapy by
Slide 6: Targovax history
Targovax history 2012-2013 1st ph I trial 2007-2012 2013-2014 115 pts treated in ATAP 3 Orphan Designations 2 collaborations Mesothelioma trial initated 2007 2009 2012 2013 2014 Melanoma trial initated Oncos founded ONCOS-102 IND 2015 2016 2017 1st TG01 trial Orphan Designation Oncos and IPO TG01 da
Slide 7: Two platforms and six clinical trials in total
Two platforms and six clinical trials in total ensures a diversified program with frequent data readouts Cancer Combined 2017 2018 2019 indication with H1 H2 H1 H2 H1 Melanoma CPI Phase l ONCOS-102 Mesothelioma Chemo* Orphan ind. Phase lb/ll Ovarian & Orphan ind. CPI Phase l/ll Colorectal Sponsor: L
Slide 8: Capital Markets Update - Agenda
Capital Markets Update - Agenda Introduction – CEO, Øystein Soug Targovax’s technology and trials – CMO, Dr Magnus Jäderberg A physician’s view on pancreatic cancer – Prof Daniel Palmer Financial update – CFO, Erik Wiklund Q&A www.targovax.com 8
Slide 9: Agenda
Agenda Introduction to immunotherapy ONCOS-102 oncolytic virus platform TG RAS-peptide vaccine platform Targovax clinical program overview www.targovax.com 9
Slide 10: Immunotherapy is revolutionizing the way we treat cancer
IMMUNOTHERAPY Immunotherapy is revolutionizing the way we treat cancer, in some cases curing previously thought incurable patients Case example – Patient in a Yervoy checkpoint inhibitor trial Prior to Yervoy* 4 weeks 8 weeks Week 72: complete remission Week 108: complete remission 20 weeks 8 months
Slide 11: The aim of cancer immunotherapy is to boost the cancer immunity cycle
IMMUNOTHERAPY The aim of cancer immunotherapy is to boost the natural cancer immunity cycle T-cell T-cell trafficking activation T-cell tumor infiltration Cancer antigen presentation Cancer cell identification Release of cancer Destruction of antigens cancer cells www.targovax.com 11
Slide 12: Immunotherapies target different aspects of the cancer immunity cycle
IMMUNOTHERAPY Immunotherapies target different aspects of the cancer immunity cycle DC-therapy: Provenge T-cell therapy: CAR-T (not yet approved) Checkpoint Inhibitors (CPIs) CTLA-4 blockade: Yervoy Oncolytic virus: PD-1 blockade: PD-L1 blockade: Imlygic Keytruda Tecentriq Opdivo Imfinzi Bavencio ww
Slide 13: Two novel proprietary immunotherapy platforms
IMMUNOTHERAPY Targovax is developing two novel proprietary immunotherapy platforms, with promising phase I/II data o Genetically tailored Adenovirus ONCOS-102 o Selectively infects and lyses cancer cells Oncolytic virus o Releases cancer antigens o Triggers immune response o Cocktail of 7 synthetic
Slide 14: TG01 and ONCOS-102 have distinct targeting mechanisms
IMMUNOTHERAPY TG01 and ONCOS-102 have distinct targeting mechanisms in the cancer immunity cycle TG01 Peptide vaccine ONCOS-102 Oncolytic virus www.targovax.com 14
Slide 15: Combining immunotherapies to modulate the cancer immunity cycle
IMMUNOTHERAPY By combining immunotherapies multiple aspects of the cancer immunity cycle can be modulated in parallel Wake up the Train cancer T-cells attack Disarm cancer Immuno-oncology mechanisms immune system specific T-cells the cancer defence Switch on GPS– Press the gas Ignite engine Release
Slide 16: Turn cancer into a manageable chronic disease
IMMUNOTHERAPY The goal is to turn cancer into a manageable chronic disease by combining immuno-oncology therapies Lifting the curve The main benefit is seen in long term overall survival Proportion alive Immunotherapy combination Immunotherapy monotherapy Chemotherapy / TKI Untreated Time from treat
Slide 17: Agenda
Agenda Introduction to immunotherapy ONCOS-102 oncolytic virus platform TG RAS-peptide vaccine platform Targovax clinical program overview www.targovax.com 17
Slide 18: ONCOS-102 makes cancer antigens visible to the immune system
ONCOS TG ONCOS-102 works by making cancer antigens visible to the immune system, thus generating tumor specific T-cells Activate immune system: Train T-cells: Attack the cancer: o Virus injected directly into o APCs present tumor o Tumor specific T-cells the tumor / peritoneum specific antigens at l
Slide 19: Most patients do not respond to checkpoint inhibitors
ONCOS TG Most patients do not respond to check point inhibitors (CPIs), due to lack of T-cells in the tumor microenvironment Response rate to checkpoint inhibitors (CPIs) Melanoma ~40% Renal Cell carcinoma ~70% Complimentary Triple Negative Breast ~70%-80% immune priming medicines may make tumors re
Slide 20: ONCOS-102 phase I: increased tumor infiltrating CD8+ T-cells
ONCOS TG ONCOS-102 phase I: Increased tumor infiltrating CD8+ T-cells in 11 of 12 cancer patients with a range of solid tumors 10000 1000 Fold-change from baseline 100 10 1 0,1 FI1-08 FI1-19 FI1-06 FI1-04 FI1-18 FI1-02 FI1-15 FI1-13 FI1-09 FI1-17 FI1-01 FI1-14 Only 1 patient 6 patients 5 patients sh
Slide 21: Initial Phase I ONCOS-102 trial immune response
ONCOS TG In the initial Phase I ONCOS-102 trial tumor specific and systemic immune response was observed Evidence that immune system Evidence that T-cells find the Evidence of production of recognizes tumor threat tumor and are cell killing tumor antigen specific T-cells Innate Immune System (biopsy
Slide 22: Broad ONCOS-102 clinical program of four new trials
ONCOS TG The encouraging Phase I results have triggered the initiation of a broad ONCOS-102 clinical program consisting of four new trials o Combination with PD-1 Melanoma CPI in refractory patients Phase I o Proof-of-concept 12 patients o Memorial Sloan Kettering Mesothelioma o Combination with che
Slide 23: Melanoma trial with ONCOS-102 immune-priming
ONCOS TG Melanoma trial – will CPI refractory patients start responding after immune-priming with ONCOS-102? Advanced malignant melanoma patients not responsing to CPIs Setting Immune activate patients with ONCOS-102, then re-challenge with a CPI (Keytruda@) 12 patients Site Memorial Sloan Kettering
Slide 24: Agenda
Agenda Introduction to immunotherapy ONCOS-102 oncolytic virus platform TG RAS-peptide vaccine platform Targovax clinical program overview www.targovax.com 24
Slide 25: RAS is mutated in 20-30% of all cancers
ONCOS TG RAS is a key regulator of cell cycle that is mutated in 20-30% of all cancer patients, and >85% of pancreatic cancers Incidence of RAS mutations One of the most common mutations in cancer RAS is one of the most well-defined neoantigens Results in cell division permanently switched on No exi
Slide 26: TG peptides prime the immune system against RAS mutated cells
ONCOS TG The TG peptides prime the immune system to recognize and destroy RAS mutated cancer cells Activate immune system: Train T-cells: Attack the cancer: o TG peptides injected into o APCs migrate to lymph o RAS specific T-cells the skin with GM-CSF nodes and present RAS identify mutated RAS adju
Slide 27: Encouraging survival data from earlier trials
ONCOS TG These results are backed by encouraging 10 year survival data and immune response correlation from earlier trials Long-term data from earlier TG mono-therapy trials – resected pancreatic cancer 100 90 80 70 4/20 (20%) patients Survival (%) 60 > 10 years survival 50 (resected patients) 40 30
Slide 28: Working to replicate and expand encouraging clinical results
ONCOS TG We are currently working to replicate and expand on these encouraging clinical results Historical trials Completing trial Planned / recruiting trials Resected pancreas o Randomized controlled trial Phase II/III (tbd) o Aim to reach registration Phase I Phase I/II Resected & Resected non-res
Slide 29: Agenda
Agenda Introduction to immunotherapy ONCOS-102 oncolytic virus platform TG RAS-peptide vaccine platform Targovax clinical program overview www.targovax.com 29
Slide 30: Two platforms and six clinical trials in total
Two platforms and six clinical trials in total ensures a diversified program with frequent data readouts Cancer Combined 2017 2018 2019 indication with H1 H2 H1 H2 H1 Melanoma CPI Phase l ONCOS-102 Mesothelioma Chemo* Orphan ind. Phase lb/ll Ovarian & Orphan ind. CPI Phase l/ll Colorectal Sponsor: L
Slide 31: Capital Markets Update - Agenda
Capital Markets Update - Agenda Introduction – CEO, Øystein Soug Targovax’s technology and trials – CMO, Dr Magnus Jäderberg A physician’s view on pancreatic cancer – Prof Daniel Palmer Financial update – CFO, Erik Wiklund Q&A www.targovax.com 31
Slide 32: Adjuvant therapy for resectable pancreatic cancer
Adjuvant therapy for resectable pancreatic cancer London, June 2017 Daniel Palmer Department of Molecular and Clinical Cancer Medicine University of Liverpool and Clatterbridge Cancer Centre
Slide 33: Plan of the Talk
Plan of the Talk • Epidemiology • The challenges of pancreatic cancer • Palliative chemotherapy: current status – Gemcitabine – Folfirinox – Nab-paclitaxel • Adjuvant therapies for resected pancreatic cancer – Clinical trials – Current state-of-the-art • Where next? – Rationale for immunotherapy • T
Slide 34: Age-Standardised Ten-Year Net Survival Trends
Age-Standardised Ten-Year Net Survival Trends, Adults England and Wales, 1971-2011
Slide 35: Why so challenging?
Why so challenging? Resectable Locally advanced Metastatic 10-20% 30-40% 50-60% – Advanced stage at time of diagnosis – Even in operable cases • Challenging (and dangerous) surgery • High recurrence rates – Relatively resistant to chemotherapy • Gemcitabine standard chemotherapy for 20 years • Gem v
Slide 36: Advanced pancreatic cancer is relatively resistant to chemotherapy
Advanced pancreatic cancer is relatively resistant to chemotherapy 5-FU Gem Response 0% 5% Median OS 4.4m 5.7m P=0.025 1yr survival 2% 18% CBR 4.8% 23.8% P=0.022 FOLFIRINOX GEM+ABRAXANE
Slide 37: Why so challenging?
Why so challenging? Resectable Locally advanced Metastatic 10-20% 30-40% 50-60% – Even in operable cases • Challenging (and dangerous) surgery • High recurrence rates – Long-term survival <10% – Is the problem due to: • Local recurrence? • Metastatic recurrence? • Both?
Slide 38: Adjuvant Therapy
Adjuvant Therapy NEJM 2004; 350:1200-10 Liverpool Freedom of the PBRU City of Liverpool
Slide 39: Chemoradiotherapy and chemotherapy after resection of pancreatic cancer - ESPAC 1
A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer – ESPAC 1 NEJM 2004; 350:1200-10
Slide 40: ESPAC-3: Survival by treatment
ESPAC-3: Survival by treatment Median S(t)= 23.0 months (95%CI:21.1, 25.0) Median S(t)= 23.6 months (95%CI:21.4, 26.4) c2LR=0.74, p=0.39, HRGEM VS 5FU/FA=0.94 (95%CI: 0.81, 1.08) Neoptolemos et al JAMA 2010; 304: 1073-81 Liverpool Freedom of the PBRU City of Liverpool
Slide 41: ESPAC-4 trial design
Stratified log-rank test with 5% 2-sided α, for a 10% difference in 2 year survival, 90% power = 480 events = 722 patients, 361 in @ arm 722 patients pancreatic ductal adenocarcinoma Target number of 722 ‘curative’ resection <12 wks patients Start date 13/01/08 Number of sites opened 106 RANDOMISATI
Slide 42: Patient Demographics
Patient Demographics GEM GEMCAP TOTAL n=366 n=364 n=730 *Age (years) 65 (37-80) 65 (39-81) 65 (37-81) Sex Male 212 (58%) 202 (55%) 414 (57%) Female 154 (42%) 162 (45%) 316 (43%) Baseline PS 0 158 (43%) 150 (41%) 308 (42%) 1 199 (54%) 202 (56%) 401 (55%) 2 9 (3%) 12 (3%) 21 (3%) Smoking Never 151 (41
Slide 43: Survival by Treatment
Survival by Treatment — Gemcitabine — Gemcitabine-Capecitabine HR = 0.82 (95% Cl, 0.68-0.98) x (1) = 4.61, p = 0.032 Overall survival (%) a fo} 20 Median S(t) = 25.5 months (95% Cl: 22.7-27.9) 104 Median S(t) = 28.0 months (95% Cl: 23.5-31.5) 0 4 T T T T T T T 0 10 20 30 40 50 60 Time from randomisa
Slide 44: ESPAC Trials Overall Survival
ESPAC Trials Overall Survival *Study time = time from surgery for ESPAC 1/3, study time = time from randomisation for ESPAC 4
Slide 45: Where next?
Where next? • Rationale for immunotherapy in cancer • Targovax trial
Slide 46: Immunotherapy approaches
Immunotherapy approaches • T cell checkpoints
Slide 47: Checkpoint inhibition in advanced melanoma and lung cancer
Checkpoint inhibition in advanced melanoma and lung cancer melanoma Non-small cell lung cancer • Significant survival benefit • Some long-term survivors • Non-specific immune stimulation • Risk of auto-immune toxicities
Slide 48: Advanced pancreatic cancer is resistant to checkpoint inhibitors
Advanced pancreatic cancer is resistant to checkpoint inhibitors Immunosuppressive tumour micro-environment Myeloid derived Macrophages suppressor cells MDSCs T cell checkpoints IDO Arginase TGF-b Regulatory CD4 TGF-b T cell T cell IL-10 IL-10 IL-6 and STAT-3 TGF-b Tumour antigen Aberrant MHC class
Slide 49: Multiple points of intervention for immunotherapy
Multiple points of intervention for immunotherapy Conventional chemotherapy Radiotherapy CTLA-4 blockade Engineered vaccines PD-1 blockade Enhanced antigen Blockade of Enhanced traffic and presentation by immunological activity of tumour- dendritic cells checkpoints specific T-cells Activation/mobil
Slide 50: Arming the immune system to fight cancer
Arming the immune system to fight cancer A Phase I/II trial of TG01/GM-CSF and gemcitabine as adjuvant therapy for treating patients with resected RAS-mutant adenocarcinoma of the pancreas
Slide 51: TG01-01 Background
TG01-01 Background injectable antigen-specific cancer immunotherapy targeted to treat patients with RAS mutation TG01 - found in more than 85% of pancreatic adenocarcinomas a mixture of 7 synthetic peptides - representing 7 of the most common 12 & 13 mutations in RAS assoc. with human cancer induces
Slide 52: TG01-01 Study design
TG01-01 Study design Modified cohort is ongoing (n=13). Last patient last visit May 2018
Slide 53: TG01-01 Study objectives
TG01-01 Study objectives Primary •To assess the safety of GM-CSF/TG01 vaccination and adjuvant chemotherapy •To assess the immune response to GM-CSF/TG01 and the effect of adjuvant chemotherapy in patients receiving GM-CSF/TG01 after primary resection of pancreatic adenocarcinoma Secondary •To asses
Slide 54: Demographics
Demographics Parameters Number of patients (N=19) Age (Y) median (min, max) 67 (49, 79) Gender, n (%) Male 10 (83%) Female 9 (47%) ECOG, n (%) 0 8 (42%) 1 11(58%) CAI9-9 (n=15) U/ml median (min, max) 16 (8, 240) Hemoglobin (g/L) median (min, max) 124.0 (104, 153) Disease staging at diagnosis Tstage
Slide 55: TG01-01 Efficacy (survival rate from resection)
TG01-01 Efficacy (survival rate from resection) 1 year* 2 years* Assessed from resection 17/19 (90%) 13/19 (68%) (8 weeks before first IMP) Compares favorably with published historical two-year survival rates of resected cancer patients treated with gemcitabine alone of 30%- 53%1-5
Slide 56: TG01-01 Immune response
TG01-01 Immune response Immune response by week 11 and entire study period (N=19) *Three patients (week 11) and two patients (entire study period) without blood samples for analysis Immune response after week 11 (n=11)
Slide 57: TG01-01 Overall survival and immune response
TG01-01 Overall survival and immune response
Slide 58: TG01-01 Safety profile (N=19)
TG01-01 Safety profile (N=19)
Slide 59: TG01-01 Conclusions
TG01-01 Conclusions TG01/GM-CSF generated early immune responses in 89% of patients with R0/R1 resected pancreatic cancer. This demonstrate that TG01 vaccination activate mutant RAS specific T cells. The regimen was generally well tolerated although some late, manageable allergic reactions were seen
Slide 60: ESPAC Trials Overall Survival
ESPAC Trials Overall Survival *Study time = time from surgery for ESPAC 1/3, study time = time from randomisation for ESPAC 4
Slide 61: ESPAC Trials Overall Survival
ESPAC Trials Overall Survival *Study time = time from surgery for ESPAC 1/3, study time = time from randomisation for ESPAC 4
Slide 62: Capital Markets Update - Agenda
Capital Markets Update - Agenda Introduction – CEO, Øystein Soug Targovax’s technology and trials – CMO, Dr Magnus Jäderberg A physician’s view on pancreatic cancer – Prof Daniel Palmer Financial update – CFO, Erik Wiklund Q&A www.targovax.com 62
Slide 63: Financial summary - end of Q1 2017
FINANCIALS Financial summary – end of Q1 2017 Raised NOK 200 million 8 June 2017 10,000,000 new shares @ NOK 20 per share Operations Cash NOK 147m USD 17m End of Q1 2017 Net cash flow NOK -24m USD -3m Total Q1 Annual run rate NOK 104m USD 12m Last four quarters Annual opex NOK 116m USD 13m Last four
Slide 64: TRVX upgraded to the main list on OSE
FINANCIALS TRVX was upgraded to the main list on OSE in March, and has showed a positive trend in share turnover in 2017 Development in daily average share turnover (NOK million / day)* • NOK ~1b market cap • NOK 10m NOK avg. daily turnover in last 3 months • NOK 850m total turnover in Q1 • 560k sha
Slide 65: Strong shareholder base as per May 2017
FINANCIALS Strong shareholder base as per May 2017 Shareholder Estimated ownership Shares m Relative HealthCap Sweden 11,2 26,4 % New shareholders in Private Placement: RadForsk Norway 4,1 9,7 % • Nyenburgh Nordea Norway 3,0 7,0 % Nordnet Livsforsikring Norway 1,5 3,5 % • Trium KLP Norway 1,3 3,1 %
Slide 66: Multiple near term value inflection points
FINANCIALS Multiple near term value inflection points ONCOS-102 Initiate phase l Ovarian/colorectal ONCOS-102 Initiate phase l/ll melanoma TG02 Initiate phase Ib in colorectal TG01 ONCOS-102 Oslo Stock Exchange ONCOS-102 Initiate phase l/ll Listing on OSE main Initiate phase l phase ll initiated mes
Slide 67: Capital Markets Update - Agenda
Capital Markets Update - Agenda Introduction – CEO, Øystein Soug Targovax’s technology and trials – CMO, Dr Magnus Jäderberg A physician’s view on pancreatic cancer – Prof Daniel Palmer Financial update – CFO, Erik Wiklund Q&A www.targovax.com 67