Activating the patient s the immune system t fight immune cancer system t Cmpany verview Cmpany presentatin fight cancer January 2019 August 2018
IMPORTANT NOTICE AND DISCLAIMER This reprt cntains certain frward-lking statements based n uncertainty, since they relate t events and depend n circumstances that will ccur in future and which, by their nature, will have an impact n the results f peratins and the financial cnditin f Targvax. Such frward-lking statements reflect the current views f Targvax and are based n the infrmatin currently available t the cmpany. Targvax cannt give any assurance as t the crrectness f such statements. There are a number f factrs that culd cause actual results and develpments t differ materially frm thse expressed r implied in these frward-lking statements. These factrs include, amng ther things, risks r uncertainties assciated with the success f future clinical trials; risks relating t persnal injury r death in cnnectin with clinical trials r fllwing cmmercializatin f the cmpany s prducts, and liability in cnnectin therewith; risks relating t the cmpany s freedm t perate (cmpetitrs patents) in respect f the prducts it develps; risks f nn-apprval f patents nt yet granted and the cmpany s ability t adequately prtect its intellectual prperty and knw-hw; risks relating t btaining regulatry apprval and ther regulatry risks relating t the develpment and future cmmercializatin f the cmpany s prducts; risks that research and develpment will nt yield new prducts that achieve cmmercial success; risks relating t the cmpany s ability t successfully cmmercialize and gain market acceptance fr Targvax s prducts; risks relating t the future develpment f the pricing envirnment and/r regulatins fr pharmaceutical prducts; risks relating t the cmpany s ability t secure additinal financing in the future, which may nt be available n favrable terms r at all; risks relating t currency fluctuatins; risks assciated with technlgical develpment, grwth management, general ecnmic and business cnditins; risks relating t the cmpany s ability t retain key persnnel; and risks relating t the impact f cmpetitin. 2
Intrductin 2. ONCOS nclytic virus prgram 3. TG mutant RAS vaccine prgram 4. Crprate verview 3
TARGOVAX S POSITION IN THE FUTURE CANCER THERAPY LANDSCAPE Targvax fcus Immune activatrs Onclytic viruses, vaccines Immune mdulatrs Checkpint inhibitrs Surgery - Radi - Chem Immune bsters CAR-Ts, TCRs Targeted therapy TKIs, PARPs, etc. 4
Targvax has tw prgrams in clinical develpment, with an ONCOLYTIC VIRUS LEAD PRODUCT CANDIDATE ONCOS Onclytic virus TG Neantigen vaccine Lead prduct candidate Genetically armed adenvirus Turns cld tumrs ht Induces tumr specific T-cells Single agent phase I cmpleted 4 nging cmbinatin trials Pipeline prduct Shared neantigen, therapeutic peptide vaccine Triggers the T-cell respnse t ncgenic RAS driver mutatins 32 patient phase I/II trial cmpleted Activates the immune system Triggers patientspecific respnses N need fr individualizatin 5
PIPELINE OVERVIEW AND MILESTONES Platfrm Prduct candidate Preclinical Phase I Phase II Phase III Last event Next expected event Mesthelima Cmb. w/ pemetrexed/cisplatin Phase Ib safety lead-in chrt, incl. immune activatin and ORR data (6 pts) 1H 2020 Randmized ORR data 30 pts ONCOS nclytic adenvirus ONCOS-102 Melanma Cmb. w/keytruda Peritneal metastases 1 Cllab: Ludwig, CRI & AZ Cmb. w/imfinzi Prstate Cllab: Sti Cmb. w/dcvac ORR and immune activatin (6 pts), 1/6 CR First dse escalatin chrt safety review (4 pts) First patient dsed 1H 2019 ORR and immune data first chrt Update by cllabratr, expected 2019 Update by cllabratr, expected 2019 Next-gen ONCOS 3 viruses undisclsed Virus cnstruct clning and in vitr validatin 2H 2019 Pre-clinical data TG neantigen cancer vaccine TG01 TG02 TG02 Pancreatic cancer Cmb. w/gemcitabine Clrectal cancer Prf-f-mechanism Cmb. w/keytruda CPI synergy TG + PD-1 mos 33.4 mnths Demnstrated mutant RASspecific immune activatin First safety review, incl. immune activatin data (3 pts) TBD 1H 2019 Immune activatin and mechanistic data (mn) 2H 2019 Pre-clinical data 1 Patients with advanced peritneal disease, wh have failed prir standard chemtherapy and have histlgically cnfirmed platinum-resistant r refractry epithelial varian r clrectal cancer Onging cllabratr spnsred trials 6
ONCOS-102 CLINICAL DATA SUMMARY Patient ppulatin Safety Immune activatin Efficacy Varius slid tumrs Phase I Mntherapy End-stage patients, 3 rd line and beynd 7 different slid tumrs 12 patients Well tlerated Innate: 12/12 Adaptive: 11/12 40% DCR 2 lng-term survivrs Survival crrelated with TIL increase Mesthelima Phase I/II randmized With SC chem Metastatic 1 st and 2 nd /3 rd line 6 patients cmpleted trial t date Well tlerated N added txicity with chem Innate: 6/6 Adaptive: 3/4 50% DCR 1 PR 2 SD Melanma Phase I Cmb with Keytruda PD-1 refractry advanced melanma 6 patients cmpleted trial t date Well tlerated N safety issues Innate: 6/6 Adaptive: 4/4 1 CR, w/supprting immune data 3 with lcal effect, but with distal prgressin Cmpleted 7 Onging trials spnsred by Targvax
TG01 IN RESECTED PANCREATIC CANCER EFFICACY SIGNAL SEEN IN PHASE I/II TRIAL Median verall survival, mnths Median disease free survival, mnths RAS-specific immune activatin 27.6 33.4 Nt yet reached 13.1 13.9 19.5 94% 30/32 pts ESPAC 4 First chrt Secnd chrt ESPAC 4 First chrt Secnd chrt TG01 is well-tlerated - imprved dsing regimen in secnd chrt First chrt: 19 pts, Secnd chrt: 13 pts. Ttal 32 pts. ESPAC4 trial fr gemcitabine alne DFS bth chrts: 16.1 mnths 8
ONCOS nclytic virus prgram 3. TG mutant RAS vaccine prgram 4. Crprate verview
ONCOS-102 is a nclytic adenvirus sertype 5 armed with a GM-CSF transgene 1 Selective replicatin in cancer cells 2 Bsting the immune activatin 3 Enhanced infectin f cancer cells 24 bp 6.7K/gp19K Ad5 knb E1A E3 Fiber knb ITR GM-CSF Transgene Ad3 knb ITR 10
BENEFITS OF ADENOVIRUS SEROTYPE 5 BACKBONE Highly immungenic, Tll like receptr 9 (TLR9) agnist Well-characterized, well-tlerated and few safety cncerns Duble stranded DNA, pssibility fr transgenes, nn-envelped Pre-existing immunity, reduced issue f immun-dminance
ONCOS CLINICAL PROGRAM OVERVIEW Mesthelima Phase I/II - randmized 30 patients Shrtest path-t-market Orphan drug designatin Cmbinatin with SC chem Randmized vs. SC Melanma Phase I 9 + up t 12 patients PC in CPI refractry patients Cmbinatin with Keytruda Memrial Slan Kettering Cmpassinate use Phase I trial prgram 12 patients 115 patients 7 indicatins Ovarian and clrectal cancers Peritneal Cmbinatin with Imfinzi metastases Intraperitneal administratin Phase I/II Cllabratin with MedImmune / up t 78 patients AZ, CRI, & Ludwig Cmpleted Onging trials spnsred by Targvax Onging trials spnsred by partner Prstate cancer Phase I up t 15 patients Cmbinatin with dendritic cell vaccine (DCVAC) Cllabratin with Sti 12
ONCOS-102 Phase I single agent IMMUNE ACTIVATION DEMONSTRATED Cld tumr turned ht, CD8+ T-cell staining ONCOS-102 Phase I trial design: 12 patients, 7 different slid tumrs All refractry t multiple lines f therapy ONCOS-102 mntherapy 9 injectins ver 5 mnths Tp-line results: 100% innate immune activatin 11/12 patients increase in CD8+ T-cells 40% SD, 2 lng-term survivrs Abscpal effect and lasting systemic immune respnses bserved Pre-treatment Baseline Pst-treatment Week 8 13 Ranki et al., Jurnal fr Immuntherapy f Cancer 2016, 4(17)
CD8+ fld-change frm baseline ONCOS-102 Phase I single agent CD8+ T-CELL INFILTRATION CORRELATES WITH SURVIVAL Fld-change CD8+ T-cell cunt vs. survival r = 0.75 p = 0.005 10,000 1,000 100 10 1 Case example Ovarian cancer, 38yr ld wman Failed n 5 types f chemtherapy >1,000-fld increase in TILs Tumr specific T-cells detected up t 2 years after treatment Stable disease fr 3 years, survived fr 3.5 years 0.1 0 5 10 15 20 40 Overall survival (mnths) 14 Ranki et al., Jurnal fr Immuntherapy f Cancer 2016, 4(17)
MELANOMA ONCOS-102 + KEYTRUDA COMBINATION inductin f tumr-specific T-cells Tumr antigen specific T-cell respnse IFN-g ELISPOT analysis fr tumr antigen activated T-cells Patient 5 Previus Yervy & Keytruda MAGE-A1 Week 3 + Increased infiltratin f MAGE-A1 tumr specific T-cells - MAGE-A1 T-cells als detected at baseline Patient 4 NY-ESO-1 Week 3 + De nv inductin f NY-ESO-1 tumr specific T-cells - Nt present at baseline Previus Yervy, Keytruda & Imlygic MAGE-A1 Week 3 + De nv inductin f MAGE-A1 tumr specific T-cells - Nt present at baseline
MELANOMA ONCOS-102 + KEYTRUDA COMBINATION ne cmplete respnse by week 9 Baseline Week 3 Week 9 Patient 5 Previus Yervy & Keytruda Prgressin n Keytruda Visible tumr regressin after 3x ONCOS-102 injectins Cmplete respnse after 3x ONCOS-102 injectins & 2x Keytruda infusins 16
ONCOS-102 + KEYTRUDA MELANOMA TRIAL data summary first 6 patients 1 Safety 2 Innate immune activatin 3 Adaptive immune activatin 4 Efficacy First safety review cmpleted with n cncerns ONCOS-102 and Keytruda cmbinatin is welltlerated Systemic increase f pr-inflammatry cytkines (6/6 patients) All patients develp fever Increase in tumr T- cell infiltratin (TILs, 3/4 patients) Tumr-specific T cells in 2/4 patients Abscpal immune respnse in ne patient Cmplete respnse in 1/6 patients (very rare) Transient regressin bserved in 3 patients Assciated with level f immune activatin 17
ONCOS-102 IN MESOTHELIOMA turning cld tumrs ht CD8+ T-cells in tumr Tumr bipsy staining CD4+ T-cells in tumr Fld change PD-L1 psitive tumr cells % f ttal Mesthelima Phase I, patient 14 6.5 19.5 130x 1 1.2 16x Baseline Week 5 Baseline Week 5 Baseline Week 5 Mesthelima Phase I, patient 9 30.0 8.8x 1 2.1 16.4 1.8x Baseline Week 5 Baseline Week 5 Baseline Week 5 18 Ranki et al., Jurnal fr Immuntherapy f Cancer 2016, 4(17)
ONCOS-102 + SC MESOTHELIOMA TRIAL data summary first 6 patients 1 Safety 2 Innate immune activatin 3 Adaptive immune activatin 4 Efficacy ONCOS-102 welltlerated in cmbinatin with chemtherapy Systemic increase f prinflammatry cytkines in 6/6 patients Increase in tumr infiltratin f CD4+ and CD8+ T-cells in 3/4 patients Tumr-specific T-cells in 2/6 patients One partial respnse (PR) and tw stable disease (SD) 50% disease cntrl rate 19
WHY ONCOS-102? 1 Innate immune activatin Strng innate immune activatin in nearly all injected patients Crrelatin with clinical utcme 2 Adaptive immune activatin Increase in T-cells systemically and in tumr (TILs) Tumr-specific T- cells identified in several patients 3 In viv efficacy Anti-tumr effect Abscpal effect Tumr-specific immune respnses Synergy with bth CPIs and chem 4 Clinical efficacy Cmplete respnse seen in CPI refractry melanma patient Outcme assciated with immune activatin Well-tlerated, >150 patients treated 20
TG mutant RAS vaccine prgram 4. Crprate verview 21
The RAS gene is central in ncgenesis and is mutated in 90% OF PANCREATIC AND 50% OF COLORECTAL CANCERS Frequency f RAS mutatins Glbal cancer incidents per 10,000 (xx) = n. f cancer patients High Med Gallbladder (180,000) Pancreas (340,000) Melanma f skin (230,000) Prstate (1,130,000) Clrectal (1,360,000) Lung (1,820,000) RAS mutatins are trunk neantigens that drive ncgenesis There are n existing therapies targeting RAS mutatins Targvax TG prgram is a unique vaccine apprach fr mutant RAS cancer Lw 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 22 Fernandez-Medarde; RAS in Cancer and Develpmental Diseases; Genes & Cancer. 2011;2(3)
The TG ne-antigen vaccine teaches the immune system t RECOGNIZE AND KILL RAS MUTATED CANCER CELLS 1. Activate immune system TG vaccine injected intradermally and picked up by APCs 2. Induce mutras T-cells CD4+ and CD8+ mut- RAS T-cells induced in the lymph nde 3. Attack the cancer mutras T-cells identify and destry RAS mutated cancer cells Ccktail f 7 peptides cvering all relevant RAS mutatins in pancreas 23
TG CLINICAL PROGRAM OVERVIEW Clrectal - TG02 Phase I 12-20 patients Mechanism f actin 2 nd generatin TG vaccine Cmbinatin w/keytruda Phase I & II - Pancreas Mntherapy >200 patients Phase I/II Resected pancreas Adjuvant, w/chem 32 patients TG in cmbinatin with CPI Phase I Pancreas Evaluate TG in cmbinatin with PD-1/L1 blckade TG01 in resected pancreatic cancer Pursue pprtunities fr cst efficient trials in cllabratins 24 Cmpleted trials Onging trials Trial under planning
Survival (%) PHASE I MONOTHERAPY SURVIVAL DATA TG vaccinatin shwed 20% 10 year survival in resected pancreatic cancer 10 year survival in histrical TG trials in resected pancreatic cancer 1 n=20, resected patients frm tw clinical trials, TG mntherapy 100 90 80 70 60 50 4/20 (20%) f treated patients alive after 10 years 0/87 untreated patients alive in a similar chrt frm the same perid, at the same hspitals 40 30 20 10 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 114 120 Histrical cntrl: 7.7% 10 year survival 2 Mnths frm resectin 1 Wedén et al., 2011 2 Oettle H et al., JAMA 2013, vl 310, n 14 25
TG01 IN PHASE I/II TRIAL SIGNAL OF EFFICACY IN RESECTED PANCREATIC CANCER Median verall survival Median disease free survival mutras immune activatin 33.4 vs. 27.6 mnths reprted in the ESPAC4 trial fr gemcitabine alne (frm time f surgery) First chrt: 33.1 mnths Secnd chrt: nt yet reached 16.1 vs. 13.1 mnths reprted in the ESPAC4 trial fr gemcitabine alne (frm time f surgery) First chrt 13.9 mnths Secnd chrt 19.5 mnths 94% (30 ut f 32 patients) had RAS-specific immune activatin Dsing and safety Dsing regimen imprved and TG01 is well-tlerated First chrt: 19 pts, Secnd chrt: 13 pts. Ttal 32 pts. 26
TG01 resected pancreas cancer trial survival - first vs. secnd patient chrts SECOND PATIENT COHORT PERFORMING BETTER 2 nd chrt; ptimized dsing regimen 77% 2-year survival rate (10/13) mdfs 19.5mnths mos nt reached 9 patients alive at time f analysis 1 st chrt; full dsing regimen 68% 2-year survival rate (13/19) mdfs 13.9 mnths mos 33.1 mnths (frm surgery) 5 patients alive at time f analysis 27
WHY THE TG APPROACH MAY WORK where ther cancer vaccines have failed Histrical lessns learned The TG apprach Target ften prly defined and nt cancer specific, mainly TAAs Mutated RAS is a well-defined, cancerspecific ne-antigen, driving the cancer N r insufficient immune activatin f the adaptive immune system TG peptides are clinically prven t induce bth CD4+ and CD8+ mutras T-cells Mst clinical trials have been dne in prgressive metastatic disease Initial fcus n earlier stage patients, with strnger immune system 28
Crprate verview
TARGOVAX HAS A SOUND FINANCIAL POSITION with cash t cmplete the planned clinical prgram int 2020 Operatins The share Cash end f 3Q - Sep 30 th 2018 173 NOK millin -27 NOK millin 21 USD millin Net cash flw - ttal 3Q 112 NOK millin -3 USD millin Annual run rate - last fur quarters 14 USD millin Market Cap - at share price NOK ~7 370 NOK millin 2.5 NOK millin 42 USD millin Daily turnver - rlling 6 mnth avg. Analyst cverage 0.3 USD millin 0.5 % f share capital DNB, ABG Sundal Cllier, Arctic, Redeye, Edisn 30
THE SHAREHOLDER BASE IS STRONG with a mix f specialist, generalist and retail investrs 1 2 3 4 5 6 7 8 9 10 Estimated wnership Sharehlder N. f shares Ownership HealthCap 12 405 584 23,6 % Nrdea 4 599 906 8,7 % RadFrsk 4 427 255 8,4 % KLP 2 062 998 3,9 % Threndahl Invest AS 1 000 000 1,9 % Danske Bank (nm.) 828 845 1,6 % Timmun AS 728 601 1,4 % Prieta AS 720 000 1,4 % Sundt AS 500 000 1,0 % Meyerløkka AS 428 000 0,8 % Other sharehlders (~4119) 24 915 259 47,4 % Ttal 52 616 448 100,0 % Shares and ptins 57.4m shares fully diluted Average strike price n ptins ~NOK 20 Ttal dilutive effect f ptins is 8.1% 52.6m rdinary shares Management wnership: 0.3% >4,000 sharehlders 31
SENIOR MANAGEMENT TEAM Highly experienced Øystein Sug, CEO Jined as CFO in April 2015 befre being appinted CEO in Nvember 2016. Befre jining Targvax Oystein was CFO at Algeta, where he built up the functins f Finance, IR, Cmpliance, IT and HR, and versaw its ultimate sale t Bayer fr USDbn 2.9 Magnus Jäderberg, MD, CMO Mre than 30 years experience in varius R&D functins Previusly CMO at Bristl Meyers Squibb in Eurpe Invlved in the clinical develpment f Yervy Anne-Kirsti Aksnes, PhD, VP Clin. Dev. Mre than 25 years f experience within clinical research and develpment in pharma/bitech Befre jining Targvax, VP Clinical Develpment at Algeta and Directr Clinical Develpment at Nycmed /Amersham Health/GE Healthcare PhD in medicine frm Karlinska Institute Erik D. Wiklund, PhD, CBO Frmer cnsultant in the Pharma & Healthcare practice f McKinsey & Cmpany PhD in cancer research (mlecular bilgy) Held several cmmercial and peratinal rles in bitech, including Algeta ASA Berit Iversen, VP CMC Mre than 25 years f experience within R&D and Operatins in the pharmaceutical and bitech industry, including CMC, Quality Assurance and Quality Cntrl. Befre jining Targvax, respnsible fr CMC and quality in Lytix Bipharma AS Trbjørn Furuseth, MD, CFO Experienced executive with a brad backgrund within life science Frmer cnsultant in the Pharma & Healthcare practice f McKinsey & Cmpany Medical Dctr frm Nrwegian University f Science and Technlgy (NTNU) 32 32
INTERNATIONAL BOARD OF DIRECTORS with brad expertise Patrick Vink, Chairman Mre than 30 years experience frm senir rles at leading pharmaceutical and bitechnlgy cmpanies On the bard f several private and listed cmpanies in the pharma and bitech space, including Santhera Pharmaceuticals, Cncrdia Healthcare and Sper Therapeutics Eva-Ltta Allan Frmer Chief Business Officer at Immuncre Mre than 25 years f experience frm the bitechnlgy and life science industry in bth private and public cmpanies Has held senir psitins at e.g. Ablynx, Vertex Pharmaceuticals and Oxfrd Asymmetry (Evtec) Jhan Christensn, MD, PhD Partner f HealthCap Previusly supervised the healthcare prtfli f SEB Företagsinvest Senir management experience frm Astra Pain Cntrl and AstraZeneca PhD in basic neurscience Authr f 17 scientific articles Per Samuelssn Partner f HealthCap Prir t jining HealthCap in 2000, he gained ver 15 years f investment banking experience, mainly with Ars Securities in Sweden Prir t this Mr. Samuelssn was head f Research, als at Ars Securities Catherine Wheeler, MD Cnsultant, Frmer CMO f Acetyln Pharmaceuticals with 20 years f experience in senir clinical and business develpment rles. Significant drug develpment experience with a strng medical nclgy fcus frm acrss academia and industry Bente-Lill Rmøren Rbert Burns, PhD Diane Mellett Bard member f Radiumhspitalets Frskningsstiftelse and chairman f Farmastat and Phtcure Previusly emplyed by Nv Nrdisk Scandinavia (1976-2012) in varius psitins, including psitin as CEO f the Nrwegian unit (1983-2002, 2008-2012). Bard member at Nrdic Nanvectr (2013-2014) Cnsultant and advisr t cmpanies develping immune based therapies in cancer Extensive experience in building bitechnlgy cmpanies, previusly CEO f 4-Antibdy, Affitech and Celldex Therapeutics Previusly Directr at the Ludwig Cancer Research Cnsultant t bitech and medical device cmpanies Qualified in bth UK and US law Frmerly General Cunsel fr Cambridge Antibdy Technlgy (CAT) Led successful defence fr CAT cncerning a cntractual dispute n Humira 33 33