Activating the immune system to fight cancer

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1 Activating the immune system t fight cancer Jefferies Investr Cnference New Yrk City Dr. Magnus Jäderberg - CMO 6 June 2018

2 Imprtant 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.

3 Intrductin 2. ONCOS nclytic virus prgram 3. TG mutras neantigen vaccine prgram 4. Targvax pipeline 5. Crprate verview

4 Frm a sequential treatment strategy directly targeting the cancer 1 Surgery When pssible, surgical resectin t remve the tumr 2 Raditherapy Tumr irradiatin t shrink tumr vlume 3 Chemtherapy Crnerstne treatment in mst cancer frms 4

5 t an integrated cmbinatin apprach HARNESSING THE POWER OF THE PATIENT S OWN IMMUNE SYSTEM Targvax fcus Immune activatrs Vaccines, nclytic viruses Immune mdulatrs Checkpint inhibitrs Surgery - Radi - Chem Immune bsters CAR-Ts, TCRs Targeted therapy PARPs, gene therapy, etc. 5

6 Mde f actin IMMUNE ACTIVATORS TURN COLD TUMORS HOT Example frm Targvax Phase I trial Ovarian cancer patient CD8+ T-cell Recgnizes and destrys cancer cells Befre injectin f nclytic virus Cld tumr N T-cell infiltratin After injectin f nclytic virus Ht tumr Full T-cell infiltratin 6

7 Targvax has tw cmplementary prgrams in clinical develpment, PROVEN TO ACTIVATE THE IMMUNE SYSTEM Genetically armed adenvirus ONCOS Onclytic virus Alerts the immune system t the presence f cancer antigens Induces T-cells specific t patients tumr Activates the immune system Triggers patientspecific respnses TG RAS neantigen vaccine Shared neantigen, therapeutic cancer vaccine Triggers the immune system t recgnize ncgenic, mutated RAS neepitpes Induces mutant RAS-specific T-cells N need fr individualizatin 7

8 ONCOS nclytic virus prgram 3. TG mutras neantigen vaccine prgram 4. Targvax pipeline 5. Crprate verview

9 ONCOS-102 Phase I prf f cncept IMMUNE ACTIVATION DEMONSTRATED Cld tumr turned ht, CD8+ T-cell staining ONCOS-102 Phase I trial design: 12 patients, 7 different slid tumrs Ovarian, Mesthelima, Clrectal, Sarcma, Liver, Lung N ther treatment ptins left All chemtherapy refractry ONCOS-102 mntherapy 9 injectins ver 5 mnths Tp-line results: 100% innate immune activatin 11/12 patients increase in CD8+ T-cells 40% stable disease 2 lng-term survivrs Abscpal effect and lasting systemic immune respnses bserved Pre-treatment Baseline Pst-treatment Week 8 9 Ranki et al., Jurnal fr Immuntherapy f Cancer 2016, 4(17)

10 CD8+ fld-change frm baseline ONCOS-102 Phase I prf f cncept CD8+ T-CELL INFILTRATION CORRELATES WITH SURVIVAL Fld-change CD8+ T-cell cunt vs. survival r = 0.75 p = ,000 1, Case example Ovarian cancer, 38yr ld wman Failed n 5 types f chemtherapy >1,000-fld increase in CD8+ T-cell infiltratin Tumr specific T-cells detected up t 2 years after treatment Stable disease fr 3 years, survived fr 3.5 years Overall survival (mnths) 10 Ranki et al., Jurnal fr Immuntherapy f Cancer 2016, 4(17)

11 ONCOS CLINICAL DEVELOPMENT STRATEGY Mesthelima Orphan disease CPI synergy Intra-tumral CPI synergy Intra-peritneal Next generatin ONCOS viruses Target launch indicatin Indicatins with n/ limited effect f CPIs Peritneal malignancies Duble transgene adenviruses Orphan drug status Aim t becme additin t SC Onging Phase I/II 15,000 patients per year Onging melanma Phase I Cmb w/pd-1 >100,000 patients per year Onging Phase I/II in varian and clrectal Cmb w/pd-l1 >100,000 patients per year Nvel targets Onging in viv testing Brad spectrum f slid tumrs 11 SOURCE: Glbal Data, EU big 5 + US

12 ONCOS CLINICAL PROGRAM OVERVIEW Melanma Phase I 12 patients Cmbinatin with pembrlizumab PC in CPI refractry patients Memrial Slan Kettering Cmpassinate use prgram Finland 115 patients Phase I trial 12 patients 7 indicatins Mesthelima Phase I/II - randmized 30 patients Orphan indicatin Cmbinatin with SC chem Randmized vs. SC Cmpleted trials Onging trials Trials spnsred by partner Peritneal cancer Phase I/II up t 78 patients Ovarian and clrectal cancers Cmbinatin with durvalumab Intraperitneal administratin Cllabratin with AZ, CRI, Ludwig 12

13 ONCOS-102 in malignant pleural mesthelima PHASE I/II STUDY DESIGN IN COMBINATION WITH SC Safety lead-in cmpleted Randmized part currently enrlling Experimental grup (n=14) Patient ppulatin Advanced malignant pleural mesthelima 1 st line / 2 nd line Nn-randmized Safety lead-in (n=6) ONCOS-102 plus SC chemtherapy (6 cycles) Randmized ONCOS-102 (6 administratins) SC (6 cycles) Cntrl grup (n=10) SC (6 cycles) 13

14 ONCOS-102 in malignant pleural mesthelima SIGNAL OF EFFICACY IN THE FIRST 6 PATIENTS 1 Safety 2 Innate immune activatin 3 Adaptive immune activatin 4 Clinical activity ONCOS-102 welltlerated in cmbinatin with chemtherapy Systemic increase f prinflammatry cytkines in 6/6 patients (IL-6, TNFα and IFNγ) Increase in tumr infiltratin f CD4+ and CD8+ T cells in 3/4 patients Clinical activity seen in 3/6 patients after 6 mnths 50% disease cntrl rate 14

15 ONCOS-102 in malignant pleural mesthelima DEVELOPMENT STRATEGY AND INDICATIVE TIMELINES Onging Phase I/II, randmized 30 patients Planned Expansin f randmized Phase II ~60 additinal patients (N=90) Future Phase III n=tbd Randmized ORR and OS data 30 patients Decide n pssible CPI cmbinatin arm EMA & FDA advisry meetings Randmized ORR and OS data 90 patients Ptentially use as basis fr a submissin fr cnditinal apprval Ptentially start Phase III OS trial fr full MAA 15

16 TG mutras neantigen vaccine prgram 4. Targvax pipeline 5. Crprate verview

17 The RAS gene 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 ncgenic and result in uncntrlled cell divisin There are n existing therapies targeting RAS mutatins Targvax TG prgram is a unique vaccine apprach fr mutant RAS cancer Lw Fernandez-Medarde; RAS in Cancer and Develpmental Diseases; Genes & Cancer. 2011;2(3)

18 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 advanced disease Initial fcus n resected patients, with strnger immune system 18

19 TG CLINICAL DEVELOPMENT STRATEGY Pancreatic cancer (resected) Clrectal cancer Lung cancer (NSCLC) All mutras cancers TG01 lead indicatin Phase I/II cmpleted Orphan drug status Up t 40,000 patients per year TG02 lead indicatin Phase I trial nging 50% RAS mutated Up t 500,000 patients per year TG02 ptential future indicatin 30% RAS mutated Up t 500,000 patients per year TG02 + TG03 ultimate lng-term ptential 30% f all cancers Up t 30% f all cancer patients 19 Surce: Glbal data, Riva et al. Pls One 2017 Estimated ttal addressable patient number with RAS mutatins in US, EU and China

20 TG CLINICAL PROGRAM OVERVIEW Phase I & II Resected & nn-resected >200 patients Phase I/II Resected pancreatic cancer 32 patients Clrectal - TG02 Phase I Up t 20 patients TG02 targets 8 RAS mutatins Neadjuvant bimarker study Cmbinatin w/keytruda Currently recruiting patients Resected pancreas TG01 - under evaluatin TG01 targets 7 RAS mutatins Cmbinatin with checkpint inhibitr Additin t standard f care Cmpleted trials Onging trials Planned trial 20

21 TG01 IN RESECTED PANCREATIC CANCER SIGNAL OF EFFICACY DEMONSTRATED IN PHASE I/II TRIAL WITH ADJUVANT CHEMOTHERAPY Median verall survival (N=32) 33.4 vs mnths reprted in the ESPAC4 trial fr gemcitabine alne (cunting frm time f surgery) 2-year survival rate 23 ut f 32 patients alive tw years after surgery (72%), cmparing t 30-53% tw-year survival with gemcitabine alne 1-year survival rate 30 ut f 32 patients alive ne year after surgery (94%) mutras immune activatin 29 ut f 32 patients (90%) had RAS-specific immune activatin by ne-year Dsing and safety Optimized dsing regimen defined fr future develpment, and TG01 is well-tlerated in cmbinatin with chemtherapy 21

22 TG01 CURRENT KAPLAN-MAIER SURVIVAL CURVES First (n=19) and secnd (n=13) patient chrt 2 nd chrt; ptimized dsing regimen 77% 2-year survival rate (10/13) mos nt reached 9 patients alive at time f analysis mos 27.6 mnths frm surgery fr gemcitabine alne in ESPAC4 trial 1 st chrt; full dsing regimen 68% 2-year survival rate (13/19) mos 33.1 mnths (frm surgery) 5 patients alive at time f analysis 22

23 Targvax pipeline 5. Crprate verview

24 ONCOS-102 TG Targvax verall CLINICAL PROGRAM TIMELINES Cancer Indicatin H1 H2 H1 H2 H Resected Pancreas Phase l/ii Resected Pancreas Randmized trial in planning Planned randmized Phase II (lead-in) Clrectal Phase lb Melanma Phase l Mesthelima Phase lb/ii Peritneal malignancies Cllabratin w/cri, Ludwig & MedImmune Phase I/II Prstate Cllab. w/sti Phase l Interim data Clinical, immune and safety data Onging clinical trials, Targvax spnsred Onging clinical trials, partner spnsred 24

25 ACTIVATING THE PATIENT`S IMMUNE SYSTEM t fight cancer Brad clinical prgram Six shts n gal Several upcming data pints Defined path t market Aim t becme frntline treatment in high unmet need cancers Orphan status in mesthelima and pancreas Innvative pipeline Next gen duble transgene viruses in testing Systemic administratin rutes under evaluatin

26 26 Crprate verview

27 TARGOVAX HAS A SOUND FINANCIAL POSITION with cash t cmplete the planned clinical prgram well int 2019 Operatins The share Cash end f Q1 - Mar 31 st NOK millin -32 NOK millin 29 USD millin Net cash flw - ttal Q1 113 NOK millin -4 USD millin Annual run rate - last fur quarters 15 USD millin Market Cap - at share price NOK ~ NOK millin 3 NOK millin 110 USD millin Daily turnver - rlling 6 mnth avg. Analyst cverage 0.4 USD millin DNB, ABG Sundal Cllier, Arctic, Redeye, Nrske Aksjeanalyser, Edisn

28 THE SHAREHOLDER BASE IS STRONG with a mix f specialist, generalist and retail investrs Sharehlder Estimated wnership Shares m Relative HealthCap Sweden 12,4 23,6 % Nrdea Nrway 4,7 8,9 % RadFrsk Nrway 4,4 8,4 % KLP Nrway 2,1 4,0 % Statil Nrway 1,2 2,3 % Threndahl Invest Nrway 1,0 1,9 % Danske Bank (nm.) Nrway 0,8 1,6 % Timmun Nrway 0,7 1,4 % Prieta Nrway 0,7 1,4 % Sundt Nrway 0,5 1,0 % Yngve S. Lillesund Nrway 0,3 0,7 % NHO - P665AK Nrway 0,3 0,5 % DNB Nrway 0,2 0,4 % Tbech Invest Nrway 0,2 0,4 % Istvan Mlnar Nrway 0,2 0,4 % Danske Bank (nm.) Nrway 0,2 0,4 % Spar Kapital Investr Nrway 0,2 0,3 % Peter Kenneth Zwilgmeyer Nrway 0,2 0,3 % Rlf Arne Olsen Nrway 0,1 0,3 % Sctt Paul Tønnessen Nrway 0,1 0,3 % Tp 20 30,6 58,3 % Other sharehlders (4138) 22,0 41,7 % Ttal 52,6 100,0 % Key internatinal investrs participating in PP 2017 Nyenburgh (NL) Trium (UK) Millenium Capital Partners (UK) Interg (SWE) AP3 (SWE) Aramea AM (DE) 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% >4,100 sharehlders 28

29 Learn mre at:

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