Activating the patient s the immune system t fight immune cancer system t Cmpany presentatin 4Q and Full Year 2018 fight cancer August 14 February 2019 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
Intr & Highlights 2. TG ne-antigen vaccine prgram 3. ONCOS nclytic virus prgram 4. 4Q 2018 Financials 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 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) 1H 2019 3-year survival data 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
2018 & 4Q HIGHLIGHTS Melanma CPI-refractry phase I: One cmplete respnse amng first six patients Innate immune activatin in all 6 patients Presented at KOL event in Octber ONCOS Mesthelima phase I/II: 50% disease cntrl rate after 6 mnths in six patient safety lead-in All patients were immune activated ONCOS-102 Peritneal cancer phase I/II: Safety evaluatin f first dse chrt cmpleted withut any cncerns TG01 TG01 Resected pancreatic cancer phase I/II: Encuraging tw-year survival, medium OS and medium DFS cmpared t histrical cntrl RAS-specific immune activatin in 94% f patients 7 Crprate Granted prduct patent in the EU fr TG t 2034 Dr. Catherine Wheeler was elected t the Bard Trbjørn Furuseth appinted CFO
TG mutant RAS vaccine prgram 3. ONCOS nclytic virus prgram 4. 4Q 2018 Financials 8
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 33.1 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 Preliminary data 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 9
TG01 resected pancreas cancer trial survival - first vs. secnd patient chrts SECOND PATIENT COHORT NOT YET REACHED MEDIAN OS 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 10 Preliminary data
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 11 Fernandez-Medarde; RAS in Cancer and Develpmental Diseases; Genes & Cancer. 2011;2(3)
THE RAS DEVELOPMENT LANDSCAPE TG is the mst advanced RAS-targeting prduct in active develpment Cmpany Mechanism f Actin Highest Phase Heat-inactivated yeast expressing target RAS mutatins Peptide cancer vaccine targeting RAS mutatins RNAi targeting mutant KRAS Antisense lignucletide (ASO) KRAS inhibitr mrna KRAS cancer vaccine Small mlecule inhibitr f RAS Small mlecule inhibitr f KRAS Small mlecule inhibitr f RAS Small mlecule inhibitrs f RAS Small mlecule inhibitrs f KRAS Small mlecule inhibitrs f mutant KRAS Small mlecule inhibitr RAS Small mlecule inhibitrs f KRAS regulatrs Small mlecule inhibitrs f KRAS Small mlecules targeting SOS (Sn Of Sevenless), a RAS regulatr Phase II (halted) Phase II Phase I/II Phase I Phase I Preclinical Preclinical Preclinical Preclinical Preclinical Preclinical Discvery Discvery Discvery Discvery Yeast based Gene silencing mrna Small melcule 12
TG DEVELOPMENT STRATEGY TG pivtal develpment Future indicatins TBD Cllabrative pancreas trial Pursue pprtunities fr cllabrative trials in pancreatic cancer CPI cmbinatin clinical trial Evaluate clinical benefit f TG vaccinatin Scin cmbinatin with PD-1/L1 blckade Pre-clinical package Generate supprting pre-clinical TG data package, incl. CPI and ONCOS cmbinatin TG01 histrical data TG01-01 phase I/II data, Hydr Pharma data 13
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 14 Cmpleted trial Onging trial Trial under planning
TG CLINICAL DEVELOPMENT STRATEGY 1 2 3 4 Resected pancreatic cancer Clrectal cancer Lung cancer (NSCLC) All mutras cancers TG01 indicatin Ph I/II cmpleted Next steps being reassessed ~40 000 incidents TG02 lead indicatin Ph I trial nging 50% mutras ~0.5m incidents TG02 ptential future indicatin 30% mutras ~0.5m incidents TG02 + TG03 lngterm ptential Up t 30% f all cancer patients 15 Surce: Glbal data, Riva et al. Pls One 2017 Estimated ttal addressable patient number with RAS mutatins in US, EU and China
ONCOS nclytic virus prgram 4. 4Q 2018 Financials
ONCOS-102 IS AN ONCOLYTIC ADENOVIRUS SEROTYPE 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 17
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 18
ONCOS-102 CLINICAL DEVELOPMENT PROGRAM CPI refractry melanma Phase I 9 +12 patients Cmbinatin with Keytruda CPI refractry PC First 6 patients cmpleted Secnd chrt pened recruitment Cmpassinate use prgram 115 patients Phase I trial 12 patients 7 indicatins Mesthelima Phase I/II - randmized 30 patients Cmbinatin with SC chem Path-t-market Orphan drug status Peritneal metastases Phase I/II up t 78 patients Cmbinatin with Imfinzi Intraperitneal administratin Cllabratin with MedImmune / 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 19
ONCOS-102 MELANOMA EARLY DATA CPI refractry melanma Phase I 9 +12 patients Cmbinatin with Keytruda CPI refractry PC First 6 patients cmpleted Secnd chrt pened recruitment Cmpassinate use prgram 115 patients Phase I trial 12 patients 7 indicatins Mesthelima Phase I/II - randmized 30 patients Cmbinatin with SC chem Path-t-market Orphan drug status Peritneal metastases Phase I/II up t 78 patients Cmbinatin with Imfinzi Intraperitneal administratin Cllabratin with MedImmune / 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 20
ONCOS-102 & Keytruda cmbinatin MELANOMA PHASE I TRIAL STUDY DESIGN 3 bipsies per patient Baseline DAY 22 DAY 64 First read ut autumn 2018: Six patients Imaging CPO: Cyclphsphamide 21
COMPLETE RESPONSE IN ONE OF SIX PATIENTS fllwing ONCOS-102 and Keytruda cmbinatin treatment 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 Patient 4 Previus Yervy, Keytruda & Imlygic Baseline Week 9 By week 15 N clinical benefit with Keytruda mntherapy SD Transient tumr regressin bserved by clinical assessment Withdrawn due t distant metastasis 22 Preliminary data
TUMOR SPECIFIC T-CELLS IN TUMOR BIOPSIES 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 23 Preliminary data
Fld change frm the baseline Fld change frm the baseline INCREASED LEVEL OF CYTOTOXIC CD8+ TILs Granzyme B expressing CD8+ T-Cells (TILs) Fld change frm baseline 150 100 50 20 15 10 5 CD8+ 150 GranzB T cells 100 50 20 15 10 5 CD8+ GranzB T cells 0 Baseline Day 22 Day 64 0 Baseline Day 22 Day 64 pt 1 pt 1 pt 2 pt 4 pt 2 pt 4 untreated reference pt 5 pt 4 pt 4 reference pt 5 CD8+ GranzB+ TILs Preliminary data 24
ONCOS-102 + KEYTRUDA MELANOMA TRIAL ne patient had a cmplete respnse by week 9 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 lcal regressin bserved in 3 patients Assciated with level f immune activatin 25 Preliminary data
SECOND DOSE COHORT IS INITIATED with up t 12 additinal patients wh will receive 12 ONCOS-102 injectins Frm: 1 st dse chrt 3x ONCOS-102 injectins T: 2 nd dse chrt 12x ONCOS-102 injectins BL 1 2 3 6 9 12 15 18 21 24 27/ET Weeks * * = ptinal DAY -3 t -1 DAYS 1, 4, 8 DAY 15 DAY 22 DAY 43 DAY 64 DAY 85 DAY 106 DAY 127 DAY 148 DAY 169 DAY 190 CPO ONCOS-102 ONCOS-102 + PEMBROLIZUMAB 26 Imaging CPO: Cyclphsphamide
NEXT GENERATION ONCOLYTIC VIRUSES ARE IN DEVELOPMENT Candidates Clning Validatin In vitr In viv Selectin A Next-gen ONCOS B C Same adenvirus backbne as ONCOS-102 Targets and transgenes nt disclsed until IP is secured Unique mdalities that affects the immune system and the tumr micrenvirnment 27
4Q 2018 Financials
PROFIT AND LOSS 4Q17 4Q18 2017 2018 Ttal revenue 0 0 0 0 External R&D expenses -12-21 -46-64 Payrll and related expenses -13-14 -48-56 Other perating expenses -7-7 -26-26 Ttal perating expenses -32-42 -120-146 Operating lss -32-42 -120-146 Net financial items -0 1-2 -1 Lss befre incme tax -33-41 -122-147 Net change in cash -24-22 90-110 Net cash EOP 262 151 262 151 29
TARGOVAX HAS CASH POSITION t cntinue the planned clinical prgram int 2020 Operatins The share Cash end f 4Q - Dec 31 th 2018 151 NOK millin -25 NOK millin 17 USD millin Net cash flw - ttal 4Q 112 NOK millin -3 USD millin Annual run rate - last fur quarters 13 USD millin Market Cap - at share price NOK ~8 420 NOK millin 1.6 NOK millin 48 USD millin Daily turnver - rlling 6 mnth avg. Analyst cverage 0.2 USD millin 0.3% DNB, ABG Sundal Cllier, Arctic, Redeye, Edisn 30
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 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) 1H 2019 3-year survival data 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 31
ACTIVATING THE PATIENT`S IMMUNE SYSTEM t fight cancer ONCOS-102: lead prduct TG: clinical effect in pancreas Innvative pipeline Strng single agent data Several upcming data pints First cancer vaccine t shw immune activatin against a driver mutatin Ideal cmbinatin prduct Next generatin viruses in testing