CMC outsourcing in small virtual biotech company

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1 Arming the patient s immune system t fight cancer CMC utsurcing in small virtual bitech cmpany

2 Subjects Intrductin t Targvax and technlgy platfrms Outsurcing t CDMOs Selectin f CDMO 2

3 Subjects Intrductin t Targvax and technlgy platfrms Outsurcing t CDMOs Selectin f CDMO 3

4 Targvax Small bitech cmpany in antigen specific cancer immuntherapy Lcated in Osl and Helsinki Histry 4

5 Targvax has tw immun-nclgy prgrams in clinical develpment ONCOS Onclytic virus Genetically designed adenvirus Makes cancer antigens visible t immune system Induces T-cells specific t patients tumr TG RAS neantigen vaccine Ccktail f synthetic peptides Mimics cancer causing RAS neantigens Induces T-cells specific t RAS mutatins 5

6 Targvax strategy is t bst the effect f immuntherapy by targeting multiple aspects f the cancer immunity cycle T-cell activatin T-cell trafficking Cancer antigen presentatin TG01 Peptide vaccine f cancer antigens ONCOS-102 Onclytic virus T-cell tumr infiltratin Cancer cell identificatin Checkpint inhibitrs Yervy, Keytruda, etc Destructin f cancer cells Adapted frm Chen et al. Immunity 2013; 39:1 6

7 ONCOS-102 is a cancer targeting adenvirus armed with an immune stimulating transgene Selective replicatin in cancer cells Immune system bster Enhanced cancer cell infectin 24 bp 6.7K/gp19K Ad5 knb E1A E3 Fiber knb ITR Transgene Ad3 knb ITR GM-CSF transgene Triggers innate immune respnse and recruits APCs 7

8 Resected pancreatic cancer is the lead indicatin, but all RAS mutated cancers are ptential TG targets Pancreatic cancer (resected) Clrectal cancer Lung cancer (NSCLC) All mutras cancers TG01 lead indicatin Cmpleting phase I/II Planning phase II/III TG02 lead indicatin Phase I trial recruiting 50% RAS mutated TG02 ptential future indicatin 30% RAS mutated TG02 + TG03 ultimate lng-term ptential 30% f all cancers > 90% RAS mutated patients Up t patients Up t patients Up t 30% f all cancer patients Surce: Glbal data, Riva et al. Pls One 2017 Estimated ttal addressable patient number with RAS mutatins in US, EU and China 8

9 ONCOS-102 TG Overview f Targvax full clinical prgram Interim data Clinical, immune and safety data Cancer Indicatin H1 H2 H1 H2 H Resected Pancreas Ph l/ii Resected Pancreas Planned registratin prgram Planned Phase II Clrectal Phase lb Melanma Phase l Mesthelima Ovarian & Clrectal Partnered w/cri & MedImmune Prstate Partnered w/sti Dse escalating Ph I Phase l Phase lb/ii Ph II 9

10 Subjects Intrductin t Targvax and technlgy platfrms Outsurcing t CDMOs Selectin f CDMO 10

11 Targvax strategy fr CMC utsurcing Targvax is a virtual cmpany and will utsurce: All develpment wrk and validatin fr manufacture prcesses and analytical methds fr ur IMPs. GMP manufacture and quality cntrl, and supply t clinical trials twards cmmercializatin. Key CDMO and cntract labratry selectin criteria: Need t have in place quality standards t supply IMPs and cmmercial prducts t relevant markets, including EU, US and thers as apprpriate. Need t have with high cmpetency, skills and regulatry knwledge fr the relevant utsurced scpes and prducts. 11

12 Targvax uses three IMPs in the clinical prgrams ONCOS Onclytic virus Genetically designed adenvirus 5 Prduced frm human cancer cell line TG RAS neantigen vaccine Mixture f 7-8 synthetic peptides f 17 amin acids Lyphilized drug prduct GM-CSF Immunmdulating adjuvant rhugm-csf expressed frm E.cli Lyphilized drug prduct 12

13 IMP supply and develpment fr clinical trials EMA and FDA Advice meetings MAA/BLA Apprval CLIN Phase I/II Clinical Trial Phase III Clinical Trial Timeline CMC IMP Supply Phase I/II IMP Supply Phase III CMC Develpment IMP fr Phase III/Cmmercial Validatin & Characterisatin IMP Phase III/Cmmercial Cmmercial Drug Supply Regulatry Affairs CLIN CMC IMP and Drug Supply CMC Prduct develpment CLIN Clinical develpment CMC Chemestry Manufacturing and Cntrls EMA Eurpean Medicines Agency FDA Fd and Drug Administratin MAA Market Authrisatin Applicatin BLA Bilgics License Applicatin Targvax is utsucing all develpment, manufacture and analytical testing fr 3 IMPs Currently Supply f IMPs t clinical Phase I/II trials Develpment f manufacture prcess and analytical methds fr Phase III and cmmercial prduct 13

14 TG peptides Supply f TG t Phase I/II clinical trials: DS Manufacture DS Manufacture Specific Develpment & manufacture f TG fr Phase III clinical trials DS Prcess Develpment Manufacture DS Manufacture Other Characterisatin And TG Develpment DS Characterisatin DS Other Characterisatin And TG Manufacture DS Characterisatin DS 14

15 TG peptides The CDMO picture fr TG peptides Well knwn middle size CDMO fr DS manufacture Lng histry with Targvax Financial strng Lcated in central Eurpe, but glbal cmpany Strng expertise in develpment and manufacture f peptides Regulatry cmpliant t EU and FDA GMP Strng prject management Small CDMO fr current manufacture Strng and lng time cnnectin t DS CDMO Cmmunicatin mainly rganized by DS CDMO Limited capacity fr large batch sizes Limited methdlgies fr release testing 15

16 Recmbinant GM-CSF Supply f GM-CSF t Phase I/II clinical trials: Cmmercial drug prduct Chinese supplier Imprt & EU QP release Develpment & manufacture f GM-CSF fr Phase III clinical trials: DS Characterisatin Frmulatin Develpment GM-CSF Develpment DS Prcess Develpment DS DS Characterisatin Manufacture GM-CSF Manufacture DS Manufacture DS DS Other DS Other DS Other DS Other 16

17 Recmbinant GM-CSF The CDMO picture fr GM-CSF Well knwn small/middle size CDMO selected fr DS manufacture Financial strng Lcated in central Eurpe Strng expertise in develpment and manufacture f recmbinant prteins Regulatry cmpliant t EU and FDA GMP Cntracts with ther CDMOs fr additinal testing methdlgies Strng prject management Small size CRO fr frmulatin develpment Large flexibility (rder f wrk packages, experimental design) Strng expertise in frmulatin develpment Request high invlvement frm custmer (experimental design & decisin making) CDMO fr manufacture is nt selected 17

18 ONCOS-102 Viral vectr Supply f ONCOS-102 viral vectr t Phase I/II clinical trials: DS Manufacture DS DS Other DS Other Manufacture Other Other Other Develpment & manufacture f ONCOS-102 viral vectr fr Phase III clinical trials: DS Other Prcess Develpment DS Other Viral vectr Develpment Other DS Other DS Prcess Develpment DS Prcess Develpment DS Characterisatin Other DS Other Prcess Develpment DS Other Viral vectr Manufacture Other DS Other DS Prcess Develpment Other DS Characterisatin DSP 18

19 ONCOS-102 viral vectr The CDMO picture fr ONCOS-102 Small CDMO fr DS and manufacture Lng histry with ONCOS Lcated in Finland Strng expertise n cell culture, viruses and quality cntrl testing Regulatry cmpliant t EU GMP Strng prject management Strng invlvement frm Targvax Limited capacity fr large batch sizes f Several CDMOs fr additinal quality cntrl testing n DS and stage Well knwn testing labs Cntracted mainly by Targvax Crdinatin respnsibility and cntracts t be mved t CDMO selected fr DS and manufacture 19

20 Subjects Intrductin t Targvax and technlgy platfrms Outsurcing t CDMOs Selectin f CDMO 20

21 Selectin f CDMO Assessment f CDMO fr TG peptides, GM-CSF and ONCOS-102 Define the strategy and gals Strategic decisin with lng-term cnsequences Define yur team: CMC, QA, Regulatry, BD Identify stakehlders Stage I Search by Internet / Netwrks / Cnsultans / Other CMOs 50 CMOs Stage II s / Cmpany presentatins / Calls / Meetings 5-10 CMOs Stage III Request fr prpsals / Prpsals /Audits 3-5 CMOs

22 Selectin f CDMO Stage I Definitin f Targvax specific requirements: Operatins, Technical, Quality, Business Lcatin DS and/r Technlgy and equipment Safety, cntainment, e.g. bisafety levels Capacities Regulatry cmpliance (EU, US) Availability f CDMOs, e.g. Directry f Bipharmaceutical Cntract Manufacturers 80 CDMOs Matrix: CDMO services vs. requirements CDMO, cnsultants & persnal cntacts Recmmendatins Partnering cnferences / Trade shws First screening 22

23 Selectin f CDMO Stage II Direct cntact with CDMO s / calls / presentatins / meetings Request fr Infrmatin (RFI) based n criteria Technical Cnfirmatin f data frm Stage I Mre detail inf vs requirements Premises, technlgy and equipment Capacities (batch sizes, new custmers) Analytical capability Quality CDA Cnfidential Disclsure Agreement Ballpark figures RFI & CDMO questinnaire Site visits Define the agenda Facility tur Financial strength Prject management, cmmunicatin, transparency Staff cmpetency and trust Track recrd Secnd screening 23

24 Selectin f CDMO Stage III Request fr prpsals (RFP) Scpe f services, technical data and milestnes Prpsal Cmmercial prpsal (breakdwn in all prject and manufacture csts) Design fr a cmpetitive bidding prcess Prprietary technlgy Master prgram incl. Gantt chart Sub-cntractrs Cntract cnditins GMP certificates & Site master file Financial statements References Prpsal evaluatin (and previus evaluatin) Technical Due Diligence / Quality audits 1-3 CDMO Selectin f Targvax CDMO fr manufacture Term Sheet, Letter f Intent Master Service Agreement, QA agreement 24

25 CDMO learnings Building trust and gd wrking relatinship Frequently cmmunicatin & site visits transparency Be present n CDMO site Stepwise apprach t CDMO services - develpment CDMO full respnsibility f sub-cntractrs Master Service Agreements & QA agreements Budget with additinal csts 25