KOL Event & Corporate Update April 6, 2017 NASDAQ: VBLT Agenda Opening remarks Dr. Ramy Ibrahim, MD – Parker institute for Cancer Immunotherapy New Targets and Immuno‐therapeutic Approaches in Oncology Prof. Dror Harats, MD – CEO, VBL Therapeutics VBL’s Novel Approach to Immune‐Oncology 2 Use of checkpoint modulators in Advanced malignancies Ramy Ibrahim, MD Head of Clinical Development Disclosures Paid consultant for Arcus therapeutics Honorarium from PER History and evolution of immunotherapy Immunotherapy Delivers In 2013, Science selected cancer immunotherapy as its Breakthrough of the Year. In 2014, the Wall Street Journal showcased cancer patients who were treated with immunotherapies and survived years beyond their initial prognosis. Ambitious goal with immunotherapy Traditional Therapies Immunotherapy 100% 100% Long Term Benefit Combinations of Traditional Immunotherapy Cancer Therapies Alive Alive Immunotherapy % of Treated %Patients of Treated % of Treated %Patients of Treated Traditional Therapies 0% 0% Time Time Patients ultimately succumb to their disease 2011: Immunotherapy delivered Long term benefit: Only 1in every 5 treated patients Mechanism of Action is simple… MEMORY cell Cancer cell It is more complicated…many pathways Some activate , others inhibit but many remain to be unknown Unleashing Immunotherapy’s Potential Multi disciplinary Genomics Immunomics Proteomics Microbiome Clinical Outcomes Data Science >1,250+ companies Biology >3,000 IO trials Oncology 100’s of research institutions Physics + Chemistry 100’s of disease and immune pathways Is it The Matrix 2.0? Unlimited Number of Potential Combinations And… That’s Actually What’s Happening in the Clinic SCLC nsqNSCLC Colorectal Phase I Pembro+chemoradiaton Pembro+ PD-1 Pathway Atezol CVA21 durva+ Pembro+INCB039110 + erlotinib AMP-224 Pancreas NSCLC Durva+Treme+HF radiation Treme++INCB050465 Pembro+XBRT +SBRT Pembro+CM-24 Avelumab +Crizotinib Durva+ carboplatin + Nivo + Pembro+azacitidine+ Phase II Durva+AZD9291 Ramucirumab Pembroetoposide FP008 Durva+ Romidepsin Pembro+RESOLYN Atezo Nivo+ Nab-Paclitaxel + Gemcitabine Atezo+ sterotactic radiation Nivo+Ipi+ACY 241 +taxol Ramucirumab Combo + bevacizumabdurva+ Pembro+ Durva+Treme+HF radiation NivoCheckmate012 Pembro+ Pembro+INCB039110 +chemo azacitidine Nivo+FP008 Nivo+Nab-Paclitaxel Nivo+ Ipi+nivo MargetuximabAM0010 Durva+treme+radiation +INCB050465 durva+ Hepatic Atezo+radiation + Gemcitabine Decitabine/Tetrahydrouridine i Nivo+FP008 Treme+ Atezo Phase III Avelumab +AZD5069 Pembro+Carboplatin/Nab-Paclitaxel Nivo+Ipi durva+ Pembro+AM0010PDR001 Nivo+CB-839 Folfox+ + bevacizumab Pembro+CM-24 Durva+Selected Small Molecules Treme+ +IMCS110 Atezo+INCB024360 +chemo Nivo+Ipi+TAK-580 Nivo+BMS-936558 radiation bevacizumab Pembro+afatinib Nivo+INC280 Nivo+HBI-8000 Pembro+Cyclophosphamide+GVAX+SBRT PDR001 TAK-202 Nivo+ class I peptides Pembro Pembro Nivolo+Vigil +INC280 Vedolizumab + ISA 51 VG+ipi Nivo+ALT803 (Keynote-021) Pembro+CDX-1401 + Azacitidine Nivo+GVAX+CRS-207 Nivo+Ipi+ Nivo+dasatinib Pembro Durva+Ramucirumab Pembro+ Pembro+crizotonib Nivo+crizotonib +PolyICLC Nivo+GVAX laser beam Pembro after + ACT Pembro+ Atezo Melanoma Peg-IFNa-2b Pembro+Vorinostat Pembro+CDX-1401 Nivo Pembro+ radoitherapy Frontline chemo Atezo Neoadjuvant Chemoradiation + bevacizumab Atezo + Vemurafenib Pembro +PolyICLC +Ipi +chemo Indoximod + carbo+ Pembro Nivo+chemo HNC Nivo+Trametinib+Dabrafenib Nivo+Ipi+ +INCB024360 Durva+ nab-Atezo+Cobimetinib Pembro+Ipi Durva+Bavituximab etoposide + cetuximab Pembro+Vemurafenib Nivo+ACT+ radiation Nivo+desatinib paclitaxel Pembro+INCB039110+ Pembro+imatinib Nivo+Ceritinib Nivo+ablation Nivo+erlotonib durva+treme Urelumab Pembro+Trametinib+Dabrafenib Nivo+BMS-986016 Pembro + gemcitabine INCB050465 Pembro+CDX-1401 Nivo+galunisertib PDR001 Pembro+IL-2+ ACT Pembro+ Pembro+GMCSF +PolyICLC + AMG 820 Nivo+FP008 +IMCS110 Pembro+ Nivo+ Nivo+HBI-8000 Atezo+SOCPembro+bevacizumab chemo ACP-196 Durva+Treme Pembro+ Cavatak Nivo + ipi + XRT Atezo Pidilizumab Nivo+Galunisertib Pembro+ doxcetaxel Durva+ADXS11-001 +HF radiation Indoximod Sargromstim Pembro+PV-10 Nivo+ Nivo+Ipi Nivo+XRT+ carbo+ +Gemcitabine Nivo+ipi Pembro+ adjuvant cisplatin + radiation Nivo+FP008 durva+treme Pembro+AM0010 Indoximod +chemo etoposide Durva+Trametnib+Debrafenib Nivo+ INCB24360 Nivo+Sunitinib durva+treme Pembro+chemoradiationPembro+chemotherapy durva+treme+ paclitaxel + carboplatin Pembro+ LV305 Pembro+IL-2 Nivo+ipi+LGX818MEK162 avelumab+doxcetaxl Pembro+ radiation Nivo+HAM Pembro+bevacizumab Atezo+Cobimetinib Pembro +GR-MD-02 Pembro+pIL12 durva+treme+Poly(ICLC) Cervical Pembro + HAM Durva+Treme+IMCgp100 Pembro+ Nivo+surg+chemo Nivo+Ipi epacadostat Atezo+chemo+bevacizumab Nivo+FP008 Durva+ADXS11-001 Nivo+CB-839 Ipi+IMO-2125 Nivo+ Ipili After Nivo progression Nivo+chemo Durva+Treme GBM + Trametinib + Dabrafenib Durva+Avastin Sarcoma Atezo+chemo +XRT durva+treme+Poly(ICLC) Durva+treme Nivo+DC vaccines Nivo+ Ipi Nivo+Ipi Nivo+Ipi Pembro+ BevacizumabDurva+Avastin Atezo+CMB305 Checkmate-401 Nivo+WT1vaccine Pembro+Axitinib Nivo+ Radiation + Urelumab+BMS-986016 Pembro+AM0010 Pembro+chemo Pembro Avelumab+carbo/tax Nivolumab Nivo+Ipi Nivo+Radiation Temozolomide durva+paclitaxel + Ipilimumab Nivo+Temozolomide durva+treme+ +carboplatin Durva+Motolomid+doxyrubicin +ACP-196 Avelumab +Doxyrubicin Nivo+Urelumab paclitaxel + carboplatin Durva+ Olaparib Atezo+chemo Pembro+chemotherapy durva+ Atezo+bevacizumab+ Pembro+ Doxyrubicin Nivo+ durva+Lenalidomide+Rituximab Ovarian Ipi durva+treme+Poly(ICLC) azacitidine aspirin Atezo+entinostat and/or anti-estrogen therapyAtezo+ Nab-Paclitaxel Nivo+Elotuzumab Pembro+CTL019 Pembro+CM-24 durva+Trastuzumab durva+ Nivo+brentuximab vedotin durva+treme+gemcitabine+ carboplatin Pembro+nabpax Atezo Pomalidamide Pembro+carbo Durva+treme Pembro+ Bendamustine+ Atezo durva+treme+ Pembro+cyclo Pembro+CDX-1401 + gem/carbo Dex Pembro durva+bev +gemcitibine Nivo+varilumab lenvatinib Pembro+Ublituximab Rituximab + Obinutuzumab+Lenalidomide nab-paclitaxel + carboplatin +PolyICLC + ACP-196 Atezo Nivo+ Pembro+eribulin Durva+Taxane-anthracycline Chemo durva+ +TGR-1202 Pembro durva+Vigil durva+INCB024360 Atezo+ Durva+MEDI6469 + Obinutuzumab+ Nab-Paclitaxel mesylate durva+treme+Poly(ICLC) treme+Poly(ICLC) Nivo+ + AFM13 Pembro+INCB054828 Pembro+Cetuximab Bevacizumab Nivo+Ipi durva+ Polatuzumab Vedotin durva+JCAR014 +Gemcitabine Pembro+Tamoxifen Nivo+BMS-986179 Durva+MEDI6469 LAG3 Pembro+ +post Bendamustine+ BreastPembro+AM0010 Pembro+Stereotactic Ablation Nivo+BMS-986156 Durva+AZACITIDINE Pembro+INCB039110 TSR-022+TSR-042 Durva+ Bevacizumab ASCT Rituximab PDR001+GWN323 Lymphomas durva+PDR001 Pembro+GSK3174998 PDR001 Durva+ Nivo+5-azacytidine +INCB050465 Mocetinostat Nivo+XRT Pidilizumab + Lenalidomide azacitidine+IMCS110 Pembro+Hypofractionated Radiotherapy + LAG25 Treme Pembro+ Nivo+cyclo+XRT Pembro+selexnor +SOC pTVG-HP Plasmid Nivo+Imbrutinib Pidilizumab +DC vaccine Lirilumab+ Nivolumab+5-azacytidine Pembro+IPI-549 PDR001 Pembro Avelumab + PF-05082566 DNA Vaccine Pembro+MK-4166 Atezo+MTIG7192A + MGB453 Pembro (Keynote-29) durva+ibrutinib Atezol+ lenalidomide Pembro+GSK3359609 Atezo+RO7009789 Durva+ Pembro+Pomalidomide +CDX-1401 Atezo+Azacitidine Pembro+PF-05082566 BGB-A317+BGB-290 Nivo+HBI-8000 Durva+LY3022855 Pembro+Birinapant +PolyICLC treme Durva+Pomalamide BGB-A317+BGB-317 nivo+Mogamulizumab Pidilizumab + Nivo+CB-839 + Dexamethasone+Dara Durva+treme+Mogamulizumab Pembro+Ziv-aflibercept durva+ Pembro+ Idelalisib Nivo Provenge+ Durva+Pomalamide Nivo+ IFNg Pembro treme+ Nivo+Dasatinib +vaccine+ PDR001 Cyclo + Dexamethasone Durva+ Nivo+lirilumab Durva+LY2510924 +ACP-196 durva+ Nivo+Urelumab Pembro+Ibrutinib NYESO1 ACT+GWN323 Nivo Pembro+ADXS31-142 treme+ Pembro+TILs AZD1775 Nivo+ABBV-399 Pembro Pembro+vaccine Nivo+ Pembro+dinaciclib + anti-LAG3 Poly(ICLC) Pembro+ Atezo+emactuzumab +EphB durva+treme Ipi or lirilumab Durva+ Pidilizumab + DC vaccine Pembro+INCB054828 Lenvatinib Atezo+IFNalpha 4-HSA +Poly(ICLC) Nivo MEDI0680 Nivo+desatnib Atezo+RO6895882 Avelumab +BMS-986205 Durva+ Nivo+PT2385 pembro Advanced Atezo+ipi AZD4547 +Pembro+Axitinib Axitinib +post Atezo+RO6958688 durva+ Hematological Atezo+GDC-0919 Atezo Nivo Checkmate016 ASCT treme+ Malignancies Durva+MEDI9447 + BCG Durva+IPH2201 Pembro+ Atezo Pembro+AM0010 CRI Venture Fund Durva+AZD4635 INCB054828 + R-223-D Pembro+INCB039110+INCB050465 pembro Pembro Merkel + BCG +CM-24 Landscape Pembro+AM0010 Bladder Prostate Renal This will happen because of “data overload” 2014: The year of phase 1 and 2 clinical trials Tsunami 250 200 150 trials of Phase I Phase II 100 Number Phase III 50 0 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Year There are 97 immune modulators in clinical development. • 38 monotherapy only • 59 in combination in ~ 1100 trials As of March 2017 : ~130,000 patients as expected to be enrolled in ongoing clinical trials Source: Beacon Data base Wide Range of Agents or Modalities Being Combined with 1st Generation IO Agents: PD1, PDL1 and CTLA4 800 700 600 Adoptive Transfer (incl. CAR‐T) Antibody Drug Conjugate 500 HDAC Inhibitor Cytokine/Chemokine trials of 400 Surgery Immunomodulator Number Vaccine 300 Radiotherapy ICM Doublet 200 Kinase Inhibitor Chemotherapy 100 0 PD‐1PD‐L1 CTLA‐4 ICM target Data: March 2017. Same Trend is Emerging with Next Wave of IO Beyond PD1, PDL1 and CTLA4 40 35 30 Adoptive Transfer (incl. CAR‐T) Antibody Drug Conjugate 25 HDAC Inhibitor Cytokine/Chemokine trials of 20 Surgery Immunomodulator Number Vaccine 15 Radiotherapy