Company Presentation. September 2018 NASDAQ: VBLT

Transcription

1 Company Presentation September 2018 NASDAQ: VBLT

2 Forward-Looking Statements To the extent that statements contained in this presentation are not descriptions of historical facts regarding Vascular Biogenics Ltd., they are forward-looking statements reflecting management s current beliefs and expectations. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry s actual results, levels of activity, performance, or achievements to be materially different from those anticipated by such statements. You can identify forward-looking statements by terminology such as may, will, should, expects, plans, anticipates, believes, estimates, predicts, potential, intends, or continue, or the negative of these terms or other comparable terminology. Forward-looking statements contained in this presentation include: (i) the timing of the commencement, progress and receipt of data from pre-clinical studies and clinical trials; (ii) the timing of the commencement, progress and receipt of data from any other clinical trials that we conduct; (iii) our plans for future trials, efficacy or clinical utility of our product candidates; (iv) our plans for future trials; (v) the scope of protection we establish and maintain for intellectual property rights covering our product candidates and our technology; (vi) our ability to obtain and maintain regulatory approval for our product candidates and the timing or likelihood of regulatory filings and approvals for our product candidates; and (vii) expectations relating to the commercialization of our product candidates. Various factors may cause differences between our expectations and actual results, including unexpected safety or efficacy data, unexpected side effects observed during preclinical studies or in clinical trials, lower than expected enrollment rates in clinical trials, changes in expected or existing competition, changes in the regulatory environment for our drug candidates and our need for future capital, the inability to protect our intellectual property, and the risk that we become a party to unexpected litigation or other disputes. You should read our filings with the Securities and Exchange Commission, including the Risk Factors set forth in our Annual Report on Form 20-F for the year ended December 31, 2017 and our other filings with the Securities and Exchange Commission, completely and with the understanding that our actual future results may be materially different from what we expect. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. 2

3 Harnessing Nature s Genius At VBL, we harness the power of natural biological processes and elements, to create innovative therapeutics 1. VB-111: Gene Therapy with Unique Dual Mechanism of Action VB The Lecinoxoids Platform 3. Our Novel MOSPD2 Program 3

4 4 Deep Pipeline with 3 Novel Technologies

5 5 VB-111: Novel, Dual Mechanism for Targeting Solid Tumors

6 VB-111: Novel, Dual Mechanism for Targeting Solid Tumors 1) Targeting Tumor Vasculature Using VBL s unique VTS platform technology VB-111 (ofranergene obadenovec) is based on a non-replicating, non-integrating Adenovirus-5 vector which is administered IV and is internalized by endothelial cells in blood vessels Angiogenesis-specific sensor (the PPE-1-3x promoter) leads to expression of a pro-apoptotic protein (the Fas-TNFR-1 chimeric receptor) only on the surface of angiogenic endothelial cells Endogenous TNF-α, which is enriched in the tumor milieu, interacts with the Fas-TNFR-1 receptor, leading to cell apoptosis Ad5 Vector 1 Modified PPE-1-3x promoter 2 Apoptotic Transgene Fas-TNFR-1 3 TNF-α TNFR1 Fas Endothelial cell in angiogenic blood vessel TNF-α 4 TNF-α 4 Angiogenic blood vessels are targeted regardless of the status of pro-angiogenic factors/pathways, leading to tumor starvation TNF-α 6

7 VB-111 Shows Overall Survival Benefit Across Three Tumor Types Phase 2: Survival Probability Recurrent GBM (rgbm) Median OS: 414 vs 223 days VB-111 Treatment Through Progression Therapeutic Dose vs. Limited Exposure Therapeutic Dose; P=0.043 Limited Exposure Therapeutic Dose Treatment Through Progression Therapeutic Dose Platinum-resistant Ovarian Cancer Median OS: 498 Vs. 172 days Therapeutic dose (n=17) vs. Low dose (n=4) P=0.030 Low Dose Therapeutic Dose Radioiodine-Refractory Thyroid Cancer Tail of >40% After 3.7 years Single Sub-therapeutic Dose Multiple Therapeutic Dose Time to Death Days and in Phase 1 all comers study Survival Probability Time to Death Days Median OS: not reached (cohort7) Vs. 173 days (cohort 1-6) Median follow-up: 222 days (Range 25-1,044 days) Days Cohorts 1-6 Cohort Days Conducted in leading centers:

8 rgbm VB-111 Durable Responses, Translated to Prolonged Survival 69 year old white male diagnosed with GBM Had a recurrence at July 2013, after getting triple therapy (resection, radiotherapy and temodar) at diagnosis Had a second, complete resection, but five months later had a 2 nd recurrence At that point started receiving VB st Recurrence & 2 nd Resection nd Recurrence 2014 Treatment timeline VB-111 : x10 13 Every 2 months Actively treated every 2 months. Patient has a Complete Response for > 56 months with no measurable disease. Ovarian Cancer Major objective response following single dose of VB-111 Thyroid Cancer 8

9 The Phase 3 Negative Readout in rgbm May Result from the Trial Design which was Changed from the Phase 2 Phase 1 (Safety) VB-111 Monotherapy Sub-Therapeutic Dose (Less than VPs; Single dose) Progression Standard of Care mos Benefit No Phase 2 Limited Exposure Phase 2 VB-111-Primed Combination VB-111 Monotherapy (1x10 13 VPs; every 8 weeks) Median of 1 dose VB-111 Monotherapy (1x10 13 VPs; every 8 weeks) Median of 4 doses Standard of Care (Bev) VB Bev No YES Phase 3 GLOBE* Un-primed Combination VB Bev ( VB-111: 1x10 13 VPs; every 8 weeks) Bev Standard of Care No 9 * The GLOBE Phase 3 trial was conducted under SPA with the FDA. VBL believes that Avastin may have diminished the activity of VB-111 in this regimen.

10 VB-111 Significantly Increased Overall Survival in Recurrent Platinum-Resistant Ovarian Cancer Median OS: 498 Vs. 172 days Therapeutic dose (n=17) vs. Low dose (n=4) P= A Phase I/II Trial of VB-111 in Combination with Paclitaxel for Recurrent Platinum- Resistant Ovarian Cancer Overall Survival

11 Durable Disease Control and Response Data from ASCO A Phase I/II Trial of VB-111 in Combination with Paclitaxel for Recurrent Platinum-Resistant Ovarian Cancer Efficacy

12 OVAL: Randomized, Controlled, Double-Blind Phase 3 Registration Trial in Platinum-Resistant Ovarian Cancer Phase III Potential Registration Study Interim readout Primary endpoints: Overall Survival or Progression Free Survival expected 4Q19 Secondary endpoints: Combined CA-125 and RECIST, CA-125, Objective Response Rate Interim analysis: CA-125, Overall Survival & Progression Free Survival Translational Scientific Objectives: histopathology, expression, genetics, antibodies and biomarkers Approx. 75 sites, 400 subjects First Patient In - Dec 2017 Clinical collaboration with the GOG Foundation, Inc. (Gynecologic Oncology Group) Patients with Recurrent Ovarian Cancer Randomize 1:1 VB-111 1X10 13 VPs I.V. Q2M+ Paclitaxel 80mg/m 2 I.V. Q1W n=200 Placebo I.V. Q2M+ Paclitaxel 80mg/m 2 I.V. Q1W n= * Treatment beyond RECIST progression is allowed if patient does not have clinically significant symptomatic progression of disease

13 13 MOSPD2: Novel Target for Immune/Oncology Indications

14 MOSPD2: Novel Target for Immune/Oncology Indications 14 Novel molecular mechanism of cell migration unraveled: MOSPD2 is a protein whose function was unknown; VBL research has discovered that it is key regulator of chemotaxis in cancer cells and monocytes. Oncology Healthy tissue Tumor tissue Metastatic tumors MOSPD2 Expression Undetectable / Signal 1 Signal 2 AND Cell movement Inflammation MOSPD2 is expressed on monocytes and regulates their chemotaxis ability. VBL data shows that it is an important target in immune setting, such as MS and NASH models. VBL is developing its VB-600 platform of biologics targeting MOSPD2 for both oncology and inflammatory diseases.

15 MOSPD2 in Inflammation 15

16 MOSPD2 Regulates the Migration of Monocytes Anti-MOSPD2 Ab inhibits migration of CD14+ primary human monocytes, regardless of the chemoattractant used: Migrating Cells (X10 3 ) Control Anti-MOSPD2 P<0.01 P<0.01 P<0.01 P< SDF-1 RANTES MCP-1 MIP-3β 16 J Immunol Mar 1;198(5):

17 MOSPD2 is Essential for EAE Development MOSPD2 Knock-out mice: Group Incidence Mean maximal score Mortality WT 10/10 (100%) 3.3±0.4 3/10 (30%) MOSPD2 KO 3/10 (30%) 0.3±0.2 0/10 (0%) 4 WT Mice (n=10) MOSPD2 KO Mice (n=10) EAE Mean Score * P<0.05 ** P<=0.01 *** P<=0.005 **** P<=0.001 Mice were injected with MOG to induce EAE **** **** **** **** **** **** * ** **** **** *** *** * ** *** **** *** *** Experimental Day

18 Anti Human-MOSPD2 mab Inhibits MOG-Induced EAE Prevention model: Group Incidence Mean maximal score Mortality Control 8/10 (80%) 2.5±0.5 Anti-MOSPD2 5/10 (50%) 0.7±0.3 0/10 (0%) 0/10 (0%) Mean Clinical Score Isotype control Anti-MOSPD2 mab Mice were injected with MOG to induce EAE. One day before disease induction, mice were treated with mab (500µg) every three days at the indicated time points 18 Antibody treatment

19 Treatment with Anti Human-MOSPD2 mab Reduces EAE Severity Treatment model: 3 Mean Clinical Score 2 1 Mice were injected with MOG to induce EAE. When mean clinical severity reached a score of 2, mice were divided to the treatment groups. Antibodies (500µg) were administered every other Days after immunization day from day 17 to day 34.

20 MOSPD2 Inflammation Program Developed antibodies using 2 techniques Classical immunization of mice Screen of human antibodies Several dozens of clones received and tested Identified lead antibodies bind MOSPD2 on the cell surface inhibit monocyte migration show high binding strength (K D in range) Proof-of-Concept demonstrated in vitro and In vivo Advancing Ab development towards IND filing in year-end

21 MOSPD2 in Cancer 21

22 MOSPD2 Expression is Elevated in Tumors Normal Colon tissue Colon adenocarcinoma Normal hepatic tissue Hepatocellular carcinoma Normal Esophagus tissue Esophagus adenocarcinoma Normal Uterus tissue Uterus adenocarcinoma 22 Salem et al., Int J Cancer Jul 6 [Epub]

23 MOSPD2 Promotes Breast Cancer Cells Metastasis in vivo 3000 Metastasis Area ( m 2 ) x100 x40 Control MOSPD2 Silencing x100 x40-95% P = CRISPR-Control CRISPR-MOSPD2 23 SCID mice were injected I.V with 10 6 CRISPR-Control or CRISPR-MOSPD2 breast cancer cells. After 3 weeks mice were sacrificed and lungs were evaluated for numbers and size of metastasis. Graph shows mean of the largest metastasis measured. Salem et al., Int J Cancer Jul 6 [Epub]

24 CD3/MOSPD2 Bi-Specific Antibody Directs Killing of Tumor Cells Dose-Dependent Killing of Melanoma (A2058) and Cervical Cancer (HeLa) Cells Mediated Through Activation of T-cells % Survival IFN-γ (pg/ml) CD3XMOSPD2 concentration (µg/ml) N.D N.D CD3x MOSPD2 - - CD3x MOSPD2 Potential for various solid tumors 24

25 VBL s MOSPD2 Program The Potential The VB-600 series of MOSPD2- based Biologics 25 Inhibition of Monocyte migration Potential Inhibition / blockade for inflammatory applications Tumor Associated Macrophages Inhibition of Cancer cell metastasis Inhibition / blockade for oncology indications Diagnosis Specific targeting of MOSPD2+ cancer cells Platform technology: different biologics may be used for various applications Ab-mediated killing by the immune system (e.g. BITEs, bi-specific antibodies ) Ab-Drug conjugate CAR-T

26 Strong Management Team with Extensive Experience in Drug Development Dror Harats, MD Amos Ron Chief Executive Officer Chief Financial Officer Chairman of the IRB Erez Feige, PhD, MBA Tami Rachmilewitz, MD Vice President, Business Operations Vice President, Clinical Development Yael Cohen, MD Medical Director Eyal Breitbart, PhD Naamit Sher, PhD Vice President, Research and Operations Vice President, Drug Development and Regulatory Corinne Epperly, MD, MPH US Chief Operating Officer 26

27 Financial Highlights Outstanding Shares as of August 31, 2018 Outstanding Shares, Options and Warrants as of June 30, 2018 Market Cap as of August 31, 2018 Cash balance on June 30, 2018 NASDAQ: VBLT 35,881,128 47,017,004 $ 60M $ 58.5 M NO DEBT We expect the cash to sufficiently fund the company for more than 3 years 27

28 The VBLT Opportunity Phase 3 company, NASDAQ listed Three novel platform technologies developed in house, with strong IP Novel Mechanisms of Action Potential best-in-class product candidate External validation through a licensing deal in Japan & clinical collaborations In house commercial-scale gene therapy manufacturing facility (20,000 sq.ft.) Opportunity for significant value creation Lead candidate VB-111 in Phase 3 for Ovarian Cancer Potential across multiple solid tumors 28 Follow on programs & pipeline, with a clear capital focus Cash position secured for more than 3 years

29 For additional information: Nasdaq: VBLT 29 Thank You!