At the forefront of cancer immunotherapy. Investor Presentation January 2018

Transcription

1 1 At the forefront of cancer immunotherapy Investor Presentation January 2018

2 Disclaimer Certain statements made in this presentation are forward looking statements within the meaning of the safe harbour provisions of the United States Private Securities Litigation Reform Act of These forward looking statements are not historical facts but rather are based on Viralytics current expectations, estimates, assumptions and projections about the industry in which Viralytics operates. Material referred to in this document that use the words estimate, project, intend, expect, plan, believe, guidance and similar expressions are intended to identify forward looking statements and should be considered an at-risk statement. These forward looking statements are not a guarantee of future performance and involve known and unknown risks and uncertainties, some of which are beyond the control of Viralytics or which are difficult to predict, which could cause the actual results, performance or achievements of Viralytics to be materially different from those which may be expressed or implied by these statements. These statements are based on our management s current expectations and are subject to a number of uncertainties and risks that could change the results described in the forward-looking statements. Risks and uncertainties include, but are not limited to, general industry conditions and competition, general economic factors, the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally, and challenges inherent in new product development. Investors should be aware that there are no assurances that results will not differ from those projected and Viralytics cautions shareholders and prospective shareholders not to place undue reliance on these forward-looking statements, which reflect the view of Viralytics only as of the date of this presentation. Viralytics is not under a duty to update any forward-looking statement as a result of new information, future events or otherwise, except as required by law or by any appropriate regulatory authority. page 2

3 Growing Momentum 3 Lead investigational product CAVATAK backed by growing body of clinical evidence Demonstrated potential across a range of indications and treatment settings Major opportunity for use in combination with new blockbuster cancer immunotherapies Resources to conduct key global clinical trials Collaborative clinical trial program with Merck in lung and bladder cancer New studies in head and neck cancer, colorectal cancer, intravenous melanoma and uveal melanoma in advanced planning Corporate strategy to license, partner, or sell at key value point CALM and CALM extension: Success in Phase 2 melanoma trial (US) KEYNOTE-200: CAVATAK / KEYTRUDA Collaboration with Merck in lung and bladder cancer (US, AU & UK) CANON: Superficial bladder cancer (UK) MITCI: CAVATAK / YERVOY Melanoma (US) CAPRA: CAVATAK / KEYTRUDA Melanoma (US)

4 CAVATAK has received capital markets validation, with strong institutional investor support 4 Key Statistics Ticker Code Share Price (as at 5-Jan-18) Market Capitalisation (as at 5-Jan-18) Trading Range (12-month) Institutional and Pharma investors ASX: VLA OTCQX: VRACY A$0.82 A$226M A$ % Cash position (31 Dec 17 pro forma) 1 A$57M Net operating cash burn (Calendar 2017) A$16.4M Company Location Comments Leading diversified life sciences company Private investment firm specialising in public biotechnology investments Financial services company with over $1.5tn in assets under management Healthcare-dedicated investment firm which manages over $14bn Independent, trans-atlantic bio-science investment firm Australian equities investment manager 1 Includes $29.6 million investment and $6.4 million R&D tax incentive received since 31 December. page 4

5 Our lead drug CAVATAK is a bio-selected form of the common cold virus that kills cancer cells 5 Intravenous CAVATAK is released from tumour, and the process repeats Intratumoural Intravesical Binds externally to tumour cell Infects cancer cell Replicates and destroys cell Stimulates patient s own immune response against the cancer throughout the body ADMINISTRATION Multiple routes maximise applicability CAVATAK kills cancer cells and stimulates the patient s immune response page 5

6 Multiple CAVATAK target areas maximise potential value, partnerships and paths to commercialisation 6 Initial focus Current focus, to demonstrate broad applicability of CAVATAK in common cancer types New high potential focus areas MELANOMA LUNG BLADDER COLORECTAL HEAD & NECK 6 th most common cancer 2 nd most common cancer 5 th most common cancer 4 th most common cancer Broad range of cancers Clinical trials completed Further underway Clinical trial underway Clinical trial underway Clinical trial in planning Clinical trial in planning Pivotal trial protocol in development Source: USA National Cancer Institute, 2016 page 6

7 7 CLINICAL TRIAL PROGRESS CALM Phase 2 Melanoma Study

8 CAVATAK Phase 2 CALM Melanoma Study (CAVATAK IN LATE STAGE MELANOMA) 8 57 Stage IIIC and IV melanoma patients At least 1 injectable lesion 10 series of multi-intratumoral CAVATAK injections (up to 3x10 8 TCID 50 ) Day 1,3,5,8,22,43,64,85,106,127 YES Eligible for Extension study 9 series of multi-intratumoral CAVATAK injections (up to 3x10 8 TCID 50 ) q21 days Day 169 (w24) irpfs NO NO 6 Weeks later, confirm disease progression YES Observation only Leading US cancer centres Responses in both injected and metastatic non injected tumors Generally well tolerated, with no Grade > 2 treatmentrelated AEs Final results presented at ASCO 2015

9 CALM Phase 2 Trial: Impressive Response Results in Monotherapy Setting 9 Best percentage change in target lesions Number of patients 57 Stage of Disease ir Progression-Free Survival - 6 months IIIC-IV 38.6% (22/57) IIIC IV M1a IV M1b IV M1c Overall Response Rate 28.1% (16/57) Durable Response Rate (>6mths) Time to Response onset 21.1% 3.4 mths One-year survival rate 75.4% (43/57) Median Overall Survival 26 months CR=Complete response, PR= Partial response, SD= Stable disease and PD= Progressive disease Courtesy Dr R Andtbacka, Lead Study Investigator, Huntsman Cancer Institute as presented at ASCO 2015

10 CAVATAK Well Tolerated in Clinical Testing 10 Safety: CAVATAK-Related Adverse Events + AE Term *Grade 1 n(%) Grade 2 n(%) Injection site pain 16 (28%) 2 (4%) Grade 3 n(%) Grade 4 n(%) No drug-related grade 3 or 4 or serious adverse events Tiredness (fatigue) 15 (26%) 2 (4%) Chills 15 (26%) Pyrexia 7 (12%) Injection site erythema 7 (12%) Pain 6 (11%) 1 (2%) Myalgia 6 (11%) Headache 6 (11%) Toxicity is a well recognized shortcoming of existing cancer therapies +, Final analysis, treatment-related adverse events were reported from 45 of the 57 treated patients (79%) enrolled in the VLA-007 CALM CAVATAK monotherapy study; *, Only Grade 1 AE s occurring in > 10% of patients are listed.

11 CALM Phase 2 Trial: Extension Cohort (Biopsy Study) When Checkpoint Inhibitors Fail 11 Patient Stage IIIC melanoma on legs Prior treatment with ipilimumab and pembrolizumab Day 0 (pre-treatment) Day 8 (post-treatment) Partial Response in both patients Patient Stage IV M1c with melanoma to the leg and lungs. Prior treatment with ipilimumab and pembrolizumab Courtesy Dr R Andtbacka, Lead Study Investigator, Huntsman Cancer Institute as presented at ASCO 2015

12 CALM Phase 2 Trial: Activation of RIG-I Pathway and Upregulation of Immune Checkpoint Target Molecules 12 Day 0 (pre-treatment) Day 8 (post-treatment) Patient Stage IV M1c with melanoma to the leg and lungs. Prior treatment with ipilimumab and pembrolizumab

13 CALM Phase 2 Trial: Results and Future Directions 13 Successful study with primary safety endpoint achieved; secondary efficacy endpoint outcomes exceeding expectations Overall response rate of 28% Durable response in 21% patients CAVATAK-induced activity in non-injected distant lesions, including lung and liver metastases Extension Trial Overall response rate of 31% CAVATAK-induced changes in the tumor: Increases in immune cell infiltrates Up-regulation of PD-L1 and other checkpoint molecules Observations suggest combination with checkpoint inhibitors may further enhance anti-tumor activity

14 14 CLINICAL TRIAL PROGRESS Combination Therapy Studies

15 CAVATAK Combined with Checkpoint Inhibitors 15 Checkpoint inhibitor / CAVATAK combination preclinical results: Well tolerated Significant anti-tumor activity demonstrated CAVATAK combination clinical trials with approved checkpoint inhibitors underway with promising results Checkpoint inhibitors active in cancers that are also CAVATAK targets, including melanoma, lung and bladder Potential for CAVATAK in combination with future checkpoint inhibitors targeting LAG-3, TIM-3 and other immunotherapies such as IDO (in development by big pharma) The world doesn t need any more [checkpoints]. We need other things. We should be finding a way to develop other medicines beyond these Roger Perlmutter, President Research Merck 1 1. Financial Times 3 July 2017

16 Checkpoint Inhibitors: Room to Improve Through Combination with New Therapies 16 % Survival Time - Control - Conventional Therapy - Checkpoint Inhibitor Therapy (eg anti-ctla4) - Future Combinations with Checkpoint Inhibitors Big Pharma focused on improving activity of the checkpoint inhibitors through combination therapy Goal: To enhance survival with manageable toxicity through combination with CAVATAK

17 17 CLINICAL TRIAL PROGRESS MITCI Phase 1b Study

18 CAVATAK - MITCI Phase 1b Study MELANOMA INTRA-TUMORAL CAVATAK AND IPILIMUMAB 18 Company-sponsored open-label study at 9 US sites evaluating intralesional CAVATAK and YERVOY (ipilimumab) Primary Objectives are safety and response rate Secondary Objectives include PFS, Durable Response Rate and OS 60 patients with late-stage melanoma (stage IIIB-C/IV), with a current focus on patients who have failed a single course of prior pembrolizumab or nivolumab Now enrolled 38 patients across all settings Lead investigator: Dr Brendan Curti MD, Providence Cancer Center, Portland Treatment with CAVATAK on days 1, 3, 5 and 8; both agents co-administered on days 22, 43, 64 and 85, with up to 19 CAVATAK treatments in total

19 CAVATAK - MITCI Phase 1b Best Percentage Change in Target Lesions 19 Checkpoint therapy naïve (n=14) Overall response rate of 57% Best Overall Response + (irrc) Per irrc 19 n (%) Disease stage Overall response rate 8/14(57%) Complete response (CR) 3/14 (21%) Partial response (PR) 5/14 (36%) Stable disease (SD) 1/14 (7%) Disease control rate (CR+PR+SD) 9/14 (64%) 8 of 14 patients (57%) demonstrated >50% reduction in sum of target lesions Preliminary but encouraging results, compared to published YERVOY alone 1 (11% response rate) * irrc criteria: Preliminary data, investigator assessed + First response assessment at Day 106 ± YERVOY FDA approved label

20 CAVATAK - MITCI Phase 1b Best Percentage Change in Target Lesions 20 Prior single line anti-pd-1 therapy (n=7) Overall response rate of 29% Disease stage Best Overall Response + (irrc) 20 Per irrc n (%) Overall response rate 2/7 (29%) Stable disease (SD) 3/7 (43%) Disease control rate (CR+PR+SD) 5/7 (72%) Preliminary but encouraging results, compared to published YERVOY alone (10-13% response rate) 2 of 7 patients (29%) demonstrated >50% reduction in sum of target lesions *, irrc criteria: Preliminary data, investigator assessed +, First response assessment at Day 106

21 CAVATAK - MITCI Phase 1b Change in target lesions sum by disease 21 Checkpoint therapy naïve (n=14) Single line anti-pd-1 therapy (n=7) Promising durability in responding patients *, irrc criteria: Preliminary data, investigator assessed +, First response assessment at Day 106

22 CAVATAK - MITCI Phase 1b Non-injected Individual Visceral Target Lesion Responses 22 Prior anti-pd-1 therapy Checkpoint therapy naïve Strong anticancer activity in non-injected liver, visceral and lung lesions

23 CAVATAK - MITCI Phase 1b Study Complete Tumor Response Stage IIIC (Pt *) 23

24 CAVATAK - MITCI Phase 1b Study Partial Tumor Response Stage IV M1c (Pt *) 24

25 CAVATAK - MITCI Phase 1b Study: Preliminary Results and Outlook 25 CAVATAK / YERVOY combination is well tolerated and has displayed durable antitumour activity in injected and non injected distant systemic disease Safety: Efficacy: No dose-limiting toxicities reported Six Grade 3+ adverse events in 4 patients (all YERVOY-related: fatigue, elevated liver enzymes [2], pruritis, dehydration, hyperglycemia) with an overall study Gr 3+ treatment-related AE rate of 11% (4/38 pts) 57% (8/14) Best overall response rate in patients naïve to checkpoint therapy 29% (2/7) Best overall response rate in patients administered prior single line anti-pd1 therapy Preliminary but encouraging response rates, versus YERVOY alone (11%*) or other YERVOY combination studies Focus on an unmet need in patients who have failed prior anti-pd1 therapy Plan to enrol 60 patients Pivotal study in patients with high unmet need that have failed a single anti-pd1 checkpoint therapy (in planning stage) Potential to lead to a pivotal study * YERVOY FDA approved label

26 26 CLINICAL TRIAL PROGRESS CAPRA Phase 1b Study

27 CAVATAK - CAPRA Phase 1b Study CAVATAK AND PEMBROLIZUMAB in ADVANCED MELANOMA 27 Phase 1b company-sponsored open-label study evaluating intralesional CAVATAK and KEYTRUDA (pembrolizumab) Primary objective: Safety and tolerability Secondary objective: Activity as assessed by PFS at 12 months, ORR, OS, DRR and TTR 50 patients with late-stage melanoma (stage IIIB-C/ IV) Now enrolled 26 patients Lead investigator: Dr Ann Silk MD, Rutgers Cancer Institute of New Jersey, New Brunswick CAVATAK on Days 1, 3, 5 and 8; KEYTRUDA starting on Day 8, both given at three-weekly intervals for up to 2 years (maximum of 19 CAVATAK injections)

28 CAVATAK - CAPRA Phase 1b Best Overall Response 28 Disease stage Best Overall Response + (irrc) Per irrc n (%) Overall response rate 14/23(61%) Disease control rate (CR+PR+SD) 18/23 (78%) 14 of 23 patients (61%) demonstrated >50% reduction in sum of target lesions Overall Response Rate of 61% for CAVATAK / KEYTRUDA combination Preliminary but encouraging response rates, versus published KEYTRUDA alone 1 (33%) *Prior ipilimumab treatment Source: 1 FDA approved label data

29 CAVATAK - CAPRA Phase 1b Changes in Tumour Burden by Disease Stage 29 Promising durability in responding patients

30 CAVATAK - CAPRA Phase 1b Study Individual Patient Responses (investigator assessed) 30 Baseline Day 197 Pt Stage IVM1c Partial response Non-injected lung lesion upper left lobe Baseline Day 113 Pt Stage IIIC Partial response Non-injected lymph node lesion Right internal Obturator region

31 CAVATAK - CAPRA Phase 1b Preliminary Results and Outlook 31 Best Overall Response Rate of 61% (14/23 pts) and DCR of 78% (18/23 pts) Tumour responses are ongoing at 12 months in 6 patients 4 patients have demonstrated complete responses in the target lesions BORR of 64% (7/11 pts) in patients with late stage IV M1c disease Reductions in a number of injected and non-injected visceral/non-visceral lesions Only two Grade 3 pembrolizumab-related adverse events in 26 enrolled patients Preliminary but encouraging response rates compared to KEYTRUDA alone (33%*) or other KEYTRUDA combination studies *Robert et al., N Engl J Med 2015; 372:

32 32 CLINICAL TRIAL PROGRESS KEYNOTE-200 Phase 1 Study Collaboration with Merck (MSD) Part A CAVATAK Monotherapy Part B CAVATAK and KEYTRUDA combination

33 Multi-Dose Intravenous CAVATAK KEYNOTE-200 Phase 1 Study: 33 Part A - Completed (CAVATAK Monotherapy) Part B Ongoing (CAVATAK Combination with KEYTRUDA) 18 subjects with advanced melanoma, prostate, NSCLC or bladder cancer with <1:16 anti-cavatak serum antibodies IV infusions of CAVATAK in 100 ml saline over 30 min on Day 1,3,5,22,43,64,85,106,127,158 Cohort 1 Any cancer 1 x10 8 TCID 50 n=3 No Dose Limiting Toxicities Cohort 1 NSCLC or Bladder cancer CAVATAK (1 x10 8 TCID 50 ) + Keytruda n=3 Cohort 2 NSCLC or Bladder cancer CAVATAK (3 x10 8 TCID 50 ) + Keytruda n=3 IV infusions of CAVATAK in 100 ml saline over 30 min on Day 1,3,5,8,29,50,71,92,11 3,134,155 + IV pembrolizumab (200mg) every 3 weeks starting Day 8 Cohort 2 Any cancer 3 x 10 8 TCID 50 n=3 Cohort 3 1 x 10 9 TCID 50 Mandatory lesion biopsy (Day 8) Melanoma, NSCLC, Bladder And Prostate cancer n=3 each Cohort Expansion NSCLC (~n=40) CAVATAK(1 x10 9 TCID 50 ) + pembrolizumab Cohort 3: NSCLC or Bladder cancer CAVATAK (1 x10 9 TCID 50 ) + Keytruda n=3 No Dose Limiting Toxicities Cohort Expansion Bladder (~n=40) CAVATAK(1 x10 9 TCID 50 ) + pembrolizumab

34 Part A - CAVATAK Monotherapy Results Best Change in Target Lesions 34 Ten patients with stable disease and one patients with a confirmed partial response *irrecist criteria: Preliminary data, investigator assessed + First response assessment at Day 42

35 Part A - CAVATAK Monotherapy Results CAVATAK Tumor Targeting: Biopsy Viral RNA levels (day 8): Cohort 3 35 CAVATAK RNA present in melanoma, lung and bladder cancer tumor tissue following 3 intravenous doses Well tolerated with no dose limiting toxicity and no grade 3 or higher treatment related adverse events

36 KEYNOTE-200 Phase 1b Study CAVATAK/ Merck s KEYTRUDA Combination 36 Phase 1b study in progress; collaboration with Merck (MSD) Combination of intravenous CAVATAK / KEYTRUDA in late-stage cancer patients (~ 90 patients) Non-small cell lung cancer Metastatic bladder cancer 17 sites in the US, Australia and UK Primary objective: Safety and tolerability Secondary objective: Efficacy Dose escalation complete with no dose limiting toxicity for the combination of CAVATAK and KEYTRUDA in heavily pre-treated patient population Currently 64 subjects enrolled at the top CAVATAK dose level used in the expansion phase Potential to lead to a pivotal study

37 KEYNOTE-200 Phase 1b Study Preliminary First Investigator Assessment in Checkpoint Naïve Patients 37 Best percentage change in target lesions of checkpoint naïve patients + * Response observed (not all yet confirmed) in 3 of 10 (30%) NSCLC and 5 of 18 (28%) metastatic bladder cancer patients * Encouraging early data in lung and bladder cancer patients Well tolerated with 11% (7 of 64 ) patients have displayed treatment related >grade 3 adverse events

38 KEYNOTE-200 Phase 1b Study: Preliminary PD-L1 Expression Levels on Paired Tumour Biopsies 38 Upregulation of PD-L1 in lung and bladder cancer patients with pre-existing low levels

39 Preclinical Study Triple Combination Intravenous CAVATAK and Anti-PD-1 and IDO Inhibitor 39 Immune competent mouse melanoma model Significantly reduced tumour burden in mice treated with CAVATAK and anti-pd-1 and the triplet combination

40 40 CLINICAL TRIAL PROGRESS CANON Phase 1 Study

41 CAVATAK CANON Phase 1 Study: (CAVATAK in NON-MUSCLE INVASIVE BLADDER CANCER) 41 NMIBC is a common cancer with high unmet need and no recent treatment advances Standard of care includes toxic chemotherapies Study to assess intravesicular CAVATAK in neo-adjuvant, frontline setting: Evaluated tolerability, pharmacodynamics Evaluated biopsies, blood and urine samples for viral replication Documented evidence of anti-tumor activity Cancer Type Rank * Estimated New Cases in the US in 2016 * Breast 1 st 249,260 Lung 2 nd 224,390 Prostate 3 rd 180,890 Colorectal 4 th 134,490 Bladder 5 th 76,960 Melanoma 6 th 76,380 * USA National Cancer Institute, 2016 Study complete, 16 patients at Royal Surrey Hospital (UK) Intravesicular instillation of CAVATAK in 30 ml saline on Day 1 and/or Day 2 +/- mitomycin C Transurethral resection of tumor tissue at Day 8-11

42 Phase 1 CANON STUDY Tumor Response 42 Surface hemorrhage and elimination of the tumor Complete clinical response (confirmed by histopathology)

43 Phase 1 CANON STUDY Viral Replication 43

44 Phase 1 CANON STUDY Upregulation of Key Checkpoint Molecules 44 CAVATAK replication up-regulates target molecules for immune-checkpoint therapies in NMIBC tissue

45 CAVATAK CANON Phase 1 Study: FINAL Results and Next Steps 45 Intravesicular administration of CAVATAK well tolerated - no Grade 2, 3 or 4 CAVATAK-related Adverse Events Evidence of tumor targeting with viral replication Complete tumor response in one of the first three patients at the highest dose CAVATAK induces increases in immune cell infiltrates and expression of PD-L1 compared to untreated NMIBC controls CAVATAK mediates increase in the immunological heat within the tumor micro-environment suggesting potential for enhanced anti-tumor activity when used in combination with immune checkpoint inhibitors Commercial opportunity in neoadjuvant setting - prior to transurethral resection of tumor or in combination with checkpoint inhibitors Potential to broaden partnering discussions

46 46 CLINICAL TRIAL PROGRESS New Studies in Planning Stage

47 CAVATAK ITCAHN Phase 1b Study: CAVATAK AND PEMBROLIZUMAB in ADVANCED HEAD & NECK CANCER 47 Phase 1b company-sponsored open-label study evaluating intralesional CAVATAK and KEYTRUDA (pembrolizumab) To be conducted in the USA Primary objective: Safety and tolerability Secondary objective: Activity as assessed by ORR, time to initial response, duration of response 24 patients with metastatic stage IV HNSCC for whom systemic treatment with palliative intent is indicated, or subjects with loco-regionally recurrent stage II-IV HNSCC for whom surgical salvage is indicated CAVATAK on Days 1, 3, 5 and 8; KEYTRUDA starting on Day 8, both given at three-weekly intervals for up to one year (maximum of 19 CAVATAK injections)

48 CAVATAK CLEVER Phase 1b Study: CAVATAK AND IPILIMUMAB in UVEAL MELANOMA METASTATIC TO LIVER 48 Phase 1b company-sponsored open-label study evaluating intravenous CAVATAK and YERVOY (ipilimumab) To be conducted in the USA Primary objective: Safety and tolerability Secondary objective: Activity as assessed by ORR, disease control rate, PFS, DRR 6-10 patients with metastatic stage IV uveal melanoma with measurable liver lesions CAVATAK on Days 1, 3, 5 and 8, then at three-weekly intervals for a maximum of 11 infusions; both agents co-administered on Days 8, 29, 50 and 71

49 CAVATAK PaCKMAN Phase 1b Study: CAVATAK AND PEMBROLIZUMAB in ADVANCED MELANOMA 49 Phase 1b company-sponsored open-label study evaluating intravenous CAVATAK and KEYTRUDA (pembrolizumab) To be conducted in the USA Primary objective: Safety and tolerability Secondary objective: Activity as assessed by PFS, PFS hazard ratio, ORR, 1-year survival, overall survival PK profile of IV CAVATAK 15 patients with metastatic stage IIIB-IV melanoma that has progressed following treatment with an anti-pd-1 inhibitor CAVATAK on Days 1, 3, 5 and 8, then at three-weekly intervals for a maximum of 11 infusions; pembrolizumab on Day 8 then every three weeks for up to one year

50 CAVATAK Phase 1b Study: CAVATAK AND CHECKPOINT in COLORECTAL CANCER METASTATIC TO LIVER 50 Study in planning stage Phase 1b company-sponsored open-label study evaluating intralesional CAVATAK and checkpoint inhibitor Primary objective: Safety and tolerability of intralesional CAVATAK administration to liver metastases Secondary objective: Assess the safety of 1, 2 or 3 intralesional CAVATAK injections patients with colorectal cancer with at least two or more metastatic liver lesions CAVATAK delivered as one, two or three weekly intratumoral injections; checkpoint begins 1 week after the last CAVATAK dose then ongoing

51 SUMMARY 51

52 OVERVIEW - CAVATAK Clinical Trial Program 52 CAVATAK Intratumoral Intravenous Intravesicular Phase 2: CALM study Advanced melanoma N=57 Phase 1: STORM study (Part A) Melanoma, NSCLC, Bladder and Prostate cancer N=18 Phase 1: CANON study Non-muscle invasive bladder cancer N = 16 Phase 2: CALM extension cohort Advanced melanoma N=13 Combination Studies Lung Cancer and Bladder Cancer STORM Part B / KEYNOTE-200: Merck collaboration CAVATAK / KEYTRUDA Phase 1b study (N=90) Melanoma: MITCI CAVATAK / YERVOY Phase 1b (N=60) CAPRA CAVATAK / KEYTRUDA Phase 1b study (N=50) PaCKMAN Intravenous CAVATAK / KEYTRUDA Phase 1b study (N=15) CLEVER - Intravenous CAVATAK / YERVOY in uveal melanoma (N=10) Head and neck/ Colorectal ITCAHN - CAVATAK / KEYTRUDA Phase 1b (N=24) Colorectal cancer CAVATAK/ checkpoint Phase 1b (planning stage)

53 A Strong Record of Achievements 53 Reported positive interim results CAPRA study Achieved Reported positive interim results MITCI study Identified potential path to market in melanoma in setting of high unmet need Sites initiated in US, Australia and UK with strong enrolment in KEYNOTE 200 study Pre-clinical work to identify further target indications Achieved Achieved Achieved Achieved Developed CAVATAK manufacture program Achieved Well advanced in preparations for clinical studies in new indications Achieved

54 54 Recognition at Pre-eminent American Cancer Conferences

55 Expected News Flow 55 Initiate CLEVER study in uveal melanoma with intravenous CAVATAK Q Initiate ITCAHN study in head and neck cancer with intralesional CAVATAK Q Initiate PaCKMAN study in melanoma with intravenous CAVATAK Q Provide clinical updates on MITCI / CAPRA trials Q Initiate study in colorectal cancer Q Report clinical update on KEYNOTE-200 study Q Potentially extend intravenous CAVATAK program into new indications Q Initiate pivotal melanoma trial Q4 2018

56 CAVATAK A Compelling Commercial Opportunity 56 Active in a range of important cancer types with broad potential: To combine with a range of checkpoint molecules (eg KEYTRUDA, YERVOY) For use in a variety of treatment settings, including intralesional (melanoma, CRC, head and neck), intravenous (melanoma, lung, metastatic bladder) and intravesical (NMIBC) Increases immunological heat within the tumor micro-environment Well tolerated across all routes of administration KEYNOTE-200 CAVATAK / KEYTRUDA combination in NSCLC and metastatic bladder completed dose escalation and recruiting strongly Preliminary results from MITCI (CAVATAK / YERVOY) and CAPRA (CAVATAK / KEYTRUDA) trials very encouraging and point to potential path to market in area of high unmet need CANON - Promising results in NMIBC strong potential in combination with checkpoints Aggressive expansion of clinical program planned, with goal of driving partnering discussions and shareholder value Recent high value transactions in growing field of cancer immunotherapy