Disclosures Information Brendan D. Curti, MD

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1 The MITCI (Phase 1b) study: A novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients with or without previous immune checkpoint therapy treatment Brendan Curti 1, Jon Richards 2, Mark Faries 3, Robert H.I. Andtbacka 4, Sigrun Hallmeyer 2, Gregory A. Daniels 5, Mark Grose 6, Roberta Karpathy 6, Darren R. Shafren 6 1 Providence Cancer Center, Portland, OR; 2 Oncology Specialists, Chicago, IL; 3 John Wayne Cancer Institute, Santa Monica, CA; 4 Huntsman Cancer Institute, Salt Lake City, UT; 5 UCSD Moores Cancer Center, La Jolla, CA; 6 Viralytics Limited, Sydney, Australia,

2 Disclosures Information Brendan D. Curti, MD I have the following financial relationships to disclose: Honoraria - Prometheus Research Funding - Bristol-Myers Squibb (Inst); MedImmune (Inst); Prometheus (Inst); Viralytics (Inst). Travel, Accommodations, Expenses - Agonox; Prometheus

3 Coxsackievirus A21 (CAVATAK ) Proprietary formulation of the bio-selected oncolytic virus, Coxsackievirus A21 Non-enveloped RNA Picornavirus, common cold virus Not genetically modified Targeted to specific receptor over expressed on cancer cells (human ICAM-1) Rapid lytic cell infection Destroys local and metastatic cells by oncolytic and immunotherapeutic activity Potential application across a range of cancer types Generally well tolerated in patients Potential combination with other immunotherapies

4 Intratumoral CVA21- mediated immune cell changes in the tumor micro-environment Pt 4-15 Day : Pre-treatment Day 8: Post-treatment Female: Stage IIIC with melanoma to legs Prior treatment with ipilimumab and pembrolizumab Pt 4-14 Male: Stage IV M1c with melanoma to the leg and lungs Prior treatment with ipilimumab and pembrolizumab

5 MITCI Phase 1b Study Design (MELANOMA INTRA-TUMORAL CAVATAK AND IPILIMUMAB) Study population: 26 Stage IIIC and IV melanoma patients at least 1 injectable lesion CVA21 intralesional 3 x1 8 TCID 5 Day 1,3,5,8,22 then Q3W till Day 358 Immune induction Ipilimumab 3 mg/kg IV Q3W x 4 Futility Clause: 4 confirmed objective responses in the first 12 patients Day 1 Day 22 Day 85 Study Objectives Primary: Safety and tolerability Secondary: BORR, DCR, 1yr survival and OS, PFS, Duration of response Complete enrolment: 14 additional patients

6 Treatment-Emergent Adverse Events Prior Checkpoint therapy (n=13) Checkpoint therapy naïve (n=12) Preferred Term Total N(%) Grade 3+ N(%) Total N(%) Grade 3+ N(%) Any event 13 (1) 4 (31%) 11 ( 92) 7 (58) Any attributable to CVA21 11 ( 85) 8 ( 67) Any attributable to ipilimumab 12 ( 92) 1 (8)* 11 ( 92) 1 (8)* Fatigue 9 ( 69) 7 ( 58) 1 (8) Pruritus 8 ( 62) 1 (8) 6 ( 5) ( ) Diarrhoea 5 ( 38) 3 ( ) Anaemia 4 ( 31) 3 ( ) 1 (8) Headache 3 ( 23) 3 ( ) Injection site pain 4 ( 31) 2 ( 17) Pruritus generalised 2 ( 15) 4 ( 33) Rash 2 ( 15) 4 ( 33) Arthralgia 3 ( 23) 2 ( 17) Nausea 5 ( 38) Pyrexia 3 ( 23) 2 ( 17) Alanine aminotransferase increased 3 ( 23) 1 ( 8) 1 (8) Aspartate aminotransferase increased 2 ( 15) 1 ( 8) 2 ( 17) Back pain 2 ( 15) 2 ( 17) Blood alkaline phosphatase increased 3 ( 23) 1 (8) Chills 3 ( 23) 1 (8) Constipation 1 (8) 3 ( ) Hypertension 1 (8) 3 ( ) 2 (17) Hypokalaemia 2 ( 15) 2 ( 17) Influenza like illness 2 ( 15) 2 ( 17) Pain 2 ( 15) 1 2 ( 17) Pain in extremity 2 ( 15) 2 ( 17) 1 (8) Rash generalised 2 ( 15) 2 ( 17) Weight decreased 3 ( 23) 1 ( 8) Patients completing standard dosing of ipilimumab (3 mg/kg IV Q3W x 4) No DLT s reported. Grade 3+ events in these patients attributed to CVA21: None. *Grade 3+ events in these patients attributed to ipilimumab: fatigue (checkpoint naïve), elevated liver enzymes (prior checkpoint). Prior Checkpoint therapy Checkpoint therapy naïve 92% (11/12) + 82% (9/11) + +, One patient from each group currently in the process of completing standard ipilimumab dosing schedule

7 Best percentage change in the target lesions Best Overall Response: Intent to Treat Population (n=22) 7 IIIC IVM1a IVM1b IVM1c Best overall Response*,+ Per irrc (irrc) n (%) Overall response rate 11 (5) Complete response (CR) 4 (18) Partial response (PR) 7 (32) Stable disease (SD) 6 (27) Progressive disease (PD) 5 (23) Disease control rate (CR+PR+SD) 17 (77), Positive level of neutralizing anti-cva21 serum antibodies at baseline (>1:16) *, irrc criteria: Preliminary data, investigator assessed +, First response assessment at Day 16, Response ongoing but not confirmed at data cutoff date

8 Best percentage change in the target lesions Best percentage change in the target lesions Prior Checkpoint therapy (n=11) Best Overall Response* Checkpoint therapy naïve (n=11) * Prior ipilimumab IIIC + Prior anti- PD1 IVM1a + # Prior anti- PD-L1 IVM1b IVM1c * # * * * * Best Overall Response + (irrc) Per irrc n (%) Overall response rate 4 (36) Complete response (CR) 1 (9) Partial response (PR) 3 (27) Stable disease (SD) 5 (46) Progressive disease (PD) 2 (18) Disease control rate (CR+PR+SD) 9 (82) Best Overall Response + (irrc) Per irrc n (%) Overall response rate 7 (64) Complete response (CR) 3 (27) Partial response (PR) 4 (36) Stable disease (SD) 1 (9) Progressive disease (PD) 3 (27) Disease control rate (CR+PR+SD) 8 (73) *, irrc criteria: Preliminary data, investigator assessed +, First response assessment at Day 16

9 Best percentage change in the target lesions Pt1351 (Stage IIIC) Complete tumor response Pre-Treatment Day 3 Prior cancer treatments (Best response) 1. BCG (PD) 2. Nivolumab (PD) 1 Pt Study Day Day 9 Day 18

10 Best percentage change in target esions Pt1345 (Stage IVM1c) Partial tumor response Pre-treatment Day 127 Prior cancer treatments (Best response) 1. Ipilimumab/Nivolumab (PR) 2. Nivolumab (PD) 3. Surgery (NE) 1 Pt Study Day Day 31

Best percentage change in the target lesions Best percentage change in the target lesions Changes in target lesion burden*,+ by disease stage Prior Checkpoint therapy (n=11) Checkpoint therapy naïve

11 Best percentage change in the target lesions Best percentage change in the target lesions Changes in target lesion burden*,+ by disease stage Prior Checkpoint therapy (n=11) Checkpoint therapy naïve (n=11) IIIC IVM1a IVM1b IVM1c Study Days Study Days *, irrc criteria: Preliminary data, investigator assessed +, First response assessment at Day 16, Patient completed study, Patient on study, No further response assessment due to index lesion excision

12 Best percentage change in individual target lesions Best percentage change in the target lesions Non-injected individual target visceral lesion response*, Prior Checkpoint therapy 5 Checkpoint therapy naïve Lung lesion Liver lesion Other visceral lesion % of non-injected target lesions regressed 5% 67% of non-injected target lesions regressed 5% *, irrc criteria: Preliminary data, investigator assessed +, First response assessment at Day 16

13 Conclusions The CVA21-ipilimumab combination immunotherapy treatment is generally well tolerated and has displayed durable antitumor activity in local, regional and distant systemic disease. At present no DLT s have been reported, with surprisingly, only 2 Gr 3 treatment-ae s (ipilimumab-related fatigue and elevated liver enzymes) with an overall study Gr 3/4 treatment-related AE rate of 8% (2/ pts). Preliminary investigator assessed Best Overall Response Rates (BORR): - 5% (11/22 pts) in ITT population; - 36% (4/11 pts) in patients administered prior checkpoint therapy; - 64% (7/11 pts) in patients naïve to checkpoint therapy; - All response rates are higher than published rates for either agent used alone (CVA21: 28.1% and ipilimumab :~11%) in advanced melanoma patients. Objective response rates of 46% (6/13 lesions) and 67% (6/9 lesions) in non-injected visceral target lesions in patients with or without prior checkpoint therapies, respectively. CVA21 + ipilimumab can increase the percentage of activated CD4 and CD8 T cells with effector and memory phenotypes in the peripheral blood. Evidence of broader CD4 T-cell subsets expanded in responding patients. While preliminary, the data suggest that a CVA21-ipilimumab combination may represent a viable treatment option for an unmet need in advanced melanoma patients refractory to prior anti-pd1+/- CTLA-4 therapies.

$patients refractory to prior immune checkpoint therapies.$ $injectable lesion, immune checkpoint refractory Recruitment commenced$

14 Future Directions A focus on an unmet clinical need in advanced melanoma patients refractory to prior immune checkpoint therapies. Expansion Cohort 44 Stage IIIC and IV melanoma patients at least 1 injectable lesion, immune checkpoint refractory Recruitment commenced Primary study Objective Response rate

Providence Cancer Center, Portland, OR; 2 Oncology Specialists, Chicago, IL; 3 John Wayne Cancer InsPtute, Santa Monica, CA; 4

Providence Cancer Center, Portland, OR; 2 Oncology Specialists, Chicago, IL; 3 John Wayne Cancer InsPtute, Santa Monica, CA; 4 The MITCI (Phase 1b) study: A novel immunotherapy combina>on of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma pa>ents with or without previous immune checkpoint therapy