asx and media release · using fact-brm questionnaire! calm study inclusion/exclusion criteria %...
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Level 2 55 Grandview St Pymble NSW 2073 Australia T +61 2 99884000: F +61 2 99880999: www.viralytics.com
ASX and Media Release
CHIEF SCIENCE OFFICER’S PRESENTATION AT THE INTERNATIONAL MELANOMA CONFERENCE
4TH November 2010, Sydney: Viralytics Limited (ASX: VLA, OTC: VRACY) Following is the presentation given by Professor Darren Shafren, Chief Science Officer of Viralytics at the 4 day International Melanoma Conference. Professor Shafren provided a summary of the clinical work to date on CAVATAK and outlined the design of the proposed Phase II Melanoma study. Interest by clinicians from around the world in joining the proposed trial has been very promising.
Enquiries Bryan Dulhunty Managing Director T: 02 9988 4000 E :[email protected] W www.viralytics.com
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Phase I Evaluation of the Intralesional administration of the Oncolytic
Picornavirus, Coxsackievirus A21 (CAVATAKTM) in patients with late stage
melanoma!
Darren Shafren, !Chief Scientific Officer,!
Viralytics Limited!
CAVATAKTM cancer cell targe4ng
• Coxsackievirus A21 is a non-enveloped, RNA virus about 28nm in diameter!
• Natural infection, mild upper respiratory illness, “common cold!
• CAVATAK™ is a bio-selected, replication competent strain of Coxsackievirus A21!
• CAVATAKTM binds to the N-terminal domain of multiple copies of intercellular adhesion molecule-1 (ICAM-1)!
• The extracellular targeting of CAVATAKTM to cell surface ICAM-1 allows the virus to enter the cytoplasm and initiate rapid replication!
• CAVATAKTM targets cancer cells expressing high surface levels of ICAM-1!
CAVATAK + ICAM-‐1
CAVATAK ICAM-‐1
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CAVATAKTM: Mechanism of Action!
Time lapse (12 hours) CAVATAK mediated melanoma cell lysis and release tumour cell antigens!
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NSWOG Feb 2009 5
Inclusion:!• Patients with Stage IV metastatic melanoma!
• Failed standard therapy!
• No significant level of anti-CAVATAK neutralising antibody (<1:16)!
• ICAM-1 positive tumour biopsy!
Treatment: !• 5 patients!
• Single injection of CAVATAKTM ~ 2 x107 TCID50!
Primary Objective:!
• Tolerance of 1 intratumoral injection!
X01 and X02: Single dose of CAVATAKTM intratumoural injection trial in melanoma patients!
(First in man study)!
Electron microscopic image of CAVATAK
• A single IT dose of CAVATAK (~ 2.0 x 107 TCID50) was administered to a single subcutaneous lesion in each of 5 subjects without the development of uncontrolled viremia, excretion of virus, or significant toxicity. !
• Transient decrease in some injected tumours!
• All subjects developed an anti-CAVATAK antibody response (>1:16) within 14 days post-injection.!
CONCLUSIONS: X01 and X02
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NSWOG Feb 2009 7
Inclusion:!
• Patients with Stage IV metastatic melanoma!
• Failed standard therapy!
• No significant level of anti-CAVATAK neutralising antibody (<1:16)!
• ICAM-1 positive tumour biopsy!
Treatment: !
• Dose escalation study (100-fold increase)!
• 3 cohorts of 3 patients!
• 2 injections of CAVATAKTM107, 108 or 109 TCID50 48 hours apart!
• Inoculum diluted in normal saline to 10% tumour volume!
Primary Objective:!
• Tolerance of 2 intratumoral injections!
X03: Phase I Dose escalation of CAVATAKTM intratumoural injection trial in melanoma patients!
ICAM-‐1 expressing melanoma cells
X03: Serum neutralising antibody production following CAVATAK injection!
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X03: Serum levels of CAVATAK genomic RNA!
X03: Tumour response following CAVATAK injection!
Elevated levels of Serum GM-‐CSF
Largest increase in perforin posi4ve cells in biopsy
No tumor cells in biopsy
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X03: Serum levels of GM-CSF following !CAVATAK injection!
107 TCID50! 108 TCID50! 109 TCID50!
NSWOG Feb 2009 12
• Primary objective was achieved with all patients adequately tolerated the multiple single tumour injections up to a final dose of 2 x 109 TCID50. !
• Five of nine (55.55 %) patients experienced reductions in injected tumour volume or tumour stabilisation following multiple single tumour injections with CAVATAK;!
• No objective responses however, 2 patients displayed stable disease (RECIST 1.0);!
• CAVATAK was detected in 3 of 5 injected lesions on trial termination, even the presence of serum anti-CAVATAK neutralising antibody; !
• Some evidence of possible CAVATAK-mediated anti-tumour immune responses;!
• Overall, the findings provide a solid foundation for Phase II multi-dose investigations of CAVATAK in patients with late stage melanoma and other advanced solid cancers.
CONCLUSIONS X03: Phase I Dose escalation intratumoural trial in melanoma patients!
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Phase II: CALM Study design!(CAVATAK in Late stage Melanoma)!
Stage IIIc/IV melanoma subjects
N=63
CAVATAKTM
Mul4ple intralesional injec4ons up to 10 4mes
Dosing up to 18 weeks
Monitor for immune-‐related Disease Control Rate at 6
months
Recruiting sites in USA, Europe and Australia!
CALM STUDY CAVATAK dosing schedule
1 3 5 8 22 43 64 85 106 127!Screening !-28 days!
• Replication in injected tumours!• Systemic targeting of non-injected tumours including micro-metastases!
• Replication in injected tumours!• Cross priming of tumour antigen Cytotoxic T-cells!
Multiple lesions, intratumoral injections!1.0-5.0 mL containing CAVATAK 108.5 TCID50
per total injection(s) !
Day of injection!
= Absence of CAVATAK an4body
= Presence of CAVATAK an4body F
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CALM STUDY OBJECTIVES!Primary Objective:!• To assess the clinical efficacy of intratumoral (IT) CAVATAK in
terms of Disease Control Rate as monitored via irRC (immune-related RECIST 1.1) at 6 months.!
Secondary Objectives:!• To assess the clinical efficacy of IT CAVATAK in terms of
Durable Response Rate (DRR) at 6 months !• To assess the clinical efficacy of IT CAVATAK in terms of
Progression-Free Survival (PFS) at 6 months, 1-year survival and Overall Survival (OS)!
• To assess the safety of IT CAVATAK in terms of adverse events, viral biodistribution, and serum antibody response to CAVATAK!
• To assess the impact of CAVATAK treatment on Quality of Life using FACT-BRM Questionnaire!
CALM Study inclusion/exclusion criteria
• Unresectable melanoma requiring first or second-line treatment!
• Performance status PS-0 or PS-1!• Absence of circulating serum neutralizing
antibodies to CAVATAK!• At least one accessible lesion for IT
injection!• Adequate hematologic, renal and liver
function!• No ocular or mucosal melanomas!F
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Acknowledgements!Clinical Collaborators!Professor Peter Hersey, !Hunter Melanoma Unit, Calvary Mater Hospital, Newcastle, Australia!
Dr Mark Smithers !Princess Alexandria Hospital, Brisbane, Australia!
Professors John Thompson and William McCarthy,!Sydney Melanoma Unit, Sydney, Australia!
Dr Mark Formby!John Hunter Hospital, Newcastle, Australia,!
Viralytics Lab!
Bronwyn Davies!Roberta Karpathy!Rebecca Ingham!Erin Green !Jaclyn Stewart!Gough Au!Susanne Johansson!Robert Herd!
www.viraly4cs.com
For further information:CALM STUDY
(see us at STAND 16)
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