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JUNE 16 2015
Conference Call Viralytics CAVATAK – Phase 2 CALM Trial results
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 1995. 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.
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Robert H.I. Andtbacka1, Brendan Curti2, Sigrun Hallmeyer3, Zipei Feng4, Christopher Paustian4, Carlo Bifulco4, Bernard Fox4, Mark Grose5, Bronwyn Davies5, Roberta Karpathy5, Darren Shafren5
1 Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; 2 Providence Cancer Center, Portland, OR; 3 Oncology Specialists SC, Park Ridge, IL; 4 Earle A Chiles Research Institute, Providence Cancer Center, Portland, OR; 5 Viralytics Limited, Sydney, Australia.
Characterisation of the oncolytic kinetics of the immunotherapeutic agent, CAVATAK, delivered
intratumorally in patients with advanced malignant melanoma.
OVC Boston, MA
June 16, 2015
CAVATAK™ (Coxsackievirus A21) an oncolytic immunotherapeutic agent
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• Proprietary formulation of the oncolytic virus, Coxsackievirus A21
• Targeted to specific receptor over expressed on cancer cells (ICAM-1)
• Kills local and metastatic cells by oncolytic and immunotherapeutic activity
• Potential application across a range of cancer types
– Prostate, lung, melanoma, bladder and others
• Well tolerated in patients - to date no treatment-related grade 3 or 4 adverse events
• Potential intravenous as well as intratumoural use
• Potential application as monotherapy or in combination
• Manufactured under cGMP at SAFC, California
Coxsackievirus A21(CVA21) Oncolytic immunotherapeutic modes of action
Day 169 (w24) irPFS Primary endpoint (≥ 22.5%)
(irCR, irPR, irSD)
57 Stage IIIC and IV melanoma patients at least 1 injectable lesion
10 series of multi-intratumoral CVA21 injections (up to 3x108 TCID50)
Day 1,3,5,8,22,43,64,85,106,127
YES
Eligible for Extension study 9 cycles of multi-intratumoral
CVA21 injections (up to 3x108 TCID50) q21 days
NO
6 Weeks later, confirm Disease progression
NO
YES
CALM Phase II CAVATAK in Late stage Melanoma study design
Observation only
Planned Interim DMC analysis: 35 patients
Adverse Event1 Grade 1* n (%)
Grade 2 n(%)
Grade 3 n(%)
Grade 4 n(%)
Injection site pain 16 (28%) 2 (4%)
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%)
Hyperhidrosis 5 (9%)
Peripheral edema 1 (2%)
Erythema 1 (2%)
Musculoskeletal stiffness 1 (2%)
Rash 1 (2%)
• only Grade 1 adverse events occurring in 5 or more patients are listed • 1 AE coded using Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0
CALM Phase II trial (VLA-007) Safety and toxicity¶
CALM Phase II trial (VLA-007) Response data
Primary endpoint (≥ 10 pts with irPFS 6 months from 54 evaluable pts)
irPFS 6 months (CR+PR+SD) 38.6% (22 / 57 pts)
Secondary endpoints
Overall response rate (CR+PR, irRECIST 1.1) 28.1% (16 / 57 pts) [8 CR+ 8 PR]
Median time to response 3.4 months (95% CI: 1.5, 4.2)
Median irPFS 5.7 months (95% CI: 2.8, 11.1)
Median Overall Survival 26 months (95% CI: 16.7, NR+)
1-year survival rate 75.4% (43 / 57 pts)
Pt 03-032: Non-injected distant visceral lesion response
Male with metastatic melanoma to left neck and lungs. Injection in left neck.
1.0 x 0.8 cm
1.3 x 0.9 cm
0.5 x 0.2 cm
0.6 x 0.5 cm
Baseline Day 86
Injected
Non-injected Non-injected
Pt 12-002: Local injected and non-injected lesion responses
Male with metastatic melanoma to the leg. Injection in leg lesions .
Baseline Day 85
Injected Non-injected
IIIC IV M1a IV M1b
IV M1c
• Analysis excludes patients satisfying protocol criteria but not on study long enough for 6 week tumor response assessment; CR=Complete response, PR= Partial response, SD= Stable disease and PD= Progressive disease
-100
-80
-60
-40
-20
0
20
40
60
80
100
Bes
t per
cent
age
chan
ge in
the
targ
et le
sion
s su
m o
f dia
met
res
rela
tive
to b
asel
ine
CR, PR or SD = 75.4%
CR or PR = 36.8%
VLA-007 (CALM study): Best Percentage changes in Target lesions
VLA-007 (CALM study): Best Percentage change in non-injected lung and liver lesions
-100-80-60-40-20
020406080
100B
est p
erce
ntag
e ch
ange
in in
divi
dual
ta
rget
lung
and
live
r le
sion
s co
mpa
red
to b
asel
ine
SD or PR= 62.5%
PR= 37.5%
Liver lesionsLung lesions
CALM extension cohort
VLA-007 (CALM study): Duration of Response
0 25 50 75 100
125
150
175
200
225
250
275
300
325
350
03-00604-00403-01208-00203-00103-03603-03903-00312-00212-00402-00103-02503-01504-01207-00103-020
Time, days
Indi
vidu
al p
atie
nts
trea
ted
with
CVA
21
X
X
response ongoing
Target lesion excised
Disease progression
Death
No injectable diseasenew therapy
IIICIVM1a
IVM1bIVM1c
+ Serum prior to CAVATAK injection from patients with CR, PR or SD * Preliminary on-going analysis
IL-1β IL-5IL-4
IL-6 IL-7 IL-8
IL-12 IL-17 IFN-γ
VLA-007 (CALM study): Patient Serum Cytokine levels. Anti-viral / anti-tumor immune response ?
CALM Phase II: Extension Cohort
YES
6 Weeks later, confirm Disease progression
Day 169 (w24) irPFS Primary endpoint (≥ 22.5%)
(irCR, irPR, irSD)
57 Stage IIIC and IV melanoma patients at least 1 injectable lesion
10 series of multi-intratumoral CVA21 injections (up to 3x108 TCID50)
Day 1,3,5,8,22,43,64,85,106,127
YES
Eligible for Extension study 9 cycles of multi-intratumoral
CVA21 injections (up to 3x108 TCID50) q21 days
NO
NO
Observation only
13 Stage IIIC and IV melanoma
patients at least 1
injectable lesion • Mandatory
biopsy • Multi-spectral
analysis • NanoString
Immune panel
Pt#03&043#Day$0$(pre*treatment)$
• Male: Stage IIIC with melanoma to the feet • Prior treatment with surgery
Injected N
on-injected
Day$0$
Day$8$(post*treatment)$
Day$8$
Pt#03&043#Multi-spectral analysis NanoString analysis: Immune
profiling panel
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
0
750
1500
2250
3000
Num
ber
of p
ositi
ve c
ells
/ m
m2
Pre-treatment (Day 0)
Post-treatment (Day 8)
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
0
50
100
150
200
250
Num
ber
of p
ositi
ve c
ells
/ m
m2
Pre-treatment (Day 0)
Post-treatment (Day 8)
Injected
Non-injected
Pt#03&044#Day$0$(pre*treatment)$
• Female: Stage IIIC with melanoma to back • Prior treatment with ipilimumab and talimogene laherparepvec
Injected N
on-injected
Day$0$
Day$8$(post*treatment)$
Day$8$
Pt#03&044#Multi-spectral analysis NanoString analysis: Immune
profiling panel
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
0
3000
6000
9000
12000
Num
ber
of p
ositi
ve c
ells
/ m
m2
Pre-treatment (Day 0)
Post-treatment (Day 8)
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
0
1500
3000
4500
Num
ber
of p
ositi
ve c
ells
/ m
m2
Pre-treatment (Day 0)
Post-treatment (Day 8)
12000
Injected
Non-injected
Pt#12&010# Day$0$(pre*treatment)$
• Male: Stage IV M1a with melanoma to neck • Prior treatment with ipilimumab and talimogene laherparepvec
Day$8$(post*treatment)$
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
0
2000
4000
6000
8000
Num
ber
of p
ositi
ve c
ells
/ m
m2
Pre-treatment (Day 0)
Post-treatment (Day 8)
When treatment with immune checkpoint inhibitors fail
• Reconstitution of the tumour micro-environment with immune cell infiltrates
• Female: Stage IIIC with melanoma to legs • Prior treatment with ipilimumab and pembrolizumab
Pt#04&015# Day$0$(pre*treatment)$ Day$8$(post*treatment)$
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
0
3000
6000
9000
12000
Num
ber
of p
ositi
ve c
ells
/ m
m2
Pre-treatment (Day 0)
Post-treatment (Day 8)
Pt#04&014# Day$0$(pre*treatment)$
• Male: Stage IV M1c with melanoma to the leg and lungs • Prior treatment with ipilimumab • and pembrolizumab
Day$8$(post*treatment)$
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
CD4CD8
FoxP3
CD163 (
PD-L1 n
eg.)
PD-L1
0
1500
3000
4500
6000N
umbe
r of
pos
itive
cel
ls /
mm
2
Pre-treatment (Day 0)
Post-treatment (Day 8)
• The CALM study achieved its primary endpoint with 22/57 pts (38.6%) irPFS at 6 months
• Multi-dose intralesional therapy with CVA21 was generally well tolerated (No Grade 3 or 4 treatment related AEs
• Responses were observed in injected lesions, non-injected non-visceral lesions and in distant non-injected visceral lesions
• CVA21 treatment induced notable changes within the tumor microenvironment by inducing increases in immune cell infiltrates and expression of PD-L1
• CVA21 treatment induces a Th1-gene shift, with increases in interferon-induced genes
CALM Phase II trial: Conclusions
Future Directions
• CVA21 treatment may be used to in combination with immune checkpoint blockade
• CVA21 treatment may be used in a rescue strategy to reconstitute the immune cells within the tumor microenvironment of lesions resistant to immune checkpoint blockade
Randomized Phase 2 melanoma trial:
Commencing Q4 2014 / Q1 2015 (US)
Question and Answer Session
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CAVATAK Clinical Trial Program
Intratumoural* Intravenous* Intravesicular*
Phase*2:*CALM*study*Advanced(melanoma(
N=57(
Phase*2:*CALM*extension*cohort*Advanced(melanoma(
N=12(
Phase*1/2:*STORM*study*
Advanced(melanoma,(NSCLC,(Bladder(and(Prostate(cancer(
N=30(
Phase*1:*CANON*study*Non=muscle(invasive(
bladder(cancer(N=30(–(40((
CAVATAKTM*
CombinaEon*Studies*• MITCI*–*iniEated*Yervoy™*Phase*1b*
study**• Further'studies'in'late'planning'stage''
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Solid Platform for Realizing CAVATAK Potential
• Lead product CAVATAK™ - potential in a range of cancer types
• Collaborating with leading oncologists in US and Europe
• Well funded following transformational $27M capital raise
• Impressive activity in CALM Study
• Encouraging initial results in STORM Phase 1/2 trial in patients with solid tumour cancers
• Promising results in preclinical studies with blockbuster new agents
• Pharma company strong interest in combination strategies
• Initiated MITCI Phase 1b Yervoy combination trial
• Initiated CANON Phase 1 bladder cancer trial
• Data from multiple clinical trials to drive partnering discussions and shareholder value
• Recent high value transactions in cancer immunotherapy
Success in Phase 2 CALM melanoma trial
! Primary endpoint achieved September 2013
! Significantly exceeded key endpoints
! Activity in metastatic (secondary) tumours
! Well tolerated with no drug-related serious adverse events
! Potential application as monotherapy or in combination with blockbuster new agents
Corporate strategy to build value through to licensing or partnering transaction
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Thank You
Dr Malcolm McColl Managing Director
Email: [email protected] Web: www.viralytics.com Follow us on:
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