Phase 3 data from the OPTiM study in melanoma with talimogene laherparepvec presented as part of a talk on oncolytic immunotherapy at The Eighth International Conference on Oncolytic Virus Therapeutics, Oxford, UK,9-13 April 2014.

1. ASCO:
OPTiM: A Randomized Phase 3 Trial Of Talimogene Laherparepvec (T-VEC) vs
Subcutaneous Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) For The
Treatment Of Unresected Stage IIIB/C And IV Melanoma
Robert H.I. Andtbacka,1 Frances Collichio,2 Thomas Amatruda,3 Neil Senzer,4 Jason Chesney,5 Keith A. Delman,6 Lynn
E. Spitler,7 Igor Puzanov,8 Susan Doleman,9 Yining Ye,10 Ari VanderWalde,10 Robert Coffin,9 Howard L. Kaufman11
1Huntsman Cancer Institute University of Utah, Salt Lake City, UT; 2University of North Carolina Medical Center, Chapel Hill, NC; 3Hubert
Humphrey Cancer Center, Robbinsdale, MN; 4Mary Crowley Cancer Research Center, Dallas, TX; 5University of Louisville, Louisville KY; 6Emory
University, Atlanta, GA; 7Northern California Melanoma Center, San Francisco, CA; 8Vanderbilt University, Nashville, TN; 9Amgen, Woburn,
MA;10Amgen Inc., Thousand Oaks, CA; 11Rush University Medical Center, Chicago, IL
Summary of data presented at ASCO & SMR 2013
SMR:
Interim Overall Survival (OS) subset analyses in OPTiM, a randomized phase 3 trial of
intralesional talimogene laherparepvec (T-VEC) vs subcutaneous (SC) granulocyte
macrophage-colony stimulating factor GM-CSF in Stage IIIB-IV melanoma
1Rush University Medical Center, Chicago, IL; 2University of Utah Huntsman Cancer Institute, Salt Lake City, UT; 3University of North Carolina Medical
Center, Chapel Hill, NC; 4Minnesota Oncology, Fridley, Minnesota; 5Mary Crowley Cancer Research Center, Dallas, TX; 6University of Louisville, Louisville,
KY; 7Emory University, Atlanta, GA; 8Northern California Melanoma Center, San Francisco, CA; 9Vanderbilt University, Nashville, TN; 10The Institute of
Cancer Research: Royal Cancer Hospital, London, UK; 11Amgen Inc., Thousand Oaks, CA; 12Amgen, Woburn, MA
Howard L. Kaufman,1 Robert H.I. Andtbacka,2 Frances Collichio,3 Thomas Amatruda,4 Neil Senzer,5 Jason Chesney,6 Keith A.
Delman,7 Lynn E. Spitler,8 Igor Puzanov,9 Kevin Harrington,10 Yining Ye,11 Ari VanderWalde,11 Robert Coffin12
ASCO & SMR 2013 data summary

2. 2
Patients were to remain on treatment beyond progression unless clinically
significant (ie, associated with reduced performance status) after 24 weeks.
Progression allowed before response.
OPTiM Phase III Study Design
Injectable, Unresectable
Stage IIIB-IV Melanoma
Talimogene
laherparepvec
Intralesional
up to 4 mL Q2W*
GM-CSF
Subcutaneous
14 days of every
28 day cycle*
2 : 1
N = 430
(planned)
Primary Endpoint:
Durable Response
Rate
(CR or PR initiating
within 12 months
and then lasting at
least
6 months)
* Dosing of intralesional talimogene laherparepvec was ≤ 4 mL x106 pfu/mL once, then after 3 weeks, ≤ 4 mL x108
pfu/mL Q2W.
Dosing of GM-CSF was 125 μg/m2 subcutaneous daily x14 days of every 28 day cycle.
Randomization Stratification:
1. Disease stage: IIIb/c, M1a, b, c
2. Prior systemic treatment: yes/no
3. Site of disease at first recurrence: local/distant
4. Presence of liver metastases: yes/no
ASCO & SMR 2013 data summary

3. 3
Baseline Demographics and Characteristics
*May exclude some patients for whom baseline data were missing
GM-CSF
(N = 141)
Talimogene
laherparepvec
(N = 295)
Total
(N = 436)
Disease substage IIIB
IIIC
IV M1a
IV M1b
IV M1c
9 %
22%
30%
18%
21%
8%
22%
25%
22%
23%
8%
22%
27%
21%
22%
Line of therapy 1st line
≥ 2nd line
46%
54%
47%
53%
47%
53%
Sex
Men
Women
55%
45%
59%
41%
57%
43%
Age
< 65 years
≥ 65 years
51%
49%
52%
48%
51%
49%
ECOG PS*
0
1
69%
23%
71%
28%
70%
26%
LDH*
≤ ULN
> ULN
88%
4%
90%
5%
89%
5%
HSV serostatus*
Positive
Negative
55%
32%
59%
33%
58%
33%
ASCO & SMR 2013 data summary

4. 4
*May exclude some patients for whom baseline data were missing
GM-CSF
(N = 141)
Talimogene
laherparepvec
(N = 295)
Total
(N = 436)
Disease substage IIIB
IIIC
IV M1a
IV M1b
IV M1c
9 %
22%
30%
18%
21%
8%
22%
25%
22%
23%
8%
22%
27%
21%
22%
Line of therapy 1st line
≥ 2nd line
46%
54%
47%
53%
47%
53%
Sex
Men
Women
55%
45%
59%
41%
57%
43%
Age
< 65 years
≥ 65 years
51%
49%
52%
48%
51%
49%
ECOG PS*
0
1
69%
23%
71%
28%
70%
26%
LDH*
≤ ULN
> ULN
88%
4%
90%
5%
89%
5%
HSV serostatus*
Positive
Negative
55%
32%
59%
33%
58%
33%
55%
Baseline Demographics and Characteristics
ASCO & SMR 2013 data summary

5. 5
*May exclude some patients for whom baseline data were missing
GM-CSF
(N = 141)
Talimogene
laherparepvec
(N = 295)
Total
(N = 436)
Disease substage IIIB
IIIC
IV M1a
IV M1b
IV M1c
9 %
22%
30%
18%
21%
8%
22%
25%
22%
23%
8%
22%
27%
21%
22%
Line of therapy 1st line
≥ 2nd line
46%
54%
47%
53%
47%
53%
Sex
Men
Women
55%
45%
59%
41%
57%
43%
Age
< 65 years
≥ 65 years
51%
49%
52%
48%
51%
49%
ECOG PS*
0
1
69%
23%
71%
28%
70%
26%
LDH*
≤ ULN
> ULN
88%
4%
90%
5%
89%
5%
HSV serostatus*
Positive
Negative
55%
32%
59%
33%
58%
33%
Baseline Demographics and Characteristics
ASCO & SMR 2013 data summary

6. 6
Safety: Adverse Events (AEs)
AEs of all grades occurring in ≥ 20% of talimogene
laherparepvec treated patients
Grade 3/4 Aes occurring in ≥ 5 patients in either
arm
No treatment-related fatal AEs were observed.
Preferred Term-
% All Grade AEs
GM-CSF
(N=127)
Talimogene
laherparepvec
(N=292)
Fatigue 36.2% 50.3%
Chills 8.7% 48.6%
Pyrexia 8.7% 42.8%
Nausea 19.7% 35.6%
Influenza-like illness 15.0% 30.5%
Injection site pain 6.3% 27.7%
Vomiting 9.4% 21.2%
Preferred Term-
% All Grade AEs
GM-CSF
(N=127)
Talimogene
laherparepvec
(N=292)
Cellulitis <1% 2.1%
Fatigue <1% 1.7%
Vomiting 0 1.7%
Dehydration 0 1.7%
Deep vein thrombosis 0 1.7%
Tumor pain 0 1.7%
ASCO & SMR 2013 data summary

7. 7
Response Rate per EAC
ITT Set
GM-CSF
(N=141)
Talimogene
laherparepvec
(N= 295)
Objective Overall
Response Rate (CR+PR)
(95% CI)
5.7%
(1.9, 9.5)
26.4%
(21.4, 31.5)
CR 0.7% 10.8%
PR 5.0% 15.6%
• Relates to ALL
lesions
• Rigorous, blinded,
independent
review of scans,
photographs and
biopsy data
ASCO & SMR 2013 data summary

8. Baseline
12 months
Loco-regional responses (phase 3 melanoma)
Previously presented at IMWG, 2010

9. 8 monthsBaseline
Loco-regional responses (phase 3 melanoma)
Previously presented at IMWG, 2010

10. Baseline 3 months
Loco-regional responses (same patient)
Previously presented at IMWG, 2010

11. Baseline 1 year
Loco-regional responses (phase 3 melanoma)
Previously presented at IMWG, 2010

12. Baseline 6 months
Uninjected nodal responses (phase 3 melanoma)
Previously presented at IMWG, 2010

13. 1 month 12 months
Injection sites (same patient)
Previously presented at IMWG, 2010

14. Vitiligo in a melanoma patient (phase 3 melanoma)
Previously presented at IMWG, 2010

15. Baseline 9 months
Systemic effects (phase 3 melanoma)
Previously presented at IMWG, 2010

16. Baseline
19 months
Systemic effects (phase 2 melanoma)
Senzer et al JCO 2009

17. 17
Response Rate per EAC
ITT Set
GM-CSF
(N=141)
Talimogene
laherparepvec
(N= 295)
Objective Overall
Response Rate (CR+PR)
(95% CI)
5.7%
(1.9, 9.5)
26.4%
(21.4, 31.5)
CR 0.7% 10.8%
PR 5.0% 15.6%
• Relates to ALL
lesions
• Rigorous, blinded,
independent
review of scans,
photographs and
biopsy data
GM-CSF
(N=141)
Talimogene
laherparepvec
(N= 295)
Stage IIIb/c/IVM1a 2.3% 40.5%
Stage M1b/c 10.9% 9.2%
First line 4.6% 37.7%
Previously treated 6.6% 16.6%
ASCO & SMR 2013 data summary

18. 18
Durable Response Rate per EAC (primary endpoint)
ITT Set
GM-CSF
(N=141)
Talimogene
laherparepvec
(N= 295)
Durable Response
Rate
2.1% 16.3% P < 0.0001
ASCO & SMR 2013 data summary

19. 2%
0%
2%
4%
3%
0%
4%
3%
0%
3%
2%
0%
4%
16%
33%
16%
3%
8%
24%
10%
18%
12%
17%
16%
13%
18%
All ITT
Stage IIIB/C
Stage IVM1a
Stage IVM1b
Stage IVM1c
Line of tx – 1st line
Line of tx – ≥ 2nd line
ECOG 0
ECOG 1
Sex- Men
Sex- Women
HSV-1 Negative
HSV-1 Positive
GM-CSF T-VEC
55%
47%
*P-values < 0.05 **P-value <0.01
P-value
(descriptive)
<0.0001
**
*
**
**
**
**
**
**
DRR By Key Covariates
19 ASCO & SMR 2013 data summary

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OverallSurvival(%)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Months from randomization
0 5 10 15 20 25 30 35 40
GM-CSF
T-VEC
141
295
125
269
101
229
84
186
63
154
42
105
25
62
12
31
3
10
Log Rank: P = 0.07*
HR: 0.79 (0.61, 1.02)
45
0
0
19.0 (16.0, 24.0) months
23.3 (19.4, 29.7) months
Median (95% CI)
GM-CSF (N = 141)
T-VEC (N = 295)
*P-value is descriptive only
Risk set, n
Interim Overall Survival (ITT)
• Data represent >85% of the
required 290 events for the final
analysis of OS
• 290 events allows
demonstration of a HR of 0.67
with 90% power
Survival
(months)
T-VEC GM-CSF
Difference
%
12 73.7% 69.4% 4.3
24 49.6% 41.3% 8.3
36 40.6% 27.8% 12.8
ASCO & SMR 2013 data summary

21. Interim OS By Line & Stage
Stage IIIb/IIIc/IVM1a (N=249)
Hazard ratio = 0.56 (0.38-0.81)
Stage IIIb/c (N=131)
Stage IVM1a (N=118)
Hazard Ratio = 0.46 (0.26, 0.83)
Median (95% CI)
T-VEC NE (NE, NE) mo
GM-CSF 24.3 (18.6, NE) mo
Hazard Ratio = 0.67 (0.41, 1.10)
Median (95% CI)
T-VEC 25.8 (18.1, NE) mo
GM-CSF 19.0 (13.3, 29.6) mo
ASCO & SMR 2013 data summary

22. Stage IVM1b (N=90)
Stage IVM1c (N=96)
Hazard Ratio = 0.97 (0.57, 1.66)
Median (95% CI)
T-VEC 13.5 (11.8, 19.4) mo
GM-CSF 13.2 (6.1, 26.4) mo
Hazard Ratio = 1.14 (0.69, 1.90)
Median (95% CI)
T-VEC 12.6 (9.1, 17.3) mo
GM-CSF 16.2 (10.2, 32.1) mo
Interim OS By Line & Stage
ASCO & SMR 2013 data summary

23. Interim OS by Line & Stage
First-line (N=203)
Second-line or
Greater (N=233)
Hazard Ratio = 0.49 (0.33, 0.74)
Median (95% CI)
T-VEC NE (24.5, NE) mo
GM-CSF 16.7 (12.8, 21.1) mo
Hazard Ratio = 1.13 (0.80, 1.60)
Median (95% CI)
T-VEC 17.1 (14.3, 22.5) mo
GM-CSF 23.7 (16.2, 32.4) mo
ASCO & SMR 2013 data summary

24. 24
CONCLUSIONS
 OPTiM met it’s primary objective
 Talimogene laherparepvec had a tolerable safety profile, consistent with
Ph 2
– The only grade 3/4 AE that occurred in >2% of patients was cellulitis
(2.1%)
 Talimogene lahrparepvec significantly improved RR, CR & DRR vs GM-
CSF in patients with Stage IIIb-IV melanoma with no or limited visceral or
CNS involvement
 As in Phase 2, effects were pronounced in patients without visceral
disease and/or who had not received prior systemic therapy
 A trend toward improved OS was seen with talimogene laherparepvec at
interim analysis in the ITT population - Final OS is pending
 Consistent with RR and DRR, OS effects were also pronounced in patients
without visceral disease and/or who had not received prior systemic
therapy
 Talimogene laherparepvec provides a novel potential therapeutic
approach for patients with unresected Stage IIIb-IV melanoma, particularly
as a first line option and/or prior to the appearance of visceral disease