Talimogene laherparepvec (T-VEC, OncoVEX GM-CSF) phase 3 data in melanoma presented at virotherapy symposium Oxford, April 2014

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.

Kaufman111Huntsman 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

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 : 1N = 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/no3. Site of disease at first recurrence: local/distant4. Presence of liver metastases: yes/no


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 IIIBIIICIV M1aIV M1bIV 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%

SexMenWomen

55%45%

59%41%

57%43%

Age< 65 years≥ 65 years

51%49%

52%48%

51%49%

ECOG PS*01

69%23%

71%28%

70%26%

LDH* ≤ ULN> ULN

88%4%

90%5%

89%5%

HSV serostatus* PositiveNegative

55%32%

59%33%

58%33%


4


GM-CSF(N = 141)


(N = 295)

Total(N = 436)


9 %22%30%18%21%

8%22%25%22%23%

8%22%27%21%22%


46%54%

47%53%

47%53%

SexMenWomen

55%45%

59%41%

57%43%


51%49%

52%48%

51%49%

ECOG PS*01

69%23%

71%28%

70%26%

LDH* ≤ ULN> ULN

88%4%

90%5%

89%5%


55%32%

59%33%

58%33%

55%



5


GM-CSF(N = 141)


(N = 295)

Total(N = 436)


9 %22%30%18%21%

8%22%25%22%23%

8%22%27%21%22%


46%54%

47%53%

47%53%

SexMenWomen

55%45%

59%41%

57%43%


51%49%

52%48%

51%49%

ECOG PS*01

69%23%

71%28%

70%26%

LDH* ≤ ULN> ULN

88%4%

90%5%

89%5%


55%32%

59%33%

58%33%



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)


(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)


(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%


7

Response Rate per EAC

ITT SetGM-CSF(N=141)


(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


Baseline

12 months

Loco-regional responses (phase 3 melanoma)

Previously presented at IMWG, 2010

8 monthsBaseline



Baseline 3 months

Loco-regional responses (same patient)


Baseline 1 year



Baseline 6 months

Uninjected nodal responses (phase 3 melanoma)


1 month 12 months

Injection sites (same patient)


Vitiligo in a melanoma patient (phase 3 melanoma)


Baseline 9 months

Systemic effects (phase 3 melanoma)


Baseline

19 months

Systemic effects (phase 2 melanoma)

Senzer et al JCO 2009

17

Response Rate per EAC



(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)


(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%


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Durable Response Rate per EAC (primary endpoint)



(N= 295)

Durable Response Rate 2.1% 16.3% P < 0.0001


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

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%

T-VEC GM-CSF

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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Ove

rall

Su

rviv

al (

%)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Months from randomization0 5 1

015

20

25

30

35

40

GM-CSFT-VEC

141

295 12

5

269 10

1

229 8

4

186 6

3

154 4

2

105 2

5

62 1

2

31 3

10

Log Rank: P = 0.07*

HR: 0.79 (0.61, 1.02)

45

00

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-CSFDifference

%

12 73.7% 69.4% 4.3

24 49.6% 41.3% 8.3

36 40.6% 27.8% 12.8


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


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


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


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

Health & Medicine

Talimogene laherparepvec (T-VEC, OncoVEX GM-CSF) phase 3 data in melanoma presented at virotherapy symposium Oxford, April 2014