1. SIMPLIFY-2: Momelotinib vs Best Available Therapy in Ruxolitinib-Experienced Pts With Myelofibrosis
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. SIMPLIFY-2: Background
JAK2 V617F mutation found in > 50% of pts with myelofibrosis[1]
Momelotinib: small molecule JAK1/2 inhibitor
Improved anemia in rodent model via inhibition of ACVR1[2]
Exhibited durable spleen and anemia responses, symptom improvement in phase I/II studies of MF[3,4]
Current phase III analysis evaluated safety, efficacy of momelotinib vs BAT in pts with MF who previously received ruxolitinib and either required RBC transfusion or dose adjusted for grade ≥ 3 hematologic toxicity[5]
BAT, best available therapy; MF, myelofibrosis; RBC, red blood cell.
1. Passamonti F, et al. Haematologica. 2009;94: Asshoff M, et al. Blood. 2017;129: Gupta V, et al. Haematologica. 2017;102: Pardanani A, et al. Leukemia. 2013;27: Harrison CN, et al. ASCO Abstract 7001.
Slide credit: clinicaloptions.com

3. SIMPLIFY-2: Study Design
Multicenter, randomized, open-label phase III study
Primary endpoint: splenic response rate at Wk 24
Secondary endpoints: TSS response rate, RBC transfusion rate, RBC transfusion (in)dependence rates, all at Wk 24
Stratified by RBC transfusion dependence (yes vs no) and TSS (< vs ≥ 18); randomized 2:1
Wk 24
Momelotinib 200 mg QD
(n = 104)
Momelotinib extension phase allowed for up to an additional 168 wks
Pts with MF,* palpable splenomegaly ≥ 5 cm, high/int-2/symptomatic int-1 DIPSS risk, and ruxolitinib for ≥ 28 days with RBC transfusion requirement or dose adjustment for grade ≥ 3 hematologic toxicity
(N = 156)
Best Available Therapy†
(n = 52)
*Primary, post-PV, or post-ET.
†Includes ruxolitinib or no MF therapy.
DIPSS, Dynamic International Prognostic Scoring System; ET, essential thrombocythemia; int, intermediate; MF, myelofibrosis; PV, polycythemia vera; RBC, red blood cell; TSS, total symptom score.
Slide credit: clinicaloptions.com
Harrison CN, et al. ASCO Abstract 7001.

4. SIMPLIFY-2: Baseline Characteristics
Momelotinib
(n = 104)
BAT
(n = 52)
Mean age, yrs (SD)
66.4 (8.1)
69.4 (7.4)
Male, n (%)
69 (66)
24 (46)
MF subtype, n (%)
Primary
Post-PV
Post-ET
64 (62)
18 (17)
22 (21)
30 (58)
12 (23)
10 (19)
Prior ruxolitinib lasting ≥ 12 wks, n (%)
75 (72)
33 (63)
Median time since MF diagnosis, yrs (range)
3.7 ( )
4.0 ( )
High/intermediate-2 DIPSS risk, n (%)
81 (78)
36 (69)
Mean TSS (SD)
18.5 (13.0)
20.5 (16.0)
Characteristic
Momelotinib
(n = 104)
BAT
(n = 52)
JAK2V617F positive, n (%)
69 (66)
37 (71)
Hemoglobin < 8 g/dL, n (%)
27 (26)
6 (12)
Transfusion independent, n (%)
32 (31)
19 (37)
Transfusion dependent, n (%)
58 (56)
27 (52)
Mean platelet count, x 103/μL (SD)
170.8 (148.0)
126.5 (95.9)
Mean ANC, x 103/μL (SD)
10.2 (13.5)
8.0 (9.9)
ANC, absolute neutrophil count; BAT, best available therapy; DIPSS, Dynamic International Prognostic Scoring System; ET, essential thrombocythemia; MF, myelofibrosis; PV, polycythemia vera; SD, standard deviation; TSS, total symptom score.
Slide credit: clinicaloptions.com
Harrison CN, et al. ASCO Abstract 7001.

5. SIMPLIFY-2: Spleen Response (Primary Endpoint)
120
MMB (n = 104)
BAT (n = 52)
88% of pts on BAT arm continued with ruxolitinib
Including 27% in combination with other agents
Only 4 pts did not receive ruxolitinib
100 80 60
No Rux (n = 4)
Change in Spleen Volume From Baseline (%) 40 20
-20
BAT, best available therapy; MMB, momelotinib; RUX, ruxolitinib; SRR, splenic response rate.
-40
35% decrease
SRR = 6.7%
SRR = 5.8%
-60
P = .899 MMB not superior to BAT
Slide credit: clinicaloptions.com
Harrison CN, et al. ASCO Abstract Reproduced with permission.

6. SIMPLIFY-2: Symptomatic Response
200
MMB (n = 103)
BAT (n = 51)
250
200
No Rux (n = 5)
150
Change in TSS From Baseline (%)
100 50
BAT, best available therapy; MMB, momelotinib; RUX, ruxolitinib; TSS, total symptom score.
-50
50% decrease
-100
TSS response rate = 26.2%
TSS response rate = 5.9%
-150
P < .001
Slide credit: clinicaloptions.com
Harrison CN, et al. ASCO Abstract Reproduced with permission.

7. SIMPLIFY-2: Hematologic Response
Transfusion Independence P = .001
Transfusion Dependence P = .101
RBC Transfusion Rate P = .388
100
100 2
MMB (n = 104)
BAT (n = 52) 80 80
1.5
63.5
1.2 60 60
55.8
1.1
1.1
51.9
Rate of Transfusion Independence (%)
Rate of Transfusion Dependence (%)
50.0
43.3
Median No. of units/month 1
36.5 40 40
30.8
0.5
21.2
0.5 20 20
Baseline
Wk 24
Baseline
Wk 24
Baseline
Wk 24
Platelets
MMB
BAT
Hemoglobin
10.5
300
BAT, best available therapy; MMB, momelotinib; RBC, red blood cell, SEM, standard error of the mean.
250 10
Mean Hemoglobin ± SEM, g/dL
Mean Platelet Count ± SEM, 103/μL
200
9.5
150 9
100
8.5 50 2 4 6 8 10 12 14 16 18 20 22 24 2 4 6 8 10 12 14 16 18 20 22 24
Wks
Wks
Slide credit: clinicaloptions.com
Harrison CN, et al. ASCO Abstract Reproduced with permission.

8. SIMPLIFY-2: Safety Event, n (%) Momelotinib (n = 104) BAT (n = 52)
Serious AE
36 (35)
12 (23)
D/c due to AE
22 (21)
1 (2)*
Reduction/interruption due to AE
17 (16)
9 (17)
Death due to any cause
8 (8)
5 (10)
Peripheral neuropathy
Resolved by Wk 24
Leading to d/c
11 (11)
4 (4)†
3 (3)
AE Occurring in ≥ 15% of Pts in Either Arm, %
Momelotinib
(n = 104)
BAT
(n = 52)
Any
Gr ≥ 3 97 57 88 38
Diarrhea 33 2 15
Asthenia 19 5 21
Nausea 10
Cough 17 12
Abdominal pain 1 6
Anemia 13
Dizziness 8
Fatigue
Headache
AE, adverse event; BAT, best available therapy; D/c, discontinuation; Gr, grade.
*Inconsistently reported.
†Additional cases resolved after Wk 24, n = 2.
Slide credit: clinicaloptions.com
Harrison CN, et al. ASCO Abstract 7001.

9. SIMPLIFY-2: Treatment-Emergent AEs
AE, n (%)
Momelotinib
(n = 104)
BAT
(n = 52)
Grade ≥ 3 treatment-emergent AEs
62 (60)
20 (38)
Serious treatment-emergent AEs
36 (35)
12 (23)
Treatment-emergent AEs leading to discontinuation
22 (21)
1(2)*
Treatment-emergent AEs leading to dose reduction or interruption
17 (16)
9 (17)
All deaths
8 (8)
5 (10)
*Inconsistently reported.
AE, adverse event; BAT, best available therapy.
Slide credit: clinicaloptions.com
Harrison CN, et al. ASCO Abstract 7001.

10. SIMPLIFY-2: Investigator Conclusions
In ruxolitinib-experienced pts with MF, splenic response rate not superior with momelotinib vs BAT, but TSS and transfusion independence rates significantly improved vs BAT at Wk 24
Majority of pts in BAT arm continued on ruxolitinib (88%); some in combination with other agents
No new safety signals observed
Peripheral neuropathy documented in 11% of pts receiving momelotinib (all low grade) vs 0% in BAT arm
Most common AEs: diarrhea, asthenia, nausea with momelotinib; asthenia, fatigue with BAT
AE, adverse event; BAT, best available therapy; MF, myelofibrosis; TSS, total symptom score.
Slide credit: clinicaloptions.com
Harrison CN, et al. ASCO Abstract 7001.

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