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.

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;94:7-10. 2. Asshoff M, et al. Blood. 2017;129:1823-1830. 3. Gupta V, et al. Haematologica. 2017;102:94-102. 4. Pardanani A, et al. Leukemia. 2013;27:1322-1327. 5. Harrison CN, et al. ASCO 2017. Abstract 7001. Slide credit: clinicaloptions.com

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 2017. Abstract 7001.

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 (0.3-33.5) 4.0 (0.2-24.9) 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 2017. Abstract 7001.

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 2017. Abstract 7001. Reproduced with permission.

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 2017. Abstract 7001. Reproduced with permission.

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 2017. Abstract 7001. Reproduced with permission.

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 2017. Abstract 7001.

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 2017. Abstract 7001.

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 2017. Abstract 7001.

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