Supplemental Materials

Long-term Efficacy and Safety of Momelotinib, a JAK1 and JAK2 Inhibitor,

for the Treatment of Myelofibrosis

Animesh Pardanani1, Jason Gotlib2, Andrew W. Roberts3, Martha Wadleigh4, Shireen

Sirhan5, Jun Kawashima6, Julie A. Maltzman6, Lixin Shao6, Vikas Gupta7, and Ayalew

Tefferi1

1Division of Hematology, Mayo Clinic, Rochester, MN, USA; 2Stanford Cancer

Institute, Stanford, CA, USA; 3Clinical Hematology & BMT, Royal Melbourne Hospital,

and University of Melbourne, Parkville, Australia; 4Dept of Medical Oncology, Dana

Farber Cancer Institute, Boston, MA, USA; 5Division of Hematology, Jewish General

Hospital, Montreal, QC, Canada; 6Gilead Sciences, Inc., Foster City, CA, USA; 7Princess Margaret Cancer Centre, Toronto, ON, Canada

Patients and Methods. Study oversight, study design and treatment, eligibility criteria, study endpoints, study assessments and statisticsSupplemental Table 1. Patient disposition in the core and extension studies

Supplemental Table 2. Baseline clinical and demographic characteristics of patients in the core and extension studiesSupplemental Table 3. Symptom response in the core study Supplemental Table 4. Dose reductionsSupplemental Table 5. Study drug-related adverse events by system organ class and preferred term in ≥5% of patients Supplemental Table 6. Neuropathy related to study drugSupplemental Table 7. Adverse events leading to study discontinuationSupplemental Table 8. Treatment-emergent adverse events leading to deathSupplemental Figure 1A, B, C. Duration of response: A) Anemia 8-weeks response; B) Anemia 12-weeks response; C) Spleen response.

Supplemental Figure 2A, B. Best percentage decrease from baseline in splenomegaly. A) Overall in both core and extension studies; B) Presented per dose cohort in both core and extension studies.Supplemental Figure 3. Summary of JAK2V617F over timeSupplemental Figure 4A, B. Kaplan-Meier curves for progression-free survival and overall survival. A) Progression-free survival; B) Overall survival.

Patients and Methods

Study oversight

The study protocol was approved by the independent ethics committee or

institutional review board at each study center prior to study initiation. The study

was conducted in accordance with the International Conference on Harmonisation

guideline for Good Clinical Practice and the principles of the Declaration of Helsinki.

All patients provided written informed consent.

Study design and treatments

The open-label, nonrandomized phase 1/2 core study (NCT00935987) was

conducted in 2 parts. Part 1 was a single-center, open-label, phase 1 dose-

escalation study that aimed to determine the MTD of momelotinib.1 Five successive

cohorts of 3 patients each at increasing oral once-daily doses of momelotinib

capsule (100, 150, 200, 300, and 400 mg) were enrolled. A Data Safety Monitoring

Board (DSMB) authorized the initiation of the next higher-dose cohort based on

safety assessments. A dose-limiting toxicity (DLT) was defined according to the

Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and the MTD

was defined as the dose level below the DLT level. Cohort expansion was authorized

by the DSMB for doses determined to be safe, tolerable, and producing therapeutic

response per International Working Group for Myelofibrosis Research and Treatment

(IWG-MRT) 2006 consensus criteria.2 The MTD determined in part 1 was 300 mg

once daily, which resulted in expansion of 300 mg once-daily dose cohorts to 20

patients, and addition of a new, 150 mg twice-daily dose cohort of 20 patients.1 The

150 mg once-daily cohort was expanded as well, due to efficacy observed with this

dose. In part 2, a multicenter, dose-confirmation phase 2 study, the 150 mg once-

daily, 300 mg once-daily, and 150 mg twice-daily cohorts were expanded further. In

the absence of toxicity, patients could continue momelotinib treatment for up to

nine 28-day cycles.

After concluding the core study, eligible patients could enroll in an open-label

extension study (ClinicalTrials.gov ID: NCT01236638) investigating the long-term

efficacy, safety, and tolerability of momelotinib. Enrolled patients continued on the

dose they received during the core study, but dose increases, reductions, or a

change to twice-daily dosing were permitted with consent from both the

investigator and the sponsor. The dose could be escalated to a maximum daily dose

of 300 mg capsule or reduced to a minimum daily dose of 100 mg.

The primary objectives for the combined core and extension studies were

long-term safety and tolerability of momelotinib and the long-term efficacy of

momelotinib as measured by complete remission (CR), partial remission (PR), and

clinical improvement rates according to IWG-MRT 2006 consensus criteria, and

progression-free survival (PFS) and overall survival (OS). Additional endpoints

included change in spleen size (examined by palpation) at each visit, and

improvement in constitutional symptoms. However, as constitutional symptoms

were not uniformly collected throughout the study, the data on constitutional

symptoms improvement have not been presented.

Eligibility criteria

Patient eligibility criteria for the core study have been previously reported.1

Briefly, eligible for enrollment were patients with PMF or post-PV/ET MF (per World

Health Organization and IWG-MRT criteria3), intermediate-2 or high-risk, or

intermediate-1 risk disease (per the International Prognostic Scoring System [IPSS])

with symptomatic hepatosplenomegaly or who were unresponsive to available

therapy.

Patients who completed nine cycles of momelotinib therapy in the core study

were eligible to enroll in the extension study if they tolerated momelotinib

treatment and achieved at least stable disease in the core study.

Study endpoints

The primary objectives for the combined core and extension studies were the

long-term safety and tolerability of momelotinib and long-term efficacy as measured

by complete remission, partial remission, and clinical improvement rates according

to IWG-MRT 2006 consensus criteria, and progression-free survival, and overall

survival.

Study Assessments

Responses were assessed by the investigator every 4 weeks in the core study

and every 3 months in the extension study, and graded per IWG-MRT 2006 criteria.2

Anemia response was defined as no red blood cell transfusions for ≥8 or ≥12 weeks

for those who were transfusion-dependent at baseline, or ≥2 g/dL increase in

hemoglobin that lasted ≥8 or ≥12 weeks for those who were not transfusion-

dependent and had hemoglobin <10 g/dL at baseline. Transfusion dependency at

baseline was defined as receiving ≥2 units of packed red blood cells within the 30

days prior to the first dose of momelotinib. For responders, the time to response

and duration of response were assessed from the date of the first dose of the drug,

not the date of the last transfusion. At each study visit, spleen and liver size was

assessed by physical examination; constitutional symptoms were assessed as well.

However, constitutional symptoms were not uniformly collected throughout the

study. Spleen response was defined as a ≥50% decrease from baseline in palpable

spleen length for baseline splenomegaly ≥10 cm that lasted ≥8 weeks, or

resolution of palpable splenomegaly for baseline splenomegaly >5 cm and <10 cm

that lasted ≥8 weeks. For responders, the time to response and duration of

response were assessed.

In both parts of the core study, patients were evaluated for safety every week

for the first cycle, every 2 weeks during cycle 2, and at the end of each subsequent

28-day cycle for up to 9 cycles of momelotinib treatment.1 Patients enrolled in the

extension study were assessed every 3 months. All patients were followed for 30

days after their last dose of momelotinib. Safety results were summarized for the

combined core and extension studies and treatment-emergent adverse events

(TEAEs) were defined as AEs that occurred on or after the start of momelotinib

treatment, up to the last study visit, or up to 30 days after study discontinuation.

TEAEs could include preexisting events that increase in severity or change in nature

during the study. Clinical and laboratory AEs were coded using the Medical

Dictionary for Regulatory Activities (MedDRA), version 17.1, and the severity of AEs

and shifts in laboratory parameters were graded by the National Cancer Institute

CTCAE version 3.0. Attribution of causality for AEs was the responsibility of the

investigator.

Statistics

The efficacy and safety data of the core and extension studies were

combined and summarized. Continuous variables were summarized using

descriptive statistics, and categorical variables were presented by frequency counts

and percentages. All results were presented based on initial momelotinib capsule

doses assigned at cycle 1 of the core study. The efficacy analysis was based on the

modified intent-to-treat (mITT) population, which consisted of all enrolled patients

who had taken at least 1 dose of study drug and had at least 1 postbaseline efficacy

evaluation of IWG-MRT 2006 consensus criteria in the core study. Median PFS and

OS, time to response, and duration of response along with their 95% confidence

intervals (CIs) were determined using the Kaplan-Meier (KM) method. The change

and percent change from baseline in spleen and liver size (by palpation) at each

visit were summarized using descriptive statistics. Disposition and safety analyses

were based on the safety population that included all patients who received at least

1 dose of momelotinib in the core study.

100 mg QD

n = 3

150 mg QD

n = 52

200 mg QD

n = 3

300 mg QD

n = 60

400 mg QD

n = 6

150 mg BID

n = 42Total

N = 166Patients who completed the core studyb, n (%) 3 (100) 40 (76.9) 2 (66.7) 47 (78.3) 4 (66.7) 28 (66.7) 124 (74.7)

Patients who discontinued the core studyc, n (%)

Disease progressionIntercurrent illnessAdverse eventInvestigator decisionConsent withdrawalOther

0000000

12 (23.1)3 (5.8)1 (1.9)5 (9.6)1 (1.9)1 (1.9)1 (1.9)

1 (33.3)00000

1 (33.3)

13 (21.7)2 (3.3)

08 (13.3)2 (1.7)1 (1.7)

0

2 (33.3)00

2 (33.3)000

14 (33.3)3 (7.1)

07 (16.7)2 (4.8)2 (4.8)

0

42 (25.3)8 (4.8)1 (0.6)

22 (13.3)5 (3.0)4 (2.4)2 (1.2)

Patients who rolled over to the extension study 3 37 2 46 4 28 120

Patients who completed the extension studyd, n (%) 0 10 (27.0) 0 13 (28.3) 1 (25.0) 6 (21.4) 30 (25.0)

Patients who discontinued the extension study

Disease progressionIntercurrent illnessAdverse eventInvestigator decisionConsent withdrawalOther

3 (100)1 (33.3)

01 (33.3)1 (33.3)

00

27 (73.0)7 (18.9)2 (5.4)

7 (18.9)3 (8.1)

5 (13.5)3 (8.1)

2 (100)000

2 (100)00

33 (71.7)7 (15.2)

010 (21.7)7 (15.2)5 (10.9)4 (8.7)

3 (75.0)1 (25.0)

02 (50.0)

000

22 (78.6)9 (32.1)

03 (10.7)6 (21.4)3 (10.7)1 (3.6)

90 (75.0)25 (20.8)

2 (1.7)23 (19.2)19 (15.8)13 (10.8)

8 (6.7)Supplemental Table 2. Patient disposition in the core and extension studiesa

aAll doses of momelotinib represent initial dose cohorts in the core study. bCompleters are those who completed either cycle 9 day 29 in the core study or rolled over to the extension study.cPatients can have only one reason for early discontinuation.

dCompleters are those who rolled over to the open-label long-term study (NCT02124746). BID, twice daily; QD, once daily.

Supplemental Table 2. Baseline clinical and demographic characteristics of patients in the core and extension studiesa

Characteristic100 mg QD

n = 3150 mg QD

n = 52200 mg QD

n = 3300 mg QD

n = 60400 mg QD

n = 6150 mg BID

n = 42Total

N = 166Age (years)

Mean (SD)MedianMin-max

72.0 (7.94)75.0

63.0–78.0

66.4 (9.20)66.5

34.0–85.0

68.0 (7.81)64.0

63.0–77.0

67.2 (7.49)68.0

46.0–83.0

60.8 (7.57)62.5

51.0–70.0

66.4 (10.14)67.0

47.0–89.0

66.6 (8.77)67.0

34.0–89.0

Sex, n (%)MaleFemale

1 (33.3)2 (66.7)

30 (57.7)22 (42.3)

3 (100.0)0

34 (56.7)26 (43.3)

3 (50.0)3 (50.0)

26 (61.9)16 (38.1)

97 (58.4)69 (41.6)

Diagnosis, n (%)PMFPost-PV MFPost-ET MF

1 (33.3)2 (66.7)

0

38 (73.1)9 (17.3)5 (9.6)

2 (66.7)1 (33.3)

0

38 (63.3)12 (20.0)10 (16.7)

5 (83.3)1 (16.7)

0

21 (50.0)12 (28.6)9 (21.4)

105 (63.3)37 (22.3)24 (14.5)

JAK2V617F status, n (%)PositiveNegativeInconclusiveMissing

2 (66.7)00

1 (33.3)

38 (73.1)10 (19.2)

04 (7.7)

2 (66.7)00

1 (33.3)

37 (61.7)19 (31.7)1 (1.7)3 (5.0)

5 (83.3)1 (16.7)

00

32 (76.2)4 (9.5)

06 (14.3)

116 (69.9)34 (20.5)1 (0.6)

15 (9.0)

Baseline ECOG statusb, n (%)0123

1 (33.3)1 (33.3)1 (33.3)

0

9 (17.3)33 (63.5)7 (13.5)1 (1.9)

1 (33.3)1 (33.3)1 (33.3)

0

11 (18.3)44 (73.3)5 (8.3)

0

05 (83.3)1 (16.7)

0

6 (14.3)29 (69.0)6 (14.3)

0

28 (16.9)113 (68.1)21 (12.7)1 (0.6)

Prior treatment, n (%)JAK2 inhibitorc

IMiDsd0

1 (33.3)5 (9.6)4 (7.7)

2 (66.7)0

8 (13.3)6 (10.0)

1 (16.7)1 (16.7)

7 (16.7)3 (7.1)

23 (13.9)15 (9.0)

Patients RBC transfusion-dependent, n (%) 1 (33.3) 24 (46.2) 0 31 (51.7) 2 (33.3) 15 (35.7) 73 (44.0)

Spleen size (cm) for

spleen-evaluable patientsnMean (SD)MedianMin–max

318.3 (10.41)

15.010.0–30.0

4718.5 (6.59)

17.08.0–34.0

323.0 (6.08)

26.016.0–27.0

5118.3 (6.38)

18.06.0–30.5

422.3 (8.34)

23.512.0–30.0

3717.3 (5.91)

18.06.0–30.0

14518.3 (6.43)

18.06.0–34.0

Hemoglobin (g/dL)Mean (SD)MedianMin–max

9.5 (2.05)8.4

8.3–11.9

9.9 (1.88)9.5

6.8–15.1

11.2 (0.85)11.1

10.4–12.1

9.7 (1.66)9.4

6.7–14.4

9.6 (0.96)9.6

8.5–10.9

9.7 (1.93)9.2

5.9–14.8

9.8 (1.77)9.4

5.9–15.1

Platelet count (x 109/L)Mean (SD)MedianMin–max

178.7 (112.63)

185.063.0–288.0

253.0 (222.91)

174.043.0–1284.0

263.3 (163.86)

334.076.0–380.0

226.8 (187.23)

165.535.0–745.0

165.7 (61.02)160.5

70.0–237.0

267.6 (190.89)

207.549.0–878.0

242.9 (195.25)

182.035.0–1284.0

ANC (x 109/L)nMean (SD)MedianMin–max

316.8 (23.79)

4.61.5–44.2

5111.8 (13.35)

7.90.8–64.2

348.3 (26.55)

60.217.9–66.9

5915.4 (24.47)

7.10.9–129.7

617.5 (23.49)

4.71.1–57.0

4216.4 (15.03)

11.70.9–53.9

16415.2 (19.53)

8.10.8–129.7

aAll doses of momelotinib represent initial dose cohorts in the core study.b2 patients were not assessed in the 150 mg QD group and 1 patient was not assessed in the 150 mg BID group. cJAK2 inhibitors: ruxolitinib (INCB018424), fedratinib (TG101348), pacritinib (SB1518) or unspecified.dIMiDs: lenalidomide, pomalidomide (CC-4047), thalidomide.ANC, absolute neutrophil count; BID, twice daily; BMI, body mass index; DIPSS, Dynamic International Prognostic Scoring System; IMiDs, immunomodulatory drugs; Max, maximum; Min, minimum; PMF, primary myelofibrosis; Post-ET MF, post-essential thrombocythemia myelofibrosis; Post-PV MF, post-polycythemia vera myelofibrosis; QD, once daily; RBC, red blood cells; SD, standard deviation.

Supplemental Table 3. Symptom response in the core study

Constitutional symptom improvement at C6D29*Site 101, n (%) Sites 102-106, n (%)

Fatigue N = 45Complete 2 (4.4)Marked 16 (35.6)None/minimal 27 (60.0)

Pruritis N = 59 N = 45Complete 55 (93.2) 26 (57.8)Marked 2 (3.4) 6 (13.3)None/minimal 2 (3.4) 13 (28.9)

Cough N = 59 N = 45Complete 55 (93.2) 23 (51.1)Marked 2 (3.4) 3 (6.7)None/minimal 2 (3.4) 19 (42.2)

Abdominal discomfort N = 45Complete 19 (42.2)Marked 8 (17.8)None/minimal 18 (40.0)

Peripheral edema N = 24Complete 16 (66.7)Marked 0None/minimal 6 (25.0), 2 not done

Bone pain N = 59 N = 45Complete 51 (86.4) 22 (48.9)Marked 5 (8.5) 6 (13.3)None/minimal 3 (5.1) 17 (37.8)

Fever N = 59 N = 43Complete 59 (100.0) 41 (95.3)Marked 0 0 None/minimal 0 2 (4.7)

Appetite N = 59 N = 44Complete 56 (94.9) 8 (18.2)Marked 0 1 (2.3)None/minimal 3 (5.1) 35 (79.5)

Night sweats N = 59 N = 45Complete 55 (93.2) 26 (57.8)Marked 3 (5.1) 9 (20.0)None/minimal 1 (1.7) 10 (22.2)

Overall QoL N = 45Complete 1 (2.2)Marked 5 (11.1)None/minimal 38 (84.4), 1 not done

Other N = 23Complete 10 (43.5)Marked 7 (30.4)None/minimal 5 (21.7), 1 not done

Percent change from baseline to C6D29 N = 39 N = 43

Median (min, max) -100.0 (-100.0, 0.0) -34.0 (-87.5, 400.0)

*C =cycle 28 days, D = days. C6D29 = 197 days

100 mg QD

n = 3

150 mg QD

n = 52

200 mg QD

n = 3

300 mg QD

n = 60

400 mg QD

n = 6

150 mg BID

n = 42Total

N = 166Patients with decreased doseb, n (%) 3 (100.0) 22 (42.3) 3 (100.0) 41 (68.3) 6 (100.0) 21 (50.0) 96 (57.8)

Reasons for decrease in dose:Adverse eventDisease progressionInvestigator decisionInvestigator discretionLack of responsePatient decisionPatient errorPatient nonadherencePer protocol

3 (100.0)0

1 (33.3)0

1 (33.3)1 (33.3)

000

17 (32.7)1 (1.9)

7 (13.5)0

1 (1.9)0

1 (1.9)00

3 (100.0)00000

1 (33.3)00

34 (56.7)0

4 (6.7)5 (8.3)1 (1.7)

000

2 (3.3)

5 (83.3)0

2 (33.3)00000

2 (33.3)

18 (42.9)1 (2.4)4 (9.5)1 (2.4)

01 (2.4)

01 (2.4)

0

80 (48.2)2 (1.2)

18 (10.8)6 (3.6)3 (1.8)2 (1.2)2 (1.2)1 (0.6)4 (2.4)

Supplemental Table 4. Dose reductionsa

aAll doses of momelotinib represent initial dose cohorts in the core study.bPatients could have more than 1 reason for a dose reduction.BID, twice daily; QD, once daily.

Supplemental Table 5. Study drug-related adverse events in ≥5% of patients

aThis group

Adverse eventSystem organ class

Preferred term

150 mg QDn = 52

300 mg QDn = 60

150 mg BIDn = 42

Totala

N = 166Grade 1 or 2

Grade 3 or 4

Grade 1 or 2

Grade 3 or 4

Grade 1 or 2

Grade 3 or 4

Grade 1 or 2

Grade 3 or 4

All Grades

Blood and Lymphatic System DisordersThrombocytopenia 14

(26.9)11

(21.2)11

(18.3) 19 (31.7) 5 (11.9) 9 (21.4)31

(18.7)46

(27.7)77 (46.4)

Anemia 2 (3.8) 1 (1.9) 4 (6.7) 3 (5.0) 1 (2.4) 3 (7.1) 8 (4.8) 8 (4.8) 16 (9.6)Neutropenia 0 3 (5.8) 2 (3.3) 4 (6.7) 1 (2.4) 1 (2.4) 3 (1.8) 9 (5.4) 12 (7.2)Leukopenia 0 3 (5.8) 5 (8.3) 1 (1.7) 0 0 5 (3.0) 5 (3.0) 10 (6.0)

Gastrointestinal DisordersDiarrhea

8 (15.4) 021

(35.0) 012

(28.6) 044

(26.5) 044 (26.5)

Nausea 11 (21.2) 0

12 (20.0) 0

10 (23.8) 0

38 (22.9) 0

38 (22.9)

Vomiting 4 (7.7) 0 6 (10.0) 0 4 (9.5) 0 14 (8.4) 0 14 (8.4)Nervous System Disorders

Peripheral neuropathy

10 (19.2) 0

15 (25.0) 0

16 (38.1) 0

44 (26.5) 0

44 (26.5)

Peripheral sensory neuropathy 9 (17.3) 0

18 (30.0) 0

11 (26.2) 0

41 (24.7) 0 41 (24.7)

Dizziness 15 (28.8) 0

14 (23.3) 0 9 (21.4) 0

41 (24.7) 0

41 (24.7)

Headache 10 (19.2) 0

11 (18.3) 1 (1.7) 5 (11.9) 0

26 (15.7) 2 (1.2)

28 (16.9)

InvestigationsIncreased ALT

6 (11.5) 1 (1.9) 9 (15.0) 3 (5.0) 8 (19.0) 024

(14.5) 4 (2.4)28 (16.9)

Increased AST4 (7.7) 1 (1.9) 9 (15.0) 1 (1.7) 6 (14.3) 0

20 (12.0) 2 (1.2)

22 (13.3)

Increased lipase 3 (5.7) 2 (3.8) 7 (11.7) 4 (6.7) 4 (9.5) 0 14 (8.4) 7 (4.2) 21 (12.7)Increased amylase

5 (9.6) 0 9 (15.0) 0 3 (7.1) 017

(10.2) 017 (10.2)

Prolonged APTT 6 (11.5) 0 6 (10.0) 0 2 (4.8) 0 16 (9.6) 0 16 (9.6)Increased blood creatinine 5 (9.6) 0 2 (3.3) 0 4 (9.5) 1 (2.4) 14 (8.4) 1 (0.6) 15 (9.0)Increased blood ALP 3 (5.8) 1 (1.9) 5 (8.3) 1 (1.7) 2 (4.8) 0 11 (6.6) 2 (1.2) 13 (7.8)Increased blood bilirubin 3 (5.8) 0 4 (6.7) 0 1 (2.4) 0 9 (5.4) 0

9 (5.4)

General Disorders and Administration Site ConditionsFatigue 5 (9.6) 0 6 (10.0) 2 (3.3) 3 (7.1) 0 14 (8.4) 2 (1.2) 16 (9.6)

Vascular disordersFlushing 5 (9.6) 0 7 (11.7) 0 1 (2.4) 0 13 (7.8) 0 13 (7.8)Hypotension 4 (7.7) 0 3 (5.0) 0 3 (7.1) 1 (2.4) 10 (6.0) 1 (0.6) 11 (6.6)

Skin and Subcutaneous Tissue Disorders

includes all initial dose cohorts from the core study, including patients treated with momelotinib 100 mg QD (N = 3), 200 mg QD (N = 3), and 400 mg QD (N = 6). ALP, alkaline phosphatase; ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; BID, twice daily; QD, once daily.

Supplemental Table 6. Neuropathy related to study druga

Presented as n (%). aAll doses of momelotinib represent initial dose cohorts in the core study.

bPatients can have multiple AEs of the same type under preferred term, but the AE is only counted once under high-level term.cNo grade 3, 4 or 5 peripheral neuropathy or peripheral sensory neuropathy was reported.AE, adverse event; BID, twice daily; NEC, not elsewhere classified; QD, once daily.

Preferred term100 mg QD

n = 3150 mg QD

n = 52200 mg QD

n = 3300 mg QD

n = 60400 mg QD

n = 6150 mg BID

n = 42Totala

N = 166

Peripheral neuropathyc 0 10 (19.2) 0 15 (25.0) 3 (50.0) 16 (38.1) 44 (26.5)Grade 1 0 8 (15.4) 0 15 (25.0) 3 (50.0) 12 (28.6) 38 (22.9)Grade 2 0 2 (3.8) 0 0 0 4 (9.5) 6 (3.6)

Peripheral sensory neuropathyc 1 (33.3) 9 (17.3) 2 (66.7) 18 (30.0) 0 11 (26.2) 41 (24.7)Grade 1 1 (33.3) 9 (17.3) 2 (66.7) 15 (25.0) 0 8 (19.0) 35 (21.1)Grade 2 0 0 0 3 (5.0) 0 3 (7.1) 6 (3.6)

Supplemental Table 7. Summary of adverse events leading to study discontinuation for at least 2 patients

All values are n (%) unless otherwise indicated.

Type of event100 mg

QD(n =3)

150 mg QD

(n = 52)

200 mg QD

(n = 3)

300 mg QD

(n = 60)

400 mg QD

(n = 6)

150 mg BID

(n = 42)Total

(n = 166)Thrombocytopenia 0 0 0 3 (5.0) 0 2 (4.8) 5 (3.0)Peripheral sensory neuropathy 0 2 (3.8) 0 1 (1.7) 0 1 (2.4) 4 (2.4)Disease progression 0 1 (1.9) 0 1 (1.7) 0 0 2 (1.2)Sepsis 0 0 0 1 (1.7) 1 (16.7) 0 2 (1.2)Subdural hematoma 1 (33.3) 0 0 0 0 1 (2.4) 2 (1.2)Peripheral neuropathy 0 1 (1.9) 0 0 0 1 (2.4) 2 (1.2)

Supplemental Table 8. Treatment-emergent adverse events leading to deatha

100 mg QD

n = 3

150 mg QD

n = 52

200 mg QD

n = 3

300 mg QD

n = 60

400 mg QD

n = 6

150 mg BID

n = 42

TotalN = 166

Patients with ≥1 TEAE leading to death, n (%) 1 (33.3) 10 (19.2) 1 (33.3) 11 (18.3) 3 (50.0) 6 (14.3) 32 (19.3)

Disease progression 3 (5.8) 3 (5.0) 1 (2.4) 7 (4.2)Death (sudden) 1 (33.3) 2 (3.3) 3 (1.8)Respiratory failure 1 (1.9) 1 (1.7)b 1 (16.7) 3 (1.8)Sepsis 1 (1.7) 1 (16.7) 2 (1.2)Subdural hematoma 1 (33.3) 1 (2.4) 2 (1.2)Acute myeloid leukemia 1 (1.9) 1 (0.6)Acute renal failure 1 (1.9) 1 (0.6)CNS hemorrhage 1 (2.4) 1 (0.6)Endocarditis 1 (1.7) 1 (0.6)Fall 1 (1.7) 1 (0.6)GI hemorrhage 1 (1.9) 1 (0.6)Infectious colitis 1 (1.9) 1 (0.6)Infection 1 (1.7) 1 (0.6)Interstitial lung disease 1 (1.9) 1 (0.6)Intracranial hemorrhage 1 (1.7) 1 (0.6)Localized infection 1 (2.4) 1 (0.6)Myelofibrosis 1 (2.4) 1 (0.6)Pneumonitis 1 (1.9) 1 (0.6)Pulmonary mass 1 (2.4) 1 (0.6)Restrictive cardiomyopathy 1 (16.7) 1 (0.6)

Adverse events were coded using MedDRA version 17.1 preferred term. If a patient experienced ≥1 episode of an adverse event, that patient was counted once within a preferred term, high-level term, and system organ class.aAll doses of momelotinib represent initial dose cohorts in the core study. Deaths are reported within 30 days of completing studybIn the source document, this event was previously listed as “uncoded” due to misspelling of the verbatim term. BID, twice daily; CNS, Central Nervous System; GI, gastrointestinal; QD, once daily; TEAE, treatment-emergent adverse event.

Supplemental Figure 1A, B, C. Duration of response. A) Anemia 8-weeks response; B) Anemia 12-weeks response; C) Spleen response

A.

65 (0)

45 (18)

31 (29)

26 (33)

23 (35)

18 (38)

16 (38)

14 (39)

11 (40)

10 (41)

9 (42)

6 (43)

4 (44)

2 (44)

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 450

20

40

60

80

100

Time (Months)

% R

espo

nder

s

8-Week Anemia Response

Number at Risk (Events)

B.

60 (0)

53 (6)

34 (21)

28 (26)

24 (29)

20 (31)

18 (31)

16 (32)

12 (33)

9 (36)

8 (37)

5 (38)

4 (39)

2 (39)

Number at Risk (Events)

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 450

20

40

60

80

100

Time (Months)

% R

espo

nder

s

12-Week Anemia Response

C.

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 540

20

40

60

80

100

Time (Months)

% R

espo

nder

sSpleen Response

59 (0)

54 (3)

42 (8)

38 (10)

30 (12)

29 (12)

28 (13)

24 (14)

22 (15)

18 (16)

14 (16)

12 (16)

9 (16)

5 (16)

3(16)

1(16)

Number at Risk (Events)

Supplemental Figure 2 A, B. Best percentage decrease from baseline in splenomegaly. A) Overall in both core and extension studies; B) Presented per dose cohort in both core and extension studies

A.

-100

-80

-60

-40

-20

0

20

40

60

80

100

Bes

t % C

hang

e in

SPD

Momelotinib Core + Extension

B.

-100

-80

-60

-40

-20

0

20

40

60

80

100

Bes

t % C

hang

e in

SPD

100 mg QD

200 mg QD300 mg QD150 mg BID400 mg QD

150 mg QD

Supplemental Figure 4. Summary of JAK2V617F over time. N is the number of patients

included in each analysis. Zero denotes baseline.

Supplemental Figure 4 A, B. Kaplan-Meier curves for progression-free survival and overall survival. A) Progression-free survival; B) Overall survival

A.

B.

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 540

20

40

60

80

100

Time (Months)

% P

rogr

essi

on-F

ree

Progression-Free Survival

165 (0)

156 (6)

134 (15)

115 (22)

101 (26)

89 (30)

81 (34)

75 (37)

65 (39)

59 (40)

50 (45)

37 (50)

29 (50)

15 (52)

5 (53)

1 (53)

Number at Risk (Events)

165 (0)

157 (5)

134 (12)

115 (16)

102 (19)

89 (19)

81 (21)

75 (23)

65 (25)

59 (26)

51 (28)

37 (30)

29 (30)

15 (31)

5 (32)

1 (32)

Number at Risk (Events)

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 540

20

40

60

80

100

Time (Months)

% S

urvi

ving

Overall Survival