2. Arizona, USA ©2011 MFMER | 3133089-1 Ruben A. Mesa, MD Professor & Chairman, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer Center Mayo Clinic – Arizona, USA What should you expect of your MPN Therapy?

3. ©2011 MFMER | 3133089-2 What should you expect of your MPN Therapy? Individualizing Therapy What is the spectrum of disease burden and risk in MPNs? What are expectations of therapy? Current and evolving treatment options for MPN patients

4. Burden of ET/PV Microvascular Symptoms Microvascular Symptoms Macrovascular Risk MPN Associate d Symptom s Burden of Myelofibrosis Anemia/ Cytopenis Anemia/ Cytopenis Splenomegaly MF Associated Symptoms Et & PV Associated Symptoms

5. Evolution of MPN Symptom Assessment Tools MF–SAF 2009 (19 items) MF-SAF 2.0 (7 items 2011) JCO in Press MF–SAF 2009 (19 items) MF-SAF 2.0 (7 items 2011) JCO in Press Brief Fatigue Inventory (BFI) – 9 Items Brief Fatigue Inventory (BFI) – 9 Items Spleen Sx 4 Items Spleen Sx 4 Items Constitutional Sx 5 Items Constitutional Sx 5 Items QOL 1 Item Vascular and Ψ Sx 9 Items Vascular and Ψ Sx 9 Items MPN–SAF 2011 (27 items) Blood 2011 MPN-SAF TSS (10 items 2012) JCO 2012 MPN–SAF 2011 (27 items) Blood 2011 MPN-SAF TSS (10 items 2012) JCO 2012 MPN-SAF Languages English French German Spanish Dutch Swedish Italian Portuguese Mandarin Japanese Hebrew MPN-SAF Languages English French German Spanish Dutch Swedish Italian Portuguese Mandarin Japanese Hebrew

6. Quartile 1 (Q1): 0-24% Quartile 2 (Q2): 25-49% Quartile 3 (Q3): 50-74% Quartile 4 (Q4): 75- 100% Percentile MPN-SAF TSS Q1 TSS <8 Q2 TSS 8 -17 Q3 TSS 18 - 31 Q4 TSS >32 ParameterP value of Comparison Age0.24 Gender F>M<0.001 MPN Diagnosis<0.001 Subtype of MF0.86 IPSET (ET Risk)0.18 PV Risk (PV)0.30 DIPSS (MF Risk)<0.001 MPN Symptom Burden by Quartiles 1858 MPN-SAF Respondents

7. ET (N=775) PV (N=654) MF (N=423) Q1 – 30%Q2 – 26% Q3 – 24%Q4 – 20% Q1 – 17%Q2 – 21% Q3 – 26% Q4 – 36% Q1 – 25%Q2 – 23% Q3 – 26%Q4 – 26%

8. MPN Symptom Burden by Quartiles Comparison between MPN Diagnosis and Quartiles P<0.001

9. EORTC QLQ-C30 Scores in MF and Other Hematologic Malignancies and Solid Tumors EORTC QLQ-C30 Myelofibrosis COMFORT-I placebo arm (N=147*) Myelofibrosis (N=96) 1 CML (N=73) 2 Myeloma (N=944) 3 Breast (N=2782) 3 Lung (N=3332) 3 Recurrent/ metastatic cancers (N=4812) 3 Global Health Status/QoL52.959.970.255.761.856.656.3 Functional Subscales Physical Functioning67.274.978.067.778.471.975.8 Role Functioning63.268.878.160.170.961.560.7 Emotional Functioning75.576.578.871.368.668.968.7 Cognitive Functioning80.177.086.178.181.582.380.5 Social Functioning66.174.984.363.277.071.370.5 Symptom Scales/Single Items Fatigue54.141.029.848.733.341.141.8 Pain29.922.610.147.128.729.733.7 Dyspnea37.029.815.52618.137.923.4 Insomnia39.133.726.928.929.831.633.6 Appetite loss33.315.113.723.218.528.128.2 = Worsening Direction

10. What is quality of life Quality of Life Increasing ?

11. Definitions HRQOL in MPNs? Σ MPN related symptoms Medication related toxicities Problems from prior MPN complications Stressors from having their MPN Financial Emotional Intrapersonal Co-morbidities Hassle of medical care

12. ©2011 MFMER | 3133089-11 What should you expect of your MPN Therapy? Individualizing Therapy What is the spectrum of disease burden and risk in MPNs? What are expectations of therapy? Current and evolving treatment options for MPN patients

13. IPSET (ET – 3 groups) Survival Thrombosis Risk PV Risk (4 groups) Survival Leukemia Rates DIPSS (PMF – 4 groups) Survival Age≥ 60 (2pts) vs. < 60≥70 (3pts) 60-69 (2pts), <60 ≥65 (1pt) vs. <65 Leukocytes≥ 11 (1pt) vs. < 11 x 10 9 /L ≥15 (1 point) vs. <15 x 10 9 /L >25 (1pt) vs. ≤25 x 10 9 /L Hemoglobin<10 (2 pts) vs. ≥10g/dL Constitutional Symptoms Present # (1pt) vs. Absent Blasts≥1% (1pt) vs. <1% Prior Thrombosis Yes (1 point) vs. No Risk Group Point Cutoffs 0; 1-2; 3-4 pts.0; 1-2; 3; 4 pts.0; 1-2; 3-4; ≥4 pts. Evolving MPN Prognostic Scales Tefferi ASH 2011 Passamonti Blood 2012 Passamonti Blood 2010 # = >10% Weight Loss over prior 6 months, Night Sweats, Unexplained Fever

14. New Response Criteria for MPNs ET 2 PV 2 MF 1 Complete response  Partial response  Clinical improvement  Stable disease  No response  Relapse  Other responsesMolecular Cytogenetic and molecular 1. Tefferi A et al. Blood. 2013;122:1395-1398. 2. Barosi G et al. Blood. 2013;121:4778-4781.

15. New Response Criteria for MF: Complete Response 1 EMH: extramedullary hematopoiesis 1. Tefferi A et al. Blood. 2013;122:1395-1398. Bone marrow: Age-adjusted normocellularity; <5% blasts; ≤Grade 1 MF; and Peripheral blood: Hemoglobin ≥ 100 g/L and <UNL; Neutrophils ≥ 1 x 10 9 /L and <UNL; Platelets ≥ 100 x 10 9 /L and <UNL; <2% immature myeloid cells; and Clinical: Resolution of disease symptoms Spleen and liver not palpable No evidence of EMH Required criteria: for all response categories, benefit must last for ≥12 wks to qualify as a response

16. New Response Criteria for MF: Partial Response 1 1. Tefferi A et al. Blood. 2013;122:1395-1398. Peripheral blood: Hemoglobin ≥ 100 g/L and <UNL; Neutrophils ≥ 1 x 10 9 /L and <UNL; Platelets ≥ 100 x 10 9 /L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH Bone marrow: Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF, and Peripheral blood: Hemoglobin ≥ 85 but <100 g/L and <UNL; Neutrophils ≥1 x 10 9 /L and <UNL; Platelets ≥50, but <100 x 10 9 /L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH or

17. New Response Criteria for MF: Other Categories 1 1. Tefferi A et al. Blood. 2013;122:1395-1398. Clinical improvement Achievement of anemia, spleen, or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia Anemia response Transfusion-independent pts: a ≥20 g/L increase in Hb level Transfusion-dependent pts: becoming transfusion independent Spleen response Baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable, OR Baseline splenomegaly that is palpable at >10 cm, below the LCM, decreases by ≥50% Baseline splenomegaly that is palpable at <5 cm, below the LCM, is not eligible for spleen response Symptoms response A ≥50% reduction in the MPN-SAF TSS CI: clinical improvement; LCM: left costal margin.

18. Revised MPN Response Criteria New response criteria remain clinically derived and focus on resolution of marrow histologic changes, blood counts, spleen size, symptom improvement, and lack of vascular events or progression All require over 12 weeks of benefit to be counted as response Value and measurement of stability (clinically or histologically) still not captured Validation of value of response levels needed ©2011 MFMER | 3133089-17

19. ©2011 MFMER | 3133089-18 What should you expect of your MPN Therapy? Individualizing Therapy What is the spectrum of disease burden and risk in MPNs? What are expectations of therapy? Current and evolving treatment options for MPN patients

20. Management of PV/ET ALL PV Patients Maintain HCT <45% Men, 42% Women Low Dose ASA Aggressive control of CV risk factors Cytoreduction High Risk or Intol to Phlebotomy, Increasing Spleen, Severe Sx Plt >1500 x 10(9)/L, or prog WBC Medications Hydroxyurea or Interferon alpha as Front line (or second) Busulfan, pipobroman, P-32 as second line Barbui T, et. al. LeukemiNET Consensus Guidelines. JCO 2011;29:761-770

21. Kiladjian JJ, et al. Blood 2008;112:3065

22. Morphologic change after IFN therapy in a patient with primary myelofibrosis (After Median 3 years of Rx). Silver R T et al. Blood 2011;117:6669-6672 Silver et. al. Blood 2011 17 “Early” PMF (MF<Grade 3) IWG (11 low, 6 Int 1) INFa2b or PEG Infa-2a IWG-MRT 2 CR, 7 PR, 1 CI (59% Response) Gowin et. al. ASH 2011 17 “Early” PMF (MF<Grade 3) PEG Infa-2a IWG-MRT 1 CR, 2 PR, 1 CI (29% Response)

23. 2014 Therapeutic options for MF Anemia Androgens rEPO IMiDs Myeloproliferation And Splenomegaly Ruxolitinib Hydroxyurea Busulfan Cladribine Splenectomy Radiation Allogeneic Stem cell Transplantation (ASCT) Cure Ruxolitinib Constitutional Symptoms Low riskInt-1 riskInt-2 riskHigh risk JAK2 inhibitor JAK1 inhibitor Telomerase Inhibitor Histone Deacetylase inhibitors IFN-α Combination therapy ASCT Experimental therapy Observation

24. JAK Inhibitors and Status of Development Myelofibrosis as lead indications ©2011 MFMER | 3133089-23 No Longer in Development For MPNs * Now Testing in PV * * * *

25. Mean Daily Dose of Ruxolitinib Over Time 24 Approximately 70% of patients had dose adjustments during the first 12 weeks of therapy By week 24, patients originally randomized to RUX 15 mg BID and 20 mg BID were titrated to a mean dose of ~10 mg BID and 15-20 mg BID, respectively 25 20 15 10 5 0 Mean Daily Dose (mg, BID) ± SEM 081624327210413614448881206456961284080112 Weeks 20 mg BID starting dose 15 mg BID starting dose 986220 mg BID 492015 mg BID Number of patients 100 55 7769 3326 73 30 93 35 ASH 2013

26. Percentage Change in Spleen Size 25 Mean reductions in spleen volume and palpable spleen length with ruxolitinib were stable over time RuxolitinibPlacebo Weeks Mean Percentage Change from Baseline 148139120107100841321073573 n = 1224487296120144122448 Weeks 12244872961201444812244848 RuxolitinibPlacebo 153152150 141130 110102 n = 147141136109 479079 Mean Percentage Change from Baseline Spleen VolumeSpleen Length ASH 2013

27. Durability of Spleen Volume Reduction 26 ≥35% reduction: Time from first 35% reduction to <35% reduction and 25% increase from nadir. ≥10% reduction: Time from first 35% reduction to <10% reduction from baseline. In patients originally randomized to ruxolitinib, 59% achieved a ≥35% reduction in spleen volume

28. Improvements in EORTC QLQ-C30 Over Time Arrows indicate improvement RUXPBO Global Health Status/QoL Mean Change From Baseline 0122436487296120144 Weeks 20 10 0 -5 -15 15 5 -10 6084108132 Fatigue Mean Change From Baseline 0122436487296 Weeks 10 0 -10 -15 -25 -35 5 -5 -20 -30 6084120144108132 Physical Functioning Mean Change From Baseline Weeks 15 5 -5 -10 10 0 01224364872966084120144108132 Role Functioning Mean Change From Baseline Weeks 25 10 0 -5 -15 -25 15 5 -10 -20 20 01224364872966084120144108132 27

29. JAK1 & 2 Inhibitors in MPNs – Efficacy Summary – As of ASH 2013 MyelofibrosisPolycythemia Vera Essential Thrombocythemia SpleenConst. Sympt. AnemiaSurvival  Counts Const. Sympt.  Vasc Events  Counts Const. Sympt.  Vasc Events Ruxolitinib - ApprovedP III P II SAR302503 – PH III JAKARTA (HOLD) P III P IIP III Pacritinib- PIII Ongoing (Persist MF) P II CYT387P II LY2784544P I NS-018 BMS-911543PH II INCB039110P I CEP701P II ©2011 MFMER | 3133089-28 Not Reported Yet Not Reported Yet Yes No Occasional Ongoing Trials

30. JAK1 & 2 Inhibitors in MPN – Toxicity ASH 2013 Hematological Toxicities Gastrointestinal/ Renal Toxicities Neurological Toxicities Anemia  ANC  PLT NauseaDiarr- hea  LFTs Or CR  Lipase Head- ache DizzyNeuroP/ Parathia Ruxolitinib - Approved 23%7%11%2%0.6% SAR302503 – PIII Ongoing (MF) 41%6%11%0%5%1%W. E. % ? Pacritinib- PIII Ongoing (MF) 6%0%18%6% CYT387 PII Ongoing (MF) 10%2%20%1% INCB039110 (JAK1) – PI/II MF 28%27%10% BMS 9115433%10% 0% LY27845443%0%3%8% Renal ©2011 MFMER | 3133089-29 <10% 11- 20% 21- 30% 31- 40% 41- 50% 51- 60% 61- 70% 71- 80% 81- 90% 91- 100% Toxicity Color – Represents All Grades ( Grade ¾ Toxicity - Percentage in Table Above)

31. MPNs – Plateau vs. Decline ©2011 MFMER | 3133089-30 ET – Possible Plateau Asymptomatic Thrombocytosis No Vascular Events ET – Possible Plateau 2 Symptomatic Thrombocytosis Sinus Venous Thrombosis Time Clinical Status PV – Possible Plateau 2 Symptomatic Erythrocytosis No Vascular Events Post PV MF 6 Months worsening Fatigue 10 kg weight loss Massive spleen MF on Successful JAK2 Rx Improving Weight Decreased Spleen Improved Survival

32. MPNs – Cumulative Benefits ©2011 MFMER | 3133089-31 Time Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival Ruxolitinib

33. MPNs – Cumulative Benefits Single Agent Trials JAK2 Inhibitors Compared to Ruxo ©2011 MFMER | 3133089-32 Time Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival ? Other Benefit -Less cytopenias -Improved activity ? Other Benefit -Less cytopenias -Improved activity STUDY (JAK2/FLT3 Inhibitor) NS-018 (PH I/II) NCT01423851 STUDY (JAK2/FLT3 Inhibitor) NS-018 (PH I/II) NCT01423851 STUDY (JAK2/FLT3 Inhibitor) Pacritinib (SB1518) (PH III vs. BAT) NCT01773187 STUDY (JAK2/FLT3 Inhibitor) Pacritinib (SB1518) (PH III vs. BAT) NCT01773187 STUDY (JAK2 Inhibitor – Also ET and PV) LY2784544 (PH I/II) NCT01520220 STUDY (JAK2 Inhibitor – Also ET and PV) LY2784544 (PH I/II) NCT01520220 STUDY (JAK2/JAK1 Inhibitor) Momelotinib (CYT387) (PH III vs. Ruxo) NCT001969838 STUDY (JAK2/JAK1 Inhibitor) Momelotinib (CYT387) (PH III vs. Ruxo) NCT001969838

34. IMiDs in MF: Summary of Clinical Data HBPLTSPLNREF THAL 29%38%41%Barosi 2002 THAL-PRED 62%75%19%Mesa 2002 LEN 22%50%33%Tefferi 2006 LEN-PRED 19%?9%Mesa 2010 LEN-PRED 30%?42%Quintas-Cardama 2009 POM (0.5mg/day) >50%?<25%Mesa 2010 POM+/-PRED 30-40%40%<10%Tefferi 2008

35. MPNs – Cumulative Benefits Ruxolitinib + drug X for Anemia ©2011 MFMER | 3133089-34 Time Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival Improved Anemia Burden STUDY COMBINATION (JAK2 PLUS Androgen) Ruxolitinib Plus Danazol Mayo Clinic (AZ) and Mt. Sinai Trial: NCT01732445 STUDY COMBINATION (JAK2 PLUS Androgen) Ruxolitinib Plus Danazol Mayo Clinic (AZ) and Mt. Sinai Trial: NCT01732445 STUDY COMBINATION(JAK2 PLUS Hypomethylation) Ruxolitinib Plus Azacitidine MDACC Trial: NCT01787487 STUDY COMBINATION(JAK2 PLUS Hypomethylation) Ruxolitinib Plus Azacitidine MDACC Trial: NCT01787487 STUDY COMBINATION (JAK2 PLUS IMID) Ruxolitinib Plus Lenalidomide NCT01375140 STUDY COMBINATION (JAK2 PLUS IMID) Ruxolitinib Plus Lenalidomide NCT01375140 STUDY COMBINATION (JAK2 PLUS IMID) Ruxolitinib Plus Pomalidomide Germany (ULM): NCT01644110 STUDY COMBINATION (JAK2 PLUS IMID) Ruxolitinib Plus Pomalidomide Germany (ULM): NCT01644110

36. MPNs – Cumulative Benefits Ruxolitinib + drug X for Deeper Marrow Changes Impact Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival Improved Marrow Dysfunction STUDY COMBINATION (JAK2 PLUS HDAC Inhibitors) Ruxolitinib Plus Panobinostat Mt. Sinai Trial: NCT01693601 UK Trial: NCT01433445 STUDY COMBINATION (JAK2 PLUS HDAC Inhibitors) Ruxolitinib Plus Panobinostat Mt. Sinai Trial: NCT01693601 UK Trial: NCT01433445 STUDY COMBINATION (JAK2 PLUS LOXL2 Inhibitors) Ruxolitinib Plus GS-6624 NCT01369498 STUDY COMBINATION (JAK2 PLUS LOXL2 Inhibitors) Ruxolitinib Plus GS-6624 NCT01369498 STUDY COMBINATION (JAK2 PLUS rhPTX-2 (Anti-fibrosing)) Ruxolitinib Plus PRM -151 Opening Soon STUDY COMBINATION (JAK2 PLUS rhPTX-2 (Anti-fibrosing)) Ruxolitinib Plus PRM -151 Opening Soon STUDY COMBINATION (JAK2 PLUS PI3 Kinase Inhibitor) Ruxolitinib Plus BKM120 NCT01730248 STUDY COMBINATION (JAK2 PLUS PI3 Kinase Inhibitor) Ruxolitinib Plus BKM120 NCT01730248 STUDY COMBINATION (JAK2 PLUS Hedgehog Inhibitor) Ruxolitinib Plus LDE225 NCT01787552 STUDY COMBINATION (JAK2 PLUS Hedgehog Inhibitor) Ruxolitinib Plus LDE225 NCT01787552

37. MPNs – Cumulative Benefits Single Agent Trials Alternate Targets Time Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival ? Other Benefit -Less cytopenias -Improved activity ? Other Benefit -Less cytopenias -Improved activity STUDY (Interferons) Peg Interferon α2b in “Early” MF Cornell Lead: NCT01758588 STUDY (Interferons) Peg Interferon α2b in “Early” MF Cornell Lead: NCT01758588 STUDY (Activin - ActRIIA-IgG1Fc) Sotatercept (ACE 011) MDACC: NCT01712308 STUDY (Activin - ActRIIA-IgG1Fc) Sotatercept (ACE 011) MDACC: NCT01712308 STUDY (Telomerase Inhibitor) Imetelstat (GRN163L) Mayo Clinic (Rochester): NCT01731951 STUDY (Telomerase Inhibitor) Imetelstat (GRN163L) Mayo Clinic (Rochester): NCT01731951 STUDY (JAK1 Inhibitor) INCB039110 (PH II) NCT01633372 STUDY (JAK1 Inhibitor) INCB039110 (PH II) NCT01633372

38. MPNs – Cumulative Benefits Difficult PV-ET Clinical Status Improved Symptom Burden Improved Spleen Burden Improved Survival Improved Marrow Dysfunction STUDY COMBINATION (PV) Ruxolitinib Vs. Hydroxyurea (RELIEF) NCT01632904 STUDY COMBINATION (PV) Ruxolitinib Vs. Hydroxyurea (RELIEF) NCT01632904 STUDY (ET and PV) MPD-RC 112 Peg Inf a2a vs. Hydroxyurea (PH III) NCT01259856 STUDY (ET and PV) MPD-RC 112 Peg Inf a2a vs. Hydroxyurea (PH III) NCT01259856 STUDY (ET and PV) MPD-RC 111 Peg Inf a2a AFTER Hydroxyurea (PH III) NCT01259856 STUDY (ET and PV) MPD-RC 111 Peg Inf a2a AFTER Hydroxyurea (PH III) NCT01259856 STUDY (PV) AOP Peg Inf a2a vs Hydroxyurea (PH III) NCT01230775 STUDY (PV) AOP Peg Inf a2a vs Hydroxyurea (PH III) NCT01230775 FUTURE STUDY COMBINATION JAK2 Inhibitor Plus PEG INF  2a/b FUTURE STUDY COMBINATION JAK2 Inhibitor Plus PEG INF  2a/b Improved Vascular Event Risk (?PV)

39. Myeloproliferative Disorders Research Consortium Trial Polycythemia Vera and Essential Thrombocythemia MPD-RC 112 (NCT01259856 – clinicaltrials.gov) Randomized Trial of Pegylated Interferon Alfa-2a versus Hydroxyurea Therapy in the Treatment of High Risk Polycythemia Vera (PV) and High Risk Essential Thrombocythemia (ET) Registered & Randomized High Risk ET and PV (< 3 Months Prior Hydroxyurea) Registered & Randomized High Risk ET and PV (< 3 Months Prior Hydroxyurea) PEG INF Alfa-2a Target dose 90 mcg/week Weekly Dosing ≥2 years of therapy in responders PEG INF Alfa-2a Target dose 90 mcg/week Weekly Dosing ≥2 years of therapy in responders HYDROXYUREA Titrated Dosing to Response Daily Dosing MPD-RC 111 in HYDROXYUREA Failures HYDROXYUREA Titrated Dosing to Response Daily Dosing MPD-RC 111 in HYDROXYUREA Failures ENDPOINTS Primary: Complete response by ELN Criteria Secondary: Partial response rate by ELN criteria, JAK2-V617F Allele Burden, Vascular Events, MPN Symptoms, Tolerability, Progression ENDPOINTS Primary: Complete response by ELN Criteria Secondary: Partial response rate by ELN criteria, JAK2-V617F Allele Burden, Vascular Events, MPN Symptoms, Tolerability, Progression Key Eligibility Criteria High risk PV or ET within 3 years from diagnosis No prior cytoreductive treatment (interferon or pegasys) other than hydroxyurea for up to 3 months (prior phlebotomy, aspirin, and/or anagrelide allowed) Age of 18 or older with relatively normal kidney and liver function No other serious medical problems Key Eligibility Criteria High risk PV or ET within 3 years from diagnosis No prior cytoreductive treatment (interferon or pegasys) other than hydroxyurea for up to 3 months (prior phlebotomy, aspirin, and/or anagrelide allowed) Age of 18 or older with relatively normal kidney and liver function No other serious medical problems Questions contact MPD-RC (www.mpd-rc.org)www.mpd-rc.org John Mascarenhas, MD john.mascarenhas@mssm.edu Phone: 1 (212) 241-6756john.mascarenhas@mssm.edu

40. Verstovsek S, et. al. Blood (ASH) 2010;116: Abstract 313

41. Time to First Phlebotomy (n=1) or Discontinuation (n=8) 40 74% (25/34) remained on study and phlebotomy-free for at least 144 weeks NOTE: Analysis does not include phlebotomies that occurred in the first 4 weeks of treatment. Verstovsek S et. al. Blood (ASH) 2012;120:abstr 804

42. Reduction in PV-Associated Symptoms Clinically meaningful improvements in pruritus, night sweats, and bone pain observed within 4 weeks of initiating therapy and sustained through Week 144 41 ITT analysis: Patients who discontinued are counted as not having response for all study visits that they would have completed up to the date of analysis. Verstovsek S et. al. Blood (ASH) 2012;120:abstr 804

43. Medicine Wheel of Health “Integrative Medicine”

44. MPN-QOL International Study Group www.mpn-qol.org MEASURE Trial Serial assessment of MPN symptoms and QOL in all currently available therapies SYMPTOM Trial Serial assessment of the BMT experience in MPN symptoms (and BMT/GVHD symptoms) and QOL Current Landmark Survey mpnsurvey.com ©2011 MFMER | 3133089-43 Supported by a grant from the MPN Foundation

45. Patient Goals & Input Improving Symptom Burden /HR QOL “Balancing” Spleen/ Cytoses/ Cytopenias Extending Life CURE ©2011 MFMER | 3133089-44 Individualizing MPN Pharmacotherapy

47. ©2011 MFMER | 3133089-46 Acknowledgements Argentina Ana Clara Kneese, MD Federico Sackmann, MD Australia David M Ross MBBS, PhD Cecily Forsyth John Seymour, MBBS, PhD Karen Hall, MD Kate Burbury MD Tam Constantine, MD Canada Lynda Foltz, MD Vikas Gupta, MD China Hsin-An Hou, MD Huan-Chau Lin, MD Hung Chang, MD Ming-Shen Dai, MD Yuan-Bin Yu, MD Yung-Chen Su, MD Zhijian Xiao, MD Denmark Christen Lykkegaard Andersen, MD Hans Hasselbalch, MD France Brigitte Dupriez, MD Jean-Jacques Kiladjian, MD Jean-Loup Demory MD Magali Demilly, PhD Germany Heike L. Pahl, PhD Ireland Mary Francis McMullen, MD Israel Martin Ellis, MD Italy Alessandro M. Vannucchi, MD Francesco Passamonti, MD Giovanni Barosi, MD Tiziano Barbui, MD Netherlands Harry Schouten, MD, PhD Jan Jacques Michiels, MD Karin Klauke, MD Peter te Boekhorst, MD Sonja Zweegman, MD PhD Stephanie Slot, MD Suzan Commandeur, MD New Zealand Hilary Blacklock, MD Panama Francis Guerra, MD Singapore Wee Joo Chng, MB ChB Spain Ana Kerguelen Fuentes, MD Carlos Besses, MD Francisco Cervantes, MD Dolores Fernandez-Casados Sweden Andreasson Bjorn, MD Elisabeth Ejerblad, MD Gunnar Birgegard, MD Jan Samuelsson, MD Johanna Ablesson, MD Peter Johansson, MD UK Anthony Green, MD Claire N. Harrison, MD Deepti Radia, MD Uruguay Pablo Muxi, MD USA Alison Moliterno, MD Brady Stein, MD MHS Casey O'Connell Catriona Jamieson Daniel Rubin, ND Elizabth Hexner Hala Simm Jason Gotlib, MD Jeff Sloan, PhD Jessica Altman, MD Joseph Prchal, MD Kimberly Hickman Martin Tallman, MD Mike Boxer, MD Olatoyosi Odenike, MD Robert Silver, MD Ross Levine, MD Soo Jin Kim Srdan Verstovsek, MD