A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF

A Phase Ib/II, Open-label, Multi-center, Dose-finding Study to Assess the Safety and Efficacy of the Oral Combination of LDE225 and INC424 (Ruxolitinib) in Patients With Myelofibrosis

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01787552

Enrollment

Registered

2013-02-08

Start date

2013-05-08

Completion date

2018-04-10

Last updated

2020-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Blood Coagulation Disorders, Blood Platelet Disorders, Bone Marrow Diseases, Essential Thrombocythemia, Hematologic Diseases, Hemorrhagic Disorders, Myeloproliferative Disorders, Polycythemia Vera, Primary Myelofibrosis, Thrombocytosis

Keywords

Dose escalation, Maximum Tolerated Dose, MTD, Safety Expansion, Safety, Efficacy, Myelofibrosis, Post-polycythemia vera myelofbrosis (Post PV-PMF), Post essential thrombocythemia myelofibrosis (Post ET-MF), Primary myelofibrosis (PMF), Intermediate risk myelofibrosis, High risk myelofibrosis, Combination Treatment, Hedgehog Signaling Pathway, Smoothened inhibitor, JAK inhibitor

Brief summary

The purpose of this phase Ib/II clinical trial was to: a) evaluate the safety of the co-administration of LDE225 and INC424 in myelofibrosis patients and establish a maximum tolerated dose and/or Recommended Phase II dose of the combination and b) to assess the efficacy of the co-administration of LDE225 and INC424 on spleen volume reduction.

Detailed description

The study is considered to have been completed because the participants completed the study as per study design at the time of trial termination. If participants were already in extension phase until discontinuation criteria were met or alternative setting was available, they were considered as completed. The study was terminated due to one of the compounds being divested.

Interventions

DRUGLDE225

DRUGINC424

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosed with PMF per 2008 WHO criteria, post-PV MF or post-ET MF per IWG-MRT criteria. * Ineligible or unwilling to undergo stem cell transplantion. * PLT counts \> or = 75X 10\^9/L not reached with the aid of transfusions. * ECOG performance status ≤ 2. * Palpable splenomegaly defined as ≥ 5 cm below the left costal margin. * Intermediate risk level 1 (1 prognostic factor which is not age), Intermediate risk level 2, or high risk. * Active symptoms of MF as demonstrated by one symptom score of at least 5 (0 to10 point scale) or two symptom scores of at least 3 (0 to 10 point scale) on the MF Symptom Assessment Form (MFSAF).

Exclusion criteria

* Previous therapy with JAK or Smoothened inhibitors. * Patient is currently on medications that interfere with coagulation (including warfarin) or platelet function with the exception of low dose aspirin (up to 100 mg) and LMWH. * Impairment of GI function or GI disease that may significantly alter the absorption of INC424 or LDE225 (e.g., uncontrolled nausea, vomiting, diarrhea; malabsorption syndrome; small bowel resection). * Splenic irradiation within 12 months prior to Screening. * Pregnant or nursing women. * WOCBP not using highly effective methods of contraception * Sexually active males who refuse condom use * Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA inhibitors (statins), clofibrate and gemfibrozil. Pravastatin may be used if necessary, with extra caution.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)	6 weeks (42 days)	A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
Percentage of Patients Achieving >= 35% Reduction in Spleen Volume in Phase Ib Expansion and Phase II Stage 1	Week 24 and Week 48	Reduction in spleen volume as measured by magnetic resonance imaging/Cat Scan (MRI/CT) in Phase Ib expansion and Phase II Stage 1 patients

Secondary

Measure	Time frame	Description
Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1	Plasma Concentration Time Curve: AUC0-24h: Area under the concentration-time curve from time zero to 24 hours extrapolate from AUClast\[mass x time x volume-1\]
Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1	AUC0-12h: Area under the concentration-time curve from time zero to 12 hours extrapolate from AUClast\[mass x time x volume-1\]. AUCinf: Area under the concentration-time curve from time zero to infinity with extrapolation of the terminal phase \[mass x time x volume-1\]. AUClast: Area under the concentration-time curve from time zero to the time of last measurable concentration \[mass x time x volume-1\].
Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1	Cmax: Maximum observed plasma concentration after drug administration \[mass x volume- 1\].
Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, Week 25 Day 1 (Week 24), Week 49 Day 1 (Week 48)	The number of patients experiencing improvement in their bone marrow fibrosis by at least one grade and assessment of cellularity.
Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Baseline, Week 25 Day 1 (Week 24), Week 49 Day 1 (Week 48)	Phase Ib and Phase ll: Change in Pharmacodynamic Biomarkers: JAK2V617F allele burden
Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Baseline, Week 25 Day 1 (Week 24), Week 49 Day 1 (Week 48)	Summary of cytokine levels in Pharmacodynamic Biomarkers for all 26 collected at Week 25 Day 1 and Week 49 Day 1
Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1	Tmax: Time to reach Cmax \[time\]
Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Baseline, Week 25, Week 49	The 7-day modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. The first 6 items assess MF symptom severity at its worst as recalled in the 7 days prior to the clinic visit assessment. The symptoms measured include night sweats, itching, abdominal discomfort, pain under the ribs (left side), early satiety, & bone/muscle pain. The 7th item captures MF-related inactivity in the past 7 days prior to the clinic visit assessment. All 7 items ask subjects to record their answers on an 11-point numeric rating scale (NRS), (0 = Absent, 10 = Worst Imaginable). The first 6 items of the instrument focus on MF symptoms & are summed to create a Total Symptom score.
Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Week 24, Week 48	EORTC QLQ-C30 is the European Organization for Research & Treatment of Cancer, Quality of Life (QoL) Questionnaire & is one of the most widely used & validated instruments to measure health-related QoL in subjects with cancer. The scale includes 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning & social functioning), global health status/QoL & 9 symptom scale/items (fatigue, nausea & vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, & financial difficulties). This instrument asks the subject to respond according to the past week, with the exception of the first 5 questions that represent physical functioning & capture the subject's current status. The range of scores for all of the scales is from 0 to 100. For functional & global health status/QoL scales, higher scores indicate better QoL & level of functioning; for symptom scales, higher scores indicate greater level of symptoms or difficulties.
Phase Ib and Phase II: LDE225: PK Parameter: Racc	0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 9 Day 1	Racc: Accumulation ratio calculated as AUC0-12h on Week 9 Day 1 divided by AUC0-12h on Week 1 Day 1 \[fold\]
Phase Ib and Phase II: INC424: PK Parameter: T1/2	0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1	T1/2: Elimination half-life associated with the terminal slope (lambda\_z) of a semi logarithmic concentration-time curve \[time\]
Phase Ib and Phase II: INC424: PK Parameter: Vss/F	0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1	Vss/F: Apparent volume of distribution at steady state after oral administration \[volume\]
Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 24, Week 48	The 7-day modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. The first 6 items assess MF symptom severity at its worst as recalled in the 7 days prior to the clinic visit assessment. The symptoms measured include night sweats, itching, abdominal discomfort, pain under the ribs (left side), early satiety, & bone/muscle pain. The 7th item captures MF-related inactivity in the past 7 days prior to the clinic visit assessment. All 7 items ask subjects to record their answers on an 11-point numeric rating scale (NRS), (0 = Absent, 10 = Worst Imaginable). The first 6 items of the instrument focus on MF symptoms & are summed to create a Total Symptom score.
Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1	CL/F: Apparent total plasma clearance of drug after oral administration \[volume x time-1\]

Countries

Australia, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, United Kingdom

Participant flow

Recruitment details

A total of 50 subjects were enrolled in the study, of which 23 subjects were enrolled in Phase Ib part of dose-escalation phase and 27 subjects were enrolled in Phase Ib dose-expansion phase and Phase II Stage 1.

Pre-assignment details

Participants by arm

Arm	Count
LDE225 400mg + INC424 10 mg (Dose Escalation Phase) Participants who took a combination of LDE225 400mg and INC424 10mg in the dose escalation phase.	8
LDE225 400mg + INC424 15 mg (Dose Escalation Phase) Participants who took a combination of LDED225 400mg and INC424 15mg in the dose escalation phase	10
LDE225 400mg + INC424 20mg (Dose Escalation Phase) Participants who took a combination of LDE225 400mg and INC424 20mg in the dose escalation phase.	5
LDED225 400mg + INC424 20mg (Dose Expansion Phase) Participants who took a combination of LDED225 400mg and INC424 20mg in the dose expansion phase	27
Total	50

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	2	5	2	16
Overall Study	Death	0	0	0	1
Overall Study	Physician Decision	2	2	1	2
Overall Study	Progressive Disease	2	2	1	1
Overall Study	Study terminated by Sponsor	0	0	1	3
Overall Study	Withdrawal by Subject	2	0	0	4

Baseline characteristics

Characteristic	LDE225 400mg + INC424 10 mg (Dose Escalation Phase)	Total	LDED225 400mg + INC424 20mg (Dose Expansion Phase)	LDE225 400mg + INC424 20mg (Dose Escalation Phase)	LDE225 400mg + INC424 15 mg (Dose Escalation Phase)
Age, Continuous	70.9 Years STANDARD_DEVIATION 5.19	66.2 Years STANDARD_DEVIATION 10.42	67.4 Years STANDARD_DEVIATION 10.02	64.6 Years STANDARD_DEVIATION 13.18	59.9 Years STANDARD_DEVIATION 11.59
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	3 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	6 Participants	47 Participants	26 Participants	5 Participants	10 Participants
Sex: Female, Male Female	1 Participants	15 Participants	8 Participants	1 Participants	5 Participants
Sex: Female, Male Male	7 Participants	35 Participants	19 Participants	4 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	1 / 8	1 / 10	1 / 5	1 / 27	4 / 50
other Total, other adverse events	8 / 8	10 / 10	5 / 5	27 / 27	50 / 50
serious Total, serious adverse events	5 / 8	6 / 10	2 / 5	13 / 27	26 / 50

Outcome results

Primary

Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)

A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.

Time frame: 6 weeks (42 days)

Population: Safety Analysis Set (SAS) included all participants in Phase Ib \& Phase II who received at least 1 dose of LDE225 and/or INC424 \& had at least 1 valid post-baseline safety assessment. DLT was measured in the Phase Ib dose escalation \& expansion phase, as part of the primary outcome. All participants in the safety set were considered for toxicities.

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)	Blood creatine phosphokinase increased	0 Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)	Blood creatine phosphokinase increased	2 Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)	Blood creatine phosphokinase increased	0 Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)	Blood creatine phosphokinase increased	1 Participants

Primary

Percentage of Patients Achieving >= 35% Reduction in Spleen Volume in Phase Ib Expansion and Phase II Stage 1

Reduction in spleen volume as measured by magnetic resonance imaging/Cat Scan (MRI/CT) in Phase Ib expansion and Phase II Stage 1 patients

Time frame: Week 24 and Week 48

Population: The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424. The data disclosed includes only participants from Phase Ib dose expansion phase and Ph II Stage 1. This data does not include dose escalation Phase Ib participants.

Arm	Measure	Group	Value (NUMBER)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Percentage of Patients Achieving >= 35% Reduction in Spleen Volume in Phase Ib Expansion and Phase II Stage 1	Week 24	44.4 Percentage of Participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Percentage of Patients Achieving >= 35% Reduction in Spleen Volume in Phase Ib Expansion and Phase II Stage 1	Week 48	29.6 Percentage of Participants

Secondary

Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48

EORTC QLQ-C30 is the European Organization for Research & Treatment of Cancer, Quality of Life (QoL) Questionnaire & is one of the most widely used & validated instruments to measure health-related QoL in subjects with cancer. The scale includes 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning & social functioning), global health status/QoL & 9 symptom scale/items (fatigue, nausea & vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, & financial difficulties). This instrument asks the subject to respond according to the past week, with the exception of the first 5 questions that represent physical functioning & capture the subject's current status. The range of scores for all of the scales is from 0 to 100. For functional & global health status/QoL scales, higher scores indicate better QoL & level of functioning; for symptom scales, higher scores indicate greater level of symptoms or difficulties.

Time frame: Week 24, Week 48

Population: The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424.

Arm	Measure	Group	Value (MEAN)	Dispersion
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Diarrhoea: Wk 25 (n=6,7,5,19)	5.6 scores on a scale	Standard Deviation 64.69
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Constipation: Wk 25 (n=6,7,5,19)	-11.1 scores on a scale	Standard Deviation 17.21
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Pain: Wk 49 (n=4,4,4,10)	25.0 scores on a scale	Standard Deviation 21.52
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Dyspnoea: Wk 25 (n=6,7,5,19)	-33.3 scores on a scale	Standard Deviation 29.81
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Appetite loss: Wk 49 (n=4,4,4,10)	-25.0 scores on a scale	Standard Deviation 41.94
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Dyspnoea: Wk 49 (n=4,4,4,10)	-33.3 scores on a scale	Standard Deviation 27.22
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Emo. Func: Wk 25 (n=6,7,5,19)	25.0 scores on a scale	Standard Deviation 16.67
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Insomnia: Wk 25 (n=6,7,5,19)	-22.2 scores on a scale	Standard Deviation 27.22
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Appetite loss: Wk 25 (n=6,7,5,19)	-27.8 scores on a scale	Standard Deviation 25.09
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Insomnia: Wk 49 (n=4,4,4,10)	-25.0 scores on a scale	Standard Deviation 31.91
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Glob. Health Status/Qol: Wk 49(n=4,4,4,10)	-2.1 scores on a scale	Standard Deviation 23.94
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fin. diff: Wk 49 (n=4,4,4,10)	8.3 scores on a scale	Standard Deviation 63.1
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Emo. Func: Wk 49 (n=4,4,4,10)	33.3 scores on a scale	Standard Deviation 11.79
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Phys. Func: Wk 49 (n=4,4,4,10)	25.0 scores on a scale	Standard Deviation 16.67
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Cog. Func: Wk 25 (n=6,7,5,19	14.6 scores on a scale	Standard Deviation 18.77
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fin. diff: Wk 25 (n=6,7,5,19)	16.7 scores on a scale	Standard Deviation 49.95
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Cog. Func: Wk 49 (n=4,4,4,10)	20.8 scores on a scale	Standard Deviation 15.96
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Phys. Func: Wk 25 (n=6,7,5,19)	15.6 scores on a scale	Standard Deviation 25.88
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Soc. Func: Wk 25 (n=6,7,4,19)	8.3 scores on a scale	Standard Deviation 39.09
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Diarrhoea: Wk 49 (n=4,4,4,10)	-8.3 scores on a scale	Standard Deviation 16.67
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Soc. Func: Wk 49 (n=3,4,4,10)	16.7 scores on a scale	Standard Deviation 16.67
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Role Func: Wk 25 (n=6,7,5,19)	33.3 scores on a scale	Standard Deviation 39.44
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fatigue: Wk 25 (n=6,7,5,19)	-20.4 scores on a scale	Standard Deviation 25.74
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fatigue: Wk 49 (n=4,4,4,10)	-27.8 scores on a scale	Standard Deviation 6.42
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Naus & Vom: Wk 25 (n=6,7,5,19)	-5.6 scores on a scale	Standard Deviation 13.61
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Glob. Health Status/Qol: Wk 25 (n=6,7,5,19)	-2.8 scores on a scale	Standard Deviation 21.52
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Constipation: Wk 49 (n=4,4,4,10)	-33.3 scores on a scale	Standard Deviation 47.14
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Naus & Vom: Wk 49 (n=4,4,4,10)	-4.2 scores on a scale	Standard Deviation 15.96
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Role Func: Wk 49 (n=4,4,4,10)	41.7 scores on a scale	Standard Deviation 21.52
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Pain: Wk 25 (n=6,7,5,18)	-11.1 scores on a scale	Standard Deviation 40.37
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Pain: Wk 25 (n=6,7,5,18)	-4.8 scores on a scale	Standard Deviation 38.14
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Cog. Func: Wk 49 (n=4,4,4,10)	-8.3 scores on a scale	Standard Deviation 28.87
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fatigue: Wk 49 (n=4,4,4,10)	0. scores on a scale	Standard Deviation 15.71
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Pain: Wk 49 (n=4,4,4,10)	-8.3 scores on a scale	Standard Deviation 56.93
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Glob. Health Status/Qol: Wk 49(n=4,4,4,10)	14.6 scores on a scale	Standard Deviation 45.33
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Appetite loss: Wk 49 (n=4,4,4,10)	8.3 scores on a scale	Standard Deviation 16.67
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Diarrhoea: Wk 49 (n=4,4,4,10)	-0.0 scores on a scale	Standard Deviation 27.22
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Dyspnoea: Wk 25 (n=6,7,5,19)	-4.8 scores on a scale	Standard Deviation 29.99
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fin. diff: Wk 49 (n=4,4,4,10)	25.0 scores on a scale	Standard Deviation 31.91
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Phys. Func: Wk 25 (n=6,7,5,19)	-1.0 scores on a scale	Standard Deviation 14.1
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Soc. Func: Wk 25 (n=6,7,4,19)	-7.1 scores on a scale	Standard Deviation 18.9
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Dyspnoea: Wk 49 (n=4,4,4,10)	-16.7 scores on a scale	Standard Deviation 43.03
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Glob. Health Status/Qol: Wk 25 (n=6,7,5,19)	-2.4 scores on a scale	Standard Deviation 21.9
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Appetite loss: Wk 25 (n=6,7,5,19)	4.8 scores on a scale	Standard Deviation 12.6
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Constipation: Wk 49 (n=4,4,4,10)	0.0 scores on a scale	Standard Deviation 27.22
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Insomnia: Wk 25 (n=6,7,5,19)	0.0 scores on a scale	Standard Deviation 38.49
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Emo. Func: Wk 25 (n=6,7,5,19)	-8.3 scores on a scale	Standard Deviation 31.18
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Constipation: Wk 25 (n=6,7,5,19)	0.0 scores on a scale	Standard Deviation 0
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Soc. Func: Wk 49 (n=3,4,4,10)	-4.2 scores on a scale	Standard Deviation 8.33
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Insomnia: Wk 49 (n=4,4,4,10)	8.3 scores on a scale	Standard Deviation 16.67
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Naus & Vom: Wk 25 (n=6,7,5,19)	-4.8 scores on a scale	Standard Deviation 18.54
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Diarrhoea: Wk 25 (n=6,7,5,19)	-9.5 scores on a scale	Standard Deviation 16.27
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Naus & Vom: Wk 49 (n=4,4,4,10)	4.2 scores on a scale	Standard Deviation 28.46
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Emo. Func: Wk 49 (n=4,4,4,10)	-12.5 scores on a scale	Standard Deviation 41.67
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fatigue: Wk 25 (n=6,7,5,19)	-1.6 scores on a scale	Standard Deviation 26.78
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fin. diff: Wk 25 (n=6,7,5,19)	19.0 scores on a scale	Standard Deviation 32.53
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Role Func: Wk 25 (n=6,7,5,19)	-7.1 scores on a scale	Standard Deviation 18.9
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Cog. Func: Wk 25 (n=6,7,5,19	-6.3 scores on a scale	Standard Deviation 19.8
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Phys. Func: Wk 49 (n=4,4,4,10)	-10.0 scores on a scale	Standard Deviation 25.82
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Role Func: Wk 49 (n=4,4,4,10)	-33.3 scores on a scale	Standard Deviation 27.22
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Diarrhoea: Wk 49 (n=4,4,4,10)	16.7 scores on a scale	Standard Deviation 57.74
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Phys. Func: Wk 25 (n=6,7,5,19)	17.3 scores on a scale	Standard Deviation 16.73
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Phys. Func: Wk 49 (n=4,4,4,10)	15.0 scores on a scale	Standard Deviation 22.03
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Role Func: Wk 25 (n=6,7,5,19)	16.7 scores on a scale	Standard Deviation 20.41
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Role Func: Wk 49 (n=4,4,4,10)	12.5 scores on a scale	Standard Deviation 25
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Emo. Func: Wk 25 (n=6,7,5,19)	5.6 scores on a scale	Standard Deviation 12.42
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Emo. Func: Wk 49 (n=4,4,4,10)	0.0 scores on a scale	Standard Deviation 15.21
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Cog. Func: Wk 25 (n=6,7,5,19	-3.3 scores on a scale	Standard Deviation 13.94
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Cog. Func: Wk 49 (n=4,4,4,10)	4.2 scores on a scale	Standard Deviation 8.33
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Soc. Func: Wk 25 (n=6,7,4,19)	12.5 scores on a scale	Standard Deviation 15.96
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Soc. Func: Wk 49 (n=3,4,4,10)	12.5 scores on a scale	Standard Deviation 25
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fatigue: Wk 25 (n=6,7,5,19)	-28.9 scores on a scale	Standard Deviation 16.85
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fatigue: Wk 49 (n=4,4,4,10)	-33.3 scores on a scale	Standard Deviation 18.14
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Naus & Vom: Wk 25 (n=6,7,5,19)	-3.3 scores on a scale	Standard Deviation 7.45
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Naus & Vom: Wk 49 (n=4,4,4,10)	0.0 scores on a scale	Standard Deviation 13.61
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Pain: Wk 25 (n=6,7,5,18)	-26.7 scores on a scale	Standard Deviation 25.28
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Pain: Wk 49 (n=4,4,4,10)	-20.8 scores on a scale	Standard Deviation 25
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Dyspnoea: Wk 25 (n=6,7,5,19)	-6.7 scores on a scale	Standard Deviation 14.91
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Dyspnoea: Wk 49 (n=4,4,4,10)	0.0 scores on a scale	Standard Deviation 0
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Insomnia: Wk 25 (n=6,7,5,19)	-33.3 scores on a scale	Standard Deviation 23.57
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Insomnia: Wk 49 (n=4,4,4,10)	-33.3 scores on a scale	Standard Deviation 27.22
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Appetite loss: Wk 25 (n=6,7,5,19)	-13.3 scores on a scale	Standard Deviation 18.26
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Appetite loss: Wk 49 (n=4,4,4,10)	-16.7 scores on a scale	Standard Deviation 19.25
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Constipation: Wk 25 (n=6,7,5,19)	13.3 scores on a scale	Standard Deviation 29.81
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Constipation: Wk 49 (n=4,4,4,10)	8.3 scores on a scale	Standard Deviation 16.67
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Diarrhoea: Wk 25 (n=6,7,5,19)	-13.3 scores on a scale	Standard Deviation 18.26
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Glob. Health Status/Qol: Wk 49(n=4,4,4,10)	-0.0 scores on a scale	Standard Deviation 20.41
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fin. diff: Wk 25 (n=6,7,5,19)	20.0 scores on a scale	Standard Deviation 50.55
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fin. diff: Wk 49 (n=4,4,4,10)	0.0 scores on a scale	Standard Deviation 27.22
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Glob. Health Status/Qol: Wk 25 (n=6,7,5,19)	16.7 scores on a scale	Standard Deviation 27.64
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Pain: Wk 25 (n=6,7,5,18)	-8.3 scores on a scale	Standard Deviation 21.58
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Naus & Vom: Wk 49 (n=4,4,4,10)	-10.0 scores on a scale	Standard Deviation 11.65
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fin. diff: Wk 49 (n=4,4,4,10)	3.3 scores on a scale	Standard Deviation 18.92
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Constipation: Wk 25 (n=6,7,5,19)	7.0 scores on a scale	Standard Deviation 30.59
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Naus & Vom: Wk 25 (n=6,7,5,19)	-3.5 scores on a scale	Standard Deviation 11.89
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fatigue: Wk 49 (n=4,4,4,10)	4.4 scores on a scale	Standard Deviation 36.74
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Role Func: Wk 25 (n=6,7,5,19)	7.9 scores on a scale	Standard Deviation 32.09
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Constipation: Wk 49 (n=4,4,4,10)	3.3 scores on a scale	Standard Deviation 36.68
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fatigue: Wk 25 (n=6,7,5,19)	-8.8 scores on a scale	Standard Deviation 26.86
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Soc. Func: Wk 49 (n=3,4,4,10)	-3.3 scores on a scale	Standard Deviation 18.92
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Phys. Func: Wk 49 (n=4,4,4,10)	6.0 scores on a scale	Standard Deviation 15.85
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Diarrhoea: Wk 25 (n=6,7,5,19)	-1.8 scores on a scale	Standard Deviation 20.71
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Soc. Func: Wk 25 (n=6,7,4,19)	-2.6 scores on a scale	Standard Deviation 24.38
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Cog. Func: Wk 49 (n=4,4,4,10)	-5.0 scores on a scale	Standard Deviation 22.29
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Glob. Health Status/Qol: Wk 49(n=4,4,4,10)	-3.3 scores on a scale	Standard Deviation 24.91
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Diarrhoea: Wk 49 (n=4,4,4,10)	-3.3 scores on a scale	Standard Deviation 18.92
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Cog. Func: Wk 25 (n=6,7,5,19	2.6 scores on a scale	Standard Deviation 18.64
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Emo. Func: Wk 49 (n=4,4,4,10)	-2.5 scores on a scale	Standard Deviation 10.43
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Glob. Health Status/Qol: Wk 25 (n=6,7,5,19)	2.6 scores on a scale	Standard Deviation 22.75
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Fin. diff: Wk 25 (n=6,7,5,19)	8.8 scores on a scale	Standard Deviation 24.45
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Emo. Func: Wk 25 (n=6,7,5,19)	2.5 scores on a scale	Standard Deviation 18.61
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Insomnia: Wk 49 (n=4,4,4,10)	-33.3 scores on a scale	Standard Deviation 41.57
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Insomnia: Wk 25 (n=6,7,5,19)	-17.5 scores on a scale	Standard Deviation 34.01
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Dyspnoea: Wk 49 (n=4,4,4,10)	6.7 scores on a scale	Standard Deviation 26.29
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Role Func: Wk 49 (n=4,4,4,10)	10.2 scores on a scale	Standard Deviation 22.5
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Appetite loss: Wk 25 (n=6,7,5,19)	-12.3 scores on a scale	Standard Deviation 29.84
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Dyspnoea: Wk 25 (n=6,7,5,19)	-1.8 scores on a scale	Standard Deviation 26
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Pain: Wk 49 (n=4,4,4,10)	3.3 scores on a scale	Standard Deviation 10.54
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Phys. Func: Wk 25 (n=6,7,5,19)	1.0 scores on a scale	Standard Deviation 23.74
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48	Appetite loss: Wk 49 (n=4,4,4,10)	0.0 scores on a scale	Standard Deviation 44.44

Secondary

Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores

The 7-day modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. The first 6 items assess MF symptom severity at its worst as recalled in the 7 days prior to the clinic visit assessment. The symptoms measured include night sweats, itching, abdominal discomfort, pain under the ribs (left side), early satiety, & bone/muscle pain. The 7th item captures MF-related inactivity in the past 7 days prior to the clinic visit assessment. All 7 items ask subjects to record their answers on an 11-point numeric rating scale (NRS), (0 = Absent, 10 = Worst Imaginable). The first 6 items of the instrument focus on MF symptoms & are summed to create a Total Symptom score.

Time frame: Baseline, Week 25, Week 49

Population: The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424.

Arm	Measure	Group	Value (MEAN)	Dispersion
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Week 49 (n = 4, 5, 4, 10)	-18.5 scores on a scale	Standard Deviation 12.07
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Week 25 (n = 6, 7, 5, 19)	-18.8 scores on a scale	Standard Deviation 15.2
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Week 25 (n = 6, 7, 5, 19)	-14.0 scores on a scale	Standard Deviation 8.58
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Week 49 (n = 4, 5, 4, 10)	-13.6 scores on a scale	Standard Deviation 10.43
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Week 25 (n = 6, 7, 5, 19)	-19.4 scores on a scale	Standard Deviation 6.43
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Week 49 (n = 4, 5, 4, 10)	-21.0 scores on a scale	Standard Deviation 5.66
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Week 49 (n = 4, 5, 4, 10)	-8.0 scores on a scale	Standard Deviation 14.61
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores	Week 25 (n = 6, 7, 5, 19)	-6.5 scores on a scale	Standard Deviation 9.26

Secondary

Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast

AUC0-12h: Area under the concentration-time curve from time zero to 12 hours extrapolate from AUClast\[mass x time x volume-1\]. AUCinf: Area under the concentration-time curve from time zero to infinity with extrapolation of the terminal phase \[mass x time x volume-1\]. AUClast: Area under the concentration-time curve from time zero to the time of last measurable concentration \[mass x time x volume-1\].

Time frame: 0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1

Population: The Pharmacokinetic Analysis set (PAS) consisted of all subjects in Phase Ib and Phase II who received at least one (full or partial) dose of LDE225 and/or INC424 and provided at least one evaluable PK blood sample for LDE225 and/or INC424.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUC0-12h: Wk 9 Day 1 (n=8,9,4,20)	489 ng*hr/mL	Geometric Coefficient of Variation 42.5
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUCinf: Wk1 Day 1 (n=7,9,4,16)	466 ng*hr/mL	Geometric Coefficient of Variation 30.9
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUC0-12h: Wk1 Day 1 (n=8,10,5,25)	473 ng*hr/mL	Geometric Coefficient of Variation 29.5
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUCinf: Wk 9 Day 1 (n=8,9,3,15)	498 ng*hr/mL	Geometric Coefficient of Variation 43.1
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUClast: Wk1 Day 1 (n=8,10,5,26)	443 ng*hr/mL	Geometric Coefficient of Variation 26.2
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUClast: Wk 9 Day 1 (n=8,9,4,20)	460 ng*hr/mL	Geometric Coefficient of Variation 44.3
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUClast: Wk 9 Day 1 (n=8,9,4,20)	776 ng*hr/mL	Geometric Coefficient of Variation 43.9
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUCinf: Wk 9 Day 1 (n=8,9,3,15)	867 ng*hr/mL	Geometric Coefficient of Variation 48.7
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUCinf: Wk1 Day 1 (n=7,9,4,16)	789 ng*hr/mL	Geometric Coefficient of Variation 46.1
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUClast: Wk1 Day 1 (n=8,10,5,26)	730 ng*hr/mL	Geometric Coefficient of Variation 39.7
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUC0-12h: Wk1 Day 1 (n=8,10,5,25)	805 ng*hr/mL	Geometric Coefficient of Variation 45.6
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUC0-12h: Wk 9 Day 1 (n=8,9,4,20)	835 ng*hr/mL	Geometric Coefficient of Variation 46.6
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUC0-12h: Wk1 Day 1 (n=8,10,5,25)	1130 ng*hr/mL	Geometric Coefficient of Variation 23
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUC0-12h: Wk 9 Day 1 (n=8,9,4,20)	962 ng*hr/mL	Geometric Coefficient of Variation 23.7
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUCinf: Wk1 Day 1 (n=7,9,4,16)	1140 ng*hr/mL	Geometric Coefficient of Variation 28
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUCinf: Wk 9 Day 1 (n=8,9,3,15)	978 ng*hr/mL	Geometric Coefficient of Variation 29.5
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUClast: Wk 9 Day 1 (n=8,9,4,20)	891 ng*hr/mL	Geometric Coefficient of Variation 24.3
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUClast: Wk1 Day 1 (n=8,10,5,26)	1030 ng*hr/mL	Geometric Coefficient of Variation 20.8
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUC0-12h: Wk1 Day 1 (n=8,10,5,25)	1190 ng*hr/mL	Geometric Coefficient of Variation 41
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUCinf: Wk1 Day 1 (n=7,9,4,16)	1130 ng*hr/mL	Geometric Coefficient of Variation 47.7
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUClast: Wk1 Day 1 (n=8,10,5,26)	1070 ng*hr/mL	Geometric Coefficient of Variation 38.6
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUC0-12h: Wk 9 Day 1 (n=8,9,4,20)	1230 ng*hr/mL	Geometric Coefficient of Variation 42.4
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUClast: Wk 9 Day 1 (n=8,9,4,20)	1130 ng*hr/mL	Geometric Coefficient of Variation 38.6
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast	AUCinf: Wk 9 Day 1 (n=8,9,3,15)	1140 ng*hr/mL	Geometric Coefficient of Variation 43

Secondary

Phase Ib and Phase II: INC424: PK Parameter: T1/2

T1/2: Elimination half-life associated with the terminal slope (lambda\_z) of a semi logarithmic concentration-time curve \[time\]

Time frame: 0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1

Arm	Measure	Value (MEDIAN)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameter: T1/2	1.81 hour (h)
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameter: T1/2	2.42 hour (h)
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameter: T1/2	2.20 hour (h)
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: INC424: PK Parameter: T1/2	1.99 hour (h)

Secondary

Phase Ib and Phase II: INC424: PK Parameter: Vss/F

Vss/F: Apparent volume of distribution at steady state after oral administration \[volume\]

Time frame: 0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1

Arm	Measure	Value (MEDIAN)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameter: Vss/F	63.7 Litre (L)
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameter: Vss/F	67.1 Litre (L)
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: INC424: PK Parameter: Vss/F	53.1 Litre (L)
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: INC424: PK Parameter: Vss/F	54.5 Litre (L)

Secondary

Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)

Cmax: Maximum observed plasma concentration after drug administration \[mass x volume- 1\].

Time frame: 0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1

Population: The pharmacokinetic analysis set (PAS) consisted of all subjects in Phase Ib and Phase II who received at least one (full or partial) dose of LDE225 and/or INC424 and provided at least one evaluable PK blood sample for LDE225 and/or INC424.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	LDE225 (Week 1, Day 1) (n=6,10,5,26)	311 ng/mL	Geometric Coefficient of Variation 35.1
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	LDE225 (Week 9, Day 1) (n=8,8,5,20)	879 ng/mL	Geometric Coefficient of Variation 38
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	INC424 (Week 1, Day 1) (n=8,10,5,27)	154 ng/mL	Geometric Coefficient of Variation 29
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	INC424 (Week 9, Day 1) (n=8,9,4,20)	168 ng/mL	Geometric Coefficient of Variation 38.8
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	LDE225 (Week 9, Day 1) (n=8,8,5,20)	720 ng/mL	Geometric Coefficient of Variation 57.5
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	INC424 (Week 1, Day 1) (n=8,10,5,27)	244 ng/mL	Geometric Coefficient of Variation 40.4
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	INC424 (Week 9, Day 1) (n=8,9,4,20)	269 ng/mL	Geometric Coefficient of Variation 33.2
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	LDE225 (Week 1, Day 1) (n=6,10,5,26)	221 ng/mL	Geometric Coefficient of Variation 103.4
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	INC424 (Week 1, Day 1) (n=8,10,5,27)	351 ng/mL	Geometric Coefficient of Variation 27.7
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	LDE225 (Week 9, Day 1) (n=8,8,5,20)	959 ng/mL	Geometric Coefficient of Variation 39.4
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	INC424 (Week 9, Day 1) (n=8,9,4,20)	281 ng/mL	Geometric Coefficient of Variation 36.5
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	LDE225 (Week 1, Day 1) (n=6,10,5,26)	161 ng/mL	Geometric Coefficient of Variation 94.9
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	INC424 (Week 9, Day 1) (n=8,9,4,20)	350 ng/mL	Geometric Coefficient of Variation 36
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	LDE225 (Week 9, Day 1) (n=8,8,5,20)	951 ng/mL	Geometric Coefficient of Variation 51.1
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	LDE225 (Week 1, Day 1) (n=6,10,5,26)	251 ng/mL	Geometric Coefficient of Variation 83.4
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)	INC424 (Week 1, Day 1) (n=8,10,5,27)	338 ng/mL	Geometric Coefficient of Variation 40.1

Secondary

Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)

CL/F: Apparent total plasma clearance of drug after oral administration \[volume x time-1\]

Time frame: 0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1

Arm	Measure	Group	Value (MEDIAN)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	INC424 (Week 1, Day 1) (n=7,9,4,16)	23.8 L/hr
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	LDE225 (Week 1, Day 1) (n=5,5,1,12)	145 L/hr
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	LDE225 (Week 9, Day 1) (n=6,6,4,14)	27.8 L/hr
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	LDE225 (Week 9, Day 1) (n=6,6,4,14)	34.5 L/hr
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	LDE225 (Week 1, Day 1) (n=5,5,1,12)	238 L/hr
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	INC424 (Week 1, Day 1) (n=7,9,4,16)	18.7 L/hr
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	INC424 (Week 1, Day 1) (n=7,9,4,16)	16.5 L/hr
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	LDE225 (Week 1, Day 1) (n=5,5,1,12)	727 L/hr
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	LDE225 (Week 9, Day 1) (n=6,6,4,14)	25.1 L/hr
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	LDE225 (Week 9, Day 1) (n=6,6,4,14)	27.0 L/hr
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	LDE225 (Week 1, Day 1) (n=5,5,1,12)	122 L/hr
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)	INC424 (Week 1, Day 1) (n=7,9,4,16)	16.9 L/hr

Secondary

Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)

Tmax: Time to reach Cmax \[time\]

Time frame: 0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1

Arm	Measure	Group	Value (MEDIAN)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	LDE225 (Week 1, Day 1) (n=6,10,5,26)	3.01 hour (hr)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	LDE225 (Week 9, Day 1) (n=8,8,5,20)	1.79 hour (hr)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	INC424 (Week 1, Day 1) (n=8,10,5,27)	0.500 hour (hr)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	INC424 (Week 9, Day 1) (n=8,9,4,20)	0.875 hour (hr)
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	LDE225 (Week 9, Day 1) (n=8,8,5,20)	2.00 hour (hr)
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	INC424 (Week 1, Day 1) (n=8,10,5,27)	0.575 hour (hr)
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	INC424 (Week 9, Day 1) (n=8,9,4,20)	0.500 hour (hr)
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	LDE225 (Week 1, Day 1) (n=6,10,5,26)	2.08 hour (hr)
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	INC424 (Week 1, Day 1) (n=8,10,5,27)	0.500 hour (hr)
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	LDE225 (Week 9, Day 1) (n=8,8,5,20)	2.00 hour (hr)
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	INC424 (Week 9, Day 1) (n=8,9,4,20)	1.00 hour (hr)
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	LDE225 (Week 1, Day 1) (n=6,10,5,26)	2.00 hour (hr)
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	INC424 (Week 9, Day 1) (n=8,9,4,20)	1.00 hour (hr)
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	LDE225 (Week 9, Day 1) (n=8,8,5,20)	3.21 hour (hr)
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	LDE225 (Week 1, Day 1) (n=6,10,5,26)	2.00 hour (hr)
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)	INC424 (Week 1, Day 1) (n=8,10,5,27)	0.580 hour (hr)

Secondary

Phase Ib and Phase II: LDE225: PK Parameter: Racc

Racc: Accumulation ratio calculated as AUC0-12h on Week 9 Day 1 divided by AUC0-12h on Week 1 Day 1 \[fold\]

Time frame: 0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 9 Day 1

Arm	Measure	Group	Value (MEDIAN)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: PK Parameter: Racc	LDE225 (Week 9, Day 1) (n=4,6,3,13)	4.60 ratio
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: PK Parameter: Racc	LDE225 (Week 9, Day 1) (n=4,6,3,13)	7.40 ratio
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: PK Parameter: Racc	LDE225 (Week 9, Day 1) (n=4,6,3,13)	10.9 ratio
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225: PK Parameter: Racc	LDE225 (Week 9, Day 1) (n=4,6,3,13)	4.75 ratio
Unknown	Phase Ib and Phase II: LDE225: PK Parameter: Racc	LDE225 (Week 1, Day 1) (n=0,0,0,0)	— ratio

Secondary

Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)

Plasma Concentration Time Curve: AUC0-24h: Area under the concentration-time curve from time zero to 24 hours extrapolate from AUClast\[mass x time x volume-1\]

Time frame: 0, 0.5, 1. 1.5, 2, 4, 6, 8 hrs on Week 1 Day 1 & Week 9 Day 1

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	LDE225 (Week 1, Day 1) (n=6,10,4,24)	2680 ng*hr/mL	Geometric Coefficient of Variation 33.1
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	LDE225 (Week 9, Day 1) (n=6,6,4,14)	15500 ng*hr/mL	Geometric Coefficient of Variation 31.8
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	LDE225 (Week 9, Day 1) (n=6,6,4,14)	13000 ng*hr/mL	Geometric Coefficient of Variation 66.8
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	LDE225 (Week 1, Day 1) (n=6,10,4,24)	1900 ng*hr/mL	Geometric Coefficient of Variation 100.4
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	LDE225 (Week 1, Day 1) (n=6,10,4,24)	1090 ng*hr/mL	Geometric Coefficient of Variation 84
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	LDE225 (Week 9, Day 1) (n=6,6,4,14)	17100 ng*hr/mL	Geometric Coefficient of Variation 30.8
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	LDE225 (Week 1, Day 1) (n=6,10,4,24)	2060 ng*hr/mL	Geometric Coefficient of Variation 78.7
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)	LDE225 (Week 9, Day 1) (n=6,6,4,14)	14500 ng*hr/mL	Geometric Coefficient of Variation 45.4

Secondary

Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores

Time frame: Week 24, Week 48

Population: The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424.

Arm	Measure	Group	Value (NUMBER)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 48	25.00 Percentage of participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 24	50.00 Percentage of participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 48	20.0 Percentage of participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 24	40.0 Percentage of participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 24	80.0 Percentage of participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 48	80.0 Percentage of participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 24	33.3 Percentage of participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores	Week 48	18.5 Percentage of participants

Secondary

Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1

The number of patients experiencing improvement in their bone marrow fibrosis by at least one grade and assessment of cellularity.

Time frame: Baseline, Week 25 Day 1 (Week 24), Week 49 Day 1 (Week 48)

Population: The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424.

Arm	Measure	Group	Value (NUMBER)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 3 (n=5,4,1,5)	62.5 Percentage of Participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 2 (n=4,6,3,8)	50.0 Percentage of Participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, missing grade (n=6,7,2,20)	75.0 Percentage of Participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, missing grade (n=2,2,2,14)	25.0 Percentage of Participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 1 (n=1,1,0,1)	12.5 Percentage of Participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 3 (n=3,3,0,8)	37.5 Percentage of Participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, grade 3 (n=2,2,2,3)	25.0 Percentage of Participants
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, missing grade (n=1,0,2,6)	12.5 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 3 (n=3,3,0,8)	30.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, grade 2 (n=0,1,1,2)	10.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, grade 3 (n=2,2,2,3)	20.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 2 (n=4,6,3,8)	50.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, missing grade (n=6,7,2,20)	70.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 1 (n=1,1,0,1)	10.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 2 (n=0,3,2,7)	30.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 1 (n=0,1,0,4)	10.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 3 (n=5,4,1,5)	40.0 Percentage of Participants
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, missing grade (n=2,2,2,14)	20.0 Percentage of Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, grade 2 (n=0,1,1,2)	20.0 Percentage of Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, grade 3 (n=2,2,2,3)	40.0 Percentage of Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, missing grade (n=2,2,2,14)	40.0 Percentage of Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, missing grade (n=6,7,2,20)	40.0 Percentage of Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 3 (n=5,4,1,5)	20.0 Percentage of Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 2 (n=4,6,3,8)	60.0 Percentage of Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, missing grade (n=1,0,2,6)	40.0 Percentage of Participants
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 2 (n=0,3,2,7)	40.0 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, missing grade (n=6,7,2,20)	74.1 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 1 (n=0,1,0,4)	14.8 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 2 (n=4,6,3,8)	29.6 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 3 (n=3,3,0,8)	29.6 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, missing grade (n=1,0,2,6)	22.2 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 1 (n=1,1,0,1)	3.7 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 2 (n=0,3,2,7)	25.9 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, grade 3 (n=5,4,1,5)	18.5 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1, missing grade (n=2,2,2,14)	51.9 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, grade 0 (n=0,0,0,1)	3.7 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49, Day 1 grade 1 (n=0,0,0,1)	3.7 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, grade 2 (n=0,1,1,2)	7.4 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1, grade 3 (n=2,2,2,3)	11.1 Percentage of Participants
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1	Baseline, grade 0 (n=0,0,0,1)	3.7 Percentage of Participants

Secondary

Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers

Summary of cytokine levels in Pharmacodynamic Biomarkers for all 26 collected at Week 25 Day 1 and Week 49 Day 1

Time frame: Baseline, Week 25 Day 1 (Week 24), Week 49 Day 1 (Week 48)

Population: The Biomarker Analysis Set (BAS) consisted of all subjects in Phase Ib and Phase II who received at least one (full or partial) dose of LDE225 and/or INC424 and provided at least one evaluable biomarker sample.

Arm	Measure	Group	Value (MEDIAN)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFRT 2: Wk 25 D1 (n=7,8,5,22)	33.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	APOA-1: Week 25 Day 1 (n=7,8,5,22)	1.10 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	B2M: Week 49 Day 1 (n=4,3,4,14)	5.75 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	RANTES: Wk 25 D1 (n=7,8,5,22)	4.80 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	AFP: Week 25 Day 1 (Wk 25 D1) (n=7,8,5,22)	0.75 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	AFP: Week 49 Day 1 (WK25 D1) (n=4,3,4,14)	0.68 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	APOA-1: Week 49 Day 1 (n=4,3,4,14)	1.30 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	B2M: Week 25 Day 1 (n=7,8,5,22)	5.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	BDNF: Week 25 Day 1 (n=7,8,5,22)	0.46 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	BDNF: Week 49 Day 1 (n=4,3,4,14)	1.16 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	C Reactive Protein: Week 25 Day 1 (n=7,8,5,22)	2.60 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	C Reactive Protein: Week 49 Day 1 (n=4,3,4,14)	4.65 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Carcinoembryyonic Antigen: Wk 25 D1 (n=7,8,5,22)	1.40 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Carcinoembryyonic Antigen: Wk 49 D1 (n=4,3,4,14)	1.72 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Cluster of. Diff 40: Wk 25 D1 (n=7,7,5,0)	1.90 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Cluster of. Diff 40: Wk 49 D1 (n=4,2,0,0)	1.65 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Eotaxin1: Wk 25 D1 (n=7,8,5,22)	155.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Eotaxin1: Wk 49 D1 (n=4,3,4,14)	136.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	ICAM1: Wk 25 D1 (n=7,8,5,22)	266.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	ICAM1: Wk 49 D1 (n=4,3,4,14)	321.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL10: Wk 25 D1 (n=7,8,5,22)	9.30 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL10: Wk 49 D1 (n=4,3,4,14)	8.10 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL18: Wk 25 D1 (n=7,8,5,22)	292.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL18: Wk 49 D1 (n=4,3,4,14)	278.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1B: Wk 25 D1 (n=7,8,5,22)	3.30 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1B: Wk 49 D1 (n=4,3,4,14)	3.30 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1RN: Wk 25 D1 (n=7,8,5,22)	130.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1RN: Wk 49 D1 (n=4,3,4,14)	98.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL6: Wk 25 D1 (n=7,8,5,22)	4.70 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL6: Wk 49 D1 (n=4,3,4,14)	3.48 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL8: Wk 25 D1 (n=7,8,5,22)	28.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL8: Wk 49 D1 (n=4,3,4,14)	18.50 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Insulin: Wk 25 D1 (n=7,8,5,22)	2.70 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Insulin: Wk 49 D1 (n=4,3,4,14)	2.90 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	LEP: Wk 25 D1 (n=7,8,5,22)	1.50 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	LEP: Wk 49 D1 (n=4,3,4,14)	3.45 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro. Inflam. Prot-1 Beta: Wk 25 D1 (n=7,8,5,22)	491.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro. Inflam. Prot-1 Beta: Wk 49 D1 (n=4,3,4,14)	406.50 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro.-derived Chemokine: Wk 25 D1 (n=7,8,5,22)	253.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro.-derived Chemokine: Wk 49 D1 (n=4,3,4,14)	190.50 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	MPO: Wk 25 D1 (n=7,8,5,22)	327.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	MPO: Wk 49 D1 (n=4,3,4,14)	175.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Thyroxine binding globulin: Wk 49 D1 (n=4,3,4,14)	42.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFA: Wk 25 D1 (n=7,8,5,22)	27.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFA: Wk 49 D1 (n=4,3,4,14)	32.50 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFRT 2: Wk 49 D1 (n=4,3,4,14)	28.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VCAM1: Wk 25 D1 (n=7,8,5,22)	2040.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VCAM1: Wk 49 D1 (n=4,3,4,14)	2425.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VEGF: Wk. 25 D1 (n=7,8,5,22)	145.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VEGF: Wks. 49 D1 (n=4,3,4,14)	227.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VWF: Wk. 25 D1 (n=7,8,5,22)	135.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VWF: Wk. 49 D1 (n=4,3,4,14)	140.50 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Myoglobin: Wk 25 D1 (n=7,8,5,22)	31.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Myoglobin: Wk 49 D1 (n=4,3,4,14)	35.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Plasmin. Activ. Inhibitor 1: Wk 25 D1 (n=7,8,5,22)	34.00 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Plasmin. Activ. Inhibitor 1: Wk 49 D1 (n=4,3,4,14)	31.50 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	RANTES: Wk 49 D1 (n=4,3,4,14)	8.25 ng/mL
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Thyroxine binding globulin Wk 25 D1 (n=7,8,5,22)	38.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VCAM1: Wk 25 D1 (n=7,8,5,22)	1130.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	B2M: Week 25 Day 1 (n=7,8,5,22)	3.15 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VWF: Wk. 49 D1 (n=4,3,4,14)	67.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL8: Wk 25 D1 (n=7,8,5,22)	9.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL10: Wk 25 D1 (n=7,8,5,22)	7.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFA: Wk 49 D1 (n=4,3,4,14)	32.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	MPO: Wk 49 D1 (n=4,3,4,14)	180.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL8: Wk 49 D1 (n=4,3,4,14)	11.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VCAM1: Wk 49 D1 (n=4,3,4,14)	1210.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFA: Wk 25 D1 (n=7,8,5,22)	18.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	BDNF: Week 49 Day 1 (n=4,3,4,14)	0.19 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Insulin: Wk 25 D1 (n=7,8,5,22)	1.35 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	RANTES: Wk 25 D1 (n=7,8,5,22)	5.85 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Plasmin. Activ. Inhibitor 1: Wk 25 D1 (n=7,8,5,22)	45.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Thyroxine binding globulin: Wk 49 D1 (n=4,3,4,14)	45.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Insulin: Wk 49 D1 (n=4,3,4,14)	2.90 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL10: Wk 49 D1 (n=4,3,4,14)	4.05 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	MPO: Wk 25 D1 (n=7,8,5,22)	323.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Thyroxine binding globulin Wk 25 D1 (n=7,8,5,22)	41.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Myoglobin: Wk 25 D1 (n=7,8,5,22)	31.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	LEP: Wk 49 D1 (n=4,3,4,14)	17.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Plasmin. Activ. Inhibitor 1: Wk 49 D1 (n=4,3,4,14)	25.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro.-derived Chemokine: Wk 49 D1 (n=4,3,4,14)	327.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	BDNF: Week 25 Day 1 (n=7,8,5,22)	0.85 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro. Inflam. Prot-1 Beta: Wk 25 D1 (n=7,8,5,22)	375.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VEGF: Wks. 49 D1 (n=4,3,4,14)	106.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Myoglobin: Wk 49 D1 (n=4,3,4,14)	18.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro.-derived Chemokine: Wk 25 D1 (n=7,8,5,22)	274.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	RANTES: Wk 49 D1 (n=4,3,4,14)	3.20 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL18: Wk 25 D1 (n=7,8,5,22)	220.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Cluster of. Diff 40: Wk 25 D1 (n=7,7,5,0)	1.10 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	APOA-1: Week 49 Day 1 (n=4,3,4,14)	1.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Carcinoembryyonic Antigen: Wk 25 D1 (n=7,8,5,22)	1.20 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL18: Wk 49 D1 (n=4,3,4,14)	199.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VEGF: Wk. 25 D1 (n=7,8,5,22)	202.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFRT 2: Wk 49 D1 (n=4,3,4,14)	21.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	APOA-1: Week 25 Day 1 (n=7,8,5,22)	1.65 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1B: Wk 25 D1 (n=7,8,5,22)	3.30 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	ICAM1: Wk 25 D1 (n=7,8,5,22)	203.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	AFP: Week 49 Day 1 (WK25 D1) (n=4,3,4,14)	0.60 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Cluster of. Diff 40: Wk 49 D1 (n=4,2,0,0)	1.3 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1B: Wk 49 D1 (n=4,3,4,14)	3.30 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	C Reactive Protein: Week 49 Day 1 (n=4,3,4,14)	2.40 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	AFP: Week 25 Day 1 (Wk 25 D1) (n=7,8,5,22)	0.79 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VWF: Wk. 25 D1 (n=7,8,5,22)	65.50 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1RN: Wk 25 D1 (n=7,8,5,22)	147.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Carcinoembryyonic Antigen: Wk 49 D1 (n=4,3,4,14)	1.20 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro. Inflam. Prot-1 Beta: Wk 49 D1 (n=4,3,4,14)	487.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	ICAM1: Wk 49 D1 (n=4,3,4,14)	173.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1RN: Wk 49 D1 (n=4,3,4,14)	281.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Eotaxin1: Wk 25 D1 (n=7,8,5,22)	119.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	LEP: Wk 25 D1 (n=7,8,5,22)	4.75 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Eotaxin1: Wk 49 D1 (n=4,3,4,14)	145.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL6: Wk 25 D1 (n=7,8,5,22)	2.3 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	C Reactive Protein: Week 25 Day 1 (n=7,8,5,22)	2.70 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	B2M: Week 49 Day 1 (n=4,3,4,14)	4.60 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFRT 2: Wk 25 D1 (n=7,8,5,22)	12.00 ng/mL
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL6: Wk 49 D1 (n=4,3,4,14)	3.40 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Carcinoembryyonic Antigen: Wk 49 D1 (n=4,3,4,14)	1.45 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Cluster of. Diff 40: Wk 25 D1 (n=7,7,5,0)	0.91 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VCAM1: Wk 49 D1 (n=4,3,4,14)	2225.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Eotaxin1: Wk 25 D1 (n=7,8,5,22)	101.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Plasmin. Activ. Inhibitor 1: Wk 49 D1 (n=4,3,4,14)	49.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	ICAM1: Wk 25 D1 (n=7,8,5,22)	168.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VEGF: Wk. 25 D1 (n=7,8,5,22)	108.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	ICAM1: Wk 49 D1 (n=4,3,4,14)	152.50 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL10: Wk 25 D1 (n=7,8,5,22)	3.40 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL10: Wk 49 D1 (n=4,3,4,14)	11.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL18: Wk 25 D1 (n=7,8,5,22)	445.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VEGF: Wks. 49 D1 (n=4,3,4,14)	163.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL18: Wk 49 D1 (n=4,3,4,14)	550.50 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1B: Wk 25 D1 (n=7,8,5,22)	3.30 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	RANTES: Wk 25 D1 (n=7,8,5,22)	4.20 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1B: Wk 49 D1 (n=4,3,4,14)	4.3 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1RN: Wk 25 D1 (n=7,8,5,22)	114.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VWF: Wk. 25 D1 (n=7,8,5,22)	398.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1RN: Wk 49 D1 (n=4,3,4,14)	88.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL6: Wk 25 D1 (n=7,8,5,22)	2.3 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL6: Wk 49 D1 (n=4,3,4,14)	3.40 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL8: Wk 25 D1 (n=7,8,5,22)	15.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL8: Wk 49 D1 (n=4,3,4,14)	58.50 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	MPO: Wk 49 D1 (n=4,3,4,14)	237.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Insulin: Wk 25 D1 (n=7,8,5,22)	2.30 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Insulin: Wk 49 D1 (n=4,3,4,14)	1.65 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	LEP: Wk 49 D1 (n=4,3,4,14)	5.95 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Myoglobin: Wk 25 D1 (n=7,8,5,22)	54.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro. Inflam. Prot-1 Beta: Wk 25 D1 (n=7,8,5,22)	410.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro.-derived Chemokine: Wk 25 D1 (n=7,8,5,22)	516.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro.-derived Chemokine: Wk 49 D1 (n=4,3,4,14)	430.50 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Myoglobin: Wk 49 D1 (n=4,3,4,14)	45.50 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	MPO: Wk 25 D1 (n=7,8,5,22)	335.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Thyroxine binding globulin Wk 25 D1 (n=7,8,5,22)	45.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	RANTES: Wk 49 D1 (n=4,3,4,14)	10.55 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Thyroxine binding globulin: Wk 49 D1 (n=4,3,4,14)	72.50 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFA: Wk 25 D1 (n=7,8,5,22)	25.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Plasmin. Activ. Inhibitor 1: Wk 25 D1 (n=7,8,5,22)	17.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFA: Wk 49 D1 (n=4,3,4,14)	26.50 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	B2M: Week 25 Day 1 (n=7,8,5,22)	3.70 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Eotaxin1: Wk 49 D1 (n=4,3,4,14)	157.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	LEP: Wk 25 D1 (n=7,8,5,22)	6.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro. Inflam. Prot-1 Beta: Wk 49 D1 (n=4,3,4,14)	970.50 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFRT 2: Wk 25 D1 (n=7,8,5,22)	15.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VWF: Wk. 49 D1 (n=4,3,4,14)	716.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	AFP: Week 25 Day 1 (Wk 25 D1) (n=7,8,5,22)	1.10 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	AFP: Week 49 Day 1 (WK25 D1) (n=4,3,4,14)	0.49 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	APOA-1: Week 25 Day 1 (n=7,8,5,22)	1.60 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	APOA-1: Week 49 Day 1 (n=4,3,4,14)	1.80 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFRT 2: Wk 49 D1 (n=4,3,4,14)	16.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	B2M: Week 49 Day 1 (n=4,3,4,14)	3.25 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	BDNF: Week 25 Day 1 (n=7,8,5,22)	0.15 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	BDNF: Week 49 Day 1 (n=4,3,4,14)	0.41 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	C Reactive Protein: Week 25 Day 1 (n=7,8,5,22)	1.30 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VCAM1: Wk 25 D1 (n=7,8,5,22)	1690.00 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	C Reactive Protein: Week 49 Day 1 (n=4,3,4,14)	1.30 ng/mL
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Carcinoembryyonic Antigen: Wk 25 D1 (n=7,8,5,22)	1.20 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL6: Wk 49 D1 (n=4,3,4,14)	3.40 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL10: Wk 25 D1 (n=7,8,5,22)	6.23 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	B2M: Week 25 Day 1 (n=7,8,5,22)	3.15 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	RANTES: Wk 25 D1 (n=7,8,5,22)	8.80 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL6: Wk 25 D1 (n=7,8,5,22)	3.40 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VWF: Wk. 25 D1 (n=7,8,5,22)	156.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Carcinoembryyonic Antigen: Wk 49 D1 (n=4,3,4,14)	1.80 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1RN: Wk 49 D1 (n=4,3,4,14)	85.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	BDNF: Week 49 Day 1 (n=4,3,4,14)	0.52 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	LEP: Wk 25 D1 (n=7,8,5,22)	6.40 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1RN: Wk 25 D1 (n=7,8,5,22)	88.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VEGF: Wk. 25 D1 (n=7,8,5,22)	168.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Plasmin. Activ. Inhibitor 1: Wk 49 D1 (n=4,3,4,14)	52.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	ICAM1: Wk 49 D1 (n=4,3,4,14)	163.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Carcinoembryyonic Antigen: Wk 25 D1 (n=7,8,5,22)	1.80 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VWF: Wk. 49 D1 (n=4,3,4,14)	154.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFRT 2: Wk 25 D1 (n=7,8,5,22)	17.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1B: Wk 49 D1 (n=4,3,4,14)	4.3 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	C Reactive Protein: Week 25 Day 1 (n=7,8,5,22)	4.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	AFP: Week 25 Day 1 (Wk 25 D1) (n=7,8,5,22)	0.49 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Plasmin. Activ. Inhibitor 1: Wk 25 D1 (n=7,8,5,22)	51.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL1B: Wk 25 D1 (n=7,8,5,22)	4.3 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Eotaxin1: Wk 25 D1 (n=7,8,5,22)	118.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VEGF: Wks. 49 D1 (n=4,3,4,14)	217.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	ICAM1: Wk 25 D1 (n=7,8,5,22)	185.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	APOA-1: Week 25 Day 1 (n=7,8,5,22)	2.10 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL18: Wk 49 D1 (n=4,3,4,14)	318.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL18: Wk 25 D1 (n=7,8,5,22)	415.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro. Inflam. Prot-1 Beta: Wk 49 D1 (n=4,3,4,14)	521.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Myoglobin: Wk 25 D1 (n=7,8,5,22)	39.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VCAM1: Wk 49 D1 (n=4,3,4,14)	1715.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro.-derived Chemokine: Wk 25 D1 (n=7,8,5,22)	254.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro. Inflam. Prot-1 Beta: Wk 25 D1 (n=7,8,5,22)	513.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	LEP: Wk 49 D1 (n=4,3,4,14)	5.60 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	APOA-1: Week 49 Day 1 (n=4,3,4,14)	2.05 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Macro.-derived Chemokine: Wk 49 D1 (n=4,3,4,14)	212.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	C Reactive Protein: Week 49 Day 1 (n=4,3,4,14)	0.79 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Insulin: Wk 49 D1 (n=4,3,4,14)	1.60 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	VCAM1: Wk 25 D1 (n=7,8,5,22)	1930.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	MPO: Wk 25 D1 (n=7,8,5,22)	164.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Myoglobin: Wk 49 D1 (n=4,3,4,14)	45.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	B2M: Week 49 Day 1 (n=4,3,4,14)	3.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Thyroxine binding globulin Wk 25 D1 (n=7,8,5,22)	54.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFRT 2: Wk 49 D1 (n=4,3,4,14)	12.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	MPO: Wk 49 D1 (n=4,3,4,14)	116.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL10: Wk 49 D1 (n=4,3,4,14)	8.40 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Thyroxine binding globulin: Wk 49 D1 (n=4,3,4,14)	54.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Insulin: Wk 25 D1 (n=7,8,5,22)	0.6 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL8: Wk 49 D1 (n=4,3,4,14)	32.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	Eotaxin1: Wk 49 D1 (n=4,3,4,14)	175.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFA: Wk 25 D1 (n=7,8,5,22)	12.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	BDNF: Week 25 Day 1 (n=7,8,5,22)	0.55 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	IL8: Wk 25 D1 (n=7,8,5,22)	29.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	RANTES: Wk 49 D1 (n=4,3,4,14)	6.50 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	TNFA: Wk 49 D1 (n=4,3,4,14)	12.00 ng/mL
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers	AFP: Week 49 Day 1 (WK25 D1) (n=4,3,4,14)	0.49 ng/mL

Secondary

Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1

Phase Ib and Phase ll: Change in Pharmacodynamic Biomarkers: JAK2V617F allele burden

Time frame: Baseline, Week 25 Day 1 (Week 24), Week 49 Day 1 (Week 48)

Arm	Measure	Group	Value (MEDIAN)
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1 (n=4,3,4,13)	86.0 Percentage of JAK allele burden mutation
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1 (n=7,6,5,21)	88.6 Percentage of JAK allele burden mutation
LDE225 400mg + INC424 10mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Baseline	84.7 Percentage of JAK allele burden mutation
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1 (n=4,3,4,13)	54.3 Percentage of JAK allele burden mutation
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Baseline	61.7 Percentage of JAK allele burden mutation
LDE225 400mg + INC424 15mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1 (n=7,6,5,21)	48.0 Percentage of JAK allele burden mutation
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Baseline	88.3 Percentage of JAK allele burden mutation
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1 (n=7,6,5,21)	74.9 Percentage of JAK allele burden mutation
LDE225 400mg + INC424 20mg (Dose Escalation Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1 (n=4,3,4,13)	75.7 Percentage of JAK allele burden mutation
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Week 49 Day 1 (n=4,3,4,13)	46.1 Percentage of JAK allele burden mutation
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Week 25 Day 1 (n=7,6,5,21)	43.8 Percentage of JAK allele burden mutation
LDED225 400mg + INC424 20mg (Dose Expansion Phase)	Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1	Baseline	55.4 Percentage of JAK allele burden mutation

Source: ClinicalTrials.gov · Data processed: Mar 6, 2026

A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)

Percentage of Patients Achieving >= 35% Reduction in Spleen Volume in Phase Ib Expansion and Phase II Stage 1

Phase I and Phase II: Change in EORTC QLQ-C30 Scores From Baseline Compared to Week 24 & Week 48

Phase Ib and Phase II: Change in Total Symptom Score (TSS) From Baseline to Week 25 & Week 49 Using the MFSAF Total Symptom Scores

Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast

Phase Ib and Phase II: INC424: PK Parameter: T1/2

Phase Ib and Phase II: INC424: PK Parameter: Vss/F

Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)

Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)

Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)

Phase Ib and Phase II: LDE225: PK Parameter: Racc

Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)

Phase Ib and Phase II: Percentage of Participants With >= 50% Reduction From Baseline in MFSAF Total Symptom Scores

Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1

Phase Ib and Phase ll: Summary of Cytokine Levels in Pharmacodynamic for All Collected Biomarkers

Phase Ib and Phase ll: Summary of JAK2V617F Allele Burden by Visit and Treatment in Phase Ib and Phase II Stage 1