Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 sparse sampling in Group 4.

AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast).

PAS: The Pharmacokinetic Analysis Set (PAS) included all subjects who provided at least one evaluable PK concentration. For a concentration to be evaluable, subjects were required to:

• Take the dose of ruxolitinib prior to PK sample.
• For pre-dose samples, to not vomit within 2 hours after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hours after the dosing of ruxolitinib.

No subjects were enrolled in Group 4.

Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4.

Cmax: The maximum (peak) observed plasma drug concentration

PAS: The Pharmacokinetic Analysis Set (PAS) included all subjects who provided at least one evaluable PK concentration. For a concentration to be evaluable, subjects were required to:

• Take the dose of ruxolitinib prior to PK sample.
• For pre-dose samples, to not vomit within 2 hours after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hours after the dosing of ruxolitinib.

No subjects were enrolled in Group 4.

Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4.

T1/2: The elimination half-life associated with the terminal slope (Lambda_z ) of a semi logarithmic concentration-time curve

PAS: The Pharmacokinetic Analysis Set (PAS) included all subjects who provided at least one evaluable PK concentration. For a concentration to be evaluable, subjects were required to:

• Take the dose of ruxolitinib prior to PK sample.
• For pre-dose samples, to not vomit within 2 hours after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hours after the dosing of ruxolitinib.

No subjects were enrolled in Group 4.

Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4. Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).

PAS: The Pharmacokinetic Analysis Set (PAS) included all subjects who provided at least one evaluable PK concentration. For a concentration to be evaluable, subjects were required to:

• Take the dose of ruxolitinib prior to PK sample.
• For pre-dose samples, not vomit within 2 hours after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hours after the dosing of ruxolitinib.

No subjects were enrolled in Group 4.

Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3

• Group 2: age ≥ 6 to < 12 years
• Group 3: age ≥ 2 to < 6 years AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast).

PAS: The Pharmacokinetic Analysis Set (PAS) included all subjects who provided at least one evaluable PK concentration. For a concentration to be evaluable, subjects were required to:

• Take the dose of ruxolitinib prior to PK sample.
• For pre-dose samples, not vomit within 2 hours after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hours after the dosing of ruxolitinib.

No subjects were enrolled in Group 4.

Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3

• Group 2: age ≥ 6 to < 12 years
• Group 3: age ≥ 2 to < 6 years Cmax: The maximum (peak) observed plasma drug concentration.

PAS: The Pharmacokinetic Analysis Set (PAS) included all subjects who provided at least one evaluable PK concentration. For a concentration to be evaluable, subjects were required to:

• Take the dose of ruxolitinib prior to PK sample.
• For pre-dose samples, not vomit within 2 hours after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hours after the dosing of ruxolitinib.

No subjects were enrolled in Group 4.

Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3

• Group 2: age ≥ 6 to < 12 years
• Group 3: age ≥ 2 to < 6 years Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).

PAS: The Pharmacokinetic Analysis Set (PAS) included all subjects who provided at least one evaluable PK concentration. For a concentration to be evaluable, subjects were required to:

• Take the dose of ruxolitinib prior to PK sample.
• For pre-dose samples, not vomit within 2 hours after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hours after the dosing of ruxolitinib.

No subjects were enrolled in Group 4.

Phase II: ORR is defined as the percentage of patients demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response was relative to the organ stage at the start of the study treatment.

Complete response (CR) is defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapy for any earlier progression, mixed response or non-response of aGvHD.

Partial response (PR) is defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapy for an earlier progression, mixed response or non-response of aGvHD.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the recommended phase 2 dose (RP2D) of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

Durable ORR at Day 56 was defined as the percentage of all subjects who achieved a complete response (CR) or partial response (PR) at Day 28 and maintained a CR or PR at Day 56.

Complete-response was defined as a score of 0 for the acute GvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of acute GvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of acute GvHD.

Partial response was defined as improvement of 1 stage in 1 or more organs involved with acute GvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of acute GvHD.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

ORR at Day 14 was defined as the percentage of participants with complete response (CR) or partial response (PR ) at Day 14 according to standard criteria.

Complete response (CR) is defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapy for any earlier progression, mixed response or non-response of aGvHD.

Partial response (PR) is defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapy for an earlier progression, mixed response or non-response of aGvHD.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with ORR at day 28). ORR is the percentage of patients with a complete response (CR) or partial response (PR) without additional systemic therapies. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the odds ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.

PK-Efficacy set includes 40 subjects from F12201. CR is a score of 0 for the aGvHD grading in all evaluable organs that indicate complete resolution of all signs of aGvHD in all evaluable organs without administration of additional systemic therapy for aGvHD.

PR is improvement of 1 stage in 1 or more organs involved with aGvHD signs without progression in other organs or sites without administration of additional systemic therapy of aGvHD. No subjects were enrolled in Group 4.

To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with DRR at day 56). Durable ORR at Day 56 was defined as the percentage of all participants who achieved a complete response (CR) or partial response (PR) at Day 28 and maintained a CR or PR at Day 56. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the odds ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.

PK-Efficacy set includes 40 subjects from F12201. CR is a score of 0 for the aGvHD grading in all evaluable organs that indicate complete resolution of all signs of aGvHD in all evaluable organs without administration of additional systemic therapy for aGvHD.

PR is improvement of 1 stage in 1 or more organs involved with aGvHD signs without progression in other organs or sites without administration of additional systemic therapy of aGvHD. No subjects were enrolled in Group 4.

To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with safety - bleeding). Bleeding was reported as an adverse event and the AE severity grade was assessed according to CTCAE grading. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the hazard ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.

PK-Safety set includes 40 subjects from F12201. No subjects were enrolled in Group 4.

To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with safety - infection). This analysis includes subjects from F12201 (pediatric and adolescent participants) study. Infections were reported as adverse events and the AE severity grade was assessed according to CTCAE grading. Given age group did not have a significant effect on the model fit, the comparison is made indirectly throughs the hazard ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence

PK-Safety set includes 40 subjects from F12201. No subjects were enrolled in Group 4.

Duration of response was defined as the time from first response (PR or CR) until acute GvHD progression, or the date of additional systemic therapy for acute GvHD. Death without prior observation of acute GvHD progression, and onset of chronic GvHD are considered to be competing risks. Duration of response will be censored at the last response assessment prior to or at the analysis cut-off date, if no events/competing risks occurred on or before 4 weeks (28 days) after the last GvHD assessment. The estimated probability of loss of response at 1, 2 and 6 months after participant's first achievement of CR or PR has been reported. Due to the presence of competing risk, the DOR results are being presented in the form of the probability of loss of response at different time points. As planned in the Statistical Analysis Plan (SAP), this outcome measure is provided for all subjects instead of per age groups.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. The DOR was assessed only for responders (i.e. those with CR or PR) at Day 28. No subjects were enrolled in Group 4.

The weekly cumulative steroid dose was calculated for each subject up to Day 56 and the overall cumulative steroid dose was calculated for each subject at Day 56.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

OS is defined as the time from the start of treatment to the date of death due to any cause. If a subject was not known to have died, then OS was censored at the latest date the subject was known to be alive. The estimated survival probability at 1,2,6,12,18 months after start of treatment has been reported. (on or before the cut-off date). As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

EFS is defined as the time from start of treatment to the date of hematologic disease relapse/progression, graft failure, or death due to any cause. If a subject was not known to have any event, then EFS was censored at the latest date the subject was known to be alive (on or before the cut-off date).The estimated probability of event free at 1,2,6,12,18 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

Failure-free (FF) survival was defined as the time from start date of treatment to any of the following: hematologic relapse/progression, non-relapse mortality (NRM) or addition of new systemic acute GvHD treatment. The cumulative incidence (CI) of the onset of failure event at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

NRM is defined as the time from start of treatment to date of death not preceded by hematologic disease relapse/progression. The cumulative incidence (CI) of non-relapse mortality at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

MR was defined as the time from start of treatment to hematologic malignancy relapse/progression. Calculated for patients with underlying hematologic malignant disease. The cumulative incidence (CI) of malignancy relapse/progression at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

cGvHD is defined as the diagnosis of any cGvHD including mild, moderate, severe. Incidence of chronic GvHD was the time from the start of treatment to onset of chronic GvHD. Cumulative incidence of chronic GvHD was estimated, accounting for deaths without prior onset of chronic GvHD and hematologic disease relapse/progression as the competing risks. The cumulative incidence (CI) of cGvHD at 1, 2, 6, 12, 18 and 24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

This was assessed by donor cell chimerism, defined as initial whole blood or marrow donor chimerism for those who had ≥5% donor cell chimerism at baseline. If donor cell chimerism declined to <5% on subsequent measurements, graft failure was declared.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. At the end of the study there were no confirmed cases of graft failure assessment. No subjects were enrolled in Group 4.

Responses from the acceptability and palatability of the study drug (only for subjects administered with oral pediatric formulation starting treatment Day 1) were evaluated from a questionnaire completed by subjects, with the help from parents or caregivers as needed at the following visits: Day 1 (after first dose), Week 4 (1 month) ((after either morning or evening dose of that visit date), Week 24 (6 months) (after either morning or evening dose of that visit date). The choices for taste of the medication were, 'Very good', 'good', 'not good or bad', 'Bad', very bad. The choices for aftertaste of the medication were, 'Very good', 'Good', 'Not good or bad' , 'Bad', Very bad'. The choices for the smell of the medication were, 'Not good or bad' or 'Bad'.

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level.

To assess pharmacokinetic/pharmacodynamic relationship (comparison of Cmax with efficacy). Cmax: The maximum (peak) observed plasma drug concentration.

Based on PK-safety/PK-efficacy analyses conducted in adult acute & chronic GvHD studies (REACH2 & REACH3), AUC was considered the most informative PK metric to assess the relationship between PK (exposure to ruxolitinib) and efficacy/safety/pharmadynamic (PD) parameters. Thus, to assess PK-safety, PK-efficacy and PK-PD biomarker in pediatric GvHD patients, AUC was selected as the PK measure of interest; the relationship between Cmax/Ctrough and efficacy/safety/PD biomarker was not investigated.

To assess pharmacokinetic/pharmacodynamic relationships (comparison of Ctrough with safety). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).

Based on PK-safety/PK-efficacy analyses conducted in adult acute & chronic GvHD studies (REACH2 & REACH3), AUC was considered the most informative PK metric to assess the relationship between PK (exposure to ruxolitinib) and efficacy/safety/pharmadynamic (PD) parameters. Thus, to assess PK-safety, PK-efficacy and PK-PD biomarker in pediatric GvHD patients, AUC was selected as the PK measure of interest; the relationship between Cmax/Ctrough and efficacy/safety/PD biomarker was not investigated.

To assess pharmacokinetic/pharmacodynamics relationship (comparison of Cmax with safety). Cmax: The maximum (peak) observed plasma drug concentration.

Based on PK-safety/PK-efficacy analyses conducted in adult acute & chronic GvHD studies (REACH2 & REACH3), AUC was considered the most informative PK metric to assess the relationship between PK (exposure to ruxolitinib) and efficacy/safety/pharmadynamic (PD) parameters. Thus, to assess PK-safety, PK-efficacy and PK-PD biomarker in pediatric GvHD patients, AUC was selected as the PK measure of interest; the relationship between Cmax/Ctrough and efficacy/safety/PD biomarker was not investigated.

To assess pharmacokinetic/pharmacodynamics relationship (comparison of Ctrough with efficacy). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).

Based on PK-safety/PK-efficacy analyses conducted in adult acute & chronic GvHD studies (REACH2 & REACH3), AUC was considered the most informative PK metric to assess the relationship between PK (exposure to ruxolitinib) and efficacy/safety/pharmadynamic (PD) parameters. Thus, to assess PK-safety, PK-efficacy and PK-PD biomarker in pediatric GvHD patients, AUC was selected as the PK measure of interest; the relationship between Cmax/Ctrough and efficacy/safety/PD biomarker was not investigated.

Describe the relationship between AUC and PD biomarkers. Provide profile of biomarker concentration changes across different AUC quantile groups from baseline. This analysis includes subjects from F12201 study. Population was divided by four level of exposure using AUClast Day 1 quartiles. As planned in SAP, this outcome measure is provided for all subjects instead of per age groups.

PAS included all subjects (subjs) who provided at least 1 evaluable PK concentration. For a concentration to be evaluable, subjs were required to: Take the dose of ruxolitinib prior to PK sample; For pre-dose samples, to not vomit within 2 hrs after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hrs after the dosing of ruxolitinib. Subjs in each age grp were combined as pre-specified in the Stats Analysis Plan. No subjs were enrolled in Grp 4.

To assess pharmacokinetic/pharmacodynamic relationship (comparison of Cmax with PD biomarkers). Cmax: The maximum (peak) observed plasma drug concentration.

Based on PK-safety/PK-efficacy analyses conducted in adult acute & chronic GvHD studies (REACH2 & REACH3), AUC was considered the most informative PK metric to assess the relationship between PK (exposure to ruxolitinib) and efficacy/safety/pharmadynamic (PD) parameters. Thus, to assess PK-safety, PK-efficacy and PK-PD biomarker in pediatric GvHD patients, AUC was selected as the PK measure of interest; the relationship between Cmax/Ctrough and efficacy/safety/PD biomarker was not investigated.

To assess pharmacokinetic/pharmacodynamics relationship (Ctrough with PD biomarkers). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).

Based on PK-safety/PK-efficacy analyses conducted in adult acute & chronic GvHD studies (REACH2 & REACH3), AUC was considered the most informative PK metric to assess the relationship between PK (exposure to ruxolitinib) and efficacy/safety/pharmadynamic (PD) parameters. Thus, to assess PK-safety, PK-efficacy and PK-PD biomarker in pediatric GvHD patients, AUC was selected as the PK measure of interest; the relationship between Cmax/Ctrough and efficacy/safety/PD biomarker was not investigated.

The best overall response (BOR) was defined as percentage of participants with (complete response (CR) or partial response (PR) at any time point and up to and including Day 28 and before the start of additional systemic therapy for acute GvHD (aGvHD).

The Efficacy Evaluable Set (EES) comprised all subjects to whom study treatment was assigned at the RP2D of ruxolitinib and who received at least one dose of study treatment at that dose level. No subjects were enrolled in Group 4.

Adverse events and on-treatment deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, for a maximum duration of 380 days.

Post-treatment survival follow-up deaths were collected 31 days after last dose of study medication until the end of the study, up to approx. 23 months.

Clinical database population: all treated patients, patients who died during screening and patients who were enrolled into the study. No subjects were enrolled in Group 4.