RPC1063

Defined as a reduction from Baseline in the complete Mayo score of ≥ 3 points and ≥ 30%, and a reduction from Baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point

The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease (CD). The CDAI uses a questionnaire with 8 disease activity variables: number of soft/liquid stools, severity of abdominal pain, general well-being, presence of complications, need for antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. The sub scores of number of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome.

Number of participants experiencing TEAEs, Serious TEAEs, TEAEs leading to discontinuation and TEAEs of special interest. TEAE is defined as any event with an onset date on or after the first dose date, or any ongoing event on the first dose date that worsens in severity on or after the first dose date, and until 90 days following the last dose of treatment with the study drug.

An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.

An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.

An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.

An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.

An absolute lymphocyte count (ALC) is a part of a blood test that measures the number of lymphocytes, a type of white blood cell, in the blood. Lymphocytes help fight infections and diseases. Reductions in ALC levels for participants in this study is expected and is a primary pharmacodynamic effect of RPC1063. LLN = Lower limit of normal

A white blood cell count is a part of a blood test that measures the number of white blood cells in the blood. White blood cells help fight infections and diseases. LLN = Lower limit of normal

An absolute neutrophil count is a part of a blood test that measures the number of neutrophils, a type of white blood cell, in the blood. Neutrophils help fight infections and diseases.

The number of participants with laboratory abnormalities in specific liver tests above ULN by category. ULN = Upper Limit of Normal

An electrocardiogram (ECG) measures electrical activity of the heart to detect cardiac problems.

Vital signs included body temperature, sitting heart rate/pulse (HR), sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP). Baseline refers to assessments made on or before the first day participants received study treatment.

The number of participants with abnormal physical examination results. The assessments included abdominal, extremity, head, heart, lungs, neck, neurological non-MS, other and skin assessments. Baseline refers to assessments made on or before the first day participants received study treatment.

The Columbia-Suicide Severity Rating Scale (C-SSRS) is a unique suicide risk assessment tool that supports suicide risk assessment through a series of simple, plain-language questions. The answers help users identify whether someone is at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the person needs. Results are displayed as the number of participants who answered "Yes" to at least one of the 10 questions in the suicidal ideation or suicidal behavior section. Ideation from 1 (wishing to be dead) - 5 (Active suicidal ideation with specific plan and intent) Behavior from 6 (Preparatory acts or behavior) - 10 (Completed suicide). Baseline refers to assessments made on or before the first day participants received study treatment.

The Columbia-Suicide Severity Rating Scale (C-SSRS) is a unique suicide risk assessment tool that supports suicide risk assessment through a series of simple, plain-language questions. The answers help users identify whether someone is at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the person needs. Results are displayed as the number of participants who answered "Yes" to at least one of the 10 questions in the suicidal ideation or suicidal behavior section. Ideation from 1 (wishing to be dead) - 5 (Active suicidal ideation with specific plan and intent) Behavior from 6 (Preparatory acts or behavior) - 10 (Completed suicide).

The PWC-20 is a rater-administered 20-item scale to assess signs and symptoms of withdrawal. Twenty items are rated on a 4-point scale as not present (0 points), mild (1 point), moderate (2 points), or severe (3 points). The points from all items are calculated as a total score. Higher scores indicate more severe withdrawal symptoms.

The HADS is a validated patient reported outcome for assessing anxiety and depression. It consists of 14 items in total, 7 items related to anxiety and 7 items related to depression. For each item patients select a statement (valued at 0 to 3 points) that closest matches their own feeling over the past week. Separate total scores for anxiety and depression are derived by adding up points. Total scores can range from 0 to 21 points. Higher scores indicate more severe anxiety and depression and scores of 8 to 10 are generally considered indicative of borderline anxiety/depression disorders and scores of 11 and higher are generally considered indicative of anxiety/depression disorders.

The ESS is a validated self administered questionnaire with 8 questions. Respondents rate on a 4-point scale (0 to 3) their chances of dozing off or falling asleep while engaged in 8 different activities. The ESS score is the sum of 8 item scores and can range from 0 to 24 points. Higher scores indicate more daytime sleepiness.

Vital signs included sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP).

Percentage of participants that are in Clinical remission at 10 weeks

Percentage of participants that are in Clinical remission at 52 weeks

The relapse rate was based on confirmed relapses. A relapse was defined as new or worsening neurological symptoms attributable to MS and preceded by a relatively stable or improving neurological state for at least 30 days. Symptoms must have persisted for \> 24 hours and not be attributable to confounding clinical factors. Relapses were confirmed when accompanied by objective neurological worsening based on examination by the blinded evaluator, consistent with an increase of ≥ 0.5 on the overall EDSS score relative to the most recent EDSS assessment, or 2 points on one of the functional system scale scores, or 1 point on ≥ two functional system scale scores. Relapse rate was calculated as the total number of relapses divided by the total number of days in the study \* 365.25. ARR was adjusted for region (Eastern Europe vs rest of world), Baseline age, and Baseline number of gadolinium-enhancing lesions; the natural log transformation of time on study was included as an offset term.

A relapse was defined as new or worsening neurological symptoms attributable to MS and preceded by a relatively stable or improving neurological state for at least 30 days. Symptoms must have persisted for \> 24 hours and not be attributable to confounding clinical factors. Relapses were confirmed when accompanied by objective neurological worsening based on examination by the blinded evaluator, consistent with an increase of ≥ 0.5 on the overall EDSS score relative to the most recent EDSS assessment, or 2 points on one of the functional system scale scores, or 1 point on ≥ two functional system scale scores. Relapse rate was calculated as the total number of confirmed relapses divided by the total number of days in the study \* 365.25. ARR was based on a Poisson regression model, adjusted for region (Eastern Europe vs Rest of the World), age, and the Baseline number of gadolinium-enhancing lesions, and included the natural log transformation of time on study as an offset term.

The simple endoscopy score (SES-CD) assesses the degree of inflammation. The SES-CD assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease.

Clinical Remission was defined as: Mayo score of \<2 points and with no individual subscore of \> 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. * Stool Frequency Subscore (SFS) * Rectal bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA) Clinical Remission was based on the 4-component Mayo definition.

The cumulative number of total GdE lesions on MRI from Week 12 to Week 24. MRI scans were assessed and scored by an independent MRI analysis center with no knowledge of treatment assignment or outcomes.

AUC from time zero to the last measured time point

Area under the plasma concentration-time curve from time zero extrapolated to infinity

Maximum observed plasma concentration

Minimum observed plasma concentration

Area under the plasma concentration-time curve from time zero to dosing interval