Proof-of-concept Trial of Apraglutide in Acute Graft Versus Host Disease (aGVHD)

Number of Participants With Adverse Events (AEs)

Time frame · Screening (up to 12 weeks) through End of Trial (up to 2 years/104 weeks) for a total of up to 116 weeks

AE=any untoward medical occurrence which does not necessarily have a causal relationship with study drug. Serious AE (SAE)=any AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study drug; is a clinically significant event in the Investigator's judgment. Treatment-emergent AE (TEAE)=AE with a start on or after the first administration of apraglutide (or present prior to the first dose of apraglutide but worsening in severity after starting treatment relative to the pre-treatment state) up to 28 days after the last dose of apraglutide. Pre-treatment AE=occurs after informed consent and before first dose; post-treatment AE=occurs after 28 days from last dose. AE are graded as follows: mild (1), moderate (2), severe (3), life-threatening (4), death (5).

Number of Participants With Treatment-Emergent Adverse Events of Special Interest (AESIs)

Time frame · From first dose of study drug through End of Trial (up to 2 years/104 weeks) for a total of up to 116 weeks

An AESI (serious or non-serious) is an AE of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring, additional information, and rapid communication by the Investigator to the Sponsor is appropriate. AESIs include: * Injection site reactions * Gastrointestinal obstructions * Gallbladder, biliary, and pancreatic disease * Fluid overload * Colorectal polyps * Newly diagnosed malignancies * Systemic hypersensitivity

Number of Participants With Clinically Significant Changes From Baseline Over Time in Vital Signs

Time frame · Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial

Systolic Blood Pressure: * High is defined as \>= 160 mmHg AND \>=20 mmHg increase from baseline * Low is defined as \<= 90 mmHg AND \>=20 mmHg decrease from baseline Diastolic Blood Pressure: * High is defined as \>= 100 mmHg AND \>=15 mmHg increase from baseline * Low is defined as \<= 50 mmHg AND \>=15 mmHg decrease from baseline Heart Rate: * High is defined as \>= 120 bpm AND \>= 15 bpm increase from baseline * Low is defined as \<= 50 bpm AND \>= 15 bpm decrease from baseline Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.

Number of Participants With Clinically Significant Changes From Baseline Over Time in QT Corrected for Heart Rate Using Fridericia's Formula (QTcF)

Time frame · Baseline, Weeks 26, 52, 104/End of Trial

Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.

Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)

Time frame · Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial

Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.

Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Total Bilirubin

Time frame · Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial

Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.

Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Potential Hy's Law Cases

Time frame · Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial

Potential Hy's Law cases were defined as ALT or AST \>= 3 x ULN AND total bilirubin \>= 2 x ULN AND alkaline phosphatase (ALP) \<= 2 x ULN at the same visit. Baseline is defined as the last measurement prior to the first dose of apraglutide.

Number of Participants With Anti-drug Antibodies (ADAs) Over Time

Time frame · Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial

Overall Response Rate at Day 56 on the Lower Gastrointestinal (GI) Tract Mount Sinai aGVHD International Consortium (MAGIC) Stage

Time frame · Day 56

Overall response rate at Day 56 on the lower GI tract MAGIC stage is defined as the percentage of participants with complete response (CR) or partial response (PR) on the lower GI tract MAGIC stage at Day 56. Lower GI (Stool Output/Day) MAGIC Stages are 0: \<500 mL/day or \<3/episodes/day; 1: 500-999 mL/day or 3-4/episodes/day; 2: 1000-1500 mL/day or 5-7/episodes/day; 3: \>1500 mL/day or \>7/episodes/day; 4: Severe abdominal pain with or without ileus or grossly bloody stool (regardless of volume). CR: Score of 0 in lower GI tract MAGIC stage that indicates complete resolution of all signs and symptoms of aGVHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGVHD. PR: Improvement of one stage in lower GI tract MAGIC stage without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGVHD.

Overall Response Rate Over Time on the Lower GI Tract MAGIC Stage

Time frame · Days 14, 28, 56, 91, 119, 147, and 182

Overall response rate on the lower GI tract MAGIC stage is defined as the percentage of participants with CR or PR on the lower GI tract MAGIC stage at given time points. Lower GI (Stool Output/Day) MAGIC Stages are 0: \<500 mL/day or \<3/episodes/day; 1: 500-999 mL/day or 3-4/episodes/day; 2: 1000-1500 mL/day or 5-7/episodes/day; 3: \>1500 mL/day or \>7/episodes/day; 4: Severe abdominal pain with or without ileus or grossly bloody stool (regardless of volume). CR: Score of 0 in lower GI tract MAGIC stage that indicates complete resolution of all signs and symptoms of aGVHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGVHD. PR: Improvement of one stage in lower GI tract MAGIC stage without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGVHD.

Overall Response Rate Over Time on the Total MAGIC Stage

Time frame · Days 14, 28, 56, 91, 119, 147, and 182

Overall response rate on Total MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver is defined as the percentage of participants with CR or PR on the total MAGIC stage. Staging values range from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.) CR: 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 4 evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGVHD. PR: An improvement of one stage in one or more evaluable organs involved with aGVHD 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 aGVHD.

Durable Overall Response Rates on the Lower GI and Total MAGIC Score From Day 28 to Day 56

Time frame · Day 28 to Day 56

Durable overall response rate on the Lower GI MAGIC Score from Day 28 to Day 56 is defined as the percentage of participants who had a response (either CR responder or PR responder, see Outcome Measure 10 description for details) on the lower GI at Day 28 and remain a CR responder or PR responder on the lower GI at Day 56. Durable overall response rate from Day 28 to Day 56 on the Total MAGIC Score is defined as the percentage of participants who had a response (either CR responder or PR responder, see Outcome Measure 12 description for details) on the total MAGIC score at Day 28 and remain a CR responder or PR responder on the total MAGIC score at Day 56. Total MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver ranges from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.)

Duration of Response From Day 56 on the Total MAGIC Score

Time frame · From Day 56 up to 2 years of follow up after the first dose

Duration of response from Day 56 on the total MAGIC score: defined as the interval from the Day 56 response (PR and CR; see definitions descriptions in Outcome Measure 12) to death or new systemic therapy for aGVHD (including an increase in steroids \>2 mg/kg/day methylprednisolone \[MP\] equivalent), whichever occurs first, with at least 182 days of follow-up. Total MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver range from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.) Full range dates are censored. Censored = participants alive and without missing overall response assessment, initiation of additional systemic therapy for aGVHD or increase of \>2 mg/kg/day MP equivalent in steroids. Subjects are right censored at their last follow-up visit.

Duration of Response From Day 28 on the Total MAGIC Score

Time frame · From Day 28 up to 2 years of follow up after the first dose

Duration of response from Day 28 on the total MAGIC score: defined as the interval from the Day 28 response (PR and CR; see definitions descriptions in Outcome Measure 12) to death or new systemic therapy for aGVHD (including an increase in steroids \>2 mg/kg/day methylprednisolone \[MP\] equivalent), whichever occurs first, with at least 182 days of follow-up. Total MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver range from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.) Full range dates are censored. Censored = participants alive and without missing overall response assessment, initiation of additional systemic therapy for aGVHD or increase of \>2 mg/kg/day MP equivalent in steroids. Subjects are right censored at their last follow-up visit.

Duration of Lower GI Response Per MAGIC Score

Time frame · Up to Day 147

Individual duration of lower GI response (either CR responder or PR responder, see Outcome Measure 10 description for details) counted from the first response to return to baseline or worse. Duration of lower GI response is defined as the duration from the first date a participant is identified as a Lower GI MAGIC Score CR or PR responder until the next date a subject is Lower GI MAGIC Score stable disease/progressed disease (SD/PD; i.e., return to baseline or worsening), experiences treatment failure, or dies, whichever occurs first.

Duration of Lower GI Response Per MAGIC Score In Retreated Participants

Time frame · Up to Day 147

Individual duration of lower GI response (either CR responder or PR responder, see Outcome Measure 10 description for details) counted from the first response to return to baseline or worse in participants that were re-treated with apraglutide because of a lower GI-aGVHD flare, counted from the first response after apraglutide restart to return to baseline or worse. Duration of lower GI response is defined as the duration from the first date a participant is identified as a Lower GI MAGIC Score CR or PR responder until the next date a subject is Lower GI MAGIC Score stable disease/progressed disease (SD/PD; i.e., return to baseline or worsening), experiences treatment failure, or dies, whichever occurs first.

Time to Partial or Complete Lower GI Response (PR or CR) Per MAGIC Score

Time frame · From first injection of apraglutide up to Day 57

Lower GI (Stool Output/Day) MAGIC Stages are 0: \<500 mL/day or \<3/episodes/day; 1: 500-999 mL/day or 3-4/episodes/day; 2: 1000-1500 mL/day or 5-7/episodes/day; 3: \>1500 mL/day or \>7/episodes/day; 4: Severe abdominal pain with or without ileus or grossly bloody stool (regardless of volume). CR: Score of 0 in lower GI tract MAGIC stage that indicates complete resolution of all signs and symptoms of aGVHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGVHD. PR: Improvement of one stage in lower GI tract MAGIC stage without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGVHD.

Best Overall Lower GI Response and Total Response at Any Time Point Up to and Including Day 91

Time frame · From first injection of apraglutide up to Day 91

Overall response rate on the Lower GI MAGIC Score is defined as the percentage of participants who had a response (either CR responder or PR responder, see Outcome Measure 10 description for details) on the lower GI score. Overall response rate on the Total MAGIC Score is defined as the percentage of participants who had a response (either CR responder or PR responder, see Outcome Measure 12 description for details) on the total MAGIC score. Best overall lower GI response and total response is defined as overall response (PR or CR) at any time point up to and including Day 91 and before the start of additional systemic therapy for lower GI aGVHD. MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver ranges from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.)