A Phase 2A Study of ALXN1007 in Participants With Newly Diagnosed Acute Lower Gastrointestinal Graft-Versus-Host Disease

This was a Phase 2A open-label, non-randomized study to evaluate the safety, tolerability,
PK/PD, and efficacy of ALXN1007 (a C5a inhibitor) in up to 36 participants with newly
diagnosed acute GVHD of the lower GI tract. All participants meeting the inclusion and
exclusion criteria for the study were to receive ALXN1007 over an 8 week treatment period.
Participants in Cohort 1, the first dosing cohort, were to receive 10 milligrams/kilogram
(mg/kg) ALXN1007 administered IV once weekly for 8 weeks. Participants in Cohort 2 were to
receive 20 mg/kg ALXN1007 IV once weekly for 8 weeks. Participants in Cohort 3 were to
receive 20 mg/kg ALXN1007 IV twice weekly for 8 weeks. All doses of ALXN1007 were to be
administered as a continuous IV infusion.

Inclusion Criteria:

- Participants must be males or females age 18 years or older.

- Participants with Stage 1 to 4 (per the Modified Keystone Grading Schema) acute GVHD
of the lower GI tract, without signs of chronic GVHD, at the time of diagnosis, which
developed in the first 180 days following allogeneic hematopoietic cell
transplantation (HCT) using bone marrow, peripheral blood, or cord blood; or after
preplanned donor lymphocyte infusion.

- Participants are willing to undergo or must have had an endoscopy of the upper and/or
lower GI tract and biopsy to confirm GI GVHD.

- Participants must be receiving systemic corticosteroids.

- Participants with an absolute neutrophil count (ANC) >500/microliter (μL) at
Screening.

- Participants and spouse/partner who are of childbearing potential must be using high
effective contraception consisting of 2 forms of birth control (at least 1 of which
much be barrier method) starting at Screening and continuing through the entire study
(for at least 3 months after the last dose of ALXN1007 if study treatment is stopped
early or participant withdraws consent).

- Male participants must not donate sperm during the Screening and Treatment periods,
and for at least 3 months after the last dose of ALXN1007.

- Stage of acute GVHD of the lower GI tract will be determined using the Modified
Keystone Grading Schema.

Exclusion Criteria:

- Participants with a body weight > 140 kg (for Cohorts dosing 20 mg/kg of ALXN1007 and
higher only).

- Participants with signs and symptoms of chronic GVHD.

- Participants with an active uncontrolled infection.

- Participants who test positive for Clostridium difficile (C. difficile) at Screening.

- Participants with relapsed/persistent malignancy requiring rapid immune suppression
withdrawal.

- Participants who received an unplanned (not part of the original transplant therapy
plan) donor lymphocyte infusion.

- Participants who received previous systemic treatment for acute GVHD, except for a
maximum of 3 days (72 hours) of 2 mg/kg corticosteroid therapy.

- Participants with unresolved veno-occlusive disease of the liver.

- Participants with creatinine clearance <40 milliliters (mL)/minute at Screening, as
calculated by the Cockcroft-Gault formula.

- Participants known to be infected with human immunodeficiency virus (HIV), hepatitis
B, or hepatitis C.

- Participants known to have an uncontrolled thyroid disorder.

- Participants who are pregnant, breast feeding, or sexually active and unwilling to use
effective birth control for the duration of the study.

- Participants who participated in any other investigational drug trial or had exposure
to any other investigational agent, device, or procedure <4 weeks prior to Screening
and throughout the entire trial, with the exception of investigational drugs
administered prophylactically for cytomegalovirus (CMV) post allogeneic HCT.