A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Esophagitis

Key Inclusion Criteria:

1. Male or female aged ≥12 and ≤80 years at the time of signing ICF.
2. Confirmed diagnosis of EoE and esophageal intraepithelial eosinophilic infiltration of ≥15 eosinophils/hpf in 1 hpf from a biopsy collected during the Screening EGD withoutany other cause for the esophageal eosinophilia.
3. History (by patient report) of an average of ≥2 episodes of dysphagia with intake ofsolid foods per week during the 4 weeks prior to Screening.
4. Subjects must have failed or not be adequately controlled on standard of caretreatments for EoE symptoms, which could include PPI, systemic or topicalcorticosteroids, and/or diet, among others.
5. If on an allowed treatment for EoE, stable dose for at least 4 weeks prior toScreening and willingness to continue that dose for the study duration.
6. If patient is on pre-existing dietary restrictions, willingness to maintain dietaryrestrictions throughout the study, as much as possible.
7. Able and willing to comply with all study procedures.
8. Female subjects must be either post-menopausal for at least 1 year with FSH level >30mIU/mL at Screening or surgically sterile (tubal ligation,hysterectomy, or bilateraloophorectomy) for at least 3 months, or if of childbearing potential, have a negativepregnancy test and agree to use dual methods of contraception, or abstain from sexualactivity from screening until the end of the study, or for 120 days following the lastdose of study drug, whichever is longer. Male subjects with female partners ofchildbearing potential must agree to use a highly effective method of contraceptionfrom Screening until the end of the study or for 120 days following the last dose ofstudy drug,whichever is longer. All fertile men with female partners of childbearingpotential should be instructed to contact the Investigator immediately if they suspecttheir partner might be pregnant at any time during study participation.

Key Exclusion Criteria:

1. Concomitant EG, EoD, or eosinophilic colitis (EC).
2. EG and/or EoD (≥30 eosinophils/hpf in 5 hpf in the stomach and/or ≥30 eosinophils/hpfin 3 hpf in the duodenum) as determined by central histology assessment of biopsiescollected during the Screening EGD.
3. Causes of esophageal eosinophilia other than EoE or one the following:hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, orperipheral blood absolute eosinophil count of >1500 eosinophils/μL.
4. History of inflammatory bowel disease, celiac disease, achalasia, and/or esophagealsurgery.
5. Any esophageal stricture unable to be passed with a standard diagnostic 9 mm to 10 mmupper endoscope or any critical esophageal stricture that requires dilation duringscreening.
6. History of bleeding disorders or esophageal varices.
7. History of malignancy; except carcinoma in situ, early stage prostate cancer, ornon-melanoma skin cancers. However, cancers that have been in remission for more than 5 years and are considered cured, can be enrolled (with the exception of breastcancer). All history of malignancy (including diagnosis, dates, and compliance withcancer screening recommendations) must be documented and certified by theInvestigator, along with the statement that in their clinical judgment the tissueeosinophilia is attributable to EGID, rather than recurrence of malignancy.
8. Active Helicobacter pylori infection (as determined by central histology staining ofthe biopsy collected during the Screening EGD), unless treated and confirmed to benegative prior to randomization and symptoms remain consistent.
9. Positive Ova and Parasite (O&P) test at Screening, seropositive for Strongyloidesstercoralis at Screening, and/or treatment for a clinically significant helminthicparasitic infection within 6 months of Screening.
10. Seropositive for HIV or hepatitis at Screening, except for vaccinated patients orpatients with a history of hepatitis that has since resolved.
11. Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
12. Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diettherapy within 4 weeks prior to Screening.
13. Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8weeks prior to Screening.
14. Use of any biologics or medications that may interfere with the study, such asimmunosuppressive or immunomodulatory drugs including azathioprine, JAK inhibitors, 6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-4receptor, e.g., dupilumab), anti-IL-5 (e.g., mepolizumab), anti-IL-5 receptor (e.g.,benralizumab), anti-IL-13 (e.g., lebrikizumab), anti-IgE (e.g., omalizumab), within 12weeks prior to Screening.
15. Participation in a concurrent interventional study with the last interventionoccurring within 30 days prior to administration of study drug or 90 days or 5half-lives, whichever is longer, for biologic products.
16. Vaccination with live attenuated vaccines ≤30 days prior to initiation of treatment inthe study, during the treatment period, or vaccination expected ≤5 half-lives (≤4months) following study drug administration.
17. Treatment with chemotherapy or radiotherapy in the preceding 6 months.
18. Presence of abnormal laboratory values considered by the Investigator to be clinicallysignificant.
19. Any disease, condition (medical or surgical), or cardiac abnormality, which in theopinion of the Investigator, would place the subject at increased risk.
20. Known history of alcohol, drug, or other substance abuse or dependence.
21. Women who are pregnant, breastfeeding, or planning to become pregnant whileparticipating in the study.
22. Any other reason that in the opinion of the Investigator or Medical Monitor makes thepatient unsuitable for enrollment.