A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of AK002 in Adult and Adolescent Subjects with Active Eosinophilic Esophagitis

1) Male or female aged >=12 and <=80 years at the time of signing ICF.
2) Confirmed diagnosis of EoE and intraepithelial eosinophilic infiltration of
>=15 eosinophils/hpf in 1 hpf from the biopsy collected during the Screening EGD
without any other cause for the esophageal eosinophilia.
3) Baseline DSQ (biweekly mean DSQ) score of >=12 from the last 2 weeks of
Screening (the 14 days prior to the first dose). per the validated Algorithm in
Appendix 11.
4) History (by subjject report) of an average of >=2 episodes of dysphagia with
intake of solid foods per week during the 4 weeks prior to Screening.
5) Subjects must have failed or not be adequately controlled on standard of
care treatments for EoE symptoms, which could include PPI, systemic or topical
corticosteroids, and/or diet, among others.
6) If on an allowed treatment for EoE (per Section 8), stable dose for at least
4 weeks prior to Screening and willingness to continue that dose for the study
duration.
7) If subject is on pre-existing dietary restrictions, willingness to maintain
dietary restrictions throughout the study, as much as possible.
8) Able and willing to comply with all study procedures.
9) Female subjects must be either post-menopausal for at least 1 year with FSH
level >30 mIU/mL at Screening or surgically sterile (tubal ligation,
hysterectomy, or bilateral oophorectomy) for at least 3 months, or if of
childbearing potential, have a negative pregnancy test and either agree to use
dual methods of contraception, have a
partner who had a vasectomy, or agree to abstain from sexual activity from
screening until the end of the study, or for 120 days following the last dose
of study drug, whichever is longer.
Non-vasectomized male subjects with female partners of childbearing potential
must agree to either abstain from sexual activity or agree to a highly
effective method of contraception from Screening until the end of the study or
for 120 days following the last dose of study drug, whichever is longer. All
fertile men with female partners of childbearing potential should be instructed
to contact the Investigator immediately if they suspect their partner might be
pregnant at any time during study participation.

1) Concomitant moderately or severely symptomatic EG and/or (with or without
EoD*,) defined as
• >=30 eosinophils/hpf in 5 hpf in the stomach (EG) and/or >=30 eosinophils/hpf
in 3 hpf in the duodenum (EoD) without any other cause for eosinophilia as
determined by central histology assessment of biopsies collected during the
Screening EGD

and
• an EG/EoD PRO Questionnaire weekly average single symptom score of >=3 during
the last 2 weeks of Screening for 1 of the following symptoms: abdominal pain,
nausea, and/or diarrhea.

* This exclusion criterion is only applicable to sites actively enrolling
patients in the AK002-016 study. If a site is not actively screening and
enrolling subjects in the AK002-016 study, then this exclusion criterion is not
applicable.

2) Causes of esophageal eosinophilia other than EoE or one the following:
hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, or
peripheral blood absolute eosinophil count of >1500 eosinophils/µL.
3) History of inflammatory bowel disease, celiac disease, achalasia, and/or
esophageal surgery.
4) Any esophageal stricture unable to be passed with a standard diagnostic 9 mm
to 10 mm upper endoscope or any critiacal esophageal stricture that requires
dilatation during screening.
5) History of bleeding disorders or esophageal varices.
6) History of malignancy; except carcinoma in situ, early stage prostate
cancer, or non-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 breast cancer). All history of malignancy (including
diagnosis, dates, and compliance with cancer screening recommendations) must be
documented and certified by the Investigator, along with the statement that in
their clinical judgment the tissue eosinophilia is attributable to EGID, rather
than recurrence of malignancy.
7) Active Heliobacter pylori infection as determined by central histology
staining of the biopsy collected during the Screening EGD, unless treated and
confirmed to be negtive prior to randomization and symptoms remain consistent.
8) Positive Ova and Parasite (O&P) test at Screening, seropositive for
Strongyloides stercoralis at Screening, and/or treatment for a clinically
significant helminthic parasitic infection within 6 months of Screening.
9) Seropositive for HIV or hepatitis at Screening, except for vaccinated
subjects or subjects with a history of hepatitis that has since resolved.
10) Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
11) Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI,
and/or diet therapy within 4 weeks prior to Screening.
12) Use of oral corticosteroids (swallowed topical or systemic corticosteroids)
within 8 weeks prior to Screening.
Exclusion Criteria cont.
13) Use of any biologics or medications that may interfere with the study, such
as immunosuppressive or immunomodulatory drugs including azathioprine, JAK
inhibitors, 6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF,
anti-IL-4 receptor, 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 12 weeks prior to Screening.
14) Participation in a concurrent interventional study with the last
intervention occurring within 30 days prior to administration of study drug or
90 days or 5 half-lives, whichever is longer, for biologic products.
15) Vaccination with live attenuated vaccines <=30 days prior to initiation of
treatment in the study, during the treatment period, or vaccination expected <=5
half-lives (<=4 months) following study drug administration. (with the exception
of a COVID-19 vaccine authorized by the FDA or other applicable regulatory
agency).

16) Treatment with chemotherapy or radiotherapy in the preceding 6 months.
17) Presence of abnormal laboratory values considered by the Investigator to be
clinically significant.
18) Any disease, condition (medical or surgical), or cardiac abnormality, which
in the opinion of the Investigator, would place the subject at increased risk.
19) Known history of alcohol, drug, or other substance abuse or dependence.
20) Women who are pregnant, breastfeeding, or planning to become pregnant while
participating in the study.
21) Any other reason that in the opinion of the Investigator or Medical Monitor
makes the subject unsuitable for enrolment.