This is a phase IIa, randomized, double-blind, placebo-controlled, multi-center proof-of-concept (POC) study in subjects with moderate to severe Atopic Dermatitis.

This is a two-part phase IIa, randomized, double-blind, placebo-controlled, multi-center proof-of-concept (POC) study in adult subjects with persistent moderate to severe Atopic Dermatitis (AD). ADX-914 or matching placebo for administered subcutaneously in the clinic setting every 2 weeks for 12 weeks, and follow-up for 12 weeks. ADX-914 or matching placebo will be in the clinic setting post-randomization. In Part A, up to 3 cohorts of subjects will be randomized 2:1 drug vs placebo. In Part B subjects will be randomized 1:1 to drug vs placebo at a doses selected in Part A.

Inclusion Criteria:

1. Age ≥18 years, inclusive, at time of informed consent, with chronic AD (duration of disease ≥3 years) diagnosed by the Eichenfield revised criteria of Hanifin and Rajka.

2. Moderate to severe disease activity at baseline and screening defined as:

   1. BSA affected ≥10%
   2. EASI Score ≥12
   3. Investigators Global Score (IGA) ≥3

3. Who, in the opinion of the Investigator, have a history of inadequate response to at least one of the following:

   1. at least 4-week course of medium-potency topical steroids or other approved topical immunomodulators (calcineurin, PDE-4 and JAK inhibitors)
   2. systemic steroids or phototherapy
   3. oral chemical synthetic immunomodulators (MTX, mycophenolate mofetil, azathioprine, cyclosporine, systemic approved biologics [dupliumab, ustekinumab or tralokinumab]), or approved systemic targeted synthetic JAK inhibitors (upadacitinib, abrocitinib)

Exclusion Criteria:

1. Body weight ≤ 50.0 kg for men and ≤ 45.0 kg for women and > 120 kg at Screening
2. Rescue therapy, topical or systemic, need anticipated within 4 weeks of randomization
3. Recent (within 2 months of informed consent) or current clinically serious viral, bacterial, fungal, or parasitic infection or mycobacterial infection
4. A positive QuantiFERON®TB Gold test at Screening or history of tuberculosis (TB)
5. Have been exposed to a live vaccine within 12 weeks prior to planned randomization or are expected to receive a live vaccine during the study
6. Systemic, topical or device-based therapy of AD
7. Serious concomitant illness that could require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring
8. Other concomitant skin conditions that would interfere with evaluations of the effect of study medication on atopic dermatitis
9. Other active autoimmune diseases other than those above that would make it difficult to appropriately assess AD disease activity or pose a risk to the subject's participation in the trial
10. Pregnant or lactating women, or women planning to become pregnant or initiate breastfeeding.
11. History of sensitivity to any of the study treatments, or components thereof, or a history of drug or other allergy that, in the opinion of the Investigator, contraindicates their participation.
12. Has been in another investigational trial within 30 days or 5 half-lives of the investigational agent (whichever is greater) prior to the informed consent.