The study is divided in 3 parts, starting with the safety assessment of BPR277 ointment in Healthy volunteers (Part 1). If found to be well tolerated in Part 1, BPR277 ointment will be assessed in two different patients groups to evaluate safety and efficacy in atopic dermatitis (Part 2) and in Netherton syndrome (Part 3).

Inclusion Criteria:

Part 1 Healthy volunteers

• Healthy male and female subjects of non childbearing potential, 18 to 65 years of age inclusive and in good health

Part 2 Patients with atopic dermatitis:

• Male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations

• Presence of atopic dermatitis confirmed by Itchy skin condition in the past 12 months (must have) Plus three or more of the following:

  1. History of involvement of the skin creases
  2. Personal history of asthma or hay fever
  3. History of generally dry skin in the past year
  4. Onset before age of 2 years
  5. Visible flexural dermatitis

• Diagnosis of at least moderate atopic dermatitis by the IGA and a minimum target area (right or left) situated on the forearm including the antecubital fossa with a corresponding baseline total lesional sign score (TLSS)

Part 3 Patients with Netherton Syndrome:

• Patients with Netherton syndrome, male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations
• Confirmed diagnosis of Netherton syndrome (SPINK5 mutation or LEKTI deficiency in the skin).
• Minimum total lesional sign score NS (TLSS-NS) of 5-9 for two selected target areas at baseline. The TLSS-NS values need to be similar between the two areas at baseline.

Exclusion Criteria:

Part 1 Healthy volunteers :

• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
• Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing.

Part 2 Patients with atopic dermatitis:

• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
• History of abnormal skin reactivity to UV light. Unusual exposure to UV light in the previous 3 weeks to study start (screening), including tanning and sun beds.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential must use highly effective contraception (as further defined in study protocol)
• Use of topical prescription treatment for eczema within 1 week prior to initial dosing of topical corticosteroids (TCS).
• Recent previous treatment with systemic treatment including phototherapy. A washout period will be required for such patients to be eligible to participate in the trial.

Part 3 Patients with Netherton Syndrome:

• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
• History of abnormal skin reactivity to UV light. Unusual exposure to UV light in the previous 3 weeks to study start (screening), including tanning and sun beds.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential must use highly effective contraception (as further defined in study protocol)
• Use of topical prescription treatment within 2 week prior to initial dosing of study drug.
• Recent previous treatment with systemic treatment. A washout period will be required for such patients to be eligible to participate in the trial.