Safety, Tolerability and PK of ATTO-1310 in Healthy Volunteers and Patients With Atopic Dermatitis and Patients With Chronic Pruritus

Parts 1 & 2 (Healthy Volunteers) Key Inclusion Criteria:

• Any sex or gender who is 18 to 65 years old

• Body weight of 50 to 125 kg and body mass index (BMI) between 18.5 and 35 kg/m2

• Considered in good general health based on medical history, physical exam, 12-leadECG, screening clinical laboratory findings, and vital signs

• Negative pregnancy test for subjects of child-bearing potential

• Use of highly effective forms of birth control

Part 3 (Subjects with Atopic Dermatitis) Inclusion Criteria:

• Any sex or gender who is 18 to 65 years old

• Body weight of 50 to 125 kg and BMI between 18.5 and 40 kg/m2

• Clinically confirmed diagnosis of active AD

• At least a 1-year history of AD and had no significant flares in AD for at least 4weeks before Screening

• Baseline weekly mean of daily PP-NRS ≥ 7 at Day 1

• EASI score of ≥ 7 at Screening and Day 1

• vIGA-AD score of ≥ 3 at Screening and Day 1

• Use of topical bland emollient (moisturizer) once or twice daily for at least 5 ofthe 7 days immediately before Day 1 and agrees to continue using that same emollientat the same frequency throughout the study

• Negative pregnancy test for subjects of child-bearing potential

• Use of highly effective forms of birth control

Part 4 (Subjects with Chronic Pruritus) Inclusion Criteria:

• Any sex or gender who is 18 to 85 years old

• Body weight of 50 to 125 kg, inclusive, and BMI between 18.5 and 40 kg/m2

• Has had chronic pruritus for at least 6 months and is unresponsive to at least a 2-week course of emollient use.

• Chronic pruritus that affects at least 2 of the following body areas: legs, arms, ortrunk

• A single PP-NRS score of ≥ 5 in the 24-hour period prior to the Screening visit

• Baseline weekly mean of daily PP-NRS ≥ 7 at Day 1

• Use of a stable dose of topical bland emollient (moisturizer) once or twice dailyfor at least 2 weeks before Day 1 and agrees to continue using that same emollientat the same frequency throughout the study

• Negative pregnancy test for subjects of child-bearing potential

• Use of highly effective forms of birth control

Parts 1 & 2 (Healthy Volunteers) Exclusion Criteria:

• Any clinically significant underlying illness.

• History of malignancy within 5 years of Screening, except adequately treated basalcarcinoma or in situ carcinoma of the cervix.

• History of major surgery within 8 weeks prior to Day 1

• History of asthma requiring regular use of a bronchodilator or a daily maintenancetherapy

• History of hypersensitivity (including anaphylaxis) to a biologic medication,vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonalantibody), or to any of the IP excipients (sucrose, polysorbate 80, or histidine)

• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or is positive for HIV

• Active or latent tuberculosis infection

• Smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent)per day

• History of drug or alcohol abuse

• Laboratory values outside of the normal range

Exclusion Criteria for Part 3 (Subjects with Atopic Dermatitis):

• Any clinically significant underlying illness

• History of a clearly defined etiology for pruritus other than AD, including but notlimited to urticaria, psoriasis, or other non-atopic dermatologic conditions,hepatic or renal disease, psychogenic pruritus, drug reaction, uncontrolledhyperthyroidism, and infection

• History of malignancy within 5 years of Screening

• History of major surgery within 8 weeks prior to Day 1 or has a major surgeryplanned during the study

• History of asthma requiring regular use of a bronchodilator or a daily maintenancetherapy

• History of recurrent eczema herpeticum

• History of known primary immunodeficiency, is considered immunocompromised, historyof untreated latent tuberculosis infection, has been treated for active tuberculosisin the past year, or has been treated for a parasitic infection in the past 6 months

• History of major depression

• History of hypersensitivity (including anaphylaxis) to a biologic medication,vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonalantibody), or to any of the IP excipients (sucrose, polysorbate 80, or histidine)

• Active HBV or HCV or is positive for HIV

• Smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent)per day

• ECG with a QTcF > 450 msec for males or > 470 msec for females at Screening

• History of drug or alcohol abuse

• Subject has applied topical corticosteroid in the 14 days preceding Day 1

• Subject has used prohibited medications or therapies during the specified washoutperiod before Day 1 (as defined in the protocol)

• Laboratory values outside of the normal range

Exclusion Criteria for Part 4 (Subjects with Chronic Pruritus):

• Primary dermatologic diagnosis associated with pruritic skin lesions at the time ofscreening

• Regional neuropathic disease associated with pruritus

• Severe renal failure requiring dialysis

• Untreated cholestatic liver disease

• Liver function tests (bilirubin, AST, ALT, alkaline phosphatase) >2.5 times abovethe upper limit of normal

• History of infectious dermatoses

• Suspected diagnosis of somatoform pruritus

• Suspected diagnosis of drug-induced pruritus

• History of malignancy within 5 years of Screening

• History of unexplained fevers, night sweats, or unintentional weight loss

• Major surgery within 8 weeks prior to Day 1 or has a major surgery planned duringthe study

• History of asthma requiring regular use of a bronchodilator or a daily maintenancetherapy

• History of known primary immunodeficiency, is considered immunocompromised,untreated latent tuberculosis infection, has been treated for active tuberculosis inthe past year, or has been treated for a parasitic infection in the past 6 months

• History of attempted suicide

• History of hypersensitivity (including anaphylaxis) to a biologic medication,vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonalantibody), or to any of the IP excipients (sucrose, polysorbate 80, or histidine)

• Active HBV or HCV or is positive for HIV.

• Smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent)per day

• ECG with a QTcF > 450 msec for males or > 470 msec for females at Screening

• History of drug or alcohol abuse

• Use of prohibited medications as defined in the Protocol