Safety, Tolerability and PK of ATTO 1091 in Healthy Adult Volunteers and Patients With Ulcerative Colitis

Criteria the registry did not label

• Parts 1\&2 (Healthy Volunteers) Key Inclusion Criteria:
• Any sex or gender who is 18 to 60 years old, inclusive, at Screening.
• Body weight of 45 to 125 kg, inclusive, and body mass index (BMI) between 18.5 and 35 kg/m2.
• Considered in good general health based on medical history, physical exam, 12-lead ECG, screening clinical laboratory findings, and vital signs.
• Meets contraception requirements
• Negative pregnancy test for participants of childbearing potential.
  • Part 3 (Participants with Ulcerative Colitis) Key Inclusion Criteria:
• Any sex or gender who is 18 to 80 years old
• Body weight of 45 to 125 kg and BMI between 17.0 and 40.0 kg/m2
• UC diagnosis confirmed by endoscopy and histology ≥3 months prior to Screening
• Moderately to severely active UC as defined by Modified Mayo Clinic Score (stool frequency, rectal bleeding, endoscopy) 5 to 9 inclusive, with Mayo endoscopic subscore ≥2 as confirmed by the central reader during Screening
• Rectal bleeding subscore ≥1 and stool frequency subscore ≥1 at Screening.
• Naïve to treatment with advanced therapies or has had an inadequate response, loss of response, or intolerance to no more than 3 drugs in 2 classes of the following:
  • Tumor necrosis factor (TNF-α) antagonists
  • Interleukin IL-12/IL-23 antagonists
  • Integrin inhibitors
  • JAK antagonists
  • S1P receptor agonists
  • Novel class with biologic-like activity (e.g. TL1A antagonists)
• Meets washout criteria for prior UC therapies as specified in the protocol.
• Negative pregnancy test for participants of childbearing potential
  • Parts 1\&2 (Healthy Volunteers) Key Exclusion Criteria
• Any clinically significant underlying illness
• History of malignancy within 5 years of Screening
• History of major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study
• History of uncontrolled asthma requiring systemic corticosteroids or hospitalization for asthma within 6 months prior to Day 1
• History of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the IP excipients
• 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 to approximately 40 mg nicotine) per day
• History of drug or alcohol abuse
• Laboratory values outside of the normal range considered clinically significant by the investigator
  • Part 3 (Participants with Ulcerative Colitis) Key Exclusion Criteria:
• Any clinically significant underlying illness
• History of malignancy within 5 years of Screening
• History of major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study
• History of uncontrolled asthma requiring systemic corticosteroids or hospitalization for asthma within 6 months prior to Day 1
• History of known primary immunodeficiency or is considered immunocompromised
• Has been treated for a parasitic infection in the past 6 months
• Participant has active HBV or HCV or is positive for HIV
• Participant has active or latent TB
• Stool positive for Clostridioides difficile toxin at Screening
• Concomitant primary sclerosing cholangitis.
• History of active major depressive episode or suicidal ideation
• History of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the IP excipients
• Diagnosis of non-UC or confounding GI conditions including Crohn's disease, indeterminate colitis, microscopic colitis, ischemic or radiation colitis.
• Disease limited to isolated ulcerative proctitis (\<15 cm).
• Unresected colonic dysplasia or unresected adenomatous colonic polyps, fulminant colitis, toxic megacolon, bowel perforation, current colonic strictures, fistulae, stoma, ileostomy, colostomy, abdominal abscess, or anticipated need for colectomy during the study.
• History of extensive colonic resection
• History of drug or alcohol abuse
• Laboratory values outside of the normal range considered clinically significant by the investigator