A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA)

Key Inclusion Criteria for the Double-blind Treatment Period:

   - Must be aged ≥18 years.

      - Must have a clinical diagnosis of AIH and signs of active disease despite
      standard-of-care therapy for ≥3 months or disease flare after experiencing
      complete remission induced by standard-of-care treatment, including:

         - Screening ALT values that are 1.25 to 10 times the upper limit of the normal
         range (ULN)

         - Liver biopsy results with Ishak score (modified HAI) ≥5/18 indicating active
         AIH, from a biopsy performed at Screening, or within 6 months prior to
         Screening

         - Mild or no hepatic impairment (Child Pugh category A)

      - Must be willing to use and taper glucocorticoid therapy.

      - Must be willing to use effective contraception.

Key Exclusion Criteria for the Double-blind Treatment Period:

   - Have a concomitant diagnosis of primary biliary sclerosis, primary sclerosing
   cholangitis, IgG 4 related cholangitis, drug related AIH (at Screening) or a history
   of drug-related AIH.

   - Have clinical evidence of significant unstable or uncontrolled diseases other than the
   disease under study.

   - Are receiving oral or injectable immunomodulating treatment for any other autoimmune
   disease prior to enrollment in the study. Patients who have been using such treatments
   must follow the specified washout periods.

   - Have an active infection (eg, acute hepatitis E, cytomegalovirus, or Epstein-Barr
   virus) requiring systemic therapy with antibiotic, antiviral, or antifungal treatment,
   or has had any febrile illness within 7 days prior to Day -1.

   - Have a history of thyroiditis, celiac disease, or other autoimmune disorder known to
   be associated with transaminitis.

   - Have liver cirrhosis with significant impairment of liver function (Child Pugh
   category B or C) or have decompensated cirrhosis.

   - Patients with histology confirmed coincident non-alcoholic steatohepatitis.

Key Inclusion Criteria for the Open-label Extension Period:

   - Same as Double-blind Treatment Period inclusion criteria, except the following
   modifications:

      - ALT value can be normal or, if elevated, in the range of 1.25 to 10 times the
      upper limit of normal

   - Must have completed the Double-blind Period study visits through Week 24, including
   all Week 24 Visit assessments.

   - Must be willing to maintain glucocorticoid therapy at 5 mg/day or continue to taper
   glucocorticoid therapy.

Key Exclusion Criteria for the Open-label Extension Period:

•. Same as Double-blind Treatment Period except no need to re-test for HIV, HBV, HCV, and
TB.