Inclusion Criteria:

1. Male or female subjects ≥18 years old

2. Subjects diagnosed with high-risk ET (either older than 60 years and JAK2V617-positive
at screening, or having disease-related thrombosis or hemorrhage in the past),
diagnosed according to the World Health Organization (WHO) 2016 criteria

3. Subjects have received prior HU for ET, while the washout between the last dose of HU
and randomization should not be shorter than 14 days

4. Interferon treatment-naïve, or anti-P1101 binding antibody negative at screening and
the washout between last dose of interferon and randomization should not be shorter
than 14 days.

5. Documented resistance/intolerance to prior HU for ET, referencing modified ELN
criteria (Barosi, et al, 2007), whereby at least one of the following criteria is met:

Platelet count >600 x 10^9/L at ≥2 g/day (or ≥2.5 g/day if subject body weight >80 kg)
or maximally tolerated dose if <2 g/day after at least 3 months of HU, or Platelet
count >400 x 10^9/L and WBC count <2.5 x 10^9/L at any dose and any duration of HU, or
Platelet count >400 x 10^9/L and hemoglobin (HGB) <10 g/dL at any dose and any
duration of HU, or Presence of HU-related toxicities at any dose and any duration of
therapy (e.g., leg ulcers, mucocutaneous manifestations, pneumonitis, or HU-related
fever), or Platelet count >450 x 10^9/L at any dose and any duration of HU. The actual
dose and duration of HU must be recorded on the eCRF. Moreover, if patient received
one dose of HU, the reason why subject was judged to be HU resistance/intolerance must
be recorded on the eCRF.

6. Platelets >450 x 10^9/L at screening

7. WBC >10 x 10^9/L at screening

8. HGB ≥11 g/dL at screening for males and 10 g/dL at screening for females

9. Neutrophil count ≥1.0 x 10^9/L at screening

10. Adequate hepatic function defined as bilirubin ≤1.5 x upper limit normal (ULN),
prothrombin time (PT) (international normalized ratio, INR) ≤1.5 x ULN, albumin >3.5
g/dL, alanine aminotransferase ≤2.0 x ULN, aspartate aminotransferase ≤2.0 x ULN at
screening

11. Creatinine clearance ≥40 mL/min (by Cockcroft-Gault equation)

12. Males and females of childbearing potential, as well as all women <2 years after the
onset of menopause, must agree to use an acceptable form of birth control until 28
days following the last dose of the study drug, and females must agree to not
breastfeed during the study

13. Written informed consent obtained from the subject and ability for the subject to
comply with the requirements of the study

Exclusion Criteria:

1. Any subject requiring a legally authorized representative

2. Any contraindications or hypersensitivity to IFN-? or ANA and their excipients

3. Known risk factors for QT-prolongation (e.g., congenital long QT, known history of
acquired QT-prolongations). Medications that can prolong QTc and induce hypokalemia
will not be allowed in the study.

4. Co-morbidity with severe or serious condition that, in the Investigator's opinion,
would jeopardize the safety of the subject or their compliance with the protocol,
including significant cardiac disease (including New York Heart Association Class
III-IV congestive heart failure and clinically significant arrhythmias) and pulmonary
hypertension

5. History of major organ transplantation

6. Pregnant or lactating females

7. Subjects with any other significant medical conditions that, in the opinion of the
Investigator, would compromise the results of the study or may impair compliance with
the requirements of the protocol, including but not limited to:

1. Documented autoimmune disease at screening or in the history (e.g., thyroid
dysfunction, hepatitis, idiopathic thrombocytopenic purpura, scleroderma,
psoriasis, or any arthritis of autoimmune origin)

2. Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis at
screening that, in the Investigator's opinion, would jeopardize the safety of the
subject or their compliance with the protocol

3. Infections with systemic manifestations (e.g., bacterial, fungal, or human
immunodeficiency virus [HIV], except hepatitis B [HBV] and/or hepatitis C [HCV],
at screening)

4. Evidence of severe retinopathy (e.g., cytomegalovirus retinitis, macular
degeneration) or clinically relevant ophthalmological disorder (due to diabetes
mellitus or hypertension)

5. History or presence of clinically relevant depression, or previous suicide
attempts or at any risk of suicide at screening, in the judgement of the
Investigator

6. History or presence of clinically significant neurodegenerative diseases

7. History of any malignancy within 5 years (except Stage 0 chronic lymphocytic
leukemia, basal cell, squamous cell, and superficial melanoma)

8. History of alcohol or drug abuse within the last year

9. History or evidence of any other MPN

8. Use of any investigational drug <4 weeks prior to the first dose of study drug or not
recovered from effects of prior administration of any investigational agent

9. Subjects with documented ANA resistance or intolerance (see Appendix 8 for
definition).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/7/22. Questions regarding updates should be directed to the study team contact.