A Single-arm, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of P1101 in Adults With ET

Inclusion Criteria:

1. Male and female subjects ≥18 years old.

2. Subjects diagnosed with ET according to the World Health Organization (WHO) 2016criteria.

3. Subjects that are cytoreductive treatment-naïve, or pre-exposed to HU and/or ANA, asspecified below (according to Investigator's judgment and documented in thepatient's medical record): a. Cytoreductive-naïve patients must be in need of cytoreductive treatment, definedas having at least one of the following: i. Progressive leukocytosis and/or thrombocytosis ii. Disease-related symptoms (i.e., pruritus, night sweats, fatigue) iii. Vasomotor/microvascular disturbances, not responsive to aspirin (includingheadache, chest pain or erythromelalgia, etc.) iv. High-risk (history of thrombosis at any age; or age >60 years with JAK2mutation) b. Patients previously exposed to HU will be classified as either: i. Documented formal HU resistance or intolerance ii. HU stopped without documented formal resistance/intolerance due to insufficientblood count control or toxicity. The last HU dose must be >7 days prior the firstdose of P1101.

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

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

6. Males and females of childbearing potential, as well as all women <2 years after theonset of menopause, must agree to use an acceptable form of birth control until 60days following the last dose of the study drug, and females must agree to notbreastfeed during the study.

7. Written informed consent obtained from the subject and ability for the subject tocomply with the requirements of the study.

8. Platelet count >450 × 109/L at screening

9. Both ANA-naïve and ANA-pretreated subjects are eligible for the study, regardless ofthe reason to terminate ANA use

Exclusion Criteria:

1. Any subject requiring a legally authorized representative

2. Subjects who stopped prior interferon alfa therapy due to low efficacy or poortolerability

3. Any contraindications or hypersensitivity to IFN-α and/or its excipients

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 ClassIII-IV congestive heart failure and clinically significant arrhythmias) andpulmonary hypertension

5. History of major organ transplantation

6. Pregnant or lactating females

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

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

9. Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis atscreening that, in the Investigator's opinion, would jeopardize the safety ofthe subject or their compliance with the protocol

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

11. Evidence of severe retinopathy (e.g., cytomegalovirus retinitis [CMV], maculardegeneration) or clinically relevant ophthalmological disorder (due to diabetesmellitus or hypertension)

12. History or presence of clinically relevant depression

13. Previous suicide attempts or at any risk of suicide at screening, in thejudgment of the Investigator

14. History or presence of clinically significant neurologic diseases

15. History of any malignancy within 5 years (except adequately treated nonmelanomaskin cancer, prostate cancer status post resection with an undetectableprostate-specific antigen [PSA], curative treated in-situ cancer of the cervix,ductal carcinoma in-situ [DCIS] of the breast, Stage 1 Grade 1 endometrialcarcinoma, or other solid tumors including lymphomas [without bone marrowinvolvement] curatively treated with no evidence of disease for ≥2 years priorto study)

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

17. History or evidence of any other MPN

18. Use of any investigational drug <4 weeks prior to the first dose of study drug ornot recovered from effects of prior administration of any investigational agent

19. Presence of more than one driver mutation (e.g., V617F JAK2 and CALR, CALR and MPL,V617F JAK2 and MPL)

20. Prior use of JAK inhibitors