DZD9008 PK Study in Hepatic Impairment Subjects

Inclusion criteria:

1. The subject is male or female 18 to 75 years of age, inclusive, at screening.

2. The subject has a BMI of 18.0 to 40.0 kg/m2, inclusive, at screening and check-in.

3. The subject has a minimum body weight of 50.0 kg, at screening and check-in.

4. The subject has a resting pulse rate of ≥ 40 and < 100 beats per minute with noclinically significant deviation as judged by the investigator.

5. The subject agrees to comply with all protocol requirements.

6. The subject is able to provide written informed consent. Additional Inclusion Criteria for Healthy Subjects Only (Cohort 2) Only (7-11):

7. The subject has normal hepatic function. No known or suspected hepatic impairmentbased on liver function tests (e.g., ALT, AST, ALP, and bilirubin), albumin, andprothrombin time is defined as the following with a single repeat permitted toassess eligibility if needed, at screening and check-in:

8. ALT and AST ≤ ULN

9. Total bilirubin ≤ ULN (subjects with a history of Gilbert syndrome are eligibleif they only have elevated total bilirubin)

10. ALP ≤ ULN

11. Albumin ≥ 3.6 g/dL

12. Prothrombin time ≤ ULN

13. The subject has a resting blood pressure of 90 to 145 mmHg (systolic) and 40 to 95mmHg (diastolic), at screening and check-in.

14. The subject has a QTcF of ≤ 450 msec, at screening and check-in.

15. The subject is judged by the investigator to be in good general health, asdetermined by medical history, clinical laboratory assessments, vital signmeasurements, 12 lead ECG results, and physical examination findings.

16. Each subject with normal hepatic function (Cohort 2) must individually match asubject with impaired hepatic function (Cohort 1) by age (± 10 years), body weight (± 10 kg), and sex (similar distribution of males and females). Additional Inclusion Criteria for Subjects with Hepatic Impairment (Cohort 1) Only (12-18):

17. The subject satisfies the Class B of the Child-Pugh classification (no albumin usewithin 14 days). Six out of 10 subjects also meet NCI ODWG Group C criteria.

18. The subject has a diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process), with features ofcirrhosis due to any etiology, except for DILI, which is confirmed by at least oneof the following criteria:

19. histologically by prior liver biopsy showing cirrhosis

20. clinically by physical examination, laboratory data, liver imaging, orendoscopic findings

21. The subject has following clinical laboratory values, at screening and check-in:

22. ALT and AST ≤ 5 × ULN

23. Total bilirubin ≤ 3 × ULN

24. ANC ≥ 1.5 × 109/L

25. Platelet count ≥ 30 × 109/L

26. Hemoglobin ≥ 90 g/L

27. The subject has chronic (more than 6 months) and stable hepatic impairment (ie, noacute episodes of illness within 30 days before screening due to deterioration ofhepatic function) as assessed by the NCI-ODWG criteria (Group C) or a Child-Pughclassification score of moderate (7 to 9 points).

28. The subject has a resting blood pressure of 90 to 155 mmHg (systolic) and 50 to 100mmHg (diastolic), at screening and check-in.

29. The subject has a QTcF of ≤ 470 msec, at screening and check-in.

30. The subject is judged by the investigator to be in good general health, asdetermined by medical history, clinical laboratory assessments, vital signmeasurements, 12 lead ECG results, and physical examination findings, except forfindings that, as judged by the investigator, are consistent with the subject'shepatic impairment or other stable concomitant medical conditions.

Exclusion criteria:

1. The subject has a history or clinical manifestations of a significant neurological,renal, cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, orpsychiatric disease that would preclude study participation, as judged by theinvestigator.

2. The subject has any surgical or medical condition that may alter the absorption,distribution, metabolism, or excretion of drugs (e.g., gastrectomy).

3. The subject has a history of cancer (malignancy) with the following exceptions:

4. adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix,or

5. other malignancies which have been successfully treated with appropriate followup and therefore unlikely to recur for the duration of the study

6. The subject has a history of being immunocompromised or has a positive test resultfor HIV types 1 or 2 antibodies at screening.

7. The subject has an acute or chronic infection requiring treatment with oralantibiotics (except, rifaximin for the treatment of hepatic encephalopathy),antivirals, antiparasitic, antiprotozoals, or antifungals within 4 weeks prior toDay 1 or superficial skin infection within 1 week prior to Day 1.

8. The subject has a history of risk factors for Torsades de Pointes (e.g., heartfailure/cardiomyopathy or family history of long QT syndrome), has clinicallysignificant hypokalemia or hypomagnesemia, and is taking concomitant medicationsthat prolong the QT/QTc interval.

9. The subject has uncontrolled hypertension despite optimal medical management.

10. The subject had arterial or venous thrombotic or embolic events such ascerebrovascular accident (including transient ischemic attacks), deep veinthrombosis or pulmonary embolism within 6 months before the start of study drugadministration.

11. The subject tests positive for breath alcohol test at screening and on check-in (Day 1).

12. The subject is unable or unwilling to restrict smoking to 5 cigarettes or less perday.

13. The subject is involved in strenuous activity or contact sports within 24 hours ofthe first dose of study drug or during the study.

14. The subject has donated blood (excluding plasma donation) of ≥ 500 mL within 60 daysbefore the first dose of study drug.

15. The subject has poor peripheral venous access.

16. The subject should not be any of the following:

17. investigator staff member or their family members

18. site staff member otherwise supervised by the investigator, or employees,including their family members, directly involved in the conduct of the study

19. The subject has a history of relevant drug and/or food allergies (ie, allergy toDZD9008 or any excipients, or any significant food allergy).

20. The subject has received DZD9008 or any other investigational drug in anotherinvestigational study within 30 days of dosing.

21. The subject is enrolled in another clinical study or has used any investigationaldrug or device within 4 weeks (or 5 times the half-life of the pervious drug [ifknown], whichever is longer), prior to dosing with study drug. The window will bederived from the date of the last dose of study drug in the previous study.

22. The subject has used a strong or moderate inhibitor or inducer of CYP3A4 and/or P gpincluding St. John's Wort, within 14 days and 28 days, respectively, prior to dosingand until the completion of the last PK sample collection unless it is deemedacceptable following consultation with Dizal Pharma's medical monitor and theinvestigator.

23. The subject has used PPIs within 5 days prior to dosing until 24 hours after dosing.Use of H2-antagonists and antacids within 12 hours prior to dosing until 12 hoursafter dosing unless it is deemed acceptable following consultation with DizalPharma's medical monitor and the investigator.

24. In the opinion of the investigator, the subject is not suitable for entry into thestudy. Additional Exclusion Criteria for Healthy Subjects Only (Cohort 2):

25. The subject with normal hepatic function has any of the following:

26. evidence or history of bleeding diathesis, or

27. any hemorrhage or moderate bleeding event within 4 weeks of start of study drugadministration

28. The subject has a positive result for HBsAg or HCV Ab.

29. The subject has an estimated glomerular filtration rate (CKD-EPI formula orCockcroft-Gault method) of < 90 mL/min.

30. The subject has used any vaccine or used any prescription (excluding hormonal birthcontrol and hormone replacement therapy) or over the counter medications (exceptparacetamol [up to 2 g per day]), including herbal or nutritional supplements,within 14 days before the first dose of study drug and throughout the study.

31. The subject has a positive test result for drugs of abuse or alcohol at screening orbefore the first dose of study drug. Additional Exclusion Criteria for Subjects with Hepatic Impairment Only (Cohort 1):

32. The subject has fluctuating or rapidly deteriorating hepatic function, as indicatedby recent history or worsening of clinical (ie, abdominal pain, nausea, vomiting,anorexia, or fever) and/or laboratory signs of hepatic impairment, as judged by theinvestigator.

33. The subject has evidence of acute viral hepatitis within 30 days before dosing withstudy drug.

34. The subject has an active hepatitis B or C viral infection.

35. The subject has history or symptoms of hepatic encephalopathy Grade 2 or abovewithin 3 months prior to screening visit.

36. The subject has a history of unstable diabetes mellitus as evidenced by HbA1c ≥ 9%at screening.

37. In the opinion of the investigator, the subject has clinically demonstrable severeascites and/or pleural effusion.

38. The subject has evidence of hepatopulmonary syndrome, hydrothorax, or hepatorenalsyndrome.

39. The subject had an organ transplant or is on a waiting list.

40. The subject had a portosystemic shunt (including transjugular intrahepaticportosystemic shunts).

41. The subject has an estimated glomerular filtration rate (CKD-EPI formula) of < 60mL/min.

42. The subject has symptoms consistent with spontaneous bacterial peritonitis, knownactive spontaneous bacterial peritonitis, or a history of spontaneous peritonitiswithin the last 6 months.

43. The subject is suspected of having hepatocellular carcinoma (ie, if α fetoprotein > 50 ng/mL at screening), subjects will undergo appropriate diagnostic studies (e.g.,CT scan or hepatic ultrasound) to exclude the possibility of hepatocellularcarcinoma.

44. The subject has received any vaccine or used any prescription (excluding hormonalbirth control and hormone replacement therapy) or over the counter medications,including herbal or nutritional supplements, within 14 days before the first dose ofstudy drug and throughout the study, except those essential for the management ofhepatic impairment or the treatment of stable concomitant medical conditions, asjudged by the investigator. The dose of an approved medication must remain stablefrom 7 days before study drug dosing and throughout the study.

45. The subject has a positive test result for drugs of abuse (except positive testresults associated with prescription medications that have been reviewed andapproved by the investigator) or alcohol at screening or prior to study drug dosing.