The Efficacy and Safety of TLL018 in Moderate-to-severe Plaque Psoriasis

Inclusion Criteria:

1. Are between the ages of 18 and 75 years, inclusive, at time of informed consent.

2. Capable of giving informed consent and complying with study procedures.

3. Willing and able to adhere to study restrictions.

4. Laboratory and medical history parameters within the protocol defined ranges.

5. Normal renal function (>90 mL/min/1.72 m2) or mild renal impairment (Stage 2 mildchronic kidney disease glomerular filtration rate [GFR] = 60 to 89 mL/min/1.73 m2)as determined by central laboratory.

6. Body mass index (BMI) of 18.0 to 35.0 kg/m2 inclusive.

7. Have had a diagnosis of moderate-to-severe PP for at least 6 months prior toBaseline.

8. Participants with moderate-to-severe PP covering ≥10% body surface area (BSA), witha Psoriasis Area and Severity Index (PASI) ≥12 and a static Physician's Global ≥3 at Baseline.

9. Participants with plaque psoriasis who are systemic treatment naïve or have receivedat least one of the conventional anti-psoriasis treatments such as acitretin,phototherapy, methotrexate, cyclosporine, apremilast, or biologic therapy (anti-TNFor anti-IL-12/17/23).

10. Participants who are candidates for systemic treatment for psoriasis at thediscretion of the Investigator.

11. Must agree to avoid prolonged exposure (> 15 minutes) to the sun and avoid use oftanning booths or other ultraviolet light sources during the study.

12. Female participants of childbearing potential (See Section 10.4.1 definition ofWoman of Childbearing Potential - WOCBP) must have a negative serum human chorionicgonadotropin (hCG) at Screening, and meet one of the following criteria:

13. Using a medically acceptable form of birth control (Appendix 4) for at least 1month prior to Screening and 3 months after the last dose of study drug (e.g.,hormonal contraceptives [oral, patch, injectable or vaginal ring], implantabledevice [implantable rod or intrauterine device], bilateral tubalocclusion/tubal ligation, azoospermic partner).

14. Abstinence as a form of birth control is generally not permitted during thestudy with the exception of participants who practice abstinence as a preferredand usual lifestyle style choice. The Investigator must confirm that abstinenceis still in accordance with the participant's lifestyle at regular intervalsthroughout the study.

15. Male participants with female partners of childbearing potential must agree to usecondoms for the duration of the study and until 13 weeks after administration of thestudy intervention and must refrain from donating sperm for this same period. Inaddition, his female partner should agree to use a highly effective method of birthcontrol per Appendix 4 or an additional barrier form of birth control (e.g.,diaphragm, cervical cap, spermicide, or sponge).)

16. Ability to swallow and retain oral study intervention.

17. Participants must have completed their coronavirus disease 2019 (COVID-19)vaccination in accordance with the latest CDC guidelines, which is based on previousvaccination history. Please reference COVID-19 vaccination guidance for individualswho are moderately or severely immunocompromised (Clinical Guidance for COVID-19Vaccination | CDC).

18. Previous Pfizer-BioNTech, Moderna or Novavax: Must have previously received atleast a 1st and 2nd dose, then must have received an updated formulationaccording to the CDCs dosing requirements; or

19. Novavax or Johnson and Johnson's Janssen: Must have previously received 1 ormore doses in combination with any original monovalent or bivalent COVID-19vaccine doses, then must receive an updated formulation according to the CDCsvaccination guidelines. ...

Exclusion Criteria:

1. Pregnant or nursing women.

2. Past history of gastrointestinal perforation, history of peptic ulcers and/orregular use of NSAIDs.

3. History of chronic alcohol or drug abuse within 6 months prior to Screening asdetermined by the Investigator based on medical history and patient interview.

4. Current or recent history of severe, progressive, or uncontrolled renal, hepatic,hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular,neurologic, or psychiatric disease.

5. Current and/or recent history (<30 days prior to Screening and/or <45 days prior torandomization) of a clinically significant viral, bacterial, fungal, parasitic, ormycobacterial infection.

6. Subject is currently being treated with or has received strong cytochrome P450 3A (CYP3A4) inhibitors, such as itraconazole, within 4 weeks prior to Baseline (Day 0).

7. Any history of malignancies, except for non-recurrent basal cell skin cancer,squamous cell skin cancer, and cervical cancer in situ that are considered to becured.

8. Tests positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).For Hepatitis B all subjects will undergo testing for Hepatitis B Surface Antigen (HBsAg) and Hepatitis B Core Antibody (HBcAb). Subjects who are HBsAg positive arenot eligible for the study. Subjects who are HBsAg negative and HBcAb positive willsubsequently need testing for Hepatitis B virus deoxyribonucleic acid (HBV DNA) andif HBV DNA negative may be enrolled in the study; if HBV DNA is positive, thesubject is not eligible for the study. Positive hepatitis C virus result is definedas having a positive hepatitis C antibody test with a positive confirmatoryhepatitis C polymerase chain reaction test.

9. Recent exposure to active tuberculosis (TB). Current evidence of active TB orcurrent evidence of latent TB. Participants with positive TB test (e.g.,QuantiFERON) that have been treated for latent TB. A borderline QuantiFERON testshould be repeated. If still indeterminant, then a chest x-ray may be performed (positive chest x-ray is exclusionary).

10. History of unexplained syncope, symptomatic hypotension, or hypoglycemia.

11. Abnormal D-dimer levels in conjunction with clinical or current and past thromboticdisease.

12. Participants with uncontrolled hypertension, uncontrolled diabetes, untreated oruncontrolled hyperlipidemia (fasting blood triglycerides >500 mg/dL and fastingcholesterol >250 mg/dL).

13. History of any significant cardiac event (e.g., myocardial infarction) within 6months prior to Screening, including:

14. History of long QTc syndrome; history or presence of an abnormal ECG, which, inthe Investigator's opinion, is clinically significant.

15. History of unstable ischemic heart disease or uncontrolled hypertension.

16. Current Class 3 or 4 heart failure per the New York Heart AssociationFunctional Classification.

17. Screening and/or Baseline QTcF > 450 msec for males and > 470 msec for females,confirmed by triplicate ECG.

18. Participants with history of thrombosis and/ or thromboembolism, or associated riskfactors (e.g., inherited thrombophilias, etc.).

19. Donated or lost >500 mL of blood in the previous 3 months.

20. Participants with chronic kidney disease with eGFR <60 mL/min/1.73 m2.

21. Participants with moderate-to-severe hepatic impairment (i.e., Child-Pugh Class Band C).

22. Major surgery within 3 months prior to Screening or participant has a planned majorsurgery during the course of the study.

23. Participants with any of the following abnormalities in clinical laboratory tests atScreening, as assessed by the study-specific laboratory and confirmed by a singlerepeat, if deemed necessary:

• Hemoglobin <100 g/L

• White blood cell (WBC) count of <3.0 × 109/L

• Platelet count of <80 × 109/L

• Absolute neutrophil count of <1.5 × 109/L

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) valuesgreater than 3 times the ULN

20. Any uncontrolled clinically significant laboratory abnormality that would affectinterpretation of study data or the participant's participation in the study.

21. Previous or current autoimmune diseases (e.g., RA, systemic lupus erythematosus,IBD, scleroderma, inflammatory myopathy, mixed connective tissue disease overlapsyndrome, etc.). Note, psoriatic arthritis patients are allowed.

22. Other types of psoriasis (such as erythrodermic psoriasis, pustular psoriasis,guttate psoriasis, drug-induced psoriasis).

23. Current enrollment in another study intervention protocol or experimental treatmentwithin 30 days or five half-lives (whichever is longer).

24. Received any topical therapy that can affect psoriasis (including topical use ofmoderate-strong glucocorticoids, retinoids, vitamin D3 derivatives, salicylic acid,anthracene, etc.) within 2 weeks of first study intervention. Low potency topicalsteroids are permitted for sensitive areas only (e.g., face, axillae, genitalia).Bland emollients without urea or α or β-hydroxy acids are permitted.

25. Use of phototherapy (including photochemotherapy, ultraviolet therapy, tanning bedself-therapy, etc.) within 4 weeks of first study intervention.

26. Use of systemic oral therapy that can affect psoriasis (including but not limited toglucocorticoids, retinoids, cyclosporine, methotrexate and apremilast) within 4weeks of first study intervention.

27. Received intravenous corticosteroids within 4 weeks of first study intervention.

28. Use of antimalarial drugs, interferon-α, lithium and beta-blockers within 4 weeks offirst study intervention.

29. Use of Chinese or herbal medicine treatment of psoriasis within 2 weeks of firststudy intervention.

30. Prior to randomization, washout periods of the following biologics are required:etanercept ≥28 days; any s.c. mAb targeting TNF (eg., infliximab, adalimumab,certolizumab) >3 months; ustekinumab or drugs that specifically target IL-23>6months; secukinumab, ixekizumab, bimekizumab, brodalumab or other IL-17 antagonists >6 months; any other anti-psoriasis treatments not listed within 5 half-lives.Topical JAK inhibitors should have a washout period > 2 weeks.

31. Prior use of three or more biologic therapies.

32. Use of natalizumab and other drugs that regulate B or T cells within 12 months offirst study intervention, such as rituximab, alemtuzumab, and abatacept.

33. Participants who have received live vaccines within 2 months prior to first studyintervention or plan to receive live vaccines during the study period.Non-live-attenuated vaccines (e.g., ribonucleic acid [RNA]-based vaccines,inactivated adenovirus-based vaccines, protein-based vaccines), includingnon-live-attenuated vaccines or boosters for coronavirus disease 2019 (COVID-19)during the study are allowed.

34. Participants who have received COVID-19 vaccines within 2 weeks of Baseline orparticipants who plan to receive COVID-19 vaccines during the study period (boostersare allowed).

35. Previously not completed COVID-19 vaccination in accordance with the CDC guidelines.

36. Participants who are allergic to any component of the study intervention or who areat risk for allergy as determined by the Investigator during the study.

37. Any condition for which the Investigator considers the participant inappropriate toparticipate in this study.

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