A Phase 2, Open Label, PK Study of TLC599 in Subject With Osteoarthritis of the Knee

This single center, Phase 2, open-label, 1 period, parallel study will enroll approximately
90 subjects to receive a single dose of TLC599 or DSP via IA injection, followed by a PK
evaluation period up to 24 weeks and an additional follow-up period of 1 to 5 weeks.
Additional subjects will be recruited as needed, to achieve at least 6 subjects per cohort
with adequate SF volume for DP and DEX concentration analysis at EOPK.

Inclusion Criteria:

1. Male or female non or moderate smokers, 50 years or older, with BMI ≤ 40.0 kg/m2.

2. Has symptoms associated with OA of the knee for at least 6 months prior to Screening
and confirmation of mild to moderate OA.

3. The study knee has OA with grade 1-3 in severity based on the Kellgren-Lawrence
grades.

4. Females of childbearing potential to use acceptable contraceptive methods for 21 weeks
after study drug administration.

5. Male subjects must to use acceptable contraceptive methods from dosing until 21 weeks
after study drug administration.

6. Willing and able to comply with study procedures and provide written informed consent.

Exclusion Criteria:

1. Clinically significant abnormality at physical examination, clinically significant
abnormal laboratory test results or positive test for hepatitis B, hepatitis C, or HIV
found during screening.

2. Positive urine drug screen at screening.

3. History of allergic reactions to TLC599, its components or other related drugs.

4. Clinically significant and unstable illness.

5. History of clinically significant autoimmune disease.

6. Evidence of intra articular bleeding of the study knee at baseline prior to study drug
administration.

7. History of infective arthritis or suspected / concurrent infection in the study knee
at baseline prior to study drug administration; clinical symptoms and signs of acute
infection or infection-related inflammation in the non-study knee before study drug
administration.

8. Skin lesion/breakdown at the anticipated injection site or any condition that would
impair penetration of the study knee joint space.

9. Platelet count < 80,000/μL, or blood coagulation disorders at the Screening.

10. Total white blood cell count <3000/ μL or >13000/ μL.

11. History of acquired or congenital immunodeficiency diseases.

12. History of treated malignancy which is disease free for ≤ 5 years prior to the
Screening, except for basal cell carcinoma and squamous cell carcinoma of skin or
carcinoma in situ of the uterine cervix.

13. Stroke or myocardial infarction within 3 months prior to the Screening.

14. Subjects with a condition or in a situation which will interfere with the subject's
ability to comply or cooperate with the dosing and visit schedules and the protocol
evaluations or may not be suitable for this study.

15. Clinically significant ECG abnormalities or vital sign abnormalities at screening.

16. History of significant alcohol abuse within one year prior to the Screening or regular
use of alcohol within six months prior to the Screening.

17. History of significant drug abuse within one year prior to the Screening or use of
soft drugs within 3 months prior to the Screening or hard drugs within 1 year prior to
the Screening.

18. Participation in a clinical research study involving the administration of an
investigational or marketed drug or device within 30 days prior to dosing,
administration of a biological product in the context of a clinical research study
within 90 days prior to dosing, or concomitant participation in an investigational
study involving no drug or device administration.

19. Any use of medication;

1. drugs known to induce or inhibit hepatic CYP 3A4 metabolism within 30 days prior
to dosing;

2. prescription medication within 14 days prior to dosing;

3. over-the-counter products and natural health products within 7 days prior to
dosing;

4. prescription medication known to affect platelet function within 14 days prior to
dosing;

5. a depot injection or an implant of any drug within 3 months prior to dosing;

6. use of IA corticosteroid, hyaluronic acid, or other IA injection in the study
knee within 4 months prior to dosing;

7. any IA injection drug that could impact endogenous steroid levels within 6 months
prior to dosing;

8. systemic corticosteroids within 30 days prior to dosing;

9. use of any chemotherapeutic or systemic immunosuppressant agents for inflammatory
diseases within 6 months prior to dosing.

20. Donation of plasma within 7 days prior to dosing. Donation or loss of blood of 50 mL
to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to dosing.

21. Female subjects who are pregnant, breast-feeding, or plan to become
pregnant/breast-feeding.

22. History of latent or active tuberculosis or exposure to endemic areas within 8 weeks
prior to the Screening.

23. Positive QuantiFERON®-TB test indicating possible tuberculosis infection at the
Screening.

24. Immunization with a live attenuated vaccine 1 month prior to dosing or planned
vaccination during the course of the study.

25. History of clinically significant opportunistic infection.

26. Serious local infection or systemic infection within the 3 months prior to the
Screening.

27. Presence of fever associated with a symptomatic viral or bacterial infection within 2
weeks prior to dosing.

28. Subjects with previous diagnosis of severe OA with grade 4 classification based on the
Kellgren-Lawrence grades.

29. Subject who had a surgery within 4 weeks prior to dosing or expected to have a knee
replacement surgery scheduled within 21 weeks after the study drug administration.