TRX103 cell therapy for active non-infectious uveitis

Inclusion Criteria:

1. ≥ 18 to ≤ 70 years of age at time of consent.
2. Weight of ≥ 40 kg at time of consent.
3. Subjects must be able to understand and sign informed consent and be willing and able to complete all specified procedures and visits.
4. Diagnosis of active non-infectious uveitis (NIU); intermediate, posterior, or panuveitis at screening as defined as having at least ONE of the following findings:

   1. .≥ 2+ VH (NEI/SUN Scale) OR
   2. Active inflammatory chorioretinal or inflammatory retinal lesion or lesions as defined by fluorescein angiography (FA) or optical coherence tomography (OCT).
5. Subjects on treatment with corticosteroids may be included if they meet the following:

   1. Prednisone ≤ 20 mg/day; or an equivalent dose of another corticosteroid
   2. Have been on a stable dose for at least 7 days prior to TRX103 dose.
   3. No ongoing treatment with a systemic non-corticosteroid, biologic, small molecules or immunomodulatory agent.
6. If the patient is on specific therapies such as systemic non-corticosteroid biologic agents, immunomodulatory agents or small molecules etc., appropriate washout periods defined in the protocol must be met prior to infusion at Day 0.

Exclusion Criteria:

1. Any condition preventing evaluation/assessment of both eyes.
2. Any significant ocular disease that could compromise vision.
3. Proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to non-uveitis causes.
4. Isolated anterior uveitis.
5. Macular edema as the only sign of uveitis, defined on OCT without active anterior/posterior inflammatory signs.
6. Age-related macular degeneration or serpiginous choroidopathy.
7. Myopic degeneration with active sub-foveal choroidal neovascularization.
8. Confirmed or suspected current infectious uveitis.
9. Has ocular masquerade syndrome, like ocular lymphoma.
10. Any of the following ongoing treatments or anticipated use of any of the following treatments prior to TRX103 dose, for the time periods specified below:

    1. Systemic immunosuppressants or immunomodulatory drugs within 4 weeks
    2. Small molecules, e.g., JAK inhibitors or TYK2 inhibitors within 4 weeks
    3. Anti-vascular endothelial growth factor (anti-VEGF) therapy within 8 weeks
    4. TNF inhibitor therapy within 8 weeks
    5. Agents that modulate T cells within 3 months
    6. IL-6 inhibitors within 8 weeks
    7. Therapeutic agents targeted to IL-17 within 4 months
    8. Agents that modulate B cells within 6 months
    9. Therapeutic agents targeted to IL-12 or IL-23 within 6 months
11. Has received intraocular or periocular (including subtenon, intracanalicular) corticosteroids within 8 weeks prior to TRX103 dose, unless otherwise specified below:

    1. Retisert® or Yutiq® (glucocorticosteroid implants) within 3 years prior or has had complications related to the implant;
    2. Retisert® (glucocorticosteroid implant) removed within 3 months prior or has had complications related to device removal;
    3. Ozurdex® (dexamethasone implant) or Xipere™ (suprachoroidal triamcinolone) within 4 months prior.
12. Ocular surgery within 90 days prior to TRX103 dose in the study eye, including glaucoma surgery (trabeculectomy or aqueous shunt device), and vitreoretinal surgery. Nd: YAG capsulotomy within 30 days prior to TRX103 dose in the study eye is also an exclusion criterion.
13. Any of the following cardiovascular risk factors:

    1. History of NYHA Class III or IV criteria cardiac insufficiency
    2. Clinically significant cardiac dysrhythmia
    3. QTcF \> 450 msec (male) or \> 470 msec for (female)
    4. Unstable angina in last 3 months;
    5. Myocardial infarction within past year
    6. CABG surgery past year.
14. Impaired kidney function, defined as any of the following:

    1. Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula or as measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation \< 40 mL/min/1.73 m2
    2. Proteinuria, defined as urine protein/creatinine ratio \> 25
    3. Symptomatic nephrolithiasis within 6 months of screening.
15. Subjects who are breastfeeding, pregnant, or planning to become pregnant, or subjects of childbearing potential who are unwilling to apply a highly effective birth control method prior to TRX103 dose.
16. Anaphylaxis to fluorescein or unwillingness to undergo fluorescein angiograms.
17. Live vaccine within 6 weeks prior to Day 0 (day of infusion) or expected to need a live vaccine during the study.
18. Active bacterial, viral, fungal, mycobacterial, or other infections that would require treatment. Active infections must be resolved prior to enrollment.
19. Have required management of infections as follows:

    1. Currently on suppressive therapy for any chronic infection
    2. Hospitalization for infection within past 60 days
    3. Use of IV or IM antibacterials, antivirals, antifungals, or anti- parasitic agents within past 60 days
    4. History of disseminated herpes zoster, history of or invasive HSV, or recurrent (≥ 2 episodes within last 5 years) localized herpes zoster
    5. Infection with Mycobacterium tuberculosis (TB).
    6. Positive hepatitis-B surface antigen. Subject may be included if they are HBV PCR negative.
    7. Hepatitis C virus (HCV RNA detectable in any subject with anti-HCV antibodies).
    8. Positive serology for HIV.
    9. Lab test results indicating active syphilis infection.
20. History of significant trauma or major surgery within 4 weeks prior to TRX103 dose or scheduled to undergo major surgery during the study.
21. History of blood transfusion within the last 3 years.
22. Prior organ transplant, or allogeneic bone marrow, peripheral blood, or cord blood stem cell transplant.
23. Received another investigational agent or therapy, within 28 days of planned TRX103 infusion (or 5 half-lives, whichever is longer) and/or have not recovered from treatment related toxicities.
24. Screening laboratory and other analyses show any of the following abnormal results:

    1. Serum aspartate transaminase or alanine transaminase \> 3.0 × upper limit of normal;
    2. Bilirubin ≥ 2 x ULN;
    3. Total white blood cell count \< 2,000/μL;
    4. Hemoglobin \< 8 g/dL;
    5. Platelet count \< 100,000/μL;
    6. Absolute neutrophil count \< 1,200/μL;
    7. Absolute lymphocytes count \< 750/μL.
25. Subjects with a history of any other significant renal, hepatic, pulmonary, or cardiac dysfunction, or on treatment to support such dysfunction.
26. Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical condition or history, including laboratory results, which, in the Investigator's opinion:

    1. Places the subject at increased risk during participation in the study, and/or;
    2. Interferes with the subject's capacity to provide informed consent and their participation in the study, and/or; interferes with the interpretation of the results.
27. Participation in any other clinical trial/ or receiving any other investigational treatment while enrolled in this study.