Efficacy/Safety of ALTB-268 in Subjects w/Moderately to Severely Active UC Refractory to Biologics

Inclusion Criteria:

1. Adult participants 18 to 75 years old, inclusive, at Screening.

2. Willing to provide informed consent and to be compliant with the schedule of studyvisits and protocol assessments.

3. Diagnosis of UC established at least 12 weeks prior to Screening by standardclinical and endoscopic evidence and corroborated by a histopathology report.

4. Moderately to severely active UC, at the time of Screening, defined as a modifiedMayo Score (mMS) of 5-9, inclusive, with an endoscopic subscore of ≥ 2 (from centralreading), and a rectal bleeding (RB) subscore of ≥ 1.

5. Evidence of active UC, extending proximal to the rectum with ≥ 15 cm of involvedcolon.

6. Stable doses of concomitant medications:

7. Subjects receiving oral corticosteroids for the treatment of UC must be on astable dose of ≤ 20 mg/day (prednisone or equivalent), or ≤ 9 mg/daybudesonide. This dose must be stable from 4 weeks prior to Screening until theend of the Induction Phase.

8. Subjects receiving oral 5-aminosalicylic acid (5-ASA) must be on a stable dosefrom 4 weeks prior to Screening until the end of study.

9. Subjects receiving immunosuppressants (azathioprine, 6-mercaptopurine [6-MP] ormethotrexate) must be on a stable dose for 4 weeks prior to Screening until theend of study treatment. Subjects taking methotrexate are also advised to takefolic acid 5 mg/week (or equivalent) if there is no contraindication.

10. Subjects receiving probiotics must be on a stable dose for ≥ 2 weeks prior toScreening until the end of study.

11. Subjects receiving an anti-diarrhetic must be on a stable dose for ≥ 2 weeksprior to Screening until the end of study.

12. Previous treatment with at least one biologic therapy that demonstrated aninadequate response and/or loss of response.

13. Negative pregnancy test during Screening and Day 1 (V0) in females of childbearingpotential.

14. Females with reproductive potential must be sexually abstinent or be willing to usea highly effective method of contraception from study start to ≥ 3 months after thefinal dose of the study drug. Highly effective methods of contraception include:

15. Hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginalring, injectables, and implants); male partner should use a condom;

16. Intrauterine device or system; or

17. Surgical sterilization or partner sterile (must have documented proof).

18. Male subjects must be either surgically sterile (must have documented proof), agreeto be sexually abstinent, or use a double-barrier method of birth control (e.g.,condom and diaphragm with spermicide, condom with cervical cap and spermicide) fromfirst study drug administration to ≥ 3 months after the final dose administration.

19. Male subjects must agree to refrain from donating sperm from first study drugadministration to ≥ 3 months after final dose administration.

Exclusion Criteria:

1. Diagnosis of Crohn's colitis, colitis yet to be classified, ischemic colitis,nonsteroidal anti-inflammatory drug (NSAID)-induced colitis, idiopathic colitis (i.e., colitis not consistent with UC), or radiation-induced colitis.

2. Ulcerative colitis limited to the rectum (ulcerative proctitis).

3. Presence of short bowel syndrome.

4. History of colectomy, or presence of an ileostomy or colostomy.

5. History of, or active colonic mucosal dysplasia.

6. Treatment with any intravenous (IV) corticosteroid or rectal therapy during theScreening period.

7. Treatment with any calcineurin inhibitor (e.g., cyclosporine, tacrolimus) within 4weeks prior to Screening.

8. Treatment with NSAIDs within 4 weeks prior to Screening. Short-term use (<7 days) ofNSAIDs for non-UC related symptoms is allowed.

9. Treatment with tofacitinib or other Janus Kinase (JAK) inhibitors within 4 weeksprior to Screening.

10. Treatment with sphingosine-1-phosphate receptor (S1PR) modulators within 4 weeksprior to Screening.

11. Biologic therapy within 56 days or 5 half-lives (whichever is longer) prior toScreening. Confirmation of undetectable or non-therapeutic serum levels, as assessedby the Investigator, will allow for eligibility.

12. Tube feeding, defined formula diets, or parenteral alimentation/nutrition within 3weeks of first dosing.

13. Treatment with oral antibiotics within 4 weeks prior to Screening or IV antibioticswithin 8 weeks prior to Screening.

14. Vaccination with a live or live-attenuated vaccine within 4 weeks prior toScreening.

15. History of dysplasia or malignancy in the past 5 years, except completely excisedbasal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ ofthe cervix.

16. Subjects with a current or recent history of severe, progressive, or uncontrolledcardiac (including uncontrolled hypertension), renal, hepatic, hematological,gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological (e.g.,history of seizures) disease, or any other severe comorbidity that, in the opinionof the Investigator, could confound the study results or put the subject atunreasonable risk.

17. Significant screening electrocardiogram (ECG) abnormalities, including evidence ofacute myocardial infarction, complete left bundle branch block, second-degree heartblock, or complete heart block.

18. For males, a QTc interval (Fridericia's correction) of >450 ms, and for females, aQTc interval (Fridericia's correction) of >470 ms.

19. Any of following laboratory abnormalities during the Screening period. If values areinitially outside prescribed limits, the evaluation may be repeated once within the Screening period to determine eligibility:

20. Calculated creatinine clearance < 60 mL/min

21. Serum transaminases > 2.0x Upper Limit Normal (ULN)

22. Alkaline phosphatase (ALP) > 2.0x ULN

23. Bilirubin > 1.5x ULN; does not apply to subjects with Gilbert's Syndrome (Meulengracht Syndrome)

24. Hemoglobin < 8g/dL

25. Platelets < 75,000/μL

26. Absolute neutrophil count < 1,500/ μL

27. Absolute lymphocyte count < 800/ μL

28. Human immune deficiency virus (HIV) infection or known HIV-related malignancy.

29. Acute or chronic hepatitis B (HBV) or hepatitis C (HCV), or carrier status. Subjectswith anti-HBc (hepatitis B core) antibodies (Ab) but with undetectable anti-HBs (hepatitis B surface) Ab should be excluded.

30. Positive immunoglobulin M (IgM) Ab titers in the presence of negative immunoglobulinG (IgG) Ab titers to Epstein-Barr virus (EBV).

31. Positive stool test for ova or parasites, positive stool culture for pathogens, orpositive stool toxin assay for Clostridium difficile at Screening.

32. Active cytomegalovirus (CMV) infection at Screening, as assessed by theInvestigator.

33. Positive QuantiFERON® TB test at Screening for latent Mycobacterium tuberculosis (TB) infection. If a QuantiFERON® TB test is indeterminate, the test should berepeated. If the result is again indeterminate, the subject should be excluded. Subjects with a history of latent TB infection who received or are receiving anappropriate and documented course of therapy can be included if the screeningexamination and a chest x-ray performed within 3 months prior to Screening revealedno evidence of current active infection.

34. History of any opportunistic infection within 12 weeks of first dosing.

35. Any current or recent symptoms/signs of infection, except nasopharyngitis, within 4weeks of first dosing.

36. Cirrhosis or active alcohol abuse, pr the judgment of the Investigator.

37. History of drug abuse according teo the Diagnostic and Statistical Manual of MentalDisorders, 5th edition (DSM-V) criteria within 12 months prior to Screening or apositive drug screening test.

38. Currently breast feeding, or pregnant.

39. Known hypersensitivity or intolerance to ALTB-268 or any of its excipients.

40. Participation in another clinical trial AND having received investigationalmedication within 30 days or 5 half-lives (whichever is longer) prior to Screeningor having used an investigational device treatment within 30 days prior toScreening. Concurrent participation in an observational or long-term follow-up studyand not actively receiving an investigational drug or device treatment may beeligible for participation in this study.

41. Inability to comply with the study protocol, in the opinion of the Investigator.