Phase 2a to Evaluate PL-8177 in Subjects with Active Ulcerative Colitis (UC)

Inclusion Criteria: * Age ≥18 to ≤75 years of age at Screening. * Has a history of UC diagnosis prior to screening; confirmed by endoscopic and histologic evidence in the subject chart. If the historical evidence is not available, then endoscopic and histologic evidence can be confirmed during the screening period. Note: If no complete colonoscopy (adequate in quality to assess for dysplasia and colorectal polyps) has been performed and documented (with reports) within the past 1 year as recommended by local and national guidelines depending on Colorectal cancer risk factors in the specified subject, a full colonoscopy should be performed at screening. If such results are available within one year, a flexible sigmoidoscopy with examination up to the splenic flexure will be used for screening. * Has active UC defined as a MES ≥2 during screening sigmoidoscopy. * Has evidence of endoscopic disease extending to at least 5 cm proximal to the anal verge. * If currently receiving 5-ASA, the duration and dose prior to the screening endoscopy must be as specified below, and a stable dose must be maintained throughout the double-blind trial: 5-aminosalicylates (5-ASA) (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide) for ≥4 weeks with the dose stable for ≥3 weeks prior to the screening endoscopy. * If recently has received any of the following treatments, they must have discontinued as specified below: * If 5-ASA has been recently discontinued, it must have been stopped for ≥3 weeks prior to the screening endoscopy. * If a thiopurine has recently been discontinued, it must have been stopped for ≥4 weeks prior to the screening endoscopy. * Oral corticosteroids must have been stopped for ≥4 weeks prior to the screening endoscopy. * Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day 1 prior to first dose of study drug. * Male and female subjects of childbearing potential must agree to use 1 highly effective form of birth control during study participation and for 30 days after the last dose of study drug, unless the subject or his/her partner is surgically sterilized, or the subject agrees to abstain from sexual intercourse. * Highly effective methods of birth control in this study include intrauterine device, hormonal contraceptives (oral, patch, long acting injectable, implant). Note: Oral hormonal contraceptives should be combined estrogen and progesterone. If a progesterone-only oral contraceptive is used, then a second method of birth control should be used as well. * Postmenopausal is defined as lack of menses for ≥12 months prior to screening, confirmed by serum FSH \>25 IU at Screening. * Has provided informed consent prior to initiation of any study specific activities/procedures. * Understands and is willing and able to comply with study requirements, including the schedule of events and follow-up visits. Exclusion Criteria: Subjects will be excluded from the study if they meet any of the following criteria at the Screening visit unless otherwise stated: * Any condition, physical finding, laboratory or ECG abnormality, which, in the opinion of the Investigator, poses a safety risk, will prevent the subject from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the subject. * Has fulminant colitis, toxic megacolon, microscopic colitis, history of colitis-associated colonic dysplasia, active peptic ulcer disease, cervical dysplasia, or primary sclerosing cholangitis. * History of Crohn's disease or indeterminate colitis, or the presence or history of a fistula consistent with Crohn's disease. * Presence of ileostomy or colostomy, or history of prior colon resection. * Presence of adenomatous colonic polyps that have not been removed. * Stools positive for C. difficile, enteric pathogens (Salmonella, Shigella, Campylobacter), or ova and parasites within 28 days of screening. Screen failures due to positive C. difficile or other enteric infection can be re-screened after appropriate treatment. * History of mitochondrial disorder. * History of primary or secondary immunodeficiency. * History of cancer within the 5 years prior to screening including solid tumors and hematological malignancies (exception: no approval needed for basal cell and in situ squamous cell carcinomas of the skin that have been adequately treated with no re-occurrence for at least 1 year prior to screening). History of one or more clinically relevant neurologic, psychologic, ophthalmologic, pulmonary, cardiovascular, gastrointestinal (other than the UC), hepatic, renal, endocrine, or other major systemic disease of moderate (or worse) severity, making implementation of the protocol or interpretation of the study difficult. Examples of (but not limited to) conditions to be excluded, are the following: * Uncontrolled hypertension, with systolic blood pressure (SBP) ≥160 mmHg, diastolic blood pressure (DBP) ≥90 mmHg. * Uncontrolled hyperlipidemia (even if therapy is ongoing, LDL\>200 mg/dl or triglycerides \>500 mg/dL). * Known uncontrolled hyperthyroidism or hypothyroidism. * Impaired hepatic function (Aspartate aminotransferase \[AST\] or Alanine aminotransferase \[ALT\] values \>2.0 times the upper limit of the reference range and/or serum bilirubin \>1.5 times the upper limit of the reference range at the screening visit). * Cardiac or pulmonary disease, such as unstable angina or myocardial infarction within the past 12 months, congestive heart failure (CHF) Grade 2, 3, or 4 according to New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, or chronic pulmonary disease requiring oxygen, venous thrombosis. * Stroke or transient ischemic attack (TIA) in the 12 months before screening. * Major depressive illness in the last 3 years; any history of severe psychiatric illness (eg, schizophrenia). * Multiple sclerosis or any other demyelinating disease. * Any of the following laboratory abnormalities: * Hemoglobin \<8.5 g/dl (international system units \[SI\]: \<85 g/L). * Neutrophils \<1500/mm3 (SI: \< 1.5 x 109/L). * White blood cell (WBC) count \<3,000/mm3 (SI: \< 3.0 x 109/L). * Platelets \<80,000 mm3 (SI: 80 x 109/L). * International normalized ratio (INR) \>1.5. * Serum creatinine \>1.5 x the upper limit of normal. * Has a current bacterial, parasitic, fungal, viral, or mycobacterial infection, or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks prior to the screening visit, and/or oral antibiotics within 2 weeks prior to screening visit and at any time during the screening period. * Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C (HCVAb) at Screening (note: HCV subjects with undetectable viral load will be eligible). * Clinically significant findings on 12-lead ECG such as, but not limited to, 2nd or 3rd degree AV block, prolongation of QRS complex over 120 msec, or QTcF interval ≥450 msec for males and ≥470 msec for females. Medications of exclusion: * Non-steroidal anti-inflammatory drugs (NSAIDs) daily. * Subjects on anti-coagulation therapy within 28 days prior to screening and through Day 56. Note: (A daily dose of ASA 81mg, taken for cardio prophylaxis, is considered acceptable to be continued during the study.) * Topical (i.e., enema or suppository) mesalamine or steroid within 14 days prior to screening endoscopy. * Azathioprine, 6-mercaptopurine, or methotrexate within the 28 days prior to screening. * Any prior use of mycohphenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide * Any prior use of biologics: rituximab, efalizumab, anti-integrines (natalizumab, vedolizumab, etrolizumab), TNF antagonists (infliximab, , golimumab, certolizumab pegol), anti-IL-12/23 (ustekinumab, guselkumab, risankizumab, or mirikizumab) ≤ 3 months prior to first dosing or ≤ 5 elimination half-lives prior to first dosing (whichever is shorter). * Any prior use of small molecules: JAK inhibitors (tofacitinib, baricitinib, upadacitinib, or other) or S1P receptor modulator (fingolimod, ozanimod, etrasimod) ≤ 3 months prior to first dosing or ≤ 5 elimination half-lives prior to first dosing (whichever is shorter). * Use of PPI (proton pump inhibitor) during the study (Should be discontinued 72 hours prior to Day 1). * Use of prescription medications started or with a dose adjustment within 4 weeks prior to study screening, or over-the-counter medications or supplements started or with a dose adjustment within 2 weeks prior to study screening. Medications under Inclusion Criterion #5 are not included. Short-term administration of drugs for acute conditions are acceptable. * Anti-diarrheal medications are not allowed within 48 hours of screening and throughout the study. * Participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to screening or is currently participating in another trial of an investigational drug (or medical device). * Subjects with planned hospitalization or surgery during the study. * Subject has known sensitivity to any of the products or components to be administered during dosing. * Has previously received PL8177. * History of alcohol or drug abuse and/or positive drug test at screening (with exception of marijuana if legal within the state and no drug abuse is noted in the PI's assessment) * Positive TB or COVID 19 test. Note: Patients with positive TB results who had active or latent TB in the two years preceding the screening visit and who were treated for TB can participate in study