Evaluation of SPH3127 in Patients With Mild-to-Moderate Ulcerative Colitis

Inclusion Criteria:

1. Signed Informed Consent Form (ICF);
2. Adult males and females ≥ 18 to < 70 years of age on the day of signing the ICF.
3. A diagnosis of UC (documented or confirmed at screening) will be eligible providedthey have mild-to-moderate active UC extending ≥ 15 cm from the anal verge.
4. At screening/baseline, a Modified Mayo Clinic Score (MMCS) from 4-9, a rectal bleedingsubscore ≥ 1, and a Mayo Clinic Endoscopic Subscale (MCES) score ≥ 2 determined bycentral reading.
5. Patient has a negative urine drug screen (e.g., amphetamines, barbiturates,benzodiazepines, cannabis, cocaine, opiates, methadone) at Screening.
6. Patient has a negative alcohol breath test at Screening.
7. Female patients who have a negative pregnancy test at Screening and who agree to useadequate birth control methods throughout the entire study (and extension, ifapplicable) or who is post-menopausal (i.e., amenorrhea ≥ 1 year) or who have beensurgically sterilized.
8. Male patients with partners of child-bearing potential who agree to use adequate birthcontrol methods throughout the entire study (and extension, if applicable) or who havebeen surgically sterilized.

Exclusion Criteria:

1. Diagnosis of severe UC, defined as the presence of ≥ 6 bloody stools daily with one ormore of the following: (1) oral temperature > 37.8°C or > 100.0°F; (2) pulse > 90beats/min; (3) hemoglobin concentration < 10.5 g/dL; or erythrocyte sedimentationratio (ESR) > 30.
2. Patients treated with oral mesalamine >2.4 g/d, systemic steroids or rectal steroidswithin 4 weeks prior to randomization, rectal mesalamine (within 2 weeks),immunomodulators or immunosuppressant drugs, including, but not limited to, IL-6inhibitors, TNF inhibitors, anti-IL-1 agents and JAK inhibitors within 5 half-livesprior to randomization, antibiotics, anti-diarrheals (within 2 weeks), drugs blockingthe renin-angiotensin system (e.g., direct renin inhibitors, angiotensin convertingenzyme inhibitors, or angiotensin II receptor blockers) (within 4 weeks) oradministration of any investigational drug (within 4 weeks). Because SPH3127 is adirect renin inhibitor with the potential to reduce blood pressure, other classes ofantihypertensives (e.g., calcium channel blockers, beta blockers, diuretics, directvasodilators, alpha blockers, central α2 antagonists) (within 4 weeks) will also beexcluded. Drugs, herbal medicines and substances that inhibit or induce CYP3A4 (e.g.,ritonavir, itraconazole, grapefruit juice) (within 2 weeks or 5 half-lives, whicheveris longer) will be excluded.
3. History of colectomy or partial colectomy, colorectal dysplasia, Crohn's disease,toxic megacolon, or bleeding disorders.
4. A stool sample positive for enteric pathogens, including Clostridium difficile.
5. Patients with an estimated glomerular filtration rate (eGFR) < 60.
6. Patients with hepatic impairment or history of liver cirrhosis.
7. Serum creatinine > 1.5 times the upper limit of normal, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL) or alkaline phosphatase (ALP) > 2 times the upper limit of normal.
8. Serious underlying disease other than UC.
9. Previous participation in clinical trials with SPH3127
10. Known hypersensitivity to tablet ingredients or history of a significant allergicreaction to any drug as determined by the investigator.
11. Known seropositivity or positive test at screening for an active viral/bacterialinfection with:

• Hepatitis B virus (HBV) (except seropositivity due to HBV vaccination)
• Hepatitis C virus
• Human immunodeficiency virus
• COVID-19 (only active infection excluded)
• Tuberculosis

12. Known clinically relevant immunological disorders.
13. History of severe allergic or anaphylactic reactions.
14. History of malignancy, unless deemed cured by adequate treatment with no evidence ofrecurrence for a minimum 3 years before screening; completely eradicated non-melanomaskin cancer (such as basal cell carcinoma or squamous cell carcinoma) is notexclusionary.
15. Clinically relevant abnormalities detected on ECG regarding either rhythm orconduction (e.g., QTcF > 450 ms or a known long QT syndrome). A first-degree heartblock or sinus arrhythmia will not be considered a significant abnormality.
16. Low blood pressure at screening (i.e., SBP < 90 mmHg or DBP < 60 mmHg).
17. Clinically relevant abnormalities detected on vital signs prior to dosing.
18. Significant blood loss (including blood donation > 500 mL) or transfusion of any bloodproduct within 12 weeks prior to the IP administration or scheduled transfusion within 4 weeks after the end of the trial.
19. Treatment with any drug known to have a well-defined potential for toxicity to a majororgan in the last 3 months preceding the initial investigational product (IP)administration.
20. Concurrent participation, or participation within 30 days prior to the IPadministration or 5 half-lives of the investigational drug (whichever is longer), inany drug/device or biologic investigational research trial.
21. Women who are breastfeeding.
22. Vaccination (including influenza and COVID-19) within the last 4 weeks prior torandomization.
23. History of drug or alcohol abuse.
24. Is an investigator, sub-investigator, research assistant, pharmacist, trialcoordinator, or other staff of a relative who is directly involved in the conduct ofthe trial.
25. Any condition or circumstances that in the opinion of the investigator may make asubject unlikely or unable to complete the trial or comply with trial procedures andrequirements.