Phase 2b Study to Investigate the Safety and Efficacy of TIN816 in Sepsis-associated Acute Kidney Injury (SA-AKI)

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.

2. ≥ 18 to ≤ 85 years of age

3. Admitted to ICU or intermediate care unit/ high dependency care unit (HDU)

4. Diagnosis of sepsis according to criteria defined by The Third International
Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) based on:

- Suspected or confirmed infection AND

- Acute increase of SOFA score of 2 or more (excluding renal component). The
baseline SOFA score should be assumed to be zero unless the participant is
known to have pre-existing (acute or chronic) organ dysfunction before the
onset of infection

5. Diagnosis of AKI Stage 1 or greater per the following criterion at randomization:

An absolute increase in serum or plasma creatinine by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within
48 hours or presumed to have occurred in the previous 48 hours as compared to the
reference serum creatinine.

- For participants with hospital-acquired AKI, a stable serum creatinine obtained in
the hospital prior to AKI diagnosis should be used as the reference serum
creatinine.

- For participants presenting from community, the reference serum creatinine should be
estimated using the following order of preference:

1. The most recent value within 3 months of the hospital admission. If not
available:

2. The most recent value between 3 and 12 months prior to hospital admission. If
not available:

3. At hospital admission

Exclusion criteria

1. Not expected to survive for 24 hours

2. Not expected to survive for 30 days due to medical conditions other than SA-AKI

3. History of CKD with a documented estimated GFR <45 mL/min prior to admission to
hospital

4. eGFR <45mL/min at admission without any other reference serum eGFR within last
12-months

5. Receiving RRT or a decision has been made to initiate RRT within 24 hours after
randomization

6. Weight is less than 40 kg or more than 125 kg.

7. Limitations to the use of mechanical ventilation, RRT or vasopressors/inotropes
(N.B. limitations on Cardiopulmonary resuscitation (CPR)e.g., do-not-resuscitate
orders are not an exclusion criterion unless associated with likely poor outcome in
next 24 hours)

8. Sepsis diagnosis according to sepsis inclusion criteria for a period longer than 72
hours prior to ICU admission

9. AKI diagnosis according to AKI inclusion criteria over 48 hours after admission to
ICU

10. Inability to administer study drug within 24 hours of diagnosis of AKI according to
AKI inclusion criteria

11. Presence of AKI, in the Investigator's opinion, as suggested by clinical
manifestation, e.g., prolonged oliguria or severe renal dysfunction on admission
without a history of CKD, for a period longer than 24 hours prior to study drug
administration

12. Evidence of recovery from AKI based on the investigator's clinical judgement prior
to randomization

13. AKI is most likely attributable to other causes than sepsis, such as nephrotoxic
drugs (Non-steroidal anti-inflammatory drugs (NSAIDs), contrast, aminoglycosides,
etc.) or renal perfusion-related (acute abdominal aortic aneurysm, dissection, renal
artery stenosis), urinary obstruction

14. Documented (biopsy proven) or suspected history of acute or sub-acute kidney
diseases such as rapidly progressive glomerular nephritis (RPGN) and acute
interstitial nephritis (AIN)

15. Patients who are post-nephrectomy

16. Patients with permanent incapacitation

17. Patients who are thrombocytopenic at screening (platelet count <50,000 per
microliter) who have active/uncontrolled bleeding or who present current or past
conditions indicating high risk for bleeding in the opinion of the investigator
(e.g. coagulopathies, previous history of major non-traumatic bleeding etc.)

18. Immunosuppressed patients

- History of immunodeficiency diseases

- Receiving immunosuppressant treatment or on chronic high doses (high-dose
therapy exceeding 2 weeks of treatment) of steroids equivalent to
prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant
patients. Patients with septic shock treated with corticosteroids (as per the
Surviving Sepsis Guidelines) can be included. See Appendix Section 10.6
Immunosuppresant drugs, (Table 10 5 Immunosuppressant drug exclusions)

19. Patients with known or presumed latent or active TB based on clinical history or
imaging e.g. patients on TB preventive therapy or close/household contacts of
pulmonary TB patients

20. Known active hepatitis B or C infection, or positive Hepatitis B Virus (HBV) or
Hepatitis C Virus (HCV) serology or patients with advanced chronic liver disease,
confirmed by a Child-Pugh score of 10-15 (Class C)

21. Acute pancreatitis with no established source of infection

22. Active hematological malignancy (previous hematological malignancies that are not
actively treated are allowable)

23. Burns requiring ICU treatment

24. Sepsis attributed to confirmed COVID-19

25. Use of other investigational drugs within 5 half-lives of enrollment, within 30 days
(e.g., small molecules) or until the expected pharmacodynamic effect has returned to
baseline (e.g., biologics), whichever is longer; or longer if required by local
regulations

26. History of hypersensitivity to the study treatment or its excipients or to drugs of
similar chemical classes

27. Any medical conditions that could significantly increase risk of participants'
safety by participating in this study according to investigator's judgement

28. Women with a positive pregnancy test, pregnancy or breast feeding

29. Women of childbearing potential, unless they are using highly effective methods of
contraception for the entire duration of the trial.