A Phase 2b Dose Finding Study of RMC-035 in Participants Undergoing Open-chest Cardiac Surgery

Inclusion Criteria:

• eGFR ≥30 ml/min/1.73m2

• Scheduled for non-emergent surgery of any of the following types, with use ofcardiopulmonary bypass (CPB): coronary artery bypass grafting (CABG), valve surgery,ascending aorta aneurysm surgery

• Risk factors for acute kidney injury are present

• Participant capable of providing written informed consent

• Participant agrees to study restrictions such as not to take part in anotherinterventional study, use contraception and not donate ova or sperm

Exclusion Criteria:

• Any medical condition that makes the participant unsuitable

• Scheduled for emergent surgeries

• Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgerycombined with additional non-emergent cardiac surgeries

• Scheduled to undergo transcatheter aortic valve implantation (TAVI) or transcatheteraortic valve replacement (TAVR), or off-pump surgeries or left ventricular assistdevice (LVAD) implantation

• Experiences a cardiogenic shock or hemodynamic instability which require inotropesor vasopressors or other mechanical devices such as intraaortic balloon pumping (IABP) within 24 hours prior to surgery

• Requires any of the following within one week prior to surgery: defibrillator orpermanent pacemaker, mechanical ventilation, IABP, LVAD, other forms of mechanicalcirculatory support.

• Diagnosed with AKI prior to surgery

• Requires cardiopulmonary resuscitation prior to surgery

• Ongoing sepsis or an untreated diagnosed clinically significant infection

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3.0 times theupper limit of normal (ULN).

• Total bilirubin ≥2.0 time ULN

• History of solid organ transplantation

• History of renal replacement therapy

• Severe allergic asthma

• Chronic immunosuppressive treatment that may have an impact on kidney function

• Ongoing chemotherapy or radiation therapy for malignancy that may have an impact onkidney function

• Current enrolment or past recent participation in any other clinical study involvingan investigational study treatment

• Previously treatment of RMC-035

• Sensitivity to any of the study interventions, or components thereof