Dose-Ranging Safety, Tolerability, and Efficacy Study of AZD2373 in Participants With APOL1-Mediated Kidney Disease

Inclusion Criteria:

• Age: Male and female participants of African descent (including, but not limited to,Black, Black African, Black Caribbean, African American, Afro-Caribbean,Afro-Latino, West African, Mixed Black backgrounds, or other self-identified Africandiaspora heritage) aged 18 to 70 years, inclusive at the time of informed consent.

• Participants who have high-risk APOL1 genotype (G1/G1; G1/G2; G2/G2). The screeningperiod can be extended if there are delays related to the shipment, handling, orprocessing of genotype results.

• A geometric mean UACR ≥ 300 mg/g calculated based on the mean of readings taken from 3 FMV urine samples collected on 3 consecutive days. Since the mean will be assessedfor eligibility, any of the 3 readings may fall below 300 mg/g.

• eGFR ≥ 25 mL/min/1.73m2.

• Contraceptive use by males or females should be consistent with local regulationsregarding the methods of contraception for those participating in clinical studies.

• Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

• Participants with diagnosis of Type 1 diabetes mellitus.

• Body Mass Index > 45 kg/m2.

• SBP > 180 mmHg/DBP > 110 mmHg (measured when the participant is considered to be atsteady state, and preferably when they have taken their BP medications that sameday).

• QTcF > 470 ms, except participants with bundle branch block who should excluded ifQTcF> 480 ms.

• Acute coronary syndrome/Acute myocardial infraction with or without any coronaryintervention within 6 months.

• Transient ischaemic attack/ stroke within 3 months.

• High grade (second to third) degree AV block or clinically significant sinus nodedysfunction untreated with pacemaker.

• A history of ventricular arrhythmias requiring treatment.

• Participants with Type 2 diabetes mellitus must be excluded if ANY of the followingconditions are present:

1. Current or past use of insulin for more than 3 months and/or any maintenancetherapy with insulin within 2 months of screening.

2. Screening Haemoglobin A1c > 8.0%

3. Receiving more than one anti-hyperglycaemic agent (excluding SGLT inhibitorsand GLP-1 receptor agonists is permitted if prescribed for a purpose other thanglycaemic control which can be taken in addition to one otheranti-hyperglycaemic agent).

• Participant on kidney replacement therapy (dialysis or kidney transplant) or anyother organ transplant.

• History or serologic evidence of autoimmune-mediated glomerular disease includingbut not limited to: lupus nephritis (positive lupus serology), ANCA associatedvasculitis (antineutrophil cytoplasmic antibody), membranous nephropathy (anti-phospholipase A2 receptor antibody or other autoantibody associated withmembranous nephropathy), anti-GBM disease (anti-GBM antibody), or IgA nephropathy.

• Another underlying cause of kidney disease that is not associated with APOL1,including but not limited to polycystic kidney disease or, congenital anomalies ofthe kidney and urinary tract.

• History of a diagnosed coagulopathy, a major unexplained bleeding event, or otherhigh-risk bleeding diathesis.

• A history of trypanosomiasis or leishmaniasis.