A Study of RG-012 in Subjects With Alport Syndrome

This is a Phase 1, multi-center study of the safety, pharmacodynamics, and pharmacokinetics
of RG-012 administered to subjects with Alport syndrome. During this open-label study, all
eligible subjects will receive RG-012. The study consists of two parts (Part A and Part B).
During Part A, half of the participants will receive a single dose of RG-012 and half will
receive 4 doses of RG-012 (one dose every other week for 6 weeks). All subjects will undergo
two renal biopsies, one before and one after receiving RG-012, to assess the effect of RG-012
on the kidney. After completing Part A, subjects will be able to enter Part B of the study.
During Part B, all subjects will receive RG-012 every other week for 48 weeks.

Inclusion Criteria:

1. Males or females, ages 18 to 65 years

2. Confirmed diagnosis of Alport syndrome

3. eGFR between 40 and 90 mL/min/1.73m2

4. Proteinuria of at least 300 mg protein/g creatinine

5. For subjects taking an ACE inhibitor or an ARB, the dosing regimen should be stable
for at least 30 days prior to screening

6. Willing to comply with contraception requirements

Exclusion Criteria:

1. Causes of chronic kidney disease aside from Alport syndrome (such as diabetic
nephropathy, hypertensive nephropathy, lupus nephritis, or IgA nephropathy)

2. End stage renal disease (ESRD) as evidenced by ongoing dialysis therapy or history of
renal transportation

3. Any other condition that may pose a risk to the subject's safety and well-being

4. Female subjects who are pregnant or lactating