A Phase 2a Study of Weekly Doses of GCS-100 in Patients With Chronic Kidney Disease

Galectin-3 contributes to fibrosis, is elevated in patients with ESRD, and correlates with
adverse outcomes (de Boer et. al., 2011, Dang et. al., 2012, Fernandes Bertocchi et. al.,
2008, Henderson et. al., 2008). Animal models with genetic knockout of galectin-3
demonstrate a reduction in structural and functional deficits in the kidney (Dang et. al.,
2012, Fernandes Bertocchi et. al., 2008, Henderson et. al., 2008). GCS-100 is a galectin- 3
antagonist that has been shown to reduce fibrosis pre-clinically. Based on the role of
galectin-3 and fibrosis in kidney disease, the Sponsor believes GCS-100 may be effective at
treating patients with CKD.

Inclusion Criteria:

1. Subject is capable of understanding the purpose and risks of the study and is able to
provide written informed consent

2. Subject is ≥18 and ≤75 years of age; patients >75 years old may be included at the
request of the investigator and discretion of the Medical Monitor

3. Subject has an eGFR of 15 - 44 mL/min/1.73m2 determined using the 4-variable
Modification of Diet in Renal Disease (MDRD) equation (see Section 10.1)

4. Patients with CKD diagnosis >12 months and stable, in the opinion of the
investigator, within the past 3 months

5. Subject is willing and able to comply with all protocol requirements

6. Female subjects of childbearing potential (i.e., women who have not been surgically
sterilized or have not been post-menopausal for at least 1 year) and male subjects
with partners of childbearing potential must agree to use medically acceptable
methods of contraception throughout the study period

Exclusion Criteria:

1. Treatment with an experimental (unlicensed) drug within 4 weeks or ≤5 half-lives
prior to screening

2. Kidney disease due to systemic lupus erythematosus (regardless of whether active or
in remission), any form of vasculitis (regardless of whether active or in remission),
IgA nephropathy, multiple myeloma, polycystic kidney disease, untreated obstructed
nephropathy or any other causes that, in the opinion of the investigator, may put the
subject at an increased risk

3. Planned renal replacement therapy of any kind within 6 months of randomization

4. Previous solid organ transplant

5. Systolic blood pressure ≤90 mmHg and ≥160 mmHg and diastolic blood pressure ≤40 mmHg
and ≥100 mmHg at screening

6. Subject has clinical laboratory values of:

1. Hemoglobin: ≤9 g/dL

2. Total bilirubin: >1.5X the upper limit of normal (ULN)

3. ALT and/or AST: >2.5X ULN

7. Current treatment with immunosuppressive agents, except for topical agents or inhaled
steroids when conditions are chronic and stable

8. Treatment with any form of IV iron therapy within 4 weeks prior to screening

9. Known history of cancer (excluding non-melanoma skin cancer that is not being
actively treated) within 5 years of screening

10. Known history of human immunodeficiency virus, active hepatitis C virus (HCV), active
hepatitis B virus (HBV), or prior history of infection with HBV (HBcAb positive); if
adequate hepatic function has been documented for patients with HCV or prior history
of hepatitis B without evidence of cirrhosis, the Medical Monitor may approve their
enrollment

11. Clinically relevant active infection and/or a serious co-morbid medical condition,
such as recent myocardial infarction (within the last 6 months), unstable angina,
difficult-to-control congestive heart failure, uncontrolled hypertension,
difficult-to-control cardiac arrhythmias, severe or uncontrolled chronic obstructive
or chronic restrictive pulmonary disease, and/or cirrhosis.

12. Subject had major surgery within 4 weeks of randomization

13. If female, subject is pregnant or breastfeeding

14. Subject has a concomitant disease or condition, including laboratory abnormalities,
which, in the opinion of the investigator, could interfere with the conduct of the
study or put the subject at unacceptable risk