Long Term Safety Study of Plecanatide

This is a phase 3, multicenter, open-label, long-term safety and tolerability study of 6 mg
daily dose of plecanatide administered orally. Patients who are Study Completers or Eligible
Screen Failures whose eligibility is confirmed at the end of their participation in the
double-blind plecanatide studies SP304203-04 or SP304203-05 will be enrolled.

Beginning on Day 1, patients will take one (1) plecanatide 6.0 mg tablet in the clinic and
thereafter every morning with approximately 240 mL (8 ounces) of liquid, with or without
meals.

Safety and tolerability assessments and patients' self-assessment of disease severity will be
performed according to the Schedule of Assessments.

Patients who discontinue early from the study will undergo an Early Withdrawal (EW) visit
within 5 days after stopping study drug.

Inclusion Criteria:

Patients with documented diagnosis of IBS-C who:

- Completed plecanatide study SP304203-04 or SP304203-05, were compliant with the
previous study's requirements, and did not experience any Serious Adverse Event (SAE)
deemed related to study drug during the course of the previous study, OR

- Failed screening in study SP304203-04 or SP304203-05 due to diary noncompliance (an
exclusion in the core study) or due to an administrative reason and is allowed to
enter this study by notification from Sponsor or delegate.

Key Exclusion Criteria:

- Patient is unwilling or unable to: participate in the study for the required duration,
understand and sign the informed consent form (ICF) and undergo all protocol related
tests and procedures throughout the study.

- Female patient of childbearing potential with a positive urine pregnancy test on Day
1.

- Male and female patients of childbearing potential who do not agree to continue to use
the method of birth control used in the core double-blind plecanatide study for the
duration of this clinical trial.

- Patient has experienced a significant negative change in health status during the
course of participation in the core double-blind plecanatide study or after completion
of the study.

- In the opinion of the Investigator or Medical Monitor, it is not in the patient's best
interest to participate in the study. The reason(s) for the patient's exclusion must
be specified.