CAMBRIDGE, MA, USA I October 16, 2014 I Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD) announced today the initiation of a Phase II clinical trial evaluating linaclotide for the treatment of adults suffering from opioid-induced constipation (OIC). Data are expected in the second half of 2015. The clinical trial is being conducted jointly by Ironwood and Actavis plc, Ironwood’s co-development and co-promotion partner for linaclotide in the United States.

Linaclotide is a guanylate cyclase-C (GC-C) agonist approved by the FDA for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). Linaclotide is not currently approved for the treatment of OIC.

“Ironwood’s pioneering research on the GC-C pathway led us to create the first and only FDA-approved GC‐C agonist, linaclotide. We believe a GC-C agonist could represent a different approach to the treatment of OIC, so we look forward to evaluating linaclotide in this category of constipation,” said Dr. Michael Hall, MB. BCh., senior vice president, clinical development of Ironwood. “This trial is designed to provide us with data on whether linaclotide can increase bowel movement frequency and impact other symptoms in adult OIC patients.”

The randomized, double-blind, placebo-controlled, multi-site Phase II clinical trial is expected to enroll approximately 240 adult patients with chronic, non-cancer pain who have been receiving a stable dose of an opioid analgesic and suffer from constipation, defined as fewer than three spontaneous bowel movements (SBMs) per week. Patients will be randomized to receive 145 mcg of linaclotide, 290 mcg of linaclotide, or placebo for eight weeks. The primary endpoint of the trial is an increase in SBM frequency. Additionally, a number of secondary endpoints and exploratory analyses intended to inform future development plans are included in the study design.

About Opioid-Induced Constipation

Opioids are a commonly prescribed class of pain medications that may reduce fluids and movement within the intestine, resulting in constipation. It is estimated that more than 8 million people in the United States suffer from opioid-induced constipation (OIC). Symptoms of OIC may include reduced bowel movement frequency, straining, incomplete evacuation and a sensation of bowel obstruction.

About Linaclotide

Linaclotide is a guanylate cyclase-C (GC-C) agonist that is thought to work in two ways based on nonclinical studies. Linaclotide binds to the GC-C receptor locally, within the intestinal epithelium. Activation of GC-C results in increased intestinal fluid secretion and accelerated transit and a decrease in the activity of pain-sensing nerves in the intestine. The clinical relevance of the effect on pain fibers, which is based on nonclinical studies, has not been established. Linaclotide is marketed by Ironwood and Actavis in the United States as LINZESS® and is indicated for the treatment of adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). Linaclotide is marketed by Almirall, S.A. for the treatment of adults with moderate to severe IBS-C in Europe under the brand name CONSTELLA®. Ironwood also has partnered with Astellas Pharma Inc. for development and commercialization of linaclotide in Japan and with AstraZeneca for development and commercialization in China.

LINZESS and CONSTELLA are trademarks owned by Ironwood Pharmaceuticals, Inc. Any other trademarks referred to in this press release are the property of their respective owners. All rights reserved.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (NASDAQ: IRWD) is focused on creating medicines that make a difference for patients, building value to earn the continued support of our fellow shareholders, and empowering our team to passionately pursue excellence. We discovered, developed and are commercializing linaclotide, which is approved in the United States and a number of other countries. Our pipeline priorities include exploring further opportunities for linaclotide, as well as leveraging our therapeutic expertise in gastrointestinal disorders and our pharmacologic expertise in guanylate cyclases to address patient needs across the upper and lower gastrointestinal tract. Ironwood was founded in 1998 and is headquartered in Cambridge, Mass. Connect with us at www.ironwoodpharma.com or on Twitter at www.twitter.com/ironwoodpharma; information that may be important to investors will be routinely posted in both these locations.

SOURCE: Ironwood Pharmaceuticals