Ironwood Pharmaceuticals Announces Publication of Positive IW-3718 Phase IIb Data in Gastroenterology

• Data showed improvement in both heartburn and regurgitation symptoms and further demonstrated the role of bile acid in refractory gastroesophageal reflux disease (GERD)
• IW-3718 is currently in two Phase III trials; top line data targeted for second half of 2020

BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD), a GI-focused healthcare company, today announced that Gastroenterology - the official journal of the American Gastroenterological Association (AGA) - has published data from its Phase IIb clinical trial evaluating IW-3718 in adults with refractory gastroesophageal reflux disease (GERD). The data demonstrated that IW-3718 1500 mg given twice daily (BID) plus a proton pump inhibitor (PPI) significantly reduced heartburn severity and reduced the frequency of regurgitation – two of the most bothersome and frequently reported symptoms of GERD¹ – compared to a PPI alone. Additionally, more than 50 percent of patients treated with IW-3718 1500 mg BID plus a PPI reported a clinically meaningful reduction in heartburn severity. IW-3718 was well-tolerated in the trial; the most common adverse event reported overall was constipation. Data from this study were previously presented at Digestive Disease Week^® (DDW) in Washington, D.C., June 2018.

The publication can be accessed at the following link: https://www.gastrojournal.org/article/S0016-5085(20)30242-0/fulltext

Refractory GERD affects an estimated 8 to 10 million Americans^2,3,4,5 who continue to suffer from heartburn and regurgitation despite receiving treatment with PPIs - the current standard of care. Research suggests that PPIs block gastric acid from refluxing into the esophagus, but do not suppress reflux of bile acids, which have been implicated as contributors to refractory GERD symptoms. IW-3718 is a novel gastric retentive formulation of a bile acid sequestrant designed to release in the stomach over an extended period where it is positioned to bind to bile before it reaches the esophagus.

“As a physician, it is very challenging to have no approved treatments to offer patients for whom standard treatments don’t work, but the reality is many of our patients continue to struggle with frequent heartburn and regurgitation despite taking their PPIs,” said lead author Michael Vaezi, M.D., Ph.D. Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Director of the Center for Swallowing and Esophageal Disorders at Vanderbilt University Medical Center. “These data provide strong evidence that bile acid plays a key role in refractory GERD and provide hope that IW-3718 may have the potential to make a meaningful difference for patients.”

Patients with refractory GERD suffer from heartburn and/or regurgitation more than twice per week despite standard of care treatment with PPIs.⁶ Additionally, a significant portion of refractory GERD patients have esophageal erosions.⁷ The Phase IIb trial evaluated 280 adult patients with refractory GERD who continued to experience heartburn and regurgitation (movement of gastric contents into the throat, often accompanied by a bitter taste in the mouth) despite taking PPIs. Patients in the study either had erosive esophagitis, a severe inflammation and erosions of the esophagus^8,9, or demonstrated evidence of pathological acid reflux.

“The publication of the Phase IIb data in Gastroenterology is further recognition of these important data and the potential for IW-3718, if approved, to be a new treatment option for the millions of Americans suffering from refractory GERD,” said Mike Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of drug development at Ironwood. “We continue to focus on advancing our two Phase III trials and look forward to presenting top line data in the second half of 2020.”

About IW-3718

IW-3718 is a novel, gastric-retentive investigational formulation of colesevelam, a bile-acid sequestrant, developed by Ironwood using the proprietary Acuform^® drug delivery formulation technology licensed from Assertio Therapeutics, Inc. IW-3718 is designed to maintain the bile-acid sequestrant in the stomach over an extended period of time where it is positioned to intercept bile before it reaches the esophagus. Data from non-clinical and clinical studies collectively support the extended release and gastric-retentive profile of IW-3718.

About Refractory Gastroesophageal Reflux Disease (GERD)

An estimated 8 to 10 million adult Americans and more than 60 million adults globally suffer from refractory gastroesophageal reflux disease (GERD), meaning they continue to experience symptoms such as heartburn and regurgitation despite receiving treatment with a proton pump inhibitor (PPI). One of the largest and most diverse population-based surveys on gastrointestinal symptoms found that more than half (54.1 percent) of GERD patients taking PPIs still reported persistent symptoms.¹⁰ While PPIs suppress production of stomach acid, Ironwood’s clinical research demonstrates that reflux of bile from the intestine into the stomach and esophagus may play a key role in the ongoing symptoms of refractory GERD. There are no FDA-approved treatment options for these patients.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (NASDAQ: IRWD) is a GI healthcare company dedicated to advancing the treatment of GI diseases and redefining the standard of care for millions of GI patients. We discovered, developed and are commercializing linaclotide, the U.S. branded prescription market leader for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC).

We are also advancing two late-stage, first-in-category GI product candidates: IW-3718 is a gastric retentive formulation of a bile acid sequestrant being developed for the potential treatment of refractory gastroesophageal reflux disease, and MD-7246 is a delayed-release formulation of linaclotide that is being evaluated as an oral, intestinal, non-opioid, pain-relieving agent for patients suffering from abdominal pain associated certain GI diseases.

Ironwood was founded in 1998 and is headquartered in Boston, Mass. For more information, please visit our website at www.ironwoodpharma.com or www.twitter.com/ironwoodpharma; information that may be important to investors will be routinely posted in both these locations.

Forward-Looking Statements
This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about refractory GERD symptoms and the role of bile acid in refractory GERD; the size of the potential patient population; the development, validation and use of patient-reported outcome instruments to measure treatment benefit in clinical trials; the mechanism of action of IW-3718; the potential of IW-3718 to offer refractory GERD patients relief from symptoms including heartburn and regurgitation; the efficacy, safety and tolerability of IW-3718; the anticipated clinical development of IW-3718, including the timing of anticipated results of the IW-3718 Phase III trials. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include those related to preclinical and clinical development, manufacturing and formulation development; the risk that future clinical studies need to be delayed or discontinued for any reason, including safety, tolerability, enrollment, manufacturing or economic reasons; the risk that findings from our completed non-clinical and clinical studies may not be replicated in later studies; efficacy, safety and tolerability of our product and product candidates; the risk that the therapeutic opportunities for our product and product candidates are not as we expect; decisions by regulatory and judicial authorities; the risk that we are unable to successfully commercialize our product and product candidates, if approved; the risk that we may never get sufficient patent protection for our products or product candidates, that patents for our product or product candidates may not provide adequate protection from competition, or that we are not able to successfully protect such patents; the outcomes in legal proceedings to protect or enforce the patents relating to our product and product candidates, including abbreviated new drug application litigation; developments in the intellectual property landscape; the risk that financial and operating results may differ from our projections; challenges from and rights of competitors or potential competitors; the risk that our planned investments do not have the anticipated effect on our company revenues; the risk that we are unable to manage our expenses or cash use, or are unable to commercialize our products as expected; and the risks listed under the heading “Risk Factors” and elsewhere in Ironwood’s Annual Report on Form 10-K for the year ended December 31, 2019, and in our subsequent SEC filings. These forward-looking statements speak only as of the date of this press release, and Ironwood undertakes no obligation to update these forward-looking statements.

¹ Vakil, N., Stelwagon M., Shea E.P., & Miller S. (2015). Symptom Burden and Consulting Behavior in Patients with Overlapping Functional Disorders in the US Population. United European Gastroenterology Journal, 4(3), 412-422.
² American Community Survey 2018 (US 18+ population)
³ Lieberman GERD Survey 2010 and 2019
⁴ My Total Health 2018
⁵ AHRI GERD Survey 2018
⁶ Sifrim D, Zerbib F. Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut. 2012;61:1340–54
⁷ Ironwood data; Dickman et al., J Neurogastroenterol Motil 2011
⁸ Lynch, Kristle Lee (2018). Gastroesophageal Reflux Disease (GERD). The Merck manual online. Retrieved from: https://www.merckmanuals.com/home/digestive-disorders/esophageal-and-swallowing-disorders/gastroesophageal-reflux-disease-gerd
⁹ National Center for Biotechnology Information. Drug Class Review: Proton Pump Inhibitors: Final Report Update 5. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK47264/
¹⁰ Delshad, S.D., Almario, C.V., Chey, W.D. & Spiegel, BMR. (2019). Prevalence of Gastroesophageal Reflux Disease and Proton Pump Inhibitor-Refractory Symptoms. Gastroenterology. S0016-5085(19)41941-0.

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