Ironwood Pharmaceuticals Expands Pipeline by Signing an Option Agreement to Acquire an Exclusive License with COUR Pharmaceuticals to Develop and Commercialize CNP-104 for the Treatment of Primary Biliary Cholangitis (PBC) in the U.S.

• IND for CNP-104 Accepted by FDA; Clinical Trials Planned for the End of 2021
• Ironwood to Make a Payment of approximately $20 Million in Upfront and Near-Term Milestones and up to $475 Million in Long-Term Commercial and Regulatory Milestones and Royalties to COUR

BOSTON--(BUSINESS WIRE)-- Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD), a GI-focused healthcare company, today announced that it is expanding its pipeline by entering into a collaboration and license option agreement with COUR Pharmaceutical Development Company, Inc. (“COUR”), a biotechnology company developing novel immune-modifying nanoparticles to treat autoimmune diseases. This agreement gives Ironwood an option to acquire an exclusive license to develop and commercialize, in the U.S., COUR’s investigational therapy CNP-104 (the “License”), which if successful, could transform the treatment of Primary Biliary Cholangitis – otherwise known as PBC - a rare autoimmune disease targeting the liver that affects an estimated 133,000 people in the U.S. Currently there is no cure, and medical care is focused on disease management. PBC can lead to irreversible damage and scarring of the liver tissue, ultimately requiring liver transplant.

CNP-104 is being developed utilizing COUR’s nanoparticle platform (CNP), a novel, proprietary system, which combines disease-specific pathogenic antigens with state-of-the-art pharmaceutical nanoparticles that mimic normal removal of dead or dying cells from the body. COUR’s platform has shown proof of technology in clinical and preclinical settings, further demonstrating the opportunity for the platform to treat PBC.

“Collaborating with COUR fits squarely within our business development framework and guiding principles; moving our strategy forward through expansion of our pipeline, leveraging our deep relationships with gastroenterologists and advancing innovation via highly differentiated opportunities like CNP-104,” said Tom McCourt, president and chief executive officer of Ironwood. “COUR’s expertise in immune reprogramming and Ironwood’s development and commercial strength and reach in the GI disease area, will help introduce a potentially new therapy to patients in significant need of new options. This option agreement highlights our focus on prudently allocating capital to value enhancing opportunities while maintaining the flexibility to simultaneously execute on our other strategic priorities.”

As previously announced on October 4, 2021, the U.S. Food and Drug Administration (FDA) accepted COUR’s investigational new drug application (IND) for CNP-104. With the FDA’s acceptance of the IND application, COUR expects to initiate a clinical trial for CNP-104 in 2021 to evaluate the safety, tolerability, pharmacodynamics and efficacy of CNP-104 in PBC patients (the “Initial Study”). After reviewing the data from the Initial Study, the Company has the right to exercise the option.

“We are delighted to collaborate with COUR to drive clinical progress behind CNP-104, which we believe has the potential to significantly shift the treatment paradigm in PBC, said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood. “With our expertise in GI, we are well positioned to further develop a potentially first-to-market treatment that offers patients the opportunity to address the underlying pathology in PBC in a way no current therapies can.”

“We are excited to collaborate with Ironwood given their commercial infrastructure and history of GI innovation,” said COUR CEO John Puisis. “Their success in commercializing and growing LINZESS and their deep relationships within the GI community make them an ideal partner for COUR as it relates to PBC. This agreement will help expand COUR’s autoimmunity portfolio and further enhance COUR’s reach in immune mediated diseases.”

Pursuant to the terms of the agreement, Ironwood will pay COUR approximately $20 million in upfront and near-term payments associated with the Initial Study. After reviewing the data from the Initial Study, if Ironwood exercises its option, COUR will be eligible to receive royalties in the high single digits to low double digits percentage of the aggregated annual net sales in the U.S. of products containing CNP-104, and additional payments of up to $475 million, inclusive of an option exercise payment and commercial milestones over the term of the agreement.

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (Nasdaq: IRWD) is a leading gastrointestinal (GI) healthcare company on a mission to advance the treatment of GI diseases and redefine the standard of care for GI patients. We are pioneers in the development of LINZESS® (linaclotide), the U.S. branded prescription market leader for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). Under the guidance of our seasoned industry leaders, we continue to build upon our history of GI innovation and challenge what has been done before to shape what the future holds. We keep patients at the heart of our R&D and commercialization efforts to reduce the burden of GI diseases and address significant unmet needs.

Founded in 1998, Ironwood Pharmaceuticals is headquartered in Boston, Massachusetts.

We routinely post information that may be important to investors on our website at www.ironwoodpharma.com. In addition, follow us on Twitter and on LinkedIn.

About LINZESS (linaclotide)

LINZESS® is the #1 prescribed brand in the U.S. for the treatment of adult patients with irritable bowel syndrome with constipation (“IBS-C”) or chronic idiopathic constipation (“CIC”), based on IQVIA data.

LINZESS is a once-daily capsule that helps relieve the abdominal pain, constipation, and overall abdominal symptoms of bloating, discomfort and pain associated with IBS-C, as well as the constipation, infrequent stools, hard stools, straining, and incomplete evacuation associated with CIC. The recommended dose is 290 mcg for IBS-C patients and 145 mcg for CIC patients, with a 72-mcg dose approved for use in CIC depending on individual patient presentation or tolerability. LINZESS should be taken at least 30 minutes before the first meal of the day.

LINZESS is contraindicated in pediatric patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism resulting in mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established.

LINZESS is not a laxative; it is the first medicine approved by the FDA in a class called GC-C agonists. LINZESS contains a peptide called linaclotide that activates the GC-C receptor in the intestine. Activation of GC-C is thought to result 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.

In the United States, Ironwood and AbbVie co-develop and co-commercialize LINZESS for the treatment of adults with IBS-C or CIC. In Europe, AbbVie markets linaclotide under the brand name CONSTELLA® for the treatment of adults with moderate to severe IBS-C. In Japan, Ironwood’s partner, Astellas, markets linaclotide under the brand name LINZESS for the treatment of adults with IBS-C or CIC. Ironwood also has partnered with AstraZeneca for development and commercialization of LINZESS in China, and with AbbVie for development and commercialization of linaclotide in all other territories worldwide.

LINZESS Important Safety Information

INDICATIONS AND USAGE

LINZESS (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).

IMPORTANT SAFETY INFORMATION

Contraindications

• LINZESS is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.
• LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Warnings and Precautions

Pediatric Risk

• LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism resulting in mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established.

Diarrhea

• Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.

Common Adverse Reactions (incidence ≥2% and greater than placebo)

• In IBS-C clinical trials: diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
• In CIC trials of a 145 mcg dose: diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%). In a CIC trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs <1%).

Please see full Prescribing Information including Boxed Warning: http://www.allergan.com/assets/pdf/linzess_pi

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

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 our option to acquire an exclusive license to develop and commercialize CNP-104 in the U.S.; the timing of initiating a clinical trial to evaluate the safety, tolerability, pharmacodynamic and efficacy of CNP-104 in PBC patients; the timing, achievement and payment of certain milestones and royalties under our agreement with COUR; the potential for CNP-104 to transform the treatment of PBC in the U.S.; the potential for CNP-104 to be the first-to-market treatment that offers patients the opportunity to address the underlying pathology in PBC; and the opportunity for COUR’s nanoparticle platform (CNP) to treat PBC. 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. 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 a statement. Applicable risks and uncertainties include those related to the effectiveness of development and commercialization efforts by us and our partners; preclinical and clinical development, manufacturing and formulation development of linaclotide and CNP-104; the risk that clinical programs and studies may not progress or develop as anticipated, including that studies are delayed or discontinued for any reason, such as safety, tolerability, enrollment, manufacturing, economic or other reasons; the risk that findings from completed nonclinical and clinical studies may not be replicated in later studies; the risk that we or our partners are unable to obtain, maintain or manufacture sufficient product candidates, or otherwise experience difficulties with respect to supply or manufacturing; the efficacy, safety and tolerability of CNP-104 and our other product candidates; the risk that the therapeutic opportunities for LINZESS, CNP-104 or our other product candidates are not as we expect; decisions by regulatory and judicial authorities; the risk we may never get additional patent protection for CNP-104 and other product candidates; the risk that we may never get sufficient patent protection for CNP-104 and other product candidates, that patents for CNP-104 or other products may not provide adequate protection from competition, or that we are not able to successfully protect such patents; outcomes in legal proceedings to protect or enforce the patents relating to our products and product candidates, including abbreviated new drug application litigation; developments in the intellectual property landscape; 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; the risk that we may elect to not exercise our option to acquire the exclusive license for CNP-104 ; the risk that the development of CNP-104 is not successful or is not successfully commercialized; the risk that the clinical trial for CNP-104 is delayed or not initiated by COUR; the impact of the COVID-19 pandemic; and the risks listed under the heading “Risk Factors” and elsewhere in Ironwood’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2021, and in our subsequent SEC filings.

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