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Item 1. Business

2026-02-26 compared with 2025-03-31 · 184 added, 106 removed, 575 unchanged (34% of the section changed)

We are a biotechnology company developing and commercializing life-changing therapies for people living with gastrointestinal, or GI, and rare diseases.

We are focused on the development and commercialization of innovative GI product opportunities in areas of significant unmet need, leveraging our demonstrated expertise and capabilities in GI diseases.

We are focused on the development and commercialization of innovative product opportunities in areas of significant unmet need, leveraging our demonstrated expertise and capabilities in GI and rare diseases.

LINZESS ® (linaclotide), our commercial product, is the first product approved by the United States Food and Drug Administration, or U.S.

FDA, in a class of GI medicines called guanylate cyclase type C agonists, or GC-C agonists, and is indicated for adult men and women suffering from irritable bowel syndrome with constipation, or IBS-C, or chronic idiopathic constipation, or CIC, and for pediatric patients ages 6-17 years-old suffering from functional constipation, or FC.

LINZESS is available to adult men and women suffering from IBS-C or CIC in the United States, or the U.S., and Mexico, adult men and women suffering from IBS-C or chronic constipation in Japan, and adult men and women suffering from IBS-C in China, and pediatric patients ages 6-17 years old with FC in the U.S.

Linaclotide is available under the trademarked name CONSTELLA ® to adult men and women suffering from IBS-C or CIC and pediatric patients ages 6-17 years old with FC in Canada, and to adult men and women suffering from IBS-C in certain European countries.

We have strategic partnerships with leading pharmaceutical companies to support the development and commercialization of linaclotide throughout the world, including with AbbVie Inc.

FDA, in a class of GI medicines called guanylate cyclase type C agonists, or GC-C agonists, and is indicated for the treatment, in the U.S., of irritable bowel syndrome with constipation, or IBS-C, in adults and pediatric patients 7 years of age and older, chronic idiopathic constipation, or CIC, in adults, and functional constipation, or FC, in pediatric patients ages 6-17 years-old.

LINZESS is also available for the treatment of adults with IBS-C or CIC in Mexico, adults with IBS-C or chronic constipation in Japan, and adults with IBS-C in China.

Linaclotide is available under the trademarked name CONSTELLA® for the treatment of adults with IBS-C or CIC and pediatric patients ages 6-17 years old with FC in Canada, and to adults with IBS-C in certain European countries.

We have strategic partnerships with leading pharmaceutical companies to support the development and commercialization of linaclotide throughout the world, including with our partner, AbbVie Inc.

(together with its affiliates), or AbbVie, in the U.S.

and all countries worldwide other than China (including Hong Kong and Macau) and Japan, AstraZeneca AB (together with its affiliates), or AstraZeneca, in China (including Hong Kong and Macau) and Astellas Pharma Inc., or Astellas, in Japan.

We also aim to leverage our development and commercialization capabilities in GI to bring additional treatment options to GI patients.

Through our acquisition of VectivBio Holding AG, or VectivBio, in June 2023, or the VectivBio Acquisition, we are advancing apraglutide, a next-generation, synthetic long-acting peptide analog of glucagon-like peptide-2, or GLP-2, for short bowel syndrome patients, or SBS, who are dependent on parenteral support, or PS.

In February 2024, we announced positive topline results from our pivotal Phase III clinical trial, STARS, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in reducing parenteral support dependency in adult patients with SBS-IF.

In January 2025, we initiated a rolling new drug application, or NDA, to the U.S.

FDA for apraglutide for use in adult patients with SBS who are dependent on PS, and plan to submit marketing applications to other regulatory authorities as well.

In November 2021, we entered into a collaboration and license option agreement, or the COUR Collaboration Agreement, with COUR Pharmaceutical Development Company, Inc., or COUR, a biotechnology company developing novel immune-modifying nanoparticles to treat autoimmune diseases.

The COUR Collaboration Agreement granted us an option to acquire an exclusive license to research, develop, manufacture and commercialize, in the U.S., products containing CNP-104, a potential treatment for primary biliary cholangitis, or PBC, a rare autoimmune disease targeting the liver.

In the third quarter of 2024, we received from COUR the topline data from COUR’s Phase II Clinical study for the treatment of PBC.

In September 2024, we notified COUR of our decision not to exercise the option to acquire an exclusive license to CNP-104.

As a result, COUR Collaboration Agreement has terminated, and we retain no rights and have no obligations related to CNP-104.

We are also advancing IW-3300, a GC-C agonist, for the potential treatment of visceral pain conditions, such as interstitial cystitis / bladder pain syndrome, or IC/BPS, and endometriosis.

In September 2024, we decided to end further recruitment for the Phase II proof of concept study in IC/BPS and analyze the data once all currently enrolled patients complete the full 12-week study assessment, which will inform the next steps in the program.

Through our acquisition of VectivBio Holding AG, or VectivBio, in June 2023, or the VectivBio Acquisition, we are advancing apraglutide, a next-generation, synthetic long-acting peptide analog of glucagon-like peptide-2, or GLP-2, for short bowel syndrome, or SBS, patients who are dependent on parenteral support, or PS.

In February 2024, we announced positive topline results from our pivotal Phase III clinical trial, STARS, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in reducing PS dependency in adult patients with short bowel syndrome with intestinal failure, or SBS-IF.

We are also conducting an open-label extension study, STARS Extend, to further assess the safety of apraglutide in adult patients with SBS-IF.

In April 2025, we announced that, based on discussions with the U.S.

FDA, a confirmatory Phase III clinical trial is needed to seek approval of a new drug application or NDA, for apraglutide for patients with SBS-IF who are dependent on PS.

In the fourth quarter of 2025, we met with the U.S.

FDA and aligned on key design elements of a confirmatory Phase III clinical trial, STARS-2, of apraglutide.

Site initiations are expected to begin in the second quarter of 2026.

We were incorporated in Delaware on January 5, 1998 as Microbia, Inc.

On April 7, 2008, we changed our name to Ironwood Pharmaceuticals, Inc.

To date, we have dedicated a majority of our activities to the research,

development and commercialization of linaclotide, as well as to the research and development of apraglutide and our other product candidates.

To date, we have dedicated a majority of our activities to the research, development and commercialization of linaclotide, as well as other research and development programs, including apraglutide.

Drug development involves a high degree of risk and investment, and the status, timing and scope of our development programs are subject to change.

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Performance Against 2025 Core Priorities

In 2024, our GI-focused strategy, building on our commercial success and GI development capabilities, continued to focus on three core priorities:

maximize LINZESS, advance our GI pipeline, and deliver sustained profits and generate cash flow.

Maximize LINZESS

In 2025, our GI and rare diseases-focused strategy, building on our commercial success and GI development capabilities, continued to focus on three core priorities:

maximizing LINZESS, advancing apraglutide, and delivering sustained profits and cash flow.

Maximizing LINZESS

● We recognized $289.3 million in collaborative arrangements revenue related to sales of LINZESS in the U.S.

during the year ended December 31, 2024, a decrease of $90.1 million compared to the year ended December 31, 2023.

The decrease was primarily driven by a decrease in our share of net profits from the sale of LINZESS in the U.S., which was driven by decreased net price (including a $43.0 million reduction to collaboration revenue as a result of changes in estimates of sales reserves and allowances associated with governmental and contractual rebates), partially offset by increases from prescription demand.

Advance GI Pipeline

● In February 2024, we announced positive topline results from our pivotal Phase III clinical trial, STARS, which evaluated the efficacy and safety of once-weekly subcutaneous apraglutide in reducing PS dependency in adult patients with SBS-IF, and in January 2025, we initiated a rolling NDA submission to the U.S.

FDA for apraglutide for use in adult patients with SBS who are dependent on PS.

We plan to submit marketing applications for other regulatory filings as well.

We are also conducting an open-label extension study, STARS Extend, to further assess the safety of apraglutide in adult patients with SBS-IF.

● Apraglutide has also been studied in patients with steroid-refractory gastrointestinal acute Graft versus Host Disease, or aGvHD, a life-threatening condition that occurs when immune cells from the donor attack a recipient’s healthy cells after an allogeneic hematopoietic stem cell transplant.

In March 2024, we announced positive, primary results up to Day 91 for our Phase II exploratory trial, STARGAZE, which evaluated the safety and tolerability of once-weekly apraglutide in aGvHD patients treated with standard of care, including systemic corticosteroids and ruxolitinib.

In December 2024, we decided to end further development of apraglutide for aGvHD to focus investment on other priorities.

● We are advancing IW-3300, a GC-C agonist, for the potential treatment of visceral pain conditions, such as IC/BPS and endometriosis.

Deliver sustained profits and cash flow

during the year ended December 31, 2025, a decrease of $51.1 million compared to the year ended

December 31, 2024.

The decrease was driven by net price and inventory channel fluctuations, partially offset by increased prescription demand.

Advancing Apraglutide

● In April 2025, we announced that, in preparation for the NDA submission to the U.S.

FDA for apraglutide, pharmacokinetic analysis indicated that the exposure and dose delivered in the STARS Phase III clinical trial were lower than planned due to dose preparation and administration.

Based on discussions with the U.S.

FDA, it became clear that a confirmatory Phase III clinical trial of apraglutide is needed to seek approval of an NDA for apraglutide for patients with SBS-IF who are dependent on PS.

In the fourth quarter of 2025, we met with the U.S.

FDA and aligned on key design elements of a confirmatory Phase III clinical trial, STARS-2, of apraglutide.

We plan to initiate the STARS-2 clincial trial in the second quarter of 2026.

Delivering sustained profits and cash flow

● We generated $127.0 million in cash from operations during the year ended December 31, 2025, ending the year with $215.5 million in cash and cash equivalents.

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In August 2012, the U.S.

FDA approved LINZESS as a once daily treatment for adult men and women suffering from IBS-C (290 mcg dose) or CIC (145 mcg dose).

FDA approved LINZESS as a once daily treatment for adults suffering from IBS-C (290 mcg dose) or CIC (145 mcg dose).

We and AbbVie began commercializing LINZESS in the U.S.

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In January 2017, the U.S.

FDA approved a 72 mcg dose of linaclotide for the treatment of adult men and women with CIC.

FDA approved a 72 mcg dose of linaclotide for the treatment of adults with CIC in the U.S.

We and AbbVie continue to explore ways to enhance the clinical profile of LINZESS by studying linaclotide in additional indications, populations, and formulations to assess its potential to treat various conditions.

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In June 2023, the U.S.

FDA approved LINZESS as a once-daily treatment for pediatric patients ages 6-17 years-old with FC, making LINZESS the first and only FDA-approved prescription therapy for FC in this patient population.

The safety and effectiveness of LINZESS in patients with FC less than 6 years of age or in patients with IBS-C less than 18 years of age have not been established.

Additional clinical pediatric programs in IBS-C and FC are ongoing.

FDA approved LINZESS as a once-daily treatment for pediatric patients ages 6-17 years-old with FC, making LINZESS the first and only U.S.

FDA-approved prescription therapy for FC in this patient population.

On October 15, 2025, the U.S.

FDA granted us a pediatric exclusivity for studies conducted on linaclotide, and in November 2025, approved LINZESS for pediatric patients 7 years of age and older with IBS-C.

Additional clinical pediatric programs in FC are ongoing.

Linaclotide—Global.

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In 2019, AstraZeneca began commercializing LINZESS in China for adults with IBS-C.

Apraglutide for SBS-IF

Through the VectivBio Acquisition, we are advancing apraglutide, a next-generation, long-acting synthetic peptide analog of GLP-2, as a potentially differentiated therapeutic for SBS patients who are dependent on PS.

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We are also conducting an open-label extension study, STARS Extend, to further assess safety of apraglutide in adult patients with SBS-IF.

In January 2025, we initiated a rolling NDA submission for apraglutide for use in adult patients with SBS who are dependent on PS.

Apraglutide has also been studied in patients in patients with steroid-refractory GI aGvHD.

In December 2024, we decided to end further development of apraglutide for aGvHD to focus investment on other priorities.

We are also advancing IW-3300, a GC-C agonist, for the potential treatment of visceral pain conditions, such as IC/BPS and endometriosis.

In preparation for an NDA submission for apraglutide, pharmacokinetic analysis indicated that the exposure and dose delivered in the STARS Phase III clinical trial of apraglutide were lower than planned due to dose preparation and administration.

In April 2025, we announced that, based on discussions with the U.S.

FDA, a confirmatory Phase III clinical trial is needed to seek approval of an NDA for apraglutide for patients with SBS-IF who are dependent on PS.

In the fourth quarter of 2025, we met with the U.S.

FDA and aligned on key design elements of a confirmatory Phase III clinical trial, STARS-2, of apraglutide.

STARS-2 is expected to be a 24-week global, randomized, double-blind, placebo-controlled trial.

The clinical trial will consist of a primary endpoint measuring relative change from baseline in actual weekly PS volume, as well as additional key secondary endpoints.

Site initiations are expected to begin in the second quarter of 2026.

We were developing IW-3300, a GC-C agonist, for the potential treatment of visceral pain conditions, such as interstitial cystitis and bladder pain syndrome, or IC/BPS.

In April 2025, based on analysis of the Phase II data, we decided to cease developing IW-3300 for IC/BPS.

Collaborations and Partnerships

As part of our GI and rare disease focus, we have development and commercial capabilities that we plan to leverage as we seek to bring multiple medicines to patients.

As part of our GI and rare disease focus, we have development and commercial capabilities that we plan to leverage as we seek to bring medicines to patients.

We intend to play an active role in the development and commercialization of our products in the U.S., either independently or with partners that have strong capabilities.

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We plan to seek collaborations that increase the value of our products by providing meaningful economics and incentives for us and any potential partner.

We intend to continue to expand our expertise in GI by accessing innovative externally developed products and to leverage our existing capabilities to develop and commercialize these products in the U.S.

We have pursued a partnering strategy for commercializing linaclotide that has allowed us to focus our commercialization efforts in the U.S.

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is highly dependent on the responsiveness of patients to fill prescriptions and other factors such as retail chain and wholesaler buying patterns, pricing and reimbursement and inventory channel levels.

Our collaborative arrangements revenue may continue to fluctuate as a result of the timing and amount of royalties from sales of linaclotide in the

markets in which it is currently approved, or any other markets where linaclotide receives approval, as well as clinical and commercial milestones received and recognized under our strategic partnerships outside of the U.S.

On November 25, 2025, the U.S.

Department of Health and Human Services, or HHS, released the Maximum Fair Price, or MFP, for LINZESS, which was selected in the most recent round of government price setting as part of the Inflation Reduction Act of 2022.

The MFP for a 30-day equivalent supply of LINZESS, which will become the new Medicare net price as of January 1, 2027, is set to $136.

The revised MFP for LINZESS was in line with our expectations.

Also, effective January 1, 2026, we and our partner, AbbVie, lowered the LINZESS list price in response to evolving health care dynamics and to support ongoing patient access.

Our collaborative arrangements revenue may continue to fluctuate as a result of the timing and amount of sales of linaclotide in the markets in which it is currently approved, or any other markets where linaclotide receives approval, as well as clinical and commercial milestones received and recognized under our strategic partnerships outside of the U.S.

Collaboration Agreement for North America with AbbVie

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Under the terms of this collaboration agreement, we received an upfront licensing fee, equity investment, and development and regulatory milestones, and we share equally with AbbVie all development costs as well as net profits or losses from the development and sale of linaclotide in the U.S.

In addition, we receive royalties from AbbVie in the mid-teens percent based on net sales in Canada and Mexico.

In addition, we receive royalties in the mid-teens percent based on net sales in Canada and Mexico.

AbbVie is solely responsible for the further development, regulatory approval and commercialization of linaclotide in those countries and funding any costs.

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Our strategy is focused on three core priorities:

maximize LINZESS, advance our GI pipeline, and deliver sustained profits and cash flow.

maximizing LINZESS, advancing apraglutide, and delivering sustained profits and cash flow.

Key elements of our strategy include:

Maximize LINZESS

Maximizing LINZESS

● Leveraging our U.S.-focused commercial capabilities with our partner, AbbVie, to expand the commercial potential of LINZESS.

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● Collaborating with global partners who share our vision, values, culture, and processes to develop and commercialize linaclotide outside the U.S.

Advance GI pipeline

● Advancing our GI pipeline programs, highlighted by apraglutide for the potential treatment of SBS-IF.

● Evaluating strategic partnership options for our wholly owned GC-C agonist, IW-3300, for the potential treatment of IC/BPS and endometriosis.

Deliver sustained profits and cash flows

Advancing Apraglutide

● Advancing apraglutide for the potential treatment of SBS-IF.

Delivering sustained profits and cash flows

● Executing our strategy by delivering sustainable profits and cash flows.

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TRULANCE® (plecanatide) was approved in the U.S.

treatment of adults with IBS-C and CIC and is being commercialized in the U.S.

for the treatment of adults with IBS-C and CIC and is being commercialized in the U.S.

by Bausch Health Companies, or Bausch.

Shire plc obtained approval of MOTEGRITY™ (prucalopride) in the U.S.

for the treatment of CIC in adults.

for the treatment of CIC in adults, and generic versions have been available in the U.S.

since January 2025.

Ardelyx, Inc.’s, or Ardelyx, IBSRELA™ (tenapanor), is approved by the U.S.

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For example, for apraglutide, we compete with companies that are commercializing or developing drugs for SBS, such as Takeda, which currently distributes the GLP-2 analog teduglutide, marketed as GATTEX® (teduglutide) in the U.S.

and REVESTIVE® (teduglutide for injection) in Europe, and Zealand Pharma A/S, or Zealand, which is developing glepaglutide, a long-acting GLP-2 analog, for the potential treatment of SBS for patients who are dependent on PS and is expecting to initiate an additional Phase III clinical trial in 2025 .

and REVESTIVE® (teduglutide for injection) in Europe, and Zealand Pharma A/S, or Zealand, which is developing glepaglutide, a long-acting GLP-2 analog, for the potential treatment of SBS for patients who are dependent on PS and initiated an additional Phase III clinical trial in the first quarter of 2026 .

Hanmi Pharmaceutical is also developing a GLP-2 analog, to be administered once a month, and which is being evaluated in a Phase II clinical trial.

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In executing our strategy, our goal is to retain oversight over the worldwide development and commercialization of our products by playing an active role in their commercialization or finding partners who share our vision, values, culture and processes.

To date, we have established a high-quality commercial organization dedicated to supporting our vision of becoming the leading GI healthcare company.

We have core commercial capabilities in place, including marketing, patient engagement and key sales support roles, designed to support our existing product and for potential future internally and externally developed products, including apraglutide.

We and/or our partners have core commercial capabilities in place, including marketing, patient engagement and key sales support roles.

We are also coordinating efforts with our linaclotide partners to launch and maintain an integrated, global linaclotide brand.

By leveraging the knowledge base and expertise of our experienced commercial team and the insights of each of our linaclotide commercialization partners, we continually improve our collective marketing strategies.

We are currently in the process of planning for the commercial launch of apraglutide, if approved, for commercialization, in the U.S.

We continue to plan for a potential commercial launch of apraglutide, if successfully developed and approved, in the U.S.

and with partners in territories outside the U.S.

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patents listed in the U.S.

FDA publication, Approved Drug Products with Therapeutic Equivalence Evaluations, or the Orange Book, six granted European patents, most of which have been validated in available European countries, ten granted Japanese patents, three granted Chinese patents, 61 issued patents in other foreign jurisdictions, and numerous pending U.S., foreign and Patent Cooperation Treaty, or PCT, patent applications.

FDA publication,

Approved Drug Products with Therapeutic Equivalence Evaluations, or the Orange Book, four granted European patents, most of which have been validated in available European countries, ten granted Japanese patents, a granted Chinese patent, 46 issued patents in other foreign jurisdictions, and numerous pending U.S., foreign and Patent Cooperation Treaty, or PCT, patent applications.

We and our partners own, either jointly or individually, all of the issued patents and pending applications.

The issued, unexpired U.S.

patents, which will expire between 2026 and 2033, contain claims directed to the linaclotide molecule, pharmaceutical compositions thereof, methods of using linaclotide to treat GI disorders, processes for making the molecule, and room temperature stable formulations of linaclotide and methods of use thereof.

The 72 mcg, 145 mcg and 290 mcg LINZESS doses are covered by composition of matter patent in the U.S., which expires in 2026.

patents, which will expire between 2026 and 2033, contain claims directed to the linaclotide molecule, pharmaceutical compositions thereof, methods of using linaclotide to treat GI disorders, and room temperature stable formulations of linaclotide and methods of use thereof.

Linaclotide, the active ingredient in the 72 mcg, 145 mcg and 290 mcg LINZESS doses, is covered by a composition of matter patent in the U.S., which recently received pediatric exclusivity, and now expires in 2027.

In addition, the commercial formulations of the 72 mcg, 145 mcg and 290 mcg LINZESS doses are covered by patents in the U.S.

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The granted, unexpired European patents, which will expire between 2027 and 2031, some of which have received patent term extension, contain claims directed to the linaclotide molecule, pharmaceutical compositions thereof, uses of linaclotide to prepare medicaments for treating GI disorders, and room temperature stable formulations of linaclotide and their use in treating IBS-C and chronic constipation.

unexpired Chinese patents, which will expire between 2029 and 2032, the granted Japanese patents, which will expire between 2026 and 2036, some of which are subject to granted and potential patent term extension, and the granted patents in other foreign jurisdictions, which will expire between 2026 and 2034, some of which may be subject to potential patent term extension, contain claims directed to the linaclotide molecule, pharmaceutical compositions of linaclotide for use in treating GI disorders, and room temperature stable formulations of linaclotide.

The granted, unexpired Chinese patent, which will expire in 2029, the granted Japanese patents, which will expire between 2026 and 2036, some of which are subject to granted and potential patent term extension, and the granted patents in other foreign jurisdictions, which will expire between 2026 and 2031, some of which may be subject to potential patent term extension, contain claims directed to the linaclotide molecule, pharmaceutical compositions of linaclotide for use in treating GI disorders, and room temperature stable formulations of linaclotide.

We have pending patent applications in certain countries worldwide that, if issued, will expire between 2029 and 2045 and which include claims covering the linaclotide molecule, methods of using linaclotide to treat GI disorders, the current commercial formulations of linaclotide and uses thereof to treat GI disorders and delayed release and other potential formulations of linaclotide.

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We have also received patent term extensions, called supplementary protection certificates, for certain linaclotide patents from several national patent offices in Europe.

In addition, in October 2025, the U.S.

FDA granted us a pediatric exclusivity for studies conducted on linaclotide, which extended the patent term of U.S.

Patent 7,304,036 by six months to February 28, 2027, as well as extending the patent term of the remaining Orange Book listed patent by six months.

We and AbbVie received Paragraph IV certification notice letters regarding abbreviated new drug applications, or ANDAs, submitted to the U.S.

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This patent family contains composition-of-matter claims covering apraglutide and methods of treatment using apraglutide.

The patents in this patent family that we exclusively license outside of the U.S.

The patents in this patent family that we exclusively license outside of the

are issued in Europe, Japan, China, Australia, Canada, as well as other jurisdictions.

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Not accounting for any patent term adjustment, regulatory patent term extensions or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely, the patents in this patent family are expected to expire in 2030.

Our apraglutide portfolio also includes two wholly owned patent families.

The first patent family includes one granted U.S.

Our apraglutide portfolio also includes five wholly owned patent families.

The first patent family includes two granted U.S.

patent and five pending U.S.

non-provisional patent applications, as well as 27 pending foreign patent applications related to apraglutide.

The granted U.S.

patent in this patent family claims a method of treating SBS at certain doses, and the pending U.S.

non-provisional patent applications, as well as 2 granted patents and 16 pending foreign patent applications related to apraglutide.

One of the granted U.S.

patents in this patent family claims a method of treating SBS at certain doses of apraglutide, and the other claims a liquid formulation of apraglutide for injection.

The pending U.S.

and foreign patent applications contain composition-of-matter claims to ultrapure compositions of apraglutide, methods of manufacturing apraglutide, and methods of treatment using apraglutide.

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patent, as well as patents granted from the pending U.S and foreign patent applications, would be expected to expire in 2041.

The second patent family which we wholly own includes two pending U.S.

non-provisional patent applications and 13 pending foreign patent applications related to methods of treating GvHD using apraglutide.

Not accounting for any patent term adjustment, regulatory patent term extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely, any U.S.

The second patent family which we wholly own includes one granted European patent which has been validated in Germany, the United Kingdom, France, Italy and Spain, one pending U.S.

non-provisional patent applications and 13 pending foreign patent applications related to methods of treating acute Graft versus Host Disease, or aGvHD, using apraglutide.

Not accounting for any patent term adjustment, regulatory patent term extension or terminal disclaimers, and assuming that all annuity and/or maintenance fees are paid timely, the granted European patent and any U.S.

and foreign patents granted from the pending patent applications would be expected to expire in 2042.

We also have two additional patent families related to methods of treating SBS using apraglutide and one patent family related to methods of treating aGvHD with a combination of apraglutide and ruxolitinib.

If granted, these patent applications will expire in 2045.

Government Regulation

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FDA may approve an NDA generally include:

● conducting non-clinical laboratory tests and animal tests in compliance with U.S.

● conducting non-clinical laboratory tests and other studies in compliance with U.S.

FDA’s good laboratory practice, or GLP, requirements;

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FDA inspections of non-clinical and clinical trial sites to assure compliance with GLP and GCP requirements;

FDA review and approval of the NDA, which may be subject to post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and any post-approval studies required by the U.S.

● payment of user fees pursuant to the Prescription Drug User Fee Act, or PDUFA, and securing U.S.

FDA approval of the NDA to allow marketing of the new drug product;

● compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and any post-approval studies required by the U.S.

Non-clinical tests include laboratory evaluation of the product candidate, as well as animal studies to assess the potential safety and efficacy of the product candidate.

The conduct of the non-clinical tests must comply with federal regulations and requirements including GLP.

With passage of the U.S.

FDA’s Modernization Act 2.0 in December 2022, Congress eliminated provisions in the FDCA that required animal testing in support of an NDA.

In April 2025, the U.S.

FDA released a roadmap to replace animal testing in preclinical safety studies with scientifically validated new approach methodologies, such as organ-on-a-chip systems, computational modeling, and advanced in vitro assays.

We must submit the results of the non-clinical tests, together with manufacturing information, analytical data and a proposed clinical trial protocol to the U.S.

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Clinical trials are typically conducted in three sequential phases, though the phases may overlap or be combined.

In Phase I, the initial introduction of the drug into healthy human subjects, the drug is usually tested for safety (adverse effects), dosage tolerance and pharmacologic action, as well as to understand how the drug is taken up by and distributed within the body.

In Phase I, the initial introduction of the drug into healthy human subjects, the drug is usually tested for safety (adverse effects), dosage tolerance and

pharmacologic action, as well as to understand how the drug is taken up by and distributed within the body.

Phase II usually involves studies in a limited patient population (individuals with the disease under study) to:

● evaluate preliminarily the efficacy of the drug for specific, targeted conditions;

● determine dosage tolerance and appropriate dosage as well as other important information about how to design larger Phase III trials;

● determine dosage tolerance and appropriate dosage as well as other important information about how to design larger Phase III clinical trials;

● identify possible adverse effects and safety risks.

Phase III trials generally further evaluate clinical efficacy and test for safety within an expanded patient population.

Phase III clinical trials further evaluate clinical efficacy and test for safety within an expanded patient population.

The conduct of clinical trials is subject to extensive regulation, including compliance with GCP regulations and guidance, and regulations designed to protect the rights and safety of subjects involved in investigations.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the U.S.

FDA and more frequently if serious adverse events occur.

In addition, IND safety reports must be submitted to the U.S.

FDA for any of the following:

serious and unexpected suspected adverse reactions;

findings from other studies or animal or in vitro testing that suggest a significant risk to humans exposed to the product;

and any clinically important increase in the case of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

FDA will typically inspect one or more clinical sites to assure compliance with GCPs, and the integrity of the clinical data submitted.

In December 2025, the U.S.

FDA released final guidance outlining its processes and practices applicable to bioresearch monitoring inspections.

FDA may order the temporary or permanent discontinuation of a clinical trial at any time or impose other sanctions if it believes that the clinical trial is not being conducted in accordance with U.S.

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The failure to submit clinical trial information to clinicaltrials.gov is a prohibited act under the FDCA with violations subject to potential civil monetary penalties, injunctions and/or criminal prosecution or disqualification from federal grants.

Although the U.S.

FDA has historically not enforced these reporting requirements, the U.S.

FDA has issued several notices of non-compliance to manufacturers since April 2021.

While these notices of non-compliance did not result in civil monetary penalties, the failure to submit clinical trial information to clinicaltrials.gov, as required, is a prohibited act under the FDCA with violations subject to potential civil monetary penalties of up to $10,000 for each day of the violation.

The results of the non-clinical studies and clinical trials, together with other detailed information, including the manufacture and composition of the product candidate, are submitted to the U.S.

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FDA will issue a “refuse-to-file” determination and request additional information before filing the NDA.

FDA reviews an NDA pursuant to certain timelines and goals established by the Prescription Drug User Fee Act.

FDA reviews an NDA pursuant to certain timelines and goals established by the PDUFA.

The review process, however, may be extended by U.S.

FDA requests for additional information, non-clinical or clinical studies, clarification regarding information already provided in the submission, or submission of a REMS.

FDA may refer an application to an advisory committee for review, evaluation and

recommendation as to whether the application should be approved.

FDA may refer an application to an advisory committee for review, evaluation and recommendation as to whether the application should be approved.

FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

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FDA decides not to approve an NDA, it will issue a Complete Response Letter outlining the deficiencies in the application and need for additional data and information.

If FDA approves an NDA, it may also limit the indications for use and/or require post marketing testing and surveillance to monitor the safety or efficacy of a product.

While Complete

Response Letters were previously treated by the U.S.

FDA as confidential and were only disclosed in action packages for approved products, the U.S.

FDA announced in September 2025 that it will release Complete Response Letters promptly after they are issued to sponsors.

Since that announcement, the U.S.

FDA has posted a number of Complete Response Letters on its website.

FDA approves an NDA, it may also limit the indications for use and/or require post marketing testing and surveillance to monitor the safety or efficacy of a product.

Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing.

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When an ANDA or 505(b)(2) application is submitted, it must contain one of several possible certifications regarding each of the patents listed in the Orange Book for the reference drug.

A certification that a listed patent is invalid, unenforceable or will not be infringed by the sale of the proposed product is called a “Paragraph IV” certification.

A certification that a listed patent is invalid, unenforceable or will not be infringed by the sale of the proposed product is called a “Paragraph

IV” certification.

A certification that provides the date a listed patent will expire, but does not challenge the validity, enforceability or infringement of the patent, is called a “Paragraph III” certification.

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FDA cannot approve the same product made by another manufacturer for the same indication during the market exclusivity period unless it has the consent of the sponsor, or the sponsor is unable to provide sufficient quantities.

Pediatric Exclusivity

Pediatric exclusivity is another type of regulatory exclusivity in the U.S.

and, if granted, provides for the attachment of an additional six months of regulatory exclusivity to the term of any existing patent or non-patent regulatory exclusivity, including orphan exclusivity, for drug products.

This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a written request from the U.S.

FDA for such data.

If the clinical trial is deemed to fairly respond to the U.S.

FDA’s request, the additional exclusivity protection is granted.

This is not a patent term extension, but it effectively extends the period during which the U.S.

FDA cannot approve another application.

Regulation of Drug-Device Combination Products in the U.S.

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These products are known as drug-device combination products.

Under the FDCA and its implementing regulations, the U.S.

Under the FDCA and its

implementing regulations, the U.S.

FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a drug-device combination product.

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FDA center responsible for premarket review of the drug product would have primary jurisdiction for the drug-device combination product.

established an Office of Combination Products to address issues surrounding combination products and provide more certainty to the regulatory review process.

FDA has also established an Office of Combination Products to address issues surrounding combination products and provide more certainty to the regulatory review process.

That office serves as a focal point for combination product issues for agency reviewers and industry.

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This final guidance calls for such communications to be truthful, non-misleading, factual, and unbiased and include all information necessary for healthcare providers to interpret the strengths and weaknesses and validity and utility of the information about the unapproved use.

On September 9, 2025, the President issued a Memorandum directing HHS to “ensure transparency and accuracy in direct-to-consumer prescription drug advertising, including by increasing the amount of information

regarding any risks associated with the use of any such prescription drug required to be provided in prescription drug advertisements.” To that end, the U.S.

FDA announced that it is initiating a rulemaking process “to eliminate the ‘adequate provision’ loophole that allows pharmaceutical advertisements to hide safety information by placing it in another format or location.” In this context, the U.S.

FDA declared that it will no longer tolerate what it characterized as “deceptive practices” in prescription drug advertising and that the agency would “aggressively deploy” its available enforcement tools, with “heightened scrutiny” of fair balance and disclosures in social media promotions.

FDA also issued a generic “notice letter” directing companies to “remove any noncompliant advertising and bring all promotional communications into compliance.”

Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and U.S.

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536/2014, or CTR, which entered into application on January 31, 2022, replacing Directive 2001/20/EC, or CTD.

The CTR is intended to harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase their transparency.

The CTR is intended to

harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase their transparency.

Prior to commencing a clinical trial, the sponsor must obtain a clinical trial authorization from competent authorities of E.U.

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Member State in which the original MA was granted.

To support the application, the MA holder must provide the EMA or the competent authority with a consolidated version of the electronic Common Technical Document providing up-to-date data concerning the quality, safety and efficacy of the product, including all variations introduced since the MA was granted, at least nine months before the MA ceases to be valid.

To support the application, the MA holder must provide the EMA or the competent authority with a consolidated version of the electronic Common Technical

Document providing up-to-date data concerning the quality, safety and efficacy of the product, including all variations introduced since the MA was granted, at least nine months before the MA ceases to be valid.

The European Commission or the competent authorities of the E.U.

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Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the E.U.

or, if there is, the new medicinal product will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of

therapy or improving existing ones.

or, if there is, the new medicinal product will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.

Benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and potentially accelerated MAA assessment once a dossier has been submitted.

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Where a medical device incorporates a medicinal product as an integral part as a single use drug delivery system, it is regulated as a medicinal product in accordance with Directive 2001/83/EC.

In this case, the relevant General Safety and Performance Requirements, or GSPRs of the MDR will apply to the safety and performance of the drug delivery device component.

In this case, the relevant General Safety and Performance Requirements of the Medical Device Regulation will apply to the safety and performance of the drug delivery device component.

Orphan Medicinal Product Designation and Exclusivity .

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Additionally, an MA may be granted to a similar medicinal product with the same orphan indication during the 10 year period if:

(i) if the applicant consents to a second original orphan medicinal product application, (ii) if the manufacturer of the original orphan medicinal product is unable to supply sufficient quantities;

(i) if the applicant consents to a second original orphan medicinal product application, (ii) if the manufacturer of the original orphan medicinal product is unable to supply sufficient

or (iii) if the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior to the original orphan medicinal product.

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A decision by a third-party payor not to cover our products or to restrict coverage of our products could reduce utilization of our products.

Moreover, a third-party payor’s decision to provide coverage for a finished drug product does not imply that an adequate reimbursement rate will be approved.

Moreover, a third-party payor’s

decision to provide coverage for a finished drug product does not imply that an adequate reimbursement rate will be approved.

Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

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Third party payors are increasingly challenging the prices charged for medical products and services and examining the medical necessity and cost effectiveness of medical products and services, in addition to their safety and efficacy.

Restrictions in coverage or decreases in third-party reimbursement for our products could have a material adverse effect

on our sales, results of operations and financial condition.

Restrictions in coverage or decreases in third-party reimbursement for our products could have a material adverse effect on our sales, results of operations and financial condition.

We expect that the pharmaceutical industry will experience pricing pressures due to the increasing influence of managed care (and related implementation of managed care strategies to control utilization), additional federal and state legislative and regulatory proposals to regulate pricing of drugs, limit coverage of drugs or reduce reimbursement for drugs, and public scrutiny of drug pricing.

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The CMS annually selects a specified number of negotiation-eligible drugs from those drugs with the highest total Medicare Part B or D expenditures over a preceding 12-month period.

Eligible drugs generally include single source brand-name drugs or biological products that have been on the market without therapeutically-equivalent generic or biosimilar alternatives for a specified number of years with certain exceptions (e.g., orphan drugs indicated for only one rare disease or condition and drugs with less than $200 million in annual Medicare expenditures).

Drugs and biologics that have been approved for a single rare disease or condition were originally categorically excluded from price negotiation.

With passage of the One Big Beautiful Bill Act on July 3, 2025, Congress extended this exemption to drugs and biologics with multiple orphan drug designations.

CMS will publish the negotiated price, known as the “Maximum Fair Price”, or MFP, for each of the selected products.

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Manufacturers who fail to negotiate or offer the MFP can face significant civil money penalties or excise tax liability on sales of that drug.

In 2024, the HHS published the results of the first Medicare drug price negotiations for ten selected drugs that treat a range of conditions, including diabetes, chronic kidney disease, and rheumatoid arthritis, and the prices of the selected drugs will become effective on January 1, 2026.

On January 17, 2025, HHS announced the selection of 15 additional drugs, which included LINZESS, covered by Medicare Part D, for the second cycle of price negotiations.

The negotiated price for LINZESS will be effective starting January 1, 2027.

In 2024, the HHS published the results of the first Medicare drug price negotiations for 10 selected drugs that treat a range of conditions, including diabetes, chronic kidney disease, and rheumatoid arthritis, and the prices of the selected drugs became effective on January 1, 2026.

On January 17, 2025, HHS announced the selection of 15 additional drugs, which included LINZESS, covered by Medicare Part D, for the second cycle of price negotiations, and on November 25, 2025, HHS released the MFP for LINZESS.

The MFP for a 30-day equivalent supply of LINZESS, which will become the new Medicare net price as of January 1, 2027, is set to $136.

The revised MFP for LINZESS was in line with our expectations.

On April 15, 2025, President Trump issued an Executive Order which directs HHS to take steps to reduce the prices of pharmaceutical products.

The new Executive Order, among other things, directs the U.S.

FDA to streamline and improve its existing drug importation program so as to make it easier for states to obtain approval without sacrificing the safety or quality of drug products.

Other provisions of the Executive Order relate to the 340B program.

With respect to the IRA’s Medicare drug pricing program, the Executive Order, among other things, calls for alignment in “the treatment of small molecule prescription drugs with that of biological products, ending the distortion that undermines

relative investment in small molecule prescription drugs, coupled with other reforms to prevent any increase in overall costs to Medicare and its beneficiaries.”

Further, on May 12, 2025, President Trump issued an additional Executive Order calling on pharmaceutical manufacturers to voluntarily reduce the prices of medicines in the U.S.

The Executive Order directs the Secretary of HHS to communicate most-favored-nation, or MFN, price targets to pharmaceutical manufacturers to bring prices in line with comparably developed nations.

The Executive Order further provides that if such actions do not lower the costs of pharmaceuticals, the Secretary of HHS would pursue other actions, including proposing a rulemaking that imposes MFN pricing in the United States.

Subsequently, on May 20, 2025, HHS indicated that the proposed MFN pricing will apply only to brand products without generic or biosimilar competition and the reference foreign countries will include only those in which the branded product similarly does not have generic or biosimilar competition.

Second, HHS indicated that the MFN target price will be the lowest price in a country that is a member of the Organization for Economic Co-operation and Development, or OECD, with a gross domestic product, or GDP, per capita of at least 60% of the U.S.

GDP per capita.

Based on previous estimates, there are likely at least 22 OECD countries that would satisfy this criterion.

The implications of these actions remain unclear and are likely to result in litigation if the administration pursues an MFN regulatory pricing requirement.

GDP per capita.

Based on previous estimates, there are likely at least 22 OECD countries that would satisfy this criterion.

On July 31, 2025, the President issued letters to 17 pharmaceutical companies reiterating the requirements of the May 12, 2025 Executive Order and demanding that such companies extend MFN pricing to Medicaid patients, guarantee MFN pricing for newly-launched drug products, return increased revenues abroad to American patients and provide for direct purchasing at MFN pricing.

The letters also urged these companies to stipulate that they will not offer other developed nations better prices for new drugs than the prices offered for such products in the U.S.

Nearly all of these pharmaceutical companies have entered into agreements with the Trump administration to provide for lower prices on certain pharmaceuticals.

While we cannot predict what executive, legislative and regulatory proposals will be adopted or other actions will occur, such events could have a material adverse effect on our business, financial condition and profitability.

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The California Confidentiality of Medical Information Act also applies to pharmaceutical companies, including requirements for written authorization to use and disclose medical information and restrictions on the circumstances under which medical information can be used for marketing purposes.

In addition, Washington state recently passed the My Health My Data Act, a health privacy law, which regulates the collection and sharing of health information, and provides a right of action for violation of the statute.

In addition, Washington state passed the My Health My Data Act, a health privacy law, which regulates the collection and sharing of health information, and provides a right of action for violation of the statute.

Other states have also recently enacted or are considering enacting comprehensive data privacy and security laws to which we may become subject, and all fifty states and U.S.

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As of December 31, 2025, we had 100 employees.

Of these employees, 69 were on our drug development team, 131 were on our sales and commercial team, and 53 were in general and administrative functions.

Of these employees, 66 were on our drug development team and 34 were in selling, general and administrative functions.

We consider our employee relations to be good.

In January 2025, following an analysis of our strategy and core business needs, and in an effort to streamline focus and support the continued development of our pipeline, we commenced a reduction in our workforce of approximately 50%, primarily consisting of field-based sales employees.

This reduction in workforce is expected to be substantially completed by the end of the first half of 2025.

This reduction in workforce was substantially completed during the first quarter of 2025.

In August 2025, we eliminated certain positions supporting apraglutide commercialization efforts, in consideration of delays in development timelines.

This reduction in workforce was comprised of 10 positions and was completed during the third quarter of 2025.

Refer to Note 16, Workforce Reductions and Restructuring , to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K for further details.

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We seek to foster an environment where employees feel included and empowered.

This approach includes diversity initiatives such as learning and development opportunities, strengthened talent acquisition strategies, and the support of equality programs in our local communities.

We are also proud to have several strong and growing employee resource groups.

This approach includes initiatives such as learning and development opportunities, strengthened talent acquisition strategies, and the support of equality programs in our local communities.

Compensation and Benefits

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business